Document VG9v2MXwmwmV6zqaRznoLR6nq

Study Title frKIZ- O g z 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 C9 ~5X0> rvoX> 0~--5oat rror 'j -o o r n *r2o er 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 FIFRA/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 noncompliance: 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: Date 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 LETTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSORS STUDY NUMBER: T-6889.6 TABLE OF CONTENTS SUBJECT l. SUMMARY AND CONCLUSION A. Methods B. Results C. Conclusion E. 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 1. 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) - Summary 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 T a b le d . 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 Cil. Maternal Relative Feed Consumption Values (g/kg/day) - Gestation Summary - P Generation Female Rats 187 Table 0 2 . Maternal Absolute Feed Consumption Values (g/day) - Lactation Summary - P Generation Female Rats 188 Table 0 3 . Maternal Relative Feed Consumption Values (g/kg/day) Lactation - Summary - P Generation Female Rats 189 Table 0 4 . Mating and Fertility, Estrous Cycling and Days in Cohabitation Summary - P Generation Female Rats 190 Table 0 5 . Necropsy Observations - Summary - P Generation Female Rats 192 Table 0 6 . Terminal Body Weights and Organ Weights - Summary P Generation Female Rats 193 Table 0 7 . Ratios (%) of Organ Weight to Terminal Body Weight - Summary - P Generation Female Rats 194 Table 0 8 . Ratios (%) of Organ Weight to Brain Weight - Summary P Generation Female Rats 195 Table 0 9 . 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 - FI 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 DIO. 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 GENERATION FEMALE 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 E12. 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 E14. 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 l 6. Necropsy Observations - Summary - FI Generation Female Rats 496 Table E17. 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 E19. 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. Methods3 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 FI generation 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 B .l. P Generation Male Rats ARGUS 418-020 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. F I 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. Page 24 ARGUS 418-020 IL 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)(1,2) 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 .ll. 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 Periodb (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 0 1 -02 MAR 01 07 NOV 00 13 NOV 00- 18 MAR 01 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 MAR 01 - 19 MAR 01 06 MAR 01 - 05 JUL 01 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 1 postpartum (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 DL 1 DG 25 Sacrifice (Rats that did not deliver a litter) DL 22 Sacrifice (FI generation dams and F2 generation pups) 06 MAR 01 - 15 JUL 01 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 JUL 01 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 o f 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 of 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 JUL 01 13 NOV 00 (all levels)a 12 JUL 01 protected from light 12 JUL 01 Stability 2 mL 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 L 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 of 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 of Laboratory Animals(8). 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 Dosage Concentration3 Dosage Volume Number of Rats Group (mg/kg/day) (mg/mL) (mL/kg) per Sex Assigned Rat Numbers Male Rats Female Rats I0 0 5 30 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, 19779d, 19780d, 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 weighta and 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 sacrifice0. 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 perioda. 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 t_ 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 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 daya. 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 postpartum15. 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 of 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 F I 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 carcass5. 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 Bouin'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 Thorne 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: I. Parametric Type of Test3 i- E. Nonparametric 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) Dunnett's Test in. 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 Variances(10) 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 Test00 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 Test(13) was used, when 75% or fewer ties were present; when more than 75% ties were present, Fisher's Exact Test00 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 III. 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 /?<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<0.01) 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 p<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 (/?<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 (p<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 B ll and B12; Individual Data Tables B20andB21) 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 C l; 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 dosagedependent; 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 cornea 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 p<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 cornea, 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, corneal 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, corneal 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, em aciation 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 of 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 /?<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 (p<0.05 or p<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 - F I 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 /?<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 (/?<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 or p<0.01) 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 /?<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 /?<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 /?<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 D12; 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 E l; 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 p<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 (p<0.01) on DPs 1 to 8 and 8 to 15. Body weights in this group were significantly reduced (p<0.05 or /?<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 /?<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 to 15. 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<0.0l) 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 EI9; 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 of 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 dosagedependent; 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.11. 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). Guide for the Care and Use of 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). Nonparametric Statisticsfor 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: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) BODY WEIGHTS P GENERATION MALE RATS Figure 1 0 MG/KG/DAY 1 MG/KG/DAY *Sa0 3 MG/KG/DAY CfQ CD 10 MG/KG/DAY 30 MG/KG/DAY * p<0.05 ** p<0.01 Last value recorded before cohabitation. First value recorded after cohabitation. Terminal body weight. % GO oo 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) BODY WEIGHTS P GENERATION FEMALE RATS Figure 2 0 MG/KG/DAY 1 MG/KG/DAY *0 CTQ 3 MG/KG/DAY CD -toJ 10 MG/KG/DAY 30 MG/KG/DAY p<0.05 a. Last value recorded before cohabitation. 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) 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 after cohabitation. 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) BODY WEIGHTS F1 GENERATION FEMALE RATS Figure 4 0 (MG/KG/DAY) 1 (MG/KG/DAY) 3 (MG/KG/DAY) fa Q O O4^ 10 (MG/KG/DAY) 30 (MG/KG/DAY) * p<0.05 ** p<0.01 a. Precohabitation body weight. DAY POSTWEANING DAY OF GESTATION DAY OF LACTATION 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) T A B LE B 1 (P A G E 1) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 76 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III IV 0 1 3 10 M AXIM U M P O S S IB L E IN C ID E N C E 3 2 40 / 30 3 2 4 0 / 30 3 240 / 30 3 2 4 0 / 30 M O R IB U N D S A C R IF IC E D 000 0 C H R O M O R H IN O R R H EA 3/ 2 10/ 2 26/ 7 15 / 5 D EH Y D R A T IO N 0/ 0 0/ 0 0/ 0 0/ 0 S O FT OR LIQ U ID FEC ES LO C A LIZE D A LO P E C IA : TO TAL LIM B S H EA D 17/ 7 39 6 / 396/ 0/ 8 8 0 12/ 8 63/ 58/ 5/ 2** 1** 1 3/ 2 84/ 84/ 0/ 3 ** 3 ** 0 11/ 3 38/ 38/ 0/ 1** 3 _ ** 0 U R IN E -S T A IN E D A B D O M IN A L FU R 0/ 0 0/ 0 0/ 0 0/ 0 UNGROOM ED CO AT 0/ 0 0/ 0 0/ 0 0/ 0 EM A C IA T IO N 0/ 0 0/ 0 0/ 0 0/ 0 D R IED R ED OR R ED P ER IN A S A L SU BSTANC E 0/ 0 0/ 0 0/ 0 0/ 0 COLD TO TOUCH 0/ 0 0/ 0 0/ 0 0/ 0 IN C IS O R S : TO TA L M IS S IN G /B R O K EN M IS A LIG N ED 16 / 16 / 0/ 1 1 0 85/ 36/ 53/ 4 4 2 15 3 / 56/ 120/ 3 2 2 35/ 16 / 19 / 2 2 1 CHROM ODACRYORRHEA 0/ 0 35/ 2 124/ 2 21/ 1 D EC R EA S ED M OTOR A C T IV IT Y 0/ 0 0/ 0 0/ 0 0/ 0 P A LE EX T R E M IT IE S 0/ 0 0/ 0 0/ 0 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L I N IC A L O B S E R V A T IO N D A T A W ERE R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H O B S E R V A T IO N S . M AXIM U M P O S S IB L E I N C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S E R V A T IO N S /N U M B E R O F R A T S W IT H O B S E R V A T IO N , a . R a t 13 73 2 w as m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 .0 1 ) . V 30 3 178 / 30 la 27/ 8 30/ 4 **a 4/ 3 14 1/ 14 1/ 0/ 3** 3** 0 13 / 3 **a 21/ 3* * 34/ 2a 8/ 2 6/ 2a 11/ 0/ 11/ 1 0 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-6889.6) T A B LE B 1 (P A G E 2) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 77 DOSAGE GROUP D O S A G E (M G /K G /D A Y) I I I I I I IV 0 1 3 10 M AXIM U M P O S S IB L E IN C ID E N C E 3 2 4 0 / 30 3 2 40 / 30 3 240 / 30 3 2 4 0 / 30 M O R IB U N D S A C R IF IC E D 00 00 D R IED , RED SUBSTANCE ON FUR b 0/ 0 0/ 0 0/ 0 0/ 0 NO FEC ES 0/ 0 0/ 0 0/ 0 0/ 0 SCANT FEC ES 0/ 0 0/ 0 0/ 0 0/ 0 R ALES 0/ 0 0/ 0 0/ 0 0/ 0 R IG H T OR BOTH EA R S : SW O LLEN SCAB C 15 / 1 0/ 0 38/ 2 46/ 4 ** 0/ 0 8/ 2* 11/ 1 0/ 0 R IG H T F O R E L IM B : A B R A S IO N 0/ 0 4/ i 0/ 0 0/ 0 P E N IS : RED SUBSTANCE 0/ 0 1/ i 0/ 0 0/ 0 V O C A LIZA T IO N 1/ 1 0/ 0 0/ 0 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L I N IC A L O B S E R V A T IO N D A T A W ERE R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H O B S E R V A T IO N S . M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . R a t 13 73 2 w as m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y . b . Lo c a te d on b o th fo re p a w s . c . L o c a te d o n th e n o s e , m o u th , h e a d , r ig h t fo r e lim b o r b a c k . * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . V 30 3 17 8 / 30 la 6/ 1 2/ 1 2/ 1 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 00 / PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E B2 (P A G E 1) : B O D Y W EIG H T S - SUM M ARY - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 78 DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TES TED B O D Y W E IG H T (G) DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 D A Y 36 DA Y 43 D A Y 50 DAY 57 D A Y 64 I 0 N 30 M EANS.D . M EANS.D . M EANS.D . M EANS.D . M EAN+S.D . M EANS. D . M EANS.D . M EANS. D . M EANS.D . M E A N + S .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 2 9 7 .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 + 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 O F STUDY ( ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h was m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S i g n i f i c a n t l y d i f f e r e n t f r o m t h e G r o u p I v a l u e ( p < : 0 . 0 1 ) . IV V 10 30 30 30 178.4 + 7.2 238.1 + 10.4 282.4 1 4 .7 * * 316.8 + 2 2 . 6* * 345.2 2 7 .4 * * 363.4 3 1 .9 * * 384.2 + 3 7 .5 ** 404.2 + 3 9 .0 ** 421.5 + 4 2 .9 ** 434.1 + 4 4 .9 ** 178.6 7.2 211.3 1 7 .0 ** 259.4 1 6 .0 ** 284.9 2 6 .3 ** 300.9 2 9 .9 ** 312.3 3 5 .2 ** 326.3 4 5 .8 ** 341.7 3 9 .1** [ 29] a 359.3 4 4 .0 ** [ 29] a 367.6 4 9 .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) T A B L E B2 (P A G E 2) : B O D Y W EIG H T S - SUM M ARY - P G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TES TED N I 0 30 II III 13 30 30 IN C LU D ED IN A N A LYS ES N 30 30 30 B O D Y W EIG H T (G) DAY 70b M EANS.D . 5 0 1.1 + 33.8 498.0 38.8 470.4 43.2* DAY 85c M EANS.D . 528.3 + 34.7 528.8 43.2 495.8 42.3* D A Y 92 D A Y 99 M EANS.D . M EANS.D . 543.8 3 7 .1 561.1 37.8 541.6 43.1 555.1 44.2 506.7 4 4 .7 ** 521.6 4 7 5 ** DAY 106 M E A N S .D . 575.5 39.7 568.3 45.2 533.8 4 6 .2 ** T ER M IN A L B O D Y W EIG H T d M EANS.D . 580.7 40.0 575.3 47.6 541.7 4 7.2 ** DAY a. b. c. d. * ** = DAY O F STUDY E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . F i r s t v a lu e re c o rd e d a ft e r c o h a b ita tio n . T e rm in a l b o d y w e ig h ts w e re re c o rd e d w hen S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y . th e r a ts w ere d a y 106 to 109 o f s tu d y . v a lu e ( p < 0 .0 5 ) . v a lu e ( p < 0 .0 1 ) . IV 10 30 30 444.2 4 6 .2 ** 468.3 4 9 .2 ** 479.9 5 2 .0 ** 495.8 5 3 .0 ** 504.9 5 4 .4 ** 513.0 53 .9 ** V 30 30 29a 375.0 54.0** 389.9 6 4 .4 ** 400.9 6 9 .2 ** 414.6 64.3** 424.3 62.9** 431.8 6 4 .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) T A B L E B3 (P A G E 1 ) : B O D Y W EIG H T C H A N G ES - SUM M ARY - P G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 80 DOSAGE GROUP D O S AG E (M G /K G /D AY) RATS TES TED B O D Y W EIG H T C H A N G E (G) DAYS 1 - 8 DAYS 8 - 15 D AYS 15 - 22 D AYS 22 - 29 D AYS 29 - 36 D AYS 36 - 43 D A YS 43 - 50 D A YS 50 - 5 7 D A Y S 5 7 - 64 N M E A N S .D . M EAN+S.D . M EANS.D . M EANS.D . M EANS.D . M E A N S .D . M E A N S .D . M E A N S .D . M EANS.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 +2 2 .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 10 .7 +21.0 + 6 . 6 * * +22.7 + 9.7 +18.7 + 5 .2 ** +19.1 8.3 +15.1 + 7.0 DAYS = DAYS O F STUDY [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r if ic e d on d a y 45 o f s tu d y . * S i g n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S i g n i f i c a n t l y d i f f e r e n t f r o m t h e G r o u p I v a l u e ( p ^ O . O l ) . IV 10 30 +59.7 + 6.2 +44.3 + 1 0 . 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 1 7 .0 ** +48.1 + 10.8* +25.5 1 7 .8 * * +16.0 16 .5 ** +11.4 10.5** +14.0 2 6 .7 ** +10.7 16 .5 ** [ 29] a +17.6 1 4 . 7 ( 29] a +8.2 9 .6 ** [ 29] a GUS 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) T A B L E B3 (P A G E 2 ) : B O D Y W EIG H T C H A N G ES - SUM M ARY - P G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 RATS TES TED N 30 30 30 IN C LU D ED IN A N A LYS ES N 30 30 30 B O D Y W EIG H T C H A N G E (G) D A Y S 64 - 70 b DAYS 1 - 70b M EAN+S. D . M EANS.D . +13.2 7.4 + 3 2 0 .2 30.8 +11.9 10.8 + 3 1 7 . 3 3 7 . 3 +10.5 10.7 + 2 9 0 . 5 4 3 . 1 * D A Y S 8 5 c - 92 M EANS. D . +15.5 + 7.4 +12.8 5.4 +10.9 6 . 8* D A Y S 92 - 99 M EAN+S. D . +17.3 5.8 +13.6 5.5 +14.9 7.6 D A Y S 99 - 1 0 6 M EANS. D . +14.4 7 .1 +13.2 6.1 +12.3 10.0 DAYS 1 -106 M EANS.D . +394.6 36.8 + 3 8 7.7 43.4 + 3 5 3 . 9 4 6 . 6 * * DAY 1- T ER M IN A T IO N d M EANS.D . +399.8 37.0 +394.7 45.7 + 3 6 1 . 8 4 7 . 7 * * D A Y (S ) = D A Y(S ) O F STUDY a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as b . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . c . F i r s t v a lu e re c o rd e d a ft e r c o h a b ita tio n . d . T e rm in a l b o d y w e ig h ts w ere re c o rd e d w hen * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I * * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y . th e r a ts w ere da y 106 to 109 o f s tu d y . v a lu e (p < 0 .0 5 ) . v a lu e ( p < 0 .0 1 ) . IV 10 30 30 + 1 0 . 1 7 .0 + 2 6 5 . 8 4 4 . 5 * * +11.6 7 .7 +15.9 + 6 .7 +9 .1 9.2 + 3 2 6 . 5 5 3 . 1 * * +334.5+ 5 2 .6 ** V 30 30 2 9a +7.4 9.8 + 1 9 6 . 6 5 3 . 2 * * +11.0 18.4 +13.7 16.5 +9.7 11.3 + 2 4 6 . 0 6 1 . 5 * * +253.4 6 2 .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) T A B L E B4 (P A G E 1) : A B S O LU T E F E E D C O N S U M PTIO N V A LU E S (G /D A Y ) - SUM M ARY - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 82 DOSAGE GROUP D O S A G E (M G /K G /D A Y) I II III 013 RATS TES TED N 30 30 30 F E E D C O N S U M P TIO N (G /D A Y ) DAYS 1 - 8 M EANS.D . 23.8 1.6 23.9 1.3 23.9 1.2 D AYS 8 - 15 DAYS 15 - 22 M E A N S .D . M EANS. D . 26.6 28.7 3.2 1.6 26.4 28.8 1.8 2.3 26.1 [ 28] a 28.6 2.2 2.0 D AYS 22 - 29 D A YS 29 - 36 D A YS 36 - 43 M EAN+S.D . M EANS.D . M EANS.D . 28.0 27.8 28.3 1.9 1.9 2.1 28.6 2.2 28.2 [ 29] a 28.3 2.1 2.3 28.2 2.6 28.1 [ 28] a 28.4 2.6 2 .7 D A Y S 43 - 50 D A YS 50 - 57 D A Y S 5 7 - 64 M EANS. D . M EANS.D . M EAN+S.D . 28.7 [ 29] a 29.4 [ 29] a 29.8 1.9 1.8 2.2 28.6 29.6 29.9 2.4 3.0 2.5 28.4 + [ 29] a 29.4 2 .7 2.9 29.4 3.5 D AYS 64 - 70 c DAYS 1 - 70c D A Y S 8 5 d - 92 D A Y S 92 - 99 D A Y S 99 - 10 6 D AYS 1 - 106 M E A N S .D . M EANS. D . M EANS.D . M EANS.D . M EANS. D . M EANS.D . 28.2 [ 29] a 27.9 [ 29] a 29.9 t 29] a 29.0 2.1 1.5 2.4 2.4 28.9 2.1 28.3 1.6 29.3 [ 29] a 28.1 [ 29] a 29.8 2.8 1.8 3 .1 29.2 2.8 29.3 [ 29] a 28.3 ( 29] a 2.4 1.8 29.3 [ 26] a 28.1 [ 26] a 29.7 4.0 2.0 3.0 29.1 3.2 28.7 ( 27] a 28.1 [ 27] a 2 .7 2.2 DAYS = DAYS O F STUDY [ ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e . b . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h was m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . c . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . d . F i r s t v a lu e re c o rd e d a fte r c o h a b ita tio n . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . IV 10 30 23.0 1.6 25.7 2.2 28.9 3 .1 28.5 [ 29] a 28.4 3.2 3.4 28.5 3.4 28.7 [ 28] a 29.2 3.4 3.4 29.5 3.5 28.5 [ 29] a 27.9 [ 29] a 29.5 3.5 2 .7 3.9 28.9 3.8 28.2 [ 29] a 28.1 [ 29] a 3.8 2.8 V 30 30 19.5 [ 29] a 25.1 3 .3 ** 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 ** [ 2 9] b 25.8 3 .2** ( 29] b 25.6 2 .2** [ 29] b 26.3 5 .3 ** [ 29] b 26.6 3 . 0* * [ 29] b 25.8 3 .2** [ 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) T A B L E B5 (P A G E 1 ) : R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - SUM M ARY - P G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 83 DOSAGE GROUP D O S A G E (M G /K G /D A Y) I II III 013 RATS TES TED N 30 30 30 F E E D C O N S U M P TIO N (G /K G /D A Y) DAYS 1 - 8 D AYS 8 - 15 DAYS 15 - 22 M EANS.D . M EANS.D . M EANS.D . 112.2 + 5.7 98.8 10.9 90.6 4.6 112.8 97.8 90.2 5.0 6.5 5.7 112.2 4.4 96.7 [ 28] a 90.7 7.8 5.4 D A YS 22 - 29 M EANS. D . 78.8 3.8 79.6 4.5 80.8 5.4 D AYS 29 - 36 DAYS 36 - 43 M EANS. D . M EANS.D . 72.4 + 69.0 3 .1 3.6 71.9 [ 29] a 68.2 3.4 5.1 75.4 [ 28] a 71.7 4 .6 * 5.3 D A YS 43 - 50 D AYS 50 - 57 D A Y S 5 7 - 64 M EANS.D . M EANS.D . M EAN+S.D . 66.0 [ 29] a 64.0 [ 29] a 62.2 3 .7 2.9 3 .1 65.3 64.6 62.7 4 .7 6.1 4.0 68.5 [ 29] a 67.6 5.2 5.5* 65.2 7 .1 * D AYS 64 - 70 c DAYS 1 - 70c D A Y S 8 5 d - 92 D A Y S 92 - 99 M EANS.D . M EANS.D . M EANS.D . M EANS.D . 57.1 [ 29] a 73.7 [ 29] a 55.7 [ 29] a 52.6 2.4 2.2 3.5 2 .7 59.8 [ 29] a 74.3 [ 29] a 55.9 5.6 3 .7 5.2 53.3 4.4 63.4 [ 26] a 77.1 + [ 26] a 59.4 9 .1** 4 .7 * 4 .7 ** 56.7 4 .8 ** D A YS 99 - 106 DAYS 1 - 106 M EANS.D . M E A N + S .D . 50.9 65.8 2.8 2.4 52.6 [ 29] a 66.4 [ 29] a 3.4 3.6 54.7 [ 27] a 69.2 [ 27] a 4 .0** 4 .3 ** DAYS = DAYS O F STUDY [ ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e . b . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r if ic e d o n d a y 45 o f s tu d y . c . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . d . F i r s t v a lu e re c o rd e d a ft e r c o h a b ita tio n . * S ig n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S i g n i f i c a n t l y d i f f e r e n t f r o m t h e G r o u p I v a l u e ( p < 0 . 0 1 ) . IV 10 30 110.6 + 5.6 98.6 6.4 96.2 7.4 ** 85.7 [ 29] a 80.0 5 .6** 6 .4** 76.3 6 .2** 73.4 [ 28] a 70.7 + 7 7** 5 .6 ** 69.1 5 .8 ** 65.0 [ 29] a 80.5 ( 29] a 62.4 7 .2 ** 4 .7 ** 6 .3 ** 59.3 5 .5 ** 56.6 [ 29] a 72.6 [ 29] a 4.9 ** 4 .4 ** V 30 30 99.8 1 4 .8 * * [ 29] a 107.1 10.9** 97.9 15 .3 ** 89.0 8 .5 ** 83.2 6 .2 ** 79.0 1 4 .8 ** 78.7 7.6 ** [ 28]a,b 76.7 7.4 ** [ 29] b 74.8 7.0 ** [ 29] b 70.0 6 .9 ** [ 29] b 84.8 6 . 6* * [ 29] b 66.6 + 1 2 .4 ** ( 29] b 66.5 1 0 .5 ** ( 29] b 62.5 1 1 .8 * * [ 29] b 77.6 6 .3 ** ( 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) T A B L E B 6 (P A G E 1) : M A TIN G AN D F E R T I L I T Y - SUM M ARY - P G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 01 3 R A TS IN C O H A B IT A T IO N N 29 29 30 D A YS IN C O H A B IT A T IO N a M EAN+S. D . 3 .3 + 2 .6 1 .9 + 1 . 2 * 2.4 + 1 .7 C 29] RATS TH AT M ATED N (%) 29(100.0) 29(100.0) 30 ( 1 0 0 .0 ) F E R T IL IT Y IN D EX b R A T S W IT H C O N FIR M ED M A TIN G D A T ES N /N (*) N 2 8 / 29 ( 96.6) 29 2 7 / 29 ( 93.1) 29 3 0 / 30 (1 0 0 . 0 ) 29 R A TS M A TIN G DAYS 1 -7 DAYS 8-14 C N(%) N(%) 27( 93.1) 2( 6.9) 29(100.0) 0 ( 0 .0) 28 ( 96.6) M 3.4) RATS PREGNANT/RATS IN C O H A B IT A T IO N N /N (%) 2 8 / 29 ( 96.6) 2 7/ 29 ( 93.1) 3 0 / 30 (1 0 0 . 0 ) [ ] = NUM BER O F V A LU ES A V ER AG ED a . R e s t r ic t e d to r a ts w ith a c o n firm e d m a tin g d a te an d r a ts th a t d id n o t m a te . b . Num ber o f p re g n a n c ie s /n u m b e r o f r a t s th a t m a te d . c . R e s tr ic te d to r a ts w ith a c o n firm e d m a tin g d a te . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . IV 10 30 3 .1 + 2.4 [ 28] 29{ 96.7) 2 9 / 29 (1 0 0 . 0 ) 27 27(100.0) 0 ( 0 .0) 2 9 / 30 ( 96.7) V 30 29 2 . 6 + 1.4 ( 28] 29(100.0) 2 8 / 29 ( 96.6) 28 28 (1 0 0 . 0 ) 0 ( 0 .0) 2 8 / 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) T A B LE B 7 (P A G E 1) : N EC R O P S Y O B S ER V A TIO N S - SUM M ARY - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 85 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 R A TS EX A M IN ED a N 30 30 30 30 0 0 0 0M O R I B U N D S A C R I F I C E D N APPEARED NORM AL N 29 28 28 28 TESTES : R IG H T O R B IL A T E R A L , 0 1 0 1S M A L L A N D F L A C C I D N L E F T , LARG E N0 0 0 0 0 0 0 0B I L A T E R A L , R E D N E P ID ID Y M ID ES : R IG H T , L E F T OR B IL A T E R A L , 0 1 0 1S M A L L A N D F L A C C I D N K ID N EY S : R IG H T , P E L V IS , S LIG H T OR 0 1 2 1M O D E R A T E D I L A T I O N N LU N G S : A L L LO B E S , NUM EROUS 1 0 0 0D A R K R E D A R E A S N LIV E R : A LL LO B ES , TAN AND P A LE N0 0 0 0 a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le B 12 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . R a t 13 73 2 w as m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . 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) T A B L E B8 (P A G E 1 ) : T E R M IN A L B O D Y W EIG H T S A N D O RG AN W EIG H TS - SUM M ARY - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 86 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 RATS TESTED N 30 30 30 30 T E R M IN A L B O D Y W EIG H T M EANS. D . 580.7 40.0 575.3 47.6 541.7 4 7.2 ** 513.0 53 .9 ** E P ID ID Y M IS L E F T M EANS.D . 0 .72 10 0.0599 0.6991 0.0468 0.6901 0.0477 0.7039 0.0476 CAU DA E P ID ID Y M IS L E F T M EAN+S. D . 0.3320 0.0398 0.3172 0.0256 0.3148 0.0280 0.3215 0.0307 T E S T IS L E FT M EANS. D . 1.7953 0.1369 1.8103 0.1477 1.7868 0.1312 1.8194 0.0995 L E F T T E S T IS M IN U S T U N IC A A LB U G IN EA M EANS. D . 1.6613 0.1410 1.6822 0.1356 1.6598 0.1268 1.6955 0.0943 S EM IN A L V E S IC LE S W IT H F L U ID S EM IN A L V E S IC LE S W IT H O U T F L U ID M EANS.D . M EANS. D . 2.2662 0.3478 [ 29] b 1.2686 0.1554 2.3326 0.3472 1.2539 0.1685 2.3550 0.3246 1.2789 0.1608 2.3052 0.3281 [ 28] b 1.2664 0.1670* E P ID ID Y M IS R IG H T M EANS. D . 0.718 7 0.0573 0.6891 0.0791 0.6930 0.0521 0 .6 771 0.0958 T E S T IS R IG H T M EANS. D . 1.8173 0.1687 1.8398 0.3036 1.79 15 0.1293 1.7660 0.2117 PROSTATE M EANS.D . 1.1378 0.1852 1.142 6 0.2030 1 .1 1 8 1 0.1672 1.0368 0.2031 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . b . E x c lu d e s v a lu e s f o r r a ts th a t h a d f l u i d lo s s p r io r t o w e ig h in g o r o rg a n s dam aged * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p ^ O . O l ) . (w e ig h t a f f e c t e d ) . V 30 29a 431.8 6 4 .1** 0.6322 0.0 722** 0.2898 0.0374** 1.78 78 0.2930 1.6361 0.3290 2.0652 0.2934* 1.1329 0.1545** 0.6366 0.0663** 1 .74 75 0.2063 0.8619 0.18 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) T A B L E B8 (P A G E 2 ) : T E R M IN A L B O D Y W EIG H TS A N D O R G A N W EIG H TS - SUM M ARY - P G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D A Y) I II III 013 RATS TES TED P IT U IT A R Y B R A IN N M EANS.D . M EANS.D . 30 0.014 0.004 2.26 0 .1 7 30 0.014 + 0.003 2 . 2 8 + 0.10 30 0.012 0 . 0 0 3 * 2 . 2 6 0.12 LIV E R K ID N EY L E F T M EANS. D . M EANS. D . 20.30 2.46 2 . 1 9 + 0.20 24.27 + 3 .22** 2.51 0.28** 27.71 2.74** 02 . 5 1 + .2 1 ** K ID N E Y R IG H T M EANS.D . 2.19 0.18 2.54 0 .3 0 ** 2.50 0 .1 8 ** ADRENAL LE FT M EAN+S.D . 0.032 + 0.005 0.032 0.004 0.030 + 0.006 A D R EN A L R IG H T S P LEEN THYM US M EANS.D . M EANS.D . M EAN+S.D . 0.032 + 0.005 0.94 + 0.44 0.16 0.10 0.031 0.005 0 . 8 7 0.12 0.38 0.08 0.030 0.008 0.86 0.11 0 . 3 8 + 0.10 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h was m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . * S i g n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S i g n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . IV 10 30 0.014 0.003 2 . 2 4 + 0.12 28.74 + 3.8 8 ** 2.34 0.24* 2.36 0 .2 5 ** 0.030 0.006 0.031 0.007 0.87 0.14 0.40 0.14 V 30 2 9a 0.010 + 0 . 0 0 3 * * 2.20 0 . 1 4 27.49 + 3.68** 1.99 2.06 0 .1 9 ** 0. 2 0 * 0.028 + 0.006** 0.026 + 0 .0 0 7** 0.74 + 0 .1 7 ** 0.30 + 0 .0 9 ** 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) T A B L E B 9 (P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T - SU M M ARY - P G E N E R A T IO N M A L E R A T S ARGUS 418-020 Page 88 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV V 10 3 0 RATS TES TED N 30 30 30 30 29a T E R M IN A L B O D Y W EIG H T EP ID ID Y M IS L E F T CAUDA E P ID ID Y M IS L E F T M EANS.D . M EANS.D . M EANS.D . 580.7 + 40.0 0.123 + 0.013 0.058 0.007 575.3 47.6 0 . 1 2 3 0.010 0.055 0.007 541.7 + 4 7 .2 ** 0 . 1 2 7 + 0.011 0.057 0.006 513.0 53 .9 ** 0.138 + 0 .0 15 ** 0.062 0.008 431.8 6 4 .1** 0.150 0.023** 00 . 0 6 7 . 0 1 2 * * T E S T IS L E F T M EANS.D . 0.3 11 0.025 0.316 0.031 0.332 0.036 0.358 0 .0 4 2 ** 0.419 0.080** L E F T T E S T IS M IN U S T U N IC A A LB U G IN E A M EANS.D . 0.287 0.026 0.294 0.030 0.307 0.034 0.333 + 0 .0 4 0 ** 0.386 + 0.0 89 ** S EM IN A L V E S IC LE S W IT H F L U ID S EM IN A L V E S IC LE S W IT H O U T F L U ID E P ID ID Y M IS R IG H T M E A N S .D . M EANS.D . M EANS.D . 0.397 0.062 [ 29] b 0.219 0.026 0 . 1 2 3 + 0.012 0.407 + 0.068 0.219 0.031 0.120 0 . 0 1 7 0.436 0.064* 0.237 0.034 0 . 1 2 8 0.012 0.465 0.0 6 2** [ 28] b 0.249 0 .0 3 4 ** 00 . 1 3 3 + . 0 2 2 * * 0.484 0.0 76 ** 0.266 0.0 44** 00 . 1 4 9 . 0 2 2 * * T E S T IS R IG H T PROSTATE M E A N S .D . M EAN+S.D . 0.313 0.028 0.195 0.033 0.321 0.056 0.200 0 . 0 4 5 0.334 0.036 0.207 0.033 0.347 0.055** 0.202 0 . 0 3 8 0.410 0.064** 0.199 0.035 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . [ ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . b . E x c lu d e s v a lu e s f o r r a ts th a t h ad f l u i d lo s s p r io r to w e ig h in g o r o rg a n s dam aged (w e ig h t a f f e c t e d ) . * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p 0 . 0 5 ) . ** S ig n ific a n t ly d iff e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 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) T A B L E B 9 (P A G E 2 ) : R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T - S U M M ARY - P G E N E R A T IO N M A L E R A T S ARGUS 418-020 Page 89 DOSAGE GROUP D O S AG E (M G /K G /D AY) I II III 013 IV V 10 3 0 RATS TES TED N 30 30 30 30 29a T E R M IN A L B O D Y W EIG H T M EANS. D . 580.7 40.0 575.3 + 47.6 541.7 4 7.2 ** 513.0 5 3 .9 ** 431.8 + 6 4 .1** P IT U IT A R Y b M EANS.D . 2.409 0.607 2.435 0.533 2.248 + 0.543 2.752 0.748 2.476 0.749 B R A IN M EANS.D . 0.390 + 0.034 0.399 0.035 0.418 0.038* 0.442 0.056** 0.518 0.066** LIV E R M EANS. D . 3.490 0.286 4.223 0.500** 5.131 + 0.472** 5.606 0 .5 1 4 ** 6.420 + 0 .72 9 ** K ID N EY L E F T M EANS.D . 0.378 0.036 0.437 + 0 .0 4 7** 0.465 0.0 43** 0.457 0.040** 0.466 + 0.0 54** K ID N E Y R IG H T M EANS.D . 0.379 + 0.030 0.443 + 0 .0 48 ** 0.463 + 0.0 39 ** 0.462 0.0 34** 0.481 0.051** ADRENAL LE FT b M EAN+S. D . 5.562 0.786 5.575 0.74 9 5.594 1.125 5.879 + 1.094 6.593 + 1 .7 7 6 * A D R EN A L R IG H T b S P LEEN THYM US M EANS. D . M EANS. D . M EANS. D . 5.439 + 0.852 0.161 0.027 0.075 0.017 5.361 1.016 0 . 1 5 2 0.020 0 . 0 6 6 + 0.012 5.513 + 1.361 0.160 + 0.024 0.071 0.017 6.157 1.646 0.169 0.025 0.079 0.027 6 .1 7 7 1.589 0 .1 7 1 0.035 0 . 0 7 1 0.022 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y . b . V a lu e w as m u ltip lie d b y 1000. * S i g n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 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) T A B L E B IO (P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - S U M M ARY - P G E N E R A T IO N M A L E R A T S ARGUS 418-020 Page 90 DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV V 0 1 3 10 3 0 RATS TESTED B R A IN W EIG H T N M EANS.D . 30 2.26 0.17 30 2 . 2 8 0.10 30 2 . 2 6 0.12 30 2 . 2 4 0.12 2 9a 2.20 0 . 1 4 E P ID ID Y M IS L E F T CAUDA E P ID ID Y M IS L E F T M EANS.D . M E A N S .D . 32.08 3.12 14.75 1.80 30.68 2.33 13.92 1.32 30.68 2.74 13.99 1.38 31.47 2.72 14.37 1.58 28.82 3 .7 1 * * 11 3 . 2 1 .88** T E S T IS L E F T M EANS. D . 79.85 7.02 79.38 + 6.31 79.43 7.22 81.27 5.21 81.63 15.65 L E F T T E S T IS M IN U S T U N IC A A LB U G IN E A M E A N S .D . 73.91 7.27 73.76 5.75 73 .79 + 6.84 75.74 + 5.08 74.85 17.14 S EM IN A L V E S IC LE S W IT H F L U I D S EM IN A L V E S IC LE S W IT H O U T F L U ID M EANS. D . M EANS.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 E P ID ID Y M IS R IG H T M EANS.D . 31.96 2.81 30.21 3.52 30.81 2.85 30.29 4.62 29.00 3 .3 6 ** T E S T IS R IG H T PROSTATE M EAN+S.D . M EANS.D . 80.89 50.58 9.04 8.22 80.67 13.57 50.09 8.73 79.66 7.30 49.67 7.57 78.95 9.84 46.29 9.04 79 .6 1 10.36 39.12 8.06** A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . R A T IO S (% ) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 0 0 . [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r if ic e d o n d a y 45 o f s tu d y . b . E x c lu d e s v a lu e s f o r r a t s th a t h ad f l u i d lo s s p r io r to w e ig h in g o r o rg a n s dam aged (w e ig h t a f f e c t e d ) . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 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) T A B L E B IO (P A G E 2 ) : R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - SU M M ARY - P G E N E R A T IO N M A L E R A T S DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 0 13 IV V 10 3 0 RATS TES TED B R A IN W EIG H T P IT U IT A R Y N M EANS.D . M EANS.D . 30 2.26 0 .17 0.62 0.18 30 2 . 2 8 0.10 0 . 6 1 0.12 30 2 . 2 6 0.12 0.54 0 .14 * 30 2 . 2 4 0.12 0.62 0.14 29a 2.20 0 . 1 4 0.48 0 .1 4 ** LIV E R K ID N EY L E F T K ID N E Y R IG H T ADRENAL LE FT A D R EN A L R IG H T S P LEEN M EAN+S.D . M EANS.D . M EANS.D . M EANS.D . M EANS.D . M EANS.D . 903.14 118.64 97.52 10.67 97.52 9.94 1 . 4 3 0.20 1.40 0.23 4 1.51 6.97 1066.18 153.82** 110.12 1 2 . 6 0 * * 1 1 1 . 6 2 13 . 4 5 * * 1230.29 119 .75 ** 111.70 10.49** 110.97 9.45** 1284.45 18 2.5 0** 104.60 1 1 .7 2 * 105.62 1 2 .3 7 ** 1248.34 144.28** 89 0 . 4 1 .68* 9 3 . 5 1 8.68 1.40 0.19 1.35 0.25 38.41 5.84 1.34 0.26 1.32 0.35 3 8 . 5 5 6.02 1.34 0.26 1.40 0.35 38.86 6.15 1.28 0.30 1.20 0 . 2 9 33.40 7 .3 7 * * THYM US M EANS.D . 19.38 4.57 16.89 3.73 1 7 .1 1 4.59 18.08 6 .17 13.73 4 .0 1** A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . R A T IO S ( %) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 10 0 a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h w as m o rib u n d s a c r if ic e d on d a y 45 o f s tu d y . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p ^ O . 0 5 ) . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . ARGUS 418-020 Page 91 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B l l (P A G E 1 ) : C AU D A E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AN D S P ER M A TID CO U NT - SUMMARY - P G E N E R A T IO N M A LE R ATS DOSAGE GROUP D O SAG E (M G /K G /D AY) RATS TES TED N I 0 30 II III 13 30 30 IV V 10 3 0 30 29a NUM BER M O T ILE M O T ILE P ER C EN T M E A N S .D , M E A N + S .D . 354.0 82.6 + 98.9 11.1 346.5 84.7 118.4 7.0 373.3 102.5 86.8 6 . 7 338.2 89.0 87.4 + 4.0 327.4 83.9 130.2 + 8.8 ARGUS 418-020 Page 92 S T A T IC COUNT (N O N M O TILE) TO TAL COUNT b SPERM COUNT C M E A N S .D , M EANS. D , M E A N S .D 73.3 + 44.0 427.2 105.5 110.6 3 3 .8 63.0 33.9 409.6 135.6 119.5 38.3 56.7 32.4 4 3 0 . 0 + 112.6 111.2 3 7 . 6 48.4 386.6 117.7 + 20.3* 100.6 + 42.9 58.4 + 31.0 385.8 138.3 98.1 + 36.9 SPERM D E N S IT Y d M EANS. D 962.65 279.89 1086.87 323.61 1016.78 a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 w h ic h w as m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y 322.39 b . Sum o f n u m b e r m o tile a n d s t a t i c c o u n t. G ro u p s o f f i v e f i e l d s w e re e v a lu a te d u n t i l a sp e rm 20 f i e l d s w e r e e v a l u a t e d . c . Sperm c o u n t u s e d in th e c a lc u la t io n o f sp erm d e n s ity . Te n f i e l d s w e re e v a lu a te d . 1047.73 + 318.51 co un t o f a t le a s t 200 952.81 was a c h ie v e d 307.64 or d . Th e sp e rm d e n s it y w as c a lc u la t e d b y d i v i d i n g th e sp erm c o u n t b y th e vo lu m e in th e im a g e a re a ( 3 4 . 3 x 10~6 m L) , m u lt ip ly in g b y 2 ( d ilu t io n fa c to r ) an d m u ltip ly in g b y 10 "6 to o b ta in th e sperm c o n c e n tr a tio n . Th e c a lc u la te d sperm c o n c e n tra tio n v a lu e (ro u n d e d t o 1 d e c im a l p la c e ) w as m u lt ip lie d b y 50 (vo lu m e ) a n d d iv id e d b y th e w e ig h t o f th e l e f t c a u d a e p id id y m is (s e e T a b le B 1 7 f o r th e w e ig h t o f th e l e f t ca u d a e p id id y m is ) t o o b ta in th e sperm d e n s ity . Th e c a lc u la te d v a lu e w i l l v a r y b y a p p ro x im a te ly 0.8 % fro m th e C o m p u te r A u to m a te d S p e rm A n a l y s i s b e c a u s e th e d i g i t a l im a g e e v a lu a te d i s s l i g h t l y s m a lle r (4 p i x e ls ) th a n th e a c t u a l f i e l d c a u s in g a s l i g h t u n d e re s tim a te o f th e a c tu a l vo lu m e a n d an o v e r e s tim a te o f th e c o n c e n tr a tio n . * S i g n i f i c a n t l y d i f f e r e n t f r o m t h e G r o u p I v a l u e ( p <. 0 . 0 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) T A B LE B l l (P A G E 2 ) : CAU D A EP ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND S P ER M A TID COUNT - SUMMARY - P G E N E R A T IO N M A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TES TED N I 0 30 II III 13 30 30 IV V 10 3 0 30 29a S P E R M A T ID C O U N T b M E A N + S .D . 50.7 + 16.6 45.9 13.0 47.3 15.6 46.4 14.8 42.6 + 16.2 S P E R M A T ID D E N S IT Y C M E A N S .D . 91.99 + 30.26 79.83 + 21.97 82.38 a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 w h ic h w as m o rib u n d s a c r ific e d on d a y 45 o f s tu d y . 25.57 79.16 24.87 74.47 29.09 b . S p e rm a tid c o u n t u s e d in th e c a lc u la tio n o f s p e rm a tid d e n s ity . T e n f i e l d s w e re e v a lu a te d . c . T h e s p e r m a tid d e n s i t y w as c a lc u la t e d b y d i v i d i n g th e s p e r m a tid c o u n t b y th e v o lu m e in th e im a g e a r e a ( 3 4 . 3 x 1 0 ` 6 m L ) , m u lt ip ly in g b y 2 ( d ilu t io n fa c to r ) and m u ltip ly in g b y 10 "6 to o b ta in th e s p e rm a tid c o n c e n tr a tio n . Th e c a lc u la te d s p e rm a tid c o n c e n tr a tio n v a lu e (ro u n d e d t o 1 d e c im a l p la c e ) was m u lt ip lie d b y 50 (vo lu m e ) an d d iv id e d b y th e w e ig h t o f th e l e f t t e s t i s m in u s t u n ic a a lb u g in e a (s e e T a b le B 18 f o r th e w e ig h t o f th e l e f t t e s t i s m in u s t u n ic a a lb u g in e a ) t o o b ta in th e s p e r m a tid d e n s it y . T h e c a lc u la t e d v a lu e w i l l v a r y b y a p p r o x im a te ly 0 . 8 % fro m th e C o m p u te r A u to m a te d Spe rm A n a ly s is b e c a u s e t h e d i g i t a l im a g e e v a lu a t e d i s s l i g h t l y s m a lle r (4 p i x e ls ) th a n th e a c tu a l f i e l d c a u s in g a s l i g h t u n d e r e s tim a te o f th e a c t u a l v o lu m e a n d a n o v e re s tim a te o f th e c o n c e n tra tio n . 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) T A B L E B 12 (P A G E 1) : CAUDA E P ID ID Y M A L SPERM M ORPHOLOGY - SUMMARY - P G EN E R A T IO N M ALE R ATS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 RATS TES TED N 30 30 30 IN C LU D ED IN A N A LYS ES N 30 30 30 NORM AL PER CENT ABNORMAL D ETAC H ED HEAD M EANS. D . M E A N % S .D . M EANS. D . 18 7.1 24.4 6 .4 + 12.2 7 . 5 11.2 191.4 7.0 4 .3 + 3 .5 4 .4 + 3 .8 191.2 + 5.3 4 . 4 2.6 4 . 5 + 2.8 NO H EAD BROKEN FLA G ELLU M NO HOOK EX C ES S IV E HOOK C O ILED FLA G ELLU M B EN T FLAG ELLU M SHORT SPERM H EAD M EANS. D . M EANS. D . M EANS. D . M EANS. D . M EANS.D . M EANS.D . M EANS.D . 5 .2 + 1 3 . 3 0.2 + 0 .4 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 3.5 3.5 0.6 1.0 0.0 + 0.0 0.1 + 0.2 0.0 + 0.0 0.0 0.0 0.0 + 0.0 3.7 2.9 0 .4 0.6 0.0 0.2 0.0 0.2 0.0 0.2 0.0 + 0.0 0.0 + 0.0 a . E x c lu d e s v a lu e s f o r r a t 1 3 7 3 2 , w h ic h was m o rib u n d s a c r ific e d o n d a y 45 o f s tu d y . 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 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 1 4 . 9 6.1 1 7 . 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) T A B LE B 13 (P A G E 1 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 95 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 13601 13 6 0 2 13 6 0 3 13604 13 6 0 5 13606 13607 13 6 0 8 13609 13 6 10 13611 13 6 12 13 6 13 13 6 14 13615 13 6 16 13617 DS ( DS ( 60 ) 67 ) DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( 58- 59) 10 ) 30- 36) 1 8 - 20) 88 ) 10 - 49) 7 2 - 85) 93-107) 2 2 - 75) 44 ) 9 4 - 96) DS ( 4 4 - 84) DS ( DS ( DS ( DS ( DS ( DS { 17 ) 1 7 - 35) 25-108) 15 - 17) 94-108) 22 ) S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES L O C A L IZ E D A L O P E C IA : LIM B S S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S S O FT OR LIQ U ID FEC ES L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S S O FT OR LIQ U ID FEC ES BOTH EAR S : SW OLLEN a V O C A LIZA T IO N a a DS = DAY OF STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 13 (P A G E 2) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS DOSAGE GROUP I RAT # 13618 13619 13620 13621 13 6 2 2 13 6 2 3 13625 13626 13627 13628 13629 13 6 3 0 D S ( 69- 84) DS ( 29-109) DS ( DS ( DS ( DS ( DS ( 2 3 - 60) 39 ) 86- 8 7 ) 108 ) 8- 9 ) DS = DAY O F STUDY 0 M G/KG/DAY D ES C R IP T IO N IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S SO FT OR LIQ U ID FEC ES SO FT OR LIQ U ID FEC ES SO FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA 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) T A B LE B 13 (P A G E 3) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 97 DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 136 3 1 13 6 3 2 13 6 3 3 13 6 3 4 13 6 3 5 13636 13 6 3 7 13 6 3 8 13639 13 6 4 0 13 6 4 1 13 6 4 2 13 6 4 3 13 6 4 4 DS ( DS ( DS ( DS ( DS ( 2 - 3) 96- 97) 9) 24- 27) 2 4 - 28) DS ( 9 4 -10 7) DS ( 59 ) DS ( DS ( DS ( DS ( DS ( 7) 18 - 21) 2 2 - 79) 7 2 - 75) 86- 8 7 ) DS ( 3 6 - 60) DS ( 3 6 - 62) DS ( 6 1-10 8 ) 88D S ( - 92) DS ( 94 ) DS ( 108 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS A LIG N ED NO A D V ER S E FIN D IN G S BOTH EA R S : SW OLLEN a S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA L O C A L IZ E D A L O P E C IA : LIM B S C H R O M O R H IN O R R H EA S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED a CHROM ODACRYORRHEA CHROM ODACRYORRHEA S O FT OR LIQ U ID FEC ES DS = DAY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 13 (P A G E 4) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 13 6 4 5 13 6 4 6 13 6 4 7 13 6 4 8 13 6 4 9 13 6 5 0 13 6 5 1 13 6 5 2 13 6 5 3 13 6 5 4 13 6 5 5 13 6 5 6 1365 7 13 6 5 8 13659 13 6 6 0 DS (10 1-10 6 ) DS ( 46 ) DS ( 3 3- 36) DS ( 3 7- 39) DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( 19 - 43) 10 ) 31 ) 8 6 -10 9 ) 83 - 94) 9 5 - 99) 102 ) 59 ) DS ( 7 2 - 73) DSC10 5 -110 ) DS ( 48 ) N O S E : S C A B ( 0 .2 CM X 0 .2 CM) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S R IG H T F O R E L IM B : A B R A S IO N ( 2 .0 CM X 1 .0 CM) R IG H T F O R E L I M B : S C A B ( 1 .0 CM X 0 .5 CM) NO A D V ER S E FIN D IN G S B A C K : S C A B ( 1 .0 CM X 1 .0 CM) S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES R IG H T E A R : SW OLLEN a H E A D : S C A B ( 0 .5 CM X 0 .2 CM) LO C A LIZE D A LO P E C IA : HEAD IN C IS O R S : M IS S IN G /B R O K EN P E N IS : R ED S U B S TA N C E, S LIG H T NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN a S O FT OR LIQ U ID FEC ES DS = DAY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . 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) T A B LE B 13 (P A G E 5) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 99 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 13 6 6 1 13 6 6 2 13 6 6 3 13 6 6 4 13665 13 6 6 6 13 6 6 7 13 6 6 8 13 6 6 9 13 6 70 136 71 13 6 72 13 6 73 13 6 74 13 6 75 DS ( 74 -10 6 ) DS ( 61 ) DS ( 3 1- 32) DS ( 3 1 - 53) DS ( 3 1-10 6 ) DS ( 3 1-10 6 ) D S (10 1-10 6 ) DS ( 9- 10) DS ( 90- 94) DS ( DS ( DS ( DS ( 5 7- 69) 5 7-10 0 ) 7 2 - 75) 77-10 7) NO AD V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN a S O FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA IN C IS O R S : M IS S IN G /B R O K EN CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N ED a L O C A L IZ E D A L O P E C IA : LIM B S a S O FT OR LIQ U ID FEC ES M O U T H : S C A B ( 0 .2 CM X 0 .2 CM) NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N E D CHROM ODACRYORRHEA CHROM ODACRYORRHEA a NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S DS = D AY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 13 (P A G E 6) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 13 6 76 13 6 77 13 6 78 13 6 79 13 6 8 0 13 6 8 1 13 6 8 2 13 6 8 3 13 6 8 4 13 6 8 5 13686 13 6 8 7 13 6 8 8 13689 13 6 9 0 DS ( 16 - 17) DS ( 3 9 -10 9 ) DS { 25 - 27) DS ( 5 1- 52) D S ( 20 ) DS ( 95- 97) DS ( DS ( DS ( DS ( 10 - 23) 59 ) 16 - 22) 18 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA LO C A LIZE D A LO P E C IA : C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S N O S E : S C A B ( 0 .2 CM NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA LO C A LIZE D A LO P E C IA : C H R O M O R H IN O R R H EA LIM B S a X 0 .2 CM) LIM B S DS = DAY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . 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) T A B LE B 13 (P A G E 7 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 101 DOSAGE GROUP IV 10 M G/KG/DAY RAT # D ES C R IP T IO N 13 6 9 1 13 6 9 2 13 6 9 3 13 6 9 4 13 6 9 5 13 6 9 6 13 6 9 7 13 6 9 8 13 6 9 9 13 70 0 13 70 1 13 70 2 13 70 3 1370 4 13 70 5 DS ( 71 ) DS ( 8 2 - 84) DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( 6 4 - 65) 6 4- 78) 65- 70) 73 - 76) 79 - 97) 9 5- 96) 9 9 -10 7) 2) 23 - 28) DS ( 15 - 18) DS ( 36 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA IN C IS O R S : M IS S IN G /B R O K EN CHROM ODACRYORRHEA CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA CHROM ODACRYORRHEA a C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S DS = D AY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 13 (P A G E 8 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS DOSAGE GROUP IV 10 M G/KG/DAY RAT # D ES C R IP T IO N 1370 6 13 70 7 1370 8 13 70 9 13 710 13 711 13 712 13 713 13 714 13 715 13 716 13 717 13 718 13 719 13 72 0 DS ( 108 ) DS ( 15 - 16) DS ( 9 9 -10 9 ) DS ( 72 -10 9 ) DS ( 16 - 18) DS ( 16 - 17) DS ( 23 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN a C H R O M O R H IN O R R H EA BOTH OR R IG H T E A R S : SW O LLEN NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S a DS = DAY OF STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . 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) T A B LE B 13 (P A G E 9) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 103 DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 13 72 1 13 72 2 13 72 3 13 72 4 13 72 5 13 72 6 13 72 7 13 72 8 13 72 9 13 73 0 1373 1 1373 2 DS ( DS ( DS ( DS ( DS ( DS ( DS ( 87 ) 22 ) 85 ) 85 ) 8 7- 92) 8 7- 99) 9 4- 95) DS ( DS ( DS ( DS ( 245273 93- 26) 53) 84) 99) DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( DS ( 8) 16 - 21) 3) 58 - 68) 8- 9 ) 18 - 34) 4 1- 45) 4 4 - 45) 4 4 - 45) 45 ) 45 ) NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES R ALES D EH Y D R A T IO N UNGROOM ED C O AT UNGROOM ED C O AT D EH Y D R A T IO N D R IED R ED P ER IN A S A L SUBSTANCE NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA S O FT OR LIQ U ID FEC ES L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA IN C IS O R S : M IS A LIG N ED D EH Y D R A T IO N EM A C IA T IO N EM A C IA T IO N a COLD TO TOUCH U R IN E -S T A IN E D A B D O M IN A L FU R D EC R EA S ED M OTOR A C T IV IT Y M O R IB U N D S A C R IF IC E D DS = DAY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 13 (P A G E 10 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 104 DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 13 73 3 13 73 4 13 73 5 13 73 6 13 73 7 13 73 8 1373 9 13 74 0 13 741 13 74 2 DS ( DS ( DS ( DS ( DS ( DS ( 14- 17) 23- 24) 85- 90) 85- 92) 92 ) 20- 2 3 ) 100D S ( 3 6 - ) DS (1 0 7 - 109) DS ( 85- D S ( 86D S ( 86D S ( 86D S ( 86D S ( 88D S ( 88D S ( 88- 94) 9 1) 9 1) 9 1) 92) 9 1) 93) 99) DS ( 90- 91) DS ( 9 2- 93) 2D S ( - 3) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA D EH Y D R A T IO N UNGROOM ED CO AT D EH Y D R A T IO N C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a U R IN E -S T A IN E D A B D O M IN A L FU R D R IE D , R ED OR R ED P E R IN A S A L SUBSTANC E UNGROOM ED CO AT BOTH FOREPAW S: D R IED , R ED SUBSTANCE ON D EH Y D R A T IO N COLD TO TOUCH P A LE E X T R E M IT IE S EM A C IA T IO N NO FEC ES SCANT FEC ES C H R O M O R H IN O R R H EA FU R DS = DAY OF STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 13 (P A G E 1 1 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 13 74 3 13 74 4 13 74 5 13 74 6 13 747 13 74 8 13 74 9 13 75 0 DS ( IS ) DS ( DS ( DS ( DS ( DS ( 100 ) 3 1 - 60) 78 - 84) 9 4 -110 ) 1 7 - 21) DS ( 3 - 5) DS ( 72 ) NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA U R IN E -S T A IN E D A B D O M IN A L FU R DS = DAY O F STUDY a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . 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) T A B L E B 14 (P A G E 1 ) : B O D Y W EIG H TS - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 106 DAY RAT # 1 8 15 DOSAGE GROUP I 22 2 9 3 6 4 3 0 M G/KG/DAY 13 6 0 1 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. 392 . 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 A LL a. b. = DAY O F STUDY W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . F i r s t v a lu e re c o rd e d a fte r c o h a b ita tio n . 50 431. 462. 455. 490. 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. 70 a 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-6889.6) T A B L E B 14 (P A G E 2) : B O D Y W EIG H T S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 107 1 8 22D A Y 15 29 36 43 RAT # DOSAGE GROUP I I 1 M G/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. 3 72 . 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. 372 . 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 A LL a. b. = DAY OF STUDY W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . F i r s t v a lu e re c o rd e d a ft e r c o h a b ita tio n . 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. 64 453 . 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 . 70 a 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. 4 94. 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 . 99 532 . 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 . 106 548 . 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) T A B L E B 14 (P A G E 3 ) : B O D Y W EIG H T S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 108 1 8 22D A Y 15 29 36 43 RAT # DOSAGE GROUP I I I 3 M G/KG/DAY 13661 13662 13663 13664 13 6 6 5 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 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, 355 386 380 408 394. 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. 3 94. 433 . 441. 479. DAY A LL a. b. = DAY O F STUDY W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . F i r s t v a lu e re c o rd e d a fte r c o h a b ita tio n . 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. 70 a 486. 479. 4 94 . 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. 549. 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) T A B LE B14 (PAGE 4) : BODY W EIGHTS - IN D IV ID U A L DATA - P G EN ER A T IO N MALE RATS ARGUS 418-020 Page 109 1D A Y 8 221 5 2 9 3 6 4 3 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 ALL a. b. = DAY OF STUDY W EIGHTS WERE RECORDED I N GRAMS ( G ) . Last value recorded before cohabitation. F ir s t value recorded a fte r cohabitation. 50 414. 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 . 57 429. 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. 64 444 . 378. 494. 501. 426 . 481. 410. 450. 383 . 475. 428 . 415. 422. 489. 454 . 456. 459. 476 . 401. 335. 336. 3 92. 420. 383. 465 . 433 . 395. 477. 458. 488. 70a 464. 388. 499. 519. 429. 470. 419. 463 . 391. 481. 434. 423 . 437. 510. 470. 462. 467. 483 . 407. 347. 340. 407. 423 . 390. 471. 440. 414. 493 . 477. 509. 77 468. 389. 520. 520. 440. 479. 424 . 480. 405. 488. 435. 435 . 445. 523 . 476. 452 . 487. 507. 392. 352 . 345. 427. 434 . 3 94 . 452 . 448. 420 . 498. 483 . 512. 85b 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. 92 496. 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 . 99 509. 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 . 106 528. 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) T A B L E B 1 4 (P A G E 5) : B O D Y W EIG H TS - I N D I V I D U A L D A T A - P G E N E R A T I O N M A L E R A TS ARGUS 418-020 Page 110 1 8 22D A Y 15 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 2201 6 6 , 263 . 193 229 268. 2121 7 8 2 5 2 . 185 193 243 . 170 203 23 5. 179 227 283 . 182 227 286. 183 224 268. 2211 7 2 2 7 2 . 186 236 286. 175 232 280. 186 162 236. 1 7 1 198 254 . 188 233 2 7 1 . 178 205 249 . 18 1 214 253 . 171 206 232 . 183 218 2 7 1 . 174 192 2 5 1. 188 206 267 . 2111 7 1 2 5 7 . 185 216 255. 169 187 232 . 176 19 1 243 . 176 217 259. 190 237 282 . 169 209 255. 185 190 266. 173 217 268. 176 206 246 . 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. 30 M G /K G /D A Y 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 ALL a. b. = DAY OF STUDY W EIGHTS WERE RECORDED I N GRAMS ( G ) . Last value recorded before cohabitation. F ir s t value recorded a fte r cohabitation. 50 57 64 70a 77 85b 394. 417. 437. 344 . 355. 368. 283 . 289. 286. 326. 350. 349. 279. 288. 285. 373 . 378. 380. 338 . 351. 363 . 346. 365. 363 . 342. 357. 369. 420. 440. 459. 377. 389. 390. MORIBUND SAC R IFIC ED 442 . 475. 480. 353 . 378. 385. 347. 356. 364. 352 . 337. 342. 302 . 320. 327. 373 . 386. 399. 303 . 331. 337. 377. 405. 414 . 308. 315. 310. 296. 302. 304. 318. 331. 343 . 315. 328. 337. 328. 353 . 358. 352 . 370. 380. 286. 297. 301. 328 . 403 . 448 . 358. 375. 390. 349. 380. 391. 444 . 385. 273 . 361. 298. 394 . 380. 355. 374. 456. 402. ON DAY 506. 374 . 369. 352. 345. 412 . 334 . 429. 311. 306. 344. 340. 360. 386. 305. 475. 400. 404 . 450. 405. 285. 370. 300. 345. 390. 371. 381. 475. 406. 45 O F 518 . 390. 389. 356. 344. 418 . 339. 433 . 312. 321. 360. 349. 368. 391. 302 . 485. 383 . 390. 464 . 414 . 295. 386. 331. 419. 405 . 385. 392 . 486. 424 . STUDY 536. 396. 400. 362 . 269. 431. 353 . 449 . 268 . 325. 370. 352. 370. 415. 301. 501. 409. 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) TA B LE B15 (PAGE 1 ) : FEED CONSUMPTION VALUES - IN D IV ID U A L DATA - P GENERATIO N MALE RATS ARGUS 418-020 Page 111 DAYS 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 13630 1- 8 8- 1 5 1 5 - 2 2 DOSAGE GROUP I 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. 2 2 - 29 2 9 - 36 36 - 43 0 MG/KG/DAY 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. 4 3 - 50 208. 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. 50- 57 215. 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. 5 7 - 64 225. 218. 210 . 220. 204 . 228. 199. 204 . 213 . 239. 235. 206. 205. 198. 207. 226. 183 . 201. 199. 204 . 185. 184 . 209. 198. 203 . 232. 177. 226. 204 . 218 . 6 4 - 7 0 a 8 5 b - 92 188. 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. 199. 221. 210. 209. 9 2 - 99 214 . 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 . 99-106 220. 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 A L L W EIGHTS WERE RECORDED I N GRAMS ( G ) . a. Last value recorded before cohabitation. b. F ir s t value recorded a fte r cohabitation. c. S p ille d feed precluded the c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E B 15 (P A G E 2) : F E E D C O N S U M P TIO N V A L U E S - I N D I V I D U A L D A T A - P G E N E R A T I O N M A L E R A TS ARGUS 418-020 Page 112 DAYS 1- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a 8 5 b - 9 2 9 2 - 9 9 9 9 - 1 0 6 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 13660 DOSAGE GROUP I I 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. 1 MG/KG/DAY 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 A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. Last value recorded before co habitation. b . F ir s t value recorded a fte r co habitation. c. S p ille d feed precluded the c a lc u la tio n of th is va lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B15 (PAGE 3 ): FEED CONSUMPTION VALUES - IN D IV ID U A L DATA - P G ENERATIO N MALE RATS ARGUS 418-020 Page 113 DAYS 1- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a 8 5 b - 9 2 9 2 - 9 9 9 9 - 1 0 6 RAT # 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13 685 13686 13687 13688 13689 13690 DOSAGE GROUP I I I 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. 3 MG/KG/DAY 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 A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. La s t value recorded before co habitation . b. F ir s t value recorded a fte r cohabitation. c. S p ille d feed precluded the c a lc u la tio n of th is v a lu e . PROTOCOL 418-020:: O RAL (GAVAGE) TW O -G EN ER A T IO N (ONE L I T T E R PER G EN ERA T IO N ) R EPRO DUCTIO N STUDY O F AMMONIUM P ER FLU O R O O C TAN O ATE (APFO) I N RATS (SPONSOR 'S STUDY NUMBER: T-6889 .6) TAB LE B15 (PAGE 4 ) : FEED CONSUMPTION VALUES - IN D IV ID U A L DATA - P GENERATION MALE RATS ARGUS 418-020 Page 114 DAYS 1- 8 8 1- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 36I - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 ' - 6 4 6 4 - 7 0 a 8 5 b - 9 2 9 2 - 9 9 9 9 - 1 0 6 RAT # 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 DOSAGE GROUP IV 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. 10 MG/KG/DAY 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. 248. 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 . 13 7 . 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 A L L W EIGHTS WERE RECORDED I N GRAMS ( G ) . a. Last value recorded before coh abitation . b. F ir s t value recorded a fte r cohabitation. c. S p ille d feed precluded the ca lc u la tio n of th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E B 15 (P A G E 5) : F E E D CO N SU M PTIO N V A L U E S - I N D I V I D U A L D A T A - P G E N E R A T I O N M A L E R A T S ARGUS 418-020 Page 115 DAYS 1- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a 8 5 b - 9 2 9 2 - 9 9 9 9 - 1 0 6 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 144. 13 7 . 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. 30 M G /K G /D A Y 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 . 186. 168. 170. 156. 220. 156. 228 . 149. 219. 171. 165. 165. 217. 178. 195. 203 . 189. 200. 205. 202 . 194. 194. 208. 208. 205. 219. 240. 182. 180. 170. MORIBUND S A C R IFIC ED ON 201. 2 0 6 . 212 . 189. 189. 191. 187. 184 . 190. 167. 171. 175 . 147. 149. 159. 177. 183 . 180. 169. 202. 182 . 205 . 172 . 206. 175. 174 . 166. 172. 173 . 168. 184. 182 . 182 . 186. 185. 197. 182. 198 . 182. 183 . 181. 185. 166. c 159 . 220. 161. 245. 159. 200. 164 . 213 . 166. 233 . 154. 162. 105. 168. 156. 174 . 170. 160. 162. 166. 154. D A Y 45 188. 157. 148. 147. 129. 150. 136. 172 . 139. 146. 147. 143 . 155. 155. 129. 200. 138. 181. 206. 197. 145. 211. 185. 233 . 193 . 201. 197. 223 . 190. OF STUDY 209. 169. 183 . 185. 183 . 190. 160. 215. 23 . 177. 197. 176. 177. 175 . 156. 221. 176. 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 A L L W E IG H T S W ERE R EC O R D E D I N GRAMS (G) . a. Last value recorded before cohabitation. b. F ir s t value recorded a fte r cohabitation. c. S p ille d feed precluded the ca lcu lation of th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E B 16 (P A G E 1 ) : M A T IN G AN D F E R T I L I T Y - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 116 DOSAGE GROUP I 0 M G/KG/DAY RAT # DAYS IN C O H A B IT A T IO N M A TIN G S TA T U S M A TIN G D A T E FEM A LE PREGNANCY STATUS 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 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 1 1 4 - 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 P (13801) C P (13 802) C P(13803) C P (13 805) C P (13806) C P (13807) C P (13808) C P (13809) C P (13810) C NP(13811) C P (13812) C P (13813) C P(13814) C P (13815) C P (13816) C P (13817) C P(13818) C P (13819) C P(13820) C P(13821) C P (13822) C P (13823) C P (13824) C P (13825) C P (13826) C P(13827) C P (13828) c P (13829) c P (13830) - M= C= P= a. M ATED ( C O N FIR M ED P R EG N A N T R a t 13630 ) = FEM A LE R A T NUM BER NC = N O T C O N FIR M ED NP = NOT PREGNANT was n o t a s s ig n e d to c o h a b ita tio n because th e re w ere no a v a ila b le fe m a le 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) T A B LE B 16 (P A G E 2 ) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 117 DOSAGE GROUP I I 1 M G/KG/DAY RAT # DAYS IN C O H A B IT A T IO N M A TIN G S TATU S M A TIN G D A T E FEM ALE PREGNANCY STATUS 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13 64 9 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660a 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 - 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 P(13831) C P(13832) C P (13833) C P(13834) C P (13835) C P (13837) C P(13838) C P(13839) C NP(13840) C P(13841) C P(13842) C P(13843) C P (13844) C P(13845) C P (13846) C P (13847) C P (13848) C P (13849) C P (13850) C NP(13851) C P (13852) C P (13853) C P(13854) C P(13855) C P (13856) C P(13857) c P(13858) c P (13859) c P (13860) - M = M ATED ( ) = FEM A LE R A T NUM BER C = C O N FIR M ED NC = N O T C O N FIR M ED P = PREGNANT NP = NOT PREGNANT a . R a t 13660 was n o t a s s ig n e d to c o h a b ita tio n because th e re w ere no a v a ila b le fe m a le r a t s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 16 (P A G E 3) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 118 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # 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 DAYS IN C O H A B IT A T IO N 1 14 2 5 1 2 4 4 4 1 2 4 8 2 1 1 3 1 1 1 1 3 1 4 1 1 4 1 1 4 M = M ATED ( ) = FE M A LE R A T NUM BER C = C O N FIR M ED N C = N O T C O N FIR M ED P = PREGNANT NP = NOT PREGNANT M A TIN G S TA TU S 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 A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P (13861) P(13862) P(13863) P(13864) P (13865) P(13866) PU3867) 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) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 16 (P A G E 4 ) : M A TIN G A N D F E R T IL IT Y - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 119 DOSAGE GROUP IV 10 M G/KG/DAY RAT # DAYS IN C O H A B IT A T IO N M A TIN G S TA TU S 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 M M M M M M M M M M M M M M M M M M M M NOT M ATE M = M ATED ( ) = FEM A LE R A T NUM BER C = C O N FIR M ED NC = N O T C O N FIR M ED P = PREGNANT NP = NOT PREGNANT M A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P(13891) P (13892) P(13893) P (13894) P(13895) P (13896) P (13897) P (13898) P (13899) - (13900) P (13901) P (13902) P (13903) P(13904) P (13 905) 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) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 16 (P A G E 5 ) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 120 DOSAGE GROUP V 30 M G /KG /D AY 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 C O H A B IT A T IO N M A TIN G S TA T U S M A TIN G D A T E 2M 2M 1M 3M 1M 4M 2M 2M 1M 3M 2M 4M M O R IB U N D S A C R IF IC E D ON D A Y 45 O F S TU D Y 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 FEM ALE PREGNANCY STATUS P(13921) P(13922) P(13923) P(13950) P(13924) P(13925) P(13926) P(13927) P(13928) NP(13929) P(13930) P(13931) P(13932) P(13933) PU3934) 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) M = M ATED ( ) = FEM A LE R A T NUM BER C = C O N FIR M ED NC = N O T C O N FIR M ED P = PREGNANT NP = NOT PREGNANT a . R e s u lt o f f i r s t c o h a b ita tio n p e rio d . b . M a le r a t m a te d e a r ly in th e f i r s t c o h a b ita tio n p e r io d an d w as c o h a b ite d w ith a s e c o n d fe m a le r a t . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 1 7 (P A G E 1 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 121 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a I 0 13601 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 0 2 DS 106 105 A L L TIS S U ES A P P EA R ED NORM AL. 13 6 0 3 DS 106 105 A L L TIS S U ES A P P EA R ED NORM AL. 13 6 0 4 DS 106 105 A L L TIS S U ES A P P EA R ED NORM AL. 13 6 0 5 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 0 6 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 0 7 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 0 8 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NO RM AL. 13 6 0 9 DS 107 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 10 DS 107 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 136 11 DS 107 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 12 DS 10 7 10 6 A L L T IS S U ES A P PEA R ED NORM AL. 13 6 13 DS 108 10 7 A L L T IS S U ES A P PEA R ED NORM AL. 13 6 14 DS 108 10 7 LU N G S : A L L L O B E S , NUM EROUS D AR K R ED A R EA S ( P IN P O IN T T O 2 .0 CM X 2 .0 C M ). A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 13 6 15 13 6 16 136 17 13 6 18 13 6 19 13 6 2 0 13 6 2 1 13 6 2 2 13623 13 6 2 4 13 6 2 5 13 6 2 6 13 6 2 7 13 6 2 8 13 6 2 9 13 6 3 0 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 10 7 10 7 10 7 10 7 108 108 108 10 8 10 8 10 8 10 9 10 9 10 9 10 9 10 9 10 9 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE B 1 7 (P A G E 2 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 122 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a II 1 13631 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 3 2 DS 106 10 5 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 3 3 DS 106 10 5 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 3 4 DS 106 10 5 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 3 5 DS 106 10 5 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 3 6 DS 106 10 5 T E S T ES : R IG H T , SM ALL AND FLA C C ID . E P I D I D Y M ID E S : R IG H T ,, S M A L L A N D F L A C C I D . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 13 6 3 7 13 6 3 8 DS 10 7 DS 10 7 10 6 10 6 A L L T IS S U ES A P P EA R ED NORM AL. A L L T IS S U ES A P P EA R ED NORM AL. 13639 DS 10 7 10 6 K ID N E Y S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 13 6 4 0 13 6 4 1 13 6 4 2 13 6 4 3 13 6 4 4 13 6 4 5 13 6 4 6 13 6 4 7 13 6 4 8 13 6 4 9 13 6 5 0 1365 1 13 6 5 2 13 6 5 3 13 6 5 4 13 6 5 5 13656 13 6 5 7 13 6 5 8 13659 13 6 6 0 DS 10 7 DS 10 7 DS 10 7 DS 108 DS 108 DS 108 DS 108 DS 108 DS 108 DS 109 DS 109 DS 109 DS 109 DS 109 DS 109 D S 110 D S 110 D S 110 D S 110 D S 110 D S 110 10 6 10 6 10 6 10 7 10 7 10 7 10 7 10 7 10 7 10 8 10 8 10 8 10 8 10 8 10 8 10 9 10 9 10 9 10 9 10 9 10 9 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE B 1 7 (P A G E 3) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 123 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a III 3 13 6 6 1 13662 13 6 6 3 13 6 6 4 13 6 6 5 13 6 6 6 13 6 6 7 13 6 6 8 13 6 6 9 DS 106 DS 106 DS 106 DS 106 DS 106 DS 106 DS 10 7 DS 10 7 DS 10 7 105 105 10 5 105 105 105 10 6 10 6 10 6 A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 6 70 DS 10 7 10 6 K ID N EY S : R IG H T , P E L V IS , M ODERATE D IL A T IO N . A L L O TH ER T IS S U ES A PPEAR ED NORM AL. 136 71 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 72 DS 10 7 10 6 K ID N E Y S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A PPEAR ED NORM AL. 13 6 73 13 6 74 13 6 75 13 6 76 136 77 13 6 78 136 79 13 6 8 0 13 6 8 1 13 6 8 2 13 6 8 3 13 6 8 4 13 6 8 5 13 6 8 6 13 6 8 7 13 6 8 8 13 6 8 9 13 6 9 0 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 10 7 10 7 10 7 10 7 10 7 10 7 108 108 108 108 108 108 10 9 10 9 10 9 10 9 10 9 10 9 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE B 1 7 (P A G E 4) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 124 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a IV 10 1 3 6 9 1 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 2 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 3 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 4 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 5 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 6 DS 106 105 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 7 DS 107 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 8 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 6 9 9 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 70 0 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 1370 1 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 13 70 2 DS 10 7 10 6 A L L T IS S U ES A P P EA R ED NORM AL. 1370 3 DS 108 10 7 A L L T IS S U ES A P P EA R ED NORM AL. 13 70 4 DS 108 10 7 A L L T IS S U ES A P P EA R ED NORM AL. 13 70 5 DS 108 10 7 A L L T IS S U ES A P P EA R ED NORM AL. 13 70 6 DS 108 10 7 T E S T ES : R IG H T , SM ALL AND FLA C C ID . E P I D I D Y M ID E S : R IG H T ,, S M A L L A N D F L A C C I D . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 1370 7 13 70 8 13 70 9 13 710 13 711 13 712 13 713 13 714 13 715 13 716 DS 108 DS 108 DS 109 DS 109 DS 109 DS 109 DS 109 DS 109 DS 110 DS 110 10 7 10 7 10 8 108 108 108 108 108 10 9 10 9 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 717 DS 110 10 9 K ID N EY S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 13 718 13 719 13 72 0 DS 110 DS 110 DS 110 10 9 10 9 10 9 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 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) T A B LE B 1 7 (P A G E 5) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D AY) V 30 RAT NUM BER 13 72 1 13 72 2 13 72 3 13 72 4 13 72 5 13 72 6 13 72 7 13 72 8 13 72 9 13 73 0 1373 1 13 73 2 DAY OF N EC R O P S Y DOSAGES A D M IN IS T ER ED O B S ER V A TIO N S a DS 106 DS 106 DS 106 DS 106 DS 106 DS 106 DS 10 7 DS 10 7 DS 10 7 DS 10 7 DS 10 7 DS 45 105 105 105 10 5 10 5 10 5 10 6 10 6 10 6 10 6 10 6 44 A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. K ID N EY S : R IG H T , P E L V IS , S LIG H T D IL A T IO N A L L O TH ER T IS S U ES A P P EA R ED NORM AL. A L L T IS S U ES A P P EA R ED NORM AL. A L L T IS S U ES A P P EA R ED NORM AL. M O R IB U N D S A C R IF IC E D O N D A Y LIV E R : A LL LO B ES , TAN AND TES T ES : B ILA T ER A L, R ED . A L L O TH ER T IS S U ES A P P EA R ED 45 O F S TU D Y . P A LE. NORM AL. ARGUS 418-020 Page 125 13 73 3 DS 108 10 7 EP ID ID Y M ID ES : L E F T , SM ALL AND F LA C C ID . K ID N EY S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 13 73 4 13 73 5 13 73 6 1373 7 13 73 8 13 73 9 13 74 0 DS 108 DS 108 DS 108 DS 108 DS 108 DS 109 DS 109 10 7 10 7 10 7 10 7 10 7 108 108 A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. DS = DAY O F STUDY a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le B 12 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 1 7 (P A G E 6 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N M ALE RATS DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a V 30 (C o n t .! 13 74 1 DS 109 10 8 T E S T ES : B ILA T E R A L, SM ALL AND FLA C C ID . EP ID ID Y M ID ES : B ILA T E R A L, SM ALL AND FLA C C ID . A L L O TH ER T IS S U ES A PPEA R ED N ORM AL. 13 74 2 13 74 3 13 74 4 13 74 5 13 74 6 13 74 7 13 74 8 13 74 9 13 75 0 DS 109 DS 109 DS 109 D S 110 D S 110 D S 110 D S 110 D S 110 D S 110 108 108 108 10 9 10 9 10 9 10 9 10 9 10 9 A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. TES T ES : L E F T , LAR G E. A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. DS = DAY OF STUDY a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le B 12 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B L E B 1 8 (P A G E 1 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE RATS ARGUS 418-020 Page 127 RAT T ER M IN A L BODY NUM BER W EIG H T EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW T E S T IS LEFT ABS. R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V ES IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW DOSAGE GROUP I 13 6 0 1 13 6 0 2 13603 13 6 0 4 13 6 0 5 13 6 0 6 13 6 0 7 13608 13 6 0 9 13 6 10 13611 13 6 12 13 6 13 13 6 14 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 M G/KG/DAY 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 2.4498 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T.. = O R G A N W E I G H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 0 0 . a . D am aged d u r in g p r o c e s s in g (som e f l u i d lo s s p r i o r t o w e ig h in g ); v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 18 (P A G E 2) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 128 RAT T ER M IN A L B O D Y NUM BER W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW DOSAGE GROUP I 13601 13 6 0 2 13603 13604 13605 13606 13607 13608 13609 13610 13611 13 6 12 13 6 13 13 6 14 13 6 15 13616 13617 13618 13619 13 6 2 0 13621 13622 13 6 2 3 13 6 2 4 13625 13626 13627 13 6 2 8 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 M G/KG/DAY 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 .1 7 5 7 1.3352 1.1837 1.2359 1.2678 0.9132 1 .1 7 3 1 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 .1 7 2.10 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 1 6 .1 7 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = ORGAN W EIG H T . a . V a lu e was m u ltip lie d b y 1 0 0 0 . b . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % TBW = (OR G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE B 18 (P A G E 3) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 129 RAT T ER M IN A L BODY NUM BER W EIG H T DOSAGE GROUP I K ID N EY LEFT ABS. R EL. W T. % TBW 0 M G/KG/DAY 13601 13602 13603 13604 13605 13606 13607 13608 13609 13 6 10 13611 13 6 12 13 6 13 13 6 14 13 6 15 13616 136 17 13 6 18 13 6 19 13620 13621 13622 13 6 2 3 13 6 2 4 13 6 2 5 13 6 2 6 13627 13 6 2 8 13 6 2 9 13 6 3 0 592. 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 .1 7 2.55 1.90 2.33 2.26 2.25 2 .1 7 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . V a lu e w as m u ltip lie d b y 1000. K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW 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 .3 1 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 .1 7 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 A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE B 18 (P A G E 4) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 130 RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW T E S T IS LEFT ABS. R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW DOSAGE GROUP I I 13631 13632 13633 13 6 3 4 13635 13636 13637 13638 13639 13640 13641 13 6 4 2 13643 13 6 4 4 13645 13 6 4 6 13647 13648 13 6 4 9 13650 13651 13 6 5 2 13 6 5 3 13 6 5 4 13 6 5 5 13 6 5 6 13 6 5 7 13 6 5 8 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. 1 M G/KG/DAY 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 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 .1 5 1 7 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T.. = O R G A N W E I G H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 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) T A B LE B18 (PA G E 5) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 131 RAT T ER M IN A L BO DY NUM BER W EIG H T EP ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW DOSAGE GROUP I I 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13 6 4 2 13643 13 6 4 4 13645 13646 13647 13648 13649 13650 13651 13 6 5 2 13653 13 6 5 4 13 6 5 5 13656 13657 13 6 5 8 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. 1 M G/KG/DAY 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 .8 9 8 3 b 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 .7 1 2.74 2.78 2.45 2.01 2.22 2.34 2.43 2.13 2.07 2 .1 7 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 .3 1 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 1 7 .0 7 26.32 29.05 19.16 23.90 22.05 21.10 27.36 4.33 4 .7 1 4.01 4.07 4.43 4.69 3.92 4.18 4.62 5.17 4.60 3.40 4.15 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 A LL a. b. c. W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . WT . = V a lu e was m u ltip lie d b y 1000. R a t 13636 h a d a s m a ll an d fla c c id r ig h t e p id id y m is ta b le (T a b le B 1 6 ) . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . ORGAN W EIG H T . and rig h t t e s t i s . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s 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) T A B L E B 1 8 (P A G E 6 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 132 RAT T ER M IN A L BODY NUM BER W EIG H T K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW DOSAGE GROUP I I 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 13 6 6 0 548. 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. 1 M G/KG/DAY 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 .7 1 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 .1 7 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 .1 7 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 .7 1 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 .7 1 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 A LL a. b. W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000. R a t 13639 had s lig h t d ila tio n o f th e A B S . W T. = p e lv is o f th e ORGAN rig h t W EIG H T . k id n e y . R E L .. % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 0 0 . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 18 (PAG E 7) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 133 RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW T E S T IS LEFT ABS. R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U ID ABS. R EL. W T. % TBW DOSAGE GROUP I I I 13 6 6 1 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13 6 8 3 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, 3 M G/KG/DAY 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 .1 7 7 7 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T.. = O R G A N W E I G H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE B 18 (P A G E 8) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 134 RAT T ER M IN A L BODY NUM BER W EIG H T EP ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW DOSAGE GROUP I I I 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 13672 1 3 6 .73 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. 3 M G/KG/DAY 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 .7 3 3 1 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 .3 1 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 2 7 .0 1 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 a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000. Dam aged d u rin g p ro c e s s in g (w e ig h t n o t A B S . WT . affected). = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE B 18 (P A G E 9) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 135 RAT T ER M IN A L BODY NUM BER W EIG H T K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW DOSAGE GROUP I I I 3 M G/KG/DAY 13661 13662 13663 13664 13665 13666 13 6 6 7 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13 6 .8 3 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 5.33 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 .7 7 1.05 0.97 0.93 0.82 0.85 0.82 0 .7 7 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 b. c. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000, A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 0 0 . R a t 13670 h a d m o d e ra te d ila t io n o f th e p e lv is o f th e r ig h t k id n e y . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 6 ) . R a t 13672 had s lig h t d ila t io n o f th e p e lv is o f th e r ig h t k id n e y . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 18 (P A G E 10 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE RATS ARGUS 418-020 Page 136 RAT T ER M IN A L BODY NUM BER W EIG H T DOSAGE GROUP IV 13691 13692 13 6 9 3 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. EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW 10 M G / K G / D A Y 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 T E S T IS LEFT ABS. R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW 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 .7 1 0 7 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 .4 1 7 1 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 .3 1 7 7 1.0436 1.3581 1.4232 1.4343 1.4163 1.0055 1.1139 1 .0 70 7 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 a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . D a m a g e d d u r in g p r o c e s s in g (som e f l u i d lo s s p r i o r t o w e ig h in g ) ; v a lu e s e x c lu d e d fro m g ro u p a v e r a g e s a n d s t a t i s t i c a l a n a ly s e s . Dam aged d u rin g p ro c e s s in g (w e ig h t a f f e c t e d ) ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 18 (P A G E 1 1) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 137 RAT T ER M IN A L BODY NUM BER W EIG H T DOSAGE GROUP IV 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13 70 3 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. E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW 10 M G / K G / D A Y 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 .7 6 1 1 1.8833 1.7711 1.9822 1.8191 0.8699b 1.6624 1.9331 1 .6 7 1 1 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 PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW 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 .1 7 4 7 1.2753 0.8310 1.0523 0.7736 0.9264 0.8620 1.1091 1.0910 1 .2 1 7 7 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 .4 7 2.41 3.79 3.20 1.8 1 2.09 1 .9 7 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 .3 1 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 .1 7 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 a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . V a lu e w as m u ltip lie d b y 1000. R a t 1 3 7 0 6 h a d a s m a ll an d f la c c id r ig h t ta b le (T a b le B 1 6 ) . A B S . W T. = e p id id y m is ORGAN W EIG H T . and rig h t t e s t i s . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 0 0 . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 18 (P A G E 1 2 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 138 RAT T ER M IN A L BODY NUM BER W EIG H T DOSAGE GROUP IV K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW 10 M G / K G / D A Y A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S PLEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW 13691 13692 13693 13694 13695 13 6 9 6 13697 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13 713 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 .3 1 2.37 3 .0 1 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 .1 7 0.61 0.55 0 .7 7 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 a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000 . R at 1 3 7 1 7 had s lig h t d ila tio n o f th e A B S . WT . = O RGAN p e lv is o f th e r ig h t W EIG H T . k id n e y . R E L .. % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 18 (P A G E 1 3 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R ATS RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW T E S T IS LEFT ABS. R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW DOSAGE GROUP V 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. 30 M G /K G /D A Y 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 0.53 0.39 0.63 0.53 0.49 -- 0.36 0.43 0.46 1 .1 2 7 1 0.9897 1.0162 1.0530 1.1224 1.3574 1.2199 0.8819 1.6355 1.3529 1.3058 b 1.0945 1.0168 1.0459 0.22 0.22 0.32 0.28 0.31 0.29 0.28 0.21 0.37 0.26 0.28 -- 0.20 0.22 0.23 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T,. = O R G A N W E I G H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . R a t 1 3 7 3 2 was m o rib u n d s a c r ific e d on d a y 45 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . b . V a lu e w as n o t re c o rd e d . c . R a t 1 3 7 3 3 h a d a s m a ll a n d f l a c c i d l e f t e p id id y m is a n d l e f t t e s t i s m in u s t u n ic a a lb u g in e a . S e e th e i n d i v i d u a l n e c r o p s y o b s e rv a tio n s ta b le (T a b le B 1 6 ) . 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) T A B LE B 18 (P A G E 14 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M ALE RATS RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA E P ID ID Y M IS LEFT ABS, R EL. W T. % TBW T E S T IS LEFT ABS R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW DOSAGE GROUP V 30 M G /K G /D AY 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 a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T,. = O R G A N W E I G H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X R a t 1 3 7 4 1 h ad s m a ll an d fla c c id e p id id y m id e s an d t e s t e s . See t h e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 6 ) . R a t 1 3 7 5 0 h a d a l a r g e l e f t e p id id y m is a n d l e f t t e s t i s m in u s t u n ic a a lb u g in e a . S e e t h e i n d i v i d u a l n e c r o p s y o b s e r v a t io n s ta b le (T a b le B 1 6 ) . 100. 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) T A B LE B 18 (P A G E 15 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW DOSAGE GROUP V 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 1373 2b 13733 13734 13735 511. 452 . 321. 378. 361. 465. 443 . 418. 439. 522. 468. -- 554. 456. 446. 30 M G /K G /D A Y 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 .1 7 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 0.51 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T , R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000. b . R a t 1 3 7 3 2 was m o rib u n d s a c r if ic e d on d a y 45 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . 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) T A B LE B 18 (P A G E 16 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M A LE R ATS RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW DOSAGE GROUP V 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. 30 M G /K G /D AY 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 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = O RG AN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000. b . R a t 1 3 7 4 1 h a d s m a ll an d fla c c id e p id id y m id e s an d t e s t e s . See t h e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 6 ) . 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) T A B LE B 18 (P A G E 1 7 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 143 RAT T ER M IN A L BODY NUM BER W EIG H T K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW DOSAGE GROUP V 30 M G /KG /D AY 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 I d 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 a. b. c. d. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000. R a t 13729 had s lig h t d ila tio n o f th e R a t 1 3 7 3 2 was m o rib u n d s a c r if ic e d on R a t 13733 had s lig h t d ila tio n o f th e A B S . WT'. = O R G A N W E IG H T . p e lv is o f th e r ig h t k id n e y . See d a y 45 o f s tu d y ; v a lu e s e x c lu d e d p e lv is o f th e r ig h t k id n e y . See R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . th e in d iv id u a l n e cro p sy fro m g ro u p a v e ra g e s a n d th e in d iv id u a l n e cro p sy o b s e rv a tio n s ta b le (T a b le s t a t i s t i c a l a n a l y s e s . o b s e rv a tio n s ta b le (T a b le B16) . 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) T A B LE B18 (P A G E 18 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N M A LE R ATS RAT T ER M IN A L BODY NUM BER W EIG H T K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW DOSAGE GROUP V 30 M G /K G /D A Y 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 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . V a lu e w as m u ltip lie d b y 1000. A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . ARGUS 418-020 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) T A B LE B 19 (P A G E 1) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 145 RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % BRW DOSAGE GROUP I 0 M G/KG/DAY 13 6 0 1 13 602 13603 13604 13605 13606 13607 13608 13609 13610 13611 13 6 12 13 6 13 13 6 14 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 3 4 .1 1 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 1 4 .7 1 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 .1 5 1 7 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 111.4 4 2.5305 100.42 2 . 1 8 8 8 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 2.4498 112.89 2.6437 125.89 2.3510 111.9 5 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 7 4 .1 7 65.07 53.58 ALL a. b. W EIG H T S W ERE R EC O R D ED IN G R AM S. A B S . W T. = O RG AN W EIG H T . D a m a g e d d u r in g p r o c e s s in g (som e f l u i d lo s s p r i o r t o w e ig h in g ) ; Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % BRW = v a lu e s e x c lu d e d (O R G AN W E IG H T / B R A IN fro m g ro u p a v e ra g e s W EIG H T ) X 1 0 0 . and s ta tis tic a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E B 1 9 (P A G E 2 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE RATS ARGUS 418-020 Page 146 RAT NUM BER B R A IN W EIG H T EP ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. % BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW DOSAGE GROUP I 13601 13602 13 6 0 3 13604 13605 13 6 0 6 13607 13608 13609 13610 13611 13 6 12 13 6 13 13614 13 6 15 13616 13617 13618 13619 13620 13621 13 6 2 2 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 .1 7 2.10 2.10 2.43 0 M G/KG/DAY 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 2 7 .8 1 33.37 27.57 30.09 32.48 29.56 31.84 30.60 35.26 28.62 31.33 3 1 .1 1 30.22 38.51 33.88 3 7.2 7 33.72 34.12 32.11 33.24 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 66.55 65.97 84.17 78.46 82.40 85.61 80.13 81.59 111.05 85.08 79.15 86.54 72.31 69.59 86.34 7 8 .1 1 70.55 79.13 86.48 79.92 79.88 76.32 70.93 98.83 78.31 83.71 75.73 87.37 80.27 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 .1 7 5 7 1.3352 1.1837 1.2359 1.2678 0.9132 1 .1 7 3 1 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 1 6 .1 7 18.88 19.31 18.10 19.76 24.67 17.86 22.09 18.41 20.24 1000.42 957.14 841.55 845.83 714.41 1018.75 788.51 826.61 1101.90 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 .3 1 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 A L L W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = O RGAN W EIG H T . a . Dam aged d u r in g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T) X 1 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) T A B LE B 19 (P A G E 3) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 147 RAT NUM BER B R A IN W EIG H T DOSAGE GROUP I K ID N EY R IG H T ABS. R EL. W T. % BRW 0 M G/KG/DAY A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW 13601 13602 13603 13 6 0 4 13605 13606 13607 13608 13609 13610 13611 13 6 12 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 .2 7 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 .3 1 1.47 1.19 1.38 1.26 1.74 0.89 1.42 1.37 1.50 1.64 1.52 1 .3 1 1.23 1.73 1.39 1.23 1.58 1.42 1 .3 1 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 0.42 0.50 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 1 6 .1 1 19.52 22.37 17.78 16.27 19.84 14.10 16.74 23.53 18.60 19.82 13.47 3 1.1 5 13.78 21.03 19.35 23.81 12.38 18.93 A L L W EIG H T S W ERE R EC O R D ED I N G R A M S . A B S . W T. = ORGAN W EIG H T . a . Dam aged d u r in g p ro c e s s in g (w e ig h t n o t a ffe c te d ) R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 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) T A B L E B 1 9 (P A G E 4 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 148 RAT NUM BER B R A IN W EIG H T EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % BRW DOSAGE GROUP I I 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13 6 5 2 13653 13654 13655 13656 13657 13658 13659 13660 2.22 2.34 2.43 2.13 2.07 2 .1 7 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 .3 1 2.17a 2.28 1 M G/KG/DAY 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 2 7 .1 1 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 1 3 .1 1 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 7 7 .8 7 74.80 7 7 .0 1 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 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 108.44 122.92 132.62 79.10 72.06 107.54 112.10 96.71 95.88 119.32 105.75 102.58 113.28 87.30 107.20 89.51 116.53 92.29 93.76 104.37 105.88 1 10 .1 8 71.44 105.96 121.90 98.72 100.85 93.20 99.06 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 .1 5 1 7 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 A L L W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = O RG AN W EIG H T . a . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 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) T A B LE B 19 (P A G E 5) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 149 RAT NUM BER B R A IN W EIG H T EP ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. % BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW DOSAGE GROUP I I 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13 6 4 5 13646 13647 13648 13649 13650 13651 13652 13653 13 6 5 4 13655 13 6 5 6 13657 13658 13659 13660 2.22 2.34 2.43 2.13 2.07 2 .1 7 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 1 M G/KG/DAY 0.6184 0.7187 0.7346 0.7092 0.6527 0.3677a 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 27.86 3 0 .71 30.23 33.30 31.53 16.94 31.56 25.59 28.78 31.39 32.40 3 1 .7 2 34.04 29.02 28.36 29.91 30.03 28.24 29.64 32.01 30.59 33.03 26.65 28.64 33.82 31.38 30.76 27.22 36.59 34.50 1.6665 75.07 2.0272 86.63 1.8301 75.31 1.8432 86.54 1 .7 9 3 7 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 1 1 7 .7 9 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 .1 15 9 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 .0 7 26.32 29.05 19.16 23.90 22.05 21.10 27.36 1068.92 1123.50 828.40 1159.15 1125.60 1269.58 111 9 .9 1 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 a. b. W EIG H T S W ERE R EC O R D ED I N G R A M S . R a t 13636 h a d a s m a ll an d fla c c id ta b le (T a b le B 1 6 ) . Dam aged d u rin g p ro c e s s in g (w e ig h t A B S . W T. = ORGAN W EIG H T . r ig h t e p id id y m is an d r ig h t not affected). R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . t e s t i s . See t h e in d iv id u a l n e c ro p s y o b s e rv a tio n s PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 19 (P A G E 6) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 150 RAT NUM BER B R A IN W EIG H T K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW S PLEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW DOSAGE GROUP I I 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13 6 5 2 13653 13 6 5 4 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 .3 1 2.25 2.33 2.35 2.32 2.38 2.26 2 .3 7 2.23 2.33 2 .3 1 2.10 2 .3 1 2 .1 7 b 2.28 1 M G/KG/DAY 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 .7 1 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 1 2 3 .1 1 115.58 120.00 109.87 115.74 101.72 117.65 103.98 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 3 7 .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 3 7 .17 31.22 39.91 37.77 3 1.1 7 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 1 7 .5 7 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 2 3 .1 1 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 a. b. W EIG H T S W ERE R EC O R D ED IN G R AM S. A B S . W T. = O RG AN W EIG H T . R a t 13639 h ad s lig h t d ila tio n o f th e p e lv is o f th e r ig h t k id n e y . Dam aged d u r in g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 19 (P A G E 7) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R A TS ARGUS 418-020 Page 151 RAT NUM BER B R A IN W EIG H T EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U ID ABS. R EL. W T. % BRW DOSAGE GROUP I I I 3 M G/KG/DAY 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 .0 7 2.36 2.22 2.14 2 .3 1 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 3 1.72 28.53 27.06 3 4 .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 1 7 .3 1 1 4 .7 1 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 7 6 .7 1 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 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 .9 1 1 1 2.2724 2.4406 2.4640 126.47 82.88 94.65 97.46 92.35 106.72 95.50 87.14 121.56 134.05 90.06 112.70 1 1 3 .7 9 91.24 8 1 .1 7 108.32 113.39 91.05 1 15 .75 90.86 95.42 103.95 126.80 101.03 126.20 87.63 124.40 109.25 107.52 108.07 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 .1 7 7 7 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 64.8 8 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 A L L W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = O RGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 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) T A B LE B 19 (P A G E 8) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 152 RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. % BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW DOSAGE GROUP I I I 3 M G/KG/DAY 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 .3 1 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 3 1.1 2 26.74 31.98 37.00 29.17 28.30 31.23 2 7 .0 1 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 .7 3 3 1 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 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 33.85a 1267.41 1354.98 1127.59 118 7.8 7 1199.17 1206.00 1392.38 1183.57 1267.95 1316.98 1018.22 1171.62 1357.49 1024.15 1278.83 1064.02 1196.97 1126.81 1120.75 1286.03 1211.16 1204.08 1299.09 1042.73 1239.62 1258.26 1267.52 1248.08 1504.84 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 A L L W EIG H T S W ERE R EC O R D ED I N G R A M S . A B S . W T. = ORGAN W EIG H T . a . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . 100R E L . % B R W = ( O R G A N W E I G H T / B R A I N W E I G H T ) X . 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 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 19 (P A G E 9) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 153 RAT NUM BER B R A IN W EIG H T K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW DOSAGE GROUP I I I 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 .3 1 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 3 M G/KG/DAY 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 .2 7 1 .3 1 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 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 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 0.27 0.49 0.39 0.43 15.18 24.64 19.40 20.50 16.25 22.00 22.42 11.74 17.95 17.92 1 0 .1 7 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 a. b. W EIG H TS W ERE R EC O R D ED IN G R A M S . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G AN W E IG H T / B R A IN W EIG H T ) X 1 0 0 . R a t 136 70 h a d m o d e ra te d ila t io n o f th e p e lv is o f th e r ig h t k id n e y . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 6 ) . R a t 13672 ha d s lig h t d ila tio n o f th e p e lv is o f th e r ig h t k id n e y . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 19 (P A G E 10 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 154 RAT NUM BER B R A IN W EIG H T DOSAGE GROUP IV E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW 10 M G / K G / D A Y T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE ! W IT H O U T F L U I D ABS. R EL. W T. % 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 1376 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 .1 7 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 3 1.71 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 1 3 .1 1 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 .1 7 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 .7 1 0 7 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 7 4 .7 1 78.48 80.93 74.10 80.39 71.98 79.61 76.01 82.24 1.8099 78.35 2.3515 100.06 1.726 7a 82.62a 2.4684 116.98 1.9912 97.13 2.0129 89.46 2 . 2 8 0 0 100.88 2.6892 114.43 2.2 776 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 .1 1 1 7 100.56 2.7024 124.53 2.2975 103.49 2.3873 106.10 2 .4 171 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 .3 1 7 7 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 a. b. W EIG H T S W ERE R EC O R D ED I N G R A M S . A B S . W T. = O RGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T) X 1 0 0 . D a m a ged d u r in g p r o c e s s in g (som e f l u i d lo s s p r i o r t o w e ig h in g ) ; v a lu e s e x c lu d e d fro m g ro u p a v e r a g e s a n d s t a t i s t i c a l Dam aged d u rin g p ro c e s s in g (w e ig h t a f f e c t e d ) ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 19 (P A G E 1 1 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE RATS ARGUS 418-020 Page 155 RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. % BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW DOSAGE GROUP IV 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 10 M G/KG/DAY 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 0.3207a 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 .7 7 1 7 27.97 27.72 20.61 33.52 30.45 29.29 31.86 32.31 2 7 .5 7 29.46 29.77 35.40 29.84 33.33 29.70 13.09 36.61 35.22 28.00 30.00 29.63 27.08 31.40 34.54 29.44 32.87 29.90 33.99 32.35 35.89 1.6959 1.8472 1.5803 1.5982 1.5583 1.9059 1.8881 2.0050 1.6871 1.9501 1 .7 6 1 1 1.8833 1.7711 1.9822 1.8191 0.8699a 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 73.42 78.60 75.61 75.74 76.01 84.71 83.54 85.32 74.00 79.27 77.92 91.87 74.73 83.28 78.41 35.51 80.31 90.76 71.72 83.48 75.92 78.82 81.35 86.22 78.16 91.24 73.47 84.41 79.42 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 .2 1 7 7 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 0.82 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 .1 7 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 .3 1 2.48 96.54 102.98 111.96 130.33 111.71 132.89 95.58 111.06 92.54 96.34 89.82 100.00 106.33 109.66 105.60 88.57 120.77 113.62 93.99 94.12 86.57 86.75 103.81 109.68 107.66 110.67 97.53 111.01 104.52 115.35 ALL a. W EIG H TS W ERE R EC O R D ED R a t 1 3 70 6 h a d a s m a ll ta b le (T a b le B 1 6 ) . IN GRAM S. and fla c c id A B S . W T. = O RGAN W EIG H T . r ig h t e p id id y m is an d r ig h t R E L . % BRW = (O R G AN WEIG H T / B R A IN W EIG H T ) X 1 0 0 . t e s t i s . See t h e in d iv id u a l n e c ro p s y o b s e rv a tio n s PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 19 (PAG E 12 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 156 RAT NUM BER B R A IN W EIG H T DOSAGE GROUP IV 13691 13692 13693 13694 13 6 9 5 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 .3 1 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 K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW 10 M G / K G / D A Y 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 1 1 1 .9 1 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 1.8 1 1 .5 1 1.42 1.26 1.54 1.78 1.33 1 .3 1 1.30 1.28 1.19 1.20 1.58 1.24 1.23 1.70 1.49 1.02 A D R EN A L R IG H T ABS. R EL. W T. % BRW 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 S P LEEN ABS. W T. R EL. % BRW 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 3 1.7 6 29.86 38.42 47.44 34.28 23.96 44.14 35.11 35.80 42.66 49.77 47.91 THYM US ABS. W T. R EL. % BRW 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 26.41 23.40 36.84 23.70 19.51 24.00 22.12 22.13 18.42 17.89 11.50 1 3 .1 7 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 A L L W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = ORGAN W EIG H T . a . R a t 1 3 7 1 7 had s lig h t d ila tio n o f th e p e lv is o f th e r ig h t k id n e y . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T) X 1 0 0 . See th e in d iv id u a l n e c ro p sy o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 19 (P A G E 13 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE R ATS RAT NUM BER B R A IN W EIG H T EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC L E S W I T H O U T :F L U I D ABS. R EL. W T. % BRW DOSAGE GROUP V 13 72 1 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 30 M G /K G /D A Y 0.6074 26.18 0.6274 29.59 0.6173 28.32 0.6288 28.32 0.5636 27.4 9 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 1.7 7 0 7 1.6260 7 1 .3 7 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 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 65.82 89.93 73.86 72.86 72.12 59.44 74.96 66.82 75.42 80.92 80.38 31.93 73.14 66.99 2.1394 92.22 1.9349 91.27 1.8 18 7 83.43 1.8648 84.00 2.0211 9 8 . 5 9 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 .1 2 7 1 0.9897 1.0162 1.0530 1.1224 1.3574 1.2199 0.8819 1.6355 1.3529 1.3058 b 1.0945 1.0168 1.0459 48.58 46.68 46.61 47.43 54.75 56.79 58.37 36.74 72.37 62.06 62.18 45.41 45.19 4 7 .1 1 ALL a. b. c. W EIG H T S W ERE R EC O R D ED I N G R A M S . R a t 1 3 7 3 2 was m o rib u n d s a c r if ic e d V a lu e was n o t re c o rd e d . R a t 1 3733 h a d a s m a ll an d fla c c id o b s e rv a tio n s ta b le (T a b le B 1 6 ) . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . on d a y 45 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . l e f t e p id id y m is a n d l e f t t e s t i s m in u s t u n ic a a lb u g in e a . S e e th e i n d i v i d u a l n e c r o p s y 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) T A B LE B 19 (P A G E 14 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE RATS RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % BRW S EM IN A L V E S IC L E S W IT H F L U ID ABS. R EL. W T. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U ID ABS. R EL. W T. % BRW DOSAGE GROUP V 30 M G /K G /D AY 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 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 34.22 29.98 32.75 29.38 27.89 18.94 29.40 28.18 28.08 25.74 31.49 32.76 32.41 32.52 31.70 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 15.44 13.68 15.54 13.59 12.94 8.32 14.32 13.91 12.20 12.00 13.06 15.04 14.22 15.41 13.48 1.8057 92.60 1.8269 87.41 1.8806 83.58 1.7360 80.37 1.8928 76.63 0.9095a 4 1 .7 2 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 1.6 9 57 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 1.7412 2 .2 7 7 1 2.1199 1.9407 1.5799 2.0911 2.2751 2.1831 1.6923 2.0396 1.8077 2.1969 2.0347 1.6893 115.36 83.31 101.20 98.14 78.57 72.47 101.51 100.22 97.03 72.94 92.71 96.15 96.36 89.63 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 a. b. W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 0 0 . R a t 1 3 7 4 1 h a d s m a ll an d fla c c id e p id id y m id e s an d t e s t e s . See t h e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 6 ) . R a t 1 3 7 5 0 h a d a la r g e l e f t e p id id y m is a n d l e f t t e s t i s m in u s t u n ic a a lb u g in e a . S e e th e i n d i v i d u a l n e c r o p s y o b s e r v a t io n s ta b le (T a b le B 1 6 ) . 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) T A B LE B 19 (P A G E 15 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE RATS RAT NUM BER B R A IN W EIG H T EP ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. % BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW DOSAGE GROUP V 30 M G /K G /D A Y 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 2 7 .7 7 33.99 30.46 36.40 27.84 15.94 34.60 28.30 26.33 1399.14 1244.34 1160.09 925.68 1 17 3 .1 7 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 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 A L L W EIG H T S W ERE R EC O R D ED I N G R A M S . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . a . R a t 1 3 7 3 2 was m o rib u n d s a c r ific e d on d a y 45 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . 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) T A B LE B 1 9 (P A G E 16 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R ATS RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. % BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW DOSAGE GROUP V 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 30 M G /K G /D A Y 0.6535 0.6117 0.7239 0.6380 0.6731 0.3794a 0.6017 0.6511 0.6378 0.5834 0.6752 0.6142 0.7365 0.7260 0.6502 33.51 29.27 32.17 29.54 27.25 17.40 29.21 28.68 28.35 25.15 30.69 32.67 32.30 31.98 3 1.8 7 1.7745 1.7991 1.9556 1.7722 1.8953 0.8606a 1.5535 1.7824 1.8145 1.7338 1.6953 1.8456 2.0122 1.8831 1.7065 91.00 86.08 86.92 82.05 76.73 39.48 75.41 78.52 80.64 74.73 77.06 98.17 88.25 82.96 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 3 1.8 1 44.36 27.48 35.27 39.58 33.57 36.34 37.54 29.77 45.61 3 7 .4 7 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 A L L W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G AN W EIG H T /B R A IN W EIG H T) X 1 0 0 . a . R a t 1 3 7 4 1 h a d s m a ll an d f la c c id e p id id y m id e s and t e s t e s . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B 1 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) T A B LE B 19 (P A G E 1 7 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M A LE R ATS RAT NUM BER B R A IN W EIG H T K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW DOSAGE GROUP V 30 M G /KG /D AY 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 13731 1373 2b 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 .5 1 1.65 1 .5 1 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 .6 7 1 .2 7 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 2 3 .1 1 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 a. b. c. W EIG H T S W ERE R EC O R D ED IN G R AM S. A B S . WT. = R a t 13729 had s lig h t d ila tio n o f th e p e lv is o f R a t 1 3 7 3 2 was m o rib u n d s a c r ific e d on d a y 45 o f R a t 13733 had s lig h t d ila tio n o f th e p e lv is o f ORGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 0 0 . t h e r ig h t k id n e y . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . th e r ig h t k id n e y . See th e in d iv id u a l n e c ro p s y o b s e rv a tio n s ta b le (T a b le B16). B16). ARGUS 418-020 Page 161 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE B 19 (P A G E 1 8 ) : B R A IN W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N M ALE R ATS RAT NUM BER B R A IN W EIG H T K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW DOSAGE GROUP V 30 M G /K G /D A Y 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 .3 1 0.88 1.29 1.12 1 .2 7 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 3 1.1 0 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 14.3 6 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 A L L W EIG H T S W ERE R EC O R D ED IN G R A M S . A B S . W T. = O RG AN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . ARGUS 418-020 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) T A B LE B20 (P A G E 1 ) : CAU DA E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND S P ER M A TID COUNT - IN D IV ID U A L D A TA - P G EN E R A T IO N M A LE R ATS (S e e f o o t n o t e s a t th e e n d o f t h i s t a b l e ,.) ARGUS 418-020 Page 163 DOSAGE GROUP I RAT NUM BER NUM BER M O T ILE 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 M O T ILE P ER C EN T 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 S T A T IC COUNT (N O N M O TILE) 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 M G/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 D EN S IT Y c 770.5 1040.5 770.6 710.3 963.4 1089.5 1156.0 1198.0 512.5 1324.4 804.8 1202.4 913.0 635.1 1148.5 1046.1 972.8 978.7 648.0 794.5 1284.9 1345.2 1017.2 1764.4 800.6 481.4 752.2 1023.2 1093.4 637.5 S P ER M A TID COUNT d 38 36 45 33 66 36 75 68 27 59 91 56 67 52 67 71 47 38 50 53 29 82 50 45 56 37 44 37 37 30 S P ER M A TID D EN S IT Y e 85.1 68.4 78.4 56.1 111.8 59.2 124.4 113.3 54.2 115.0 158.4 99.5 120.3 1 0 1 .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 8 1 .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) T A B LE B20 (P A G E 2 ) : CAU DA E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND S P ER M A TID COUNT - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS (S e e fo o t n o t e s a t th e e n d o f t h i s t a b l e ..) ARGUS 418-020 Page 164 DOSAGE GROUP I I RAT NUM BER NUM BER M O T ILE 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 M O T ILE P ER C EN T 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 S T A T IC COUNT (N O N M O TILE) 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 M G/KG/DAY TO TAL 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 D EN S IT Y 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 S P ER M A TID 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 S P ER M A TID D EN S IT Y e 74.9 71.2 77.3 9 7 .7 91.5 72.7 7 9 .7 62.3 1 13 .5 9 1 .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) T A B LE B20 (P A G E 3 ) : CAU DA E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AN D S P ER M A TID CO U NT - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS (S e e f o o t n o t e s a t th e e n d o f t h i s t a b l e ..) ARGUS 418-020 Page 165 DOSAGE GROUP I I I RAT NUM BER NUM BER M O T ILE 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 13685 549 221 13686 411 13687 357 13688 245 13689 252 13690 317 M O T ILE P ER C EN T 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 S T A T IC COUNT (N O N M O TILE) 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 M G/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 D EN S IT Y c 773.4 1176.0 926.5 845.6 826.5 762.0 684.4 853.6 1053.4 1368.4 842.9 671.0 944.6 885.8 1132.9 1076.0 1319.2 704.9 1177.5 971.5 678.9 1520.7 2099.2 1033.8 1641.5 825.3 969.1 803.3 1195.2 740.3 S P ER M A TID COUNT d 40 48 48 49 53 43 39 56 63 98 50 29 47 64 32 59 46 39 27 43 80 50 54 42 43 57 34 37 26 24 S P ER M A TID D EN S IT Y 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) T A B LE B20 (P A G E 4 ) : CAU D A E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AN D S P ER M A TID COUNT - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS (S e e fo o tn o te s a t th e e n d o f t h i s ta b le .) ARGUS 418-020 Page 166 DOSAGE GROUP IV RAT NUM BER NUM BER M O T ILE 13691 353 13692 328 13693 13694 368 202 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 13717 273 210 13718 412 13719 397 13720 264 M O T ILE P ER C EN T 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 S T A T IC COUNT (N O N M O TILE) 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 M G/KG/DAY TO TA L 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 D EN S IT Y 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 S P ER M A TID 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 S P ER M A TID D EN S IT Y 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 3 1 .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) T A B LE B20 (P A G E 5 ) : CAUDA E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND S P ER M A TID COUNT - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE RATS (S ee fo o tn o te s a t th e en d o f t h is t a b l e . ) ARGUS 418-020 Page 167 DOSAGE GROUP V RAT NUM BER M O T ILE S T A T IC COUNT NUM BER M O T ILE P ER C EN T (N O N M O TILE) 13721 498 92 44 13722 375 82 81 13723 13724 386 208 84 75 71 68 13725 457 81 105 13726 368 77 107 13727 243 89 29 881 3 7 2 8 420 59 13729 188 80 46 13730 345 90 37 861 3 7 3 1 477 78 13732 13733 M O R IB U N D S A C R IF IC E D O N D A Y 45 O F S TU D Y 106 90 12 13734 321 90 34 13735 320 81 73 13736 710 92 60 13737 294 65 158 13738 266 78 73 861 3 7 3 9 262 41 861 3 7 4 0 388 61 13741 108 58 79 681 3 7 4 2 179 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 M G /K G /D A Y 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 D EN S IT Y C 850.2 891.8 646.0 1063.5 677.4 915.1 1159.2 747.7 1092.9 1230.1 1212.1 1 2 .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 S P ER M A TID 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 S P ER M A TID D EN S IT Y 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 1 3 0 .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) T A B LE B20 (P A G E 6) : C AU D A E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND S P ER M A TID CO U NT - IN D IV ID U A L D A T A - P G E N E R A T IO N M A LE R ATS FO O TN O TES : a . Sum o f n um be r m o tile a n d s t a t i c c o u n t. G ro u p s o f f i v e f i e l d s w e re e v a lu a te d u n t i l a sp erm c o u n t o f a t le a s t 200 w as a c h ie v e d o r 20 f i e l d s w e r e e v a l u a t e d . b . Sperm c o u n t u s e d in th e c a lc u la t io n o f sperm d e n s ity . Te n f i e l d s w e re e v a lu a te d . c . T h e sp e rm d e n s i t y w as c a lc u la t e d b y d i v i d i n g t h e sp e rm c o u n t b y th e v o lu m e i n th e im a g e a re a ( 3 4 . 3 x 1 0 ' 6 mL) , m u l t i p l y i n g b y 2 ( d ilu t io n fa c to r ) an d m u lt ip ly in g b y 10 ` 6 to o b ta in th e sperm c o n c e n tr a tio n . Th e c a lc u la te d sperm c o n c e n tr a tio n v a lu e (ro u n d e d t o 1 d e c im a l p la c e ) w as m u lt ip lie d b y 50 (vo lu m e ) a n d d iv id e d b y th e w e ig h t o f th e l e f t ca u d a e p id id y m is (see T a b le B 1 7 f o r th e w e ig h t o f th e l e f t ca u d a e p id id y m is ) to o b ta in th e sperm d e n s ity . Th e c a lc u la te d v a lu e w i l l v a r y b y a p p ro x im a te ly 0 .8 % fro m t h e C o m p u te r A u to m a te d S p e rm A n a ly s is b e c a u s e th e d i g i t a l im a g e e v a lu a t e d i s s l i g h t l y s m a lle r (4 p i x e ls ) th a n t h e a c t u a l f i e l d c a u s in g a s l i g h t u n d e re s tim a te o f th e a c tu a l vo lu m e an d an o v e r e s tim a te o f th e c o n c e n tr a tio n . d . S p e rm a tid c o u n t u s e d in th e c a lc u la tio n o f s p e rm a tid d e n s ity . Te n f ie ld s w e re e v a lu a te d . e . T h e s p e r m a tid d e n s i t y w as c a l c u l a t e d b y d i v i d i n g t h e s p e r m a tid c o u n t b y t h e v o lu m e i n t h e im a g e a r e a ( 3 4 . 3 x 1 0 " 6 mL) , m u lt ip ly in g b y 2 ( d ilu t io n fa c to r ) an d m u ltip ly in g b y 1 0 ` 6 to o b ta in th e s p e rm a tid c o n c e n tr a tio n . Th e c a lc u la te d s p e rm a tid c o n c e n tr a tio n v a lu e (ro u n d e d t o 1 d e c im a l p la c e ) w as m u lt ip lie d b y 50 (vo lu m e ) a n d d iv id e d b y th e w e ig h t o f th e l e f t t e s t i s m in u s t u n i c a a lb u g in e a (s e e T a b le B 18 f o r th e w e ig h t o f th e l e f t t e s t i s m in u s t u n ic a a lb u g in e a ) t o o b t a in t h e s p e r m a tid d e n s i t y . T h e c a lc u la t e d v a lu e w i l l v a r y b y a p p r o x im a te ly 0.8 % fro m th e C o m p u te r A u to m a te d Sperm A n a ly s is b e c a u s e th e d i g i t a l im a g e e v a lu a t e d i s s l i g h t l y s m a lle r (4 p i x e ls ) th a n th e a c tu a l f i e l d c a u s in g a s l i g h t u n d e r e s tim a te o f th e a c tu a l v o lu m e a n d a n o v e re s tim a te o f th e c o n c e n tra tio n . 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 DETACHED NO NUMBER NORMAL HEAD HEAD BROKEN FLAGEL LUM NO HOOK DOSAGE GROUP I 0 MG/KG/DAY 13601 193 6 1 0 0 13602 199 0 1 0 0 13603 192 3 4 1 0 13604 189 92 00 13605 189 8 3 0 0 13606 190 7 3 0 0 13607 197 2 1 0 0 13608 194 4 1 1 0 13609 60 64 75 10 13610 189 6 5 0 0 13611 179 15 6 0 0 13612 186 9 5 0 0 13613 197 2 1 0 0 13614 187 6 7 0 0 13615 189 9 2 0 0 13616 188 10 2 0 0 13617 193 6100 13618 181 10 9 0 0 13619 192 5 2 1 0 13620 191 8 1 0 0 13621 193 5 2 0 0 13622 191 3 4 1 1 13623 192 6 2 0 0 13624 191 6 3 0 0 13625 196 2 2 0 0 13626 195 4 1 0 0 13627 195 2 2 1 0 13628 197 2 1 0 0 13629 196 1 3 0 0 13630 192 5 3 0 0 EXCES SIVE HOOK COILED BENT SHORT FLAGEL FLAGEL SPERM LUM LUM HEAD OTHER 00000 00000 00000 00000 00000 00000 00000 00000 00000 0 0 000 0 0 000 0 0 000 0 0 000 0 0 000 0 0 000 00000 00000 00000 00000 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 00000 0 0 00 0 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 6.5 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 NO HOOK DOSAGE GROUP II 1 MG/KG/DAY 13531 194 3 3 0 0 13632 191 6 3 0 0 13633 193 5 2 0 0 13634 185 4 8 3 0 13635 188 7 2 3 0 13636 195 3 2 0 0 13637 195 3 2 0 0 13638 160 20 19 1 0 13639 196 1 2 1 0 13640 187 6 7 0 0 13641 195 1 4 0 0 13642 196 2 2 0 0 13643 197 3 0 0 0 13644 194 3 2 1 0 13645 197 1 1 1 0 13646 195 2 3 0 0 13647 197 0 3 0 0 13648 186 8 6 0 0 13649 197 2 1 0 0 13650 192 4 3 1 0 13651 190 5 4 1 0 13652 191 5 4 0 0 13653 185 10 2 2 0 13654 191 4 2 3 0 13655 196 1 2 1 0 13656 196 1 3 0 0 13657 193 7 0 0 0 13658 191 2 6 1 0 13659 189 7 4 0 0 13660 191 5 3 0 0 EXCES SIVE HOOK COILED BENT SHORT FLAGEL FLAGEL SPERM LUM LUM HEAD OTHER 000 00 000 00 000 00 000 00 000 00 000 00 00 0 00 00000 000 00 00 0 00 00 0 00 00000 00 0 00 00000 000 00 000 00 000 00 00000 000 00 00000 00 0 00 00 0 00 10 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00000 10000 PERCENT ABNORMAL 3.0 4.5 3.5 7.5 6.0 2.5 2.5 20.0 2.0 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 DETACHED NO NUMBER NORMAL HEAD HEAD BROKEN FLAGEL LUM NO HOOK DOSAGE GROUP III 3 MG/KG/DAY 13661 198 2 0 0 0 13662 195 4 1 0 0 13663 196 2 2 0 0 13664 185 5 8 1 0 13665 190 4 5 1 0 13666 189 6 2 2 1 13667 193 0 6 1 0 13668 194 2 4 0 0 13669 193 4 2 1 0 13670 188 4 8 0 0 13671 189 4 7 0 0 13672 194 4 2 0 0 13673 191 7 2 0 0 13674 172 13 13 1 0 13675 194 4 1 1 0 13676 189 8 3 0 0 13677 194 2 4 0 0 13678 195 1 4 0 0 13679 187 7 5 1 0 13680 195 2 2 1 0 13681 197 2 1 0 0 13682 194 5 1 0 0 13683 187 7 6 0 0 13684 191 6 2 1 0 13685 195 3 2 0 0 13686 181 11 80 0 13687 194 3 1 2 0 13688 194 3 3 0 0 13689 193 4 3 0 0 13690 189 7 4 0 0 EXCES SIVE HOOK COILED BENT SHORT FLAGEL FLAGEL SPERM LUM LUM HEAD OTHER 0 0 0 00 0 0 0 00 00 000 01 000 0 0000 00 000 00 000 0 00 00 00 000 000 00 0 00 00 00 000 0 0000 1 0000 0 00 00 0 0 0 00 0 0000 0 0000 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 0 0 0 00 00 0 00 0 0000 0 0000 0 00 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 DETACHED NO NUMBER NORMAL HEAD HEAD BROKEN FLAGEL LUM NO HOOK DOSAGE GROUP IV 10 MG/KG/DAY 13691 195 5 0 0 0 13692 193 7 0 0 0 13693 193 5 1 0 1 13694 186 6 8 0 0 13695 193 2 5 0 0 13696 186 9 4 0 1 13697 194 3 3 0 0 13698 194 4 2 0 0 13699 192 6 1 0 0 13700 192 5 2 1 0 13701 184 11 4 1 0 13702 196 2 2 0 0 13703 189 9 2 0 0 13704 191 8 0 0 0 13705 193 4 3 0 0 13706 187 9 4 0 0 13707 190 10 0 0 0 13708 183 8 9 0 0 13709 189 5 6 0 0 13710 188 9 1 1 0 13711 194 3 2 1 0 13712 192 7 1 0 0 13713 194 1 4 1 0 13714 194 1 5 0 0 13715 185 11 3 1 0 13716 193 2 5 0 0 13717 193 5 2 0 0 13718 193 6 1 0 0 13719 193 5 2 0 0 13720 188 8 4 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 00000 00000 00000 00000 00000 00000 00000 00000 00000 000 00 00000 00000 00000 00000 00000 00000 00000 10000 00000 11000 00000 00000 00000 00000 00010 00000 00000 00010 00000 PERCENT ABNORMAL 2.5 3.5 6.5 2.0 3.5 2.0 5.0 5.0 3.0 5.0 4.5 69.2 2.0 6.0 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) T A B LE C l (P A G E 1 ) : C L IN IC A L O B S ER V A TIO N S - SUM M ARY - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 175 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III IV 0 1 3 10 P R EC O H A B IT A T IO N (D A Y 1 O F S TU D Y TO TH E D A Y O F C O H A B IT A T IO N ) M A XIM U M P O S S IB L E IN C ID E N C E 20 9 8 / 30 20 8 9 / 30 2 1 0 0 / 30 2 1 0 0 / 30 M O R IB U N D S A C R IF IC E D la lb 0 0 IN C IS O R S : TO TAL M IS S IN G /B R O K EN M IS A LIG N ED C H R O M O R H IN O R R H EA UNGROOM ED CO AT 13 / 12/ 1/ 3 2 la 1 / la 0/ 0 6/ 1 6/ 1 0/ 0 6/ 1 0/ 0 16 / 0/ 16 / 1 0 1 5/ 3 0/ 0 26/ 13 / 13 / 1 1 1 1/ 1 0/ 0 S C A B (S ) C CHROM ODACRYORRHEA LO C A LIZE D A LO P E C IA : TO TA L LIM B S U N D ER S ID E L E F T FO R ELIM B AND FOREPAW : SW OLLEN 7/ 1 1 / la 84/ 84/ 0/ 2 2 0 0/ 0 0/ 0 0/ 0 5 1/ 39/ 12/ 2 1 1 3/ lb 0/ 0 3/ 1 0/ 0 0/ 0 0/ 0 0/ 0 7/ 1 13/ 1 0/ 0 0/ 0 0/ 0 0/ 0 SO FT OR LIQ U ID FEC ES 0/ 0 3/ 1 0/ 0 0/ 0 L E F T FO R ELIM B : FRAC TU RED 0/ 0 1 / lb 0/ 0 0/ 0 P A LA T E : BROKEN 1 / la 0/ 0 0/ 0 0/ 0 SW OLLEN SNOUT 1 / la 0/ 0 0/ 0 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L IN IC A L O B S E R V A T IO N D A T A W ERE R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H O B S E R V A T IO N S . M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . R a t 13 8 0 4 w as m o rib u n d s a c r if ic e d o n d a y 68 o f s tu d y . b . R a t 13 8 3 6 w as m o rib u n d s a c r ific e d o n d a y 59 o f s tu d y . c . Lo c a te d on th e b a c k , r ig h t fo re lim b o r l e f t fo re lim b . V 30 2 1 0 0 / 30 0 48/ 2 7/ 39/ 2 2 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) T A B LE C l (P A G E 2 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - P G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 176 DOSAGE GROUP D O S A G E (M G /K G /D AY) PRESUM ED G E S T A T IO N : a I I I I I I IV 0 1 3 10 M AXIM U M P O S S IB L E IN C ID E N C E 640/ 29 6 42/ 29 6 4 1/ 29 595/ 27 M O R T A LIT Y 0 0 00 LO C A LIZE D A LO P E C IA : TO TAL LIM B S U N D ER S ID E 26/ 26/ 0/ 3 3 0 3 7/ 22/ 15 / 2 1 1 7/ 1 7/ 1 0/ 0 17/ 17/ 0/ 1 1 0 R IG H T OR B O TH E A R S : S W O LLEN 18 / 1 0/ 0 15 / 1 15 / 1 IN C IS O R S : TOTAL M IS S IN G /B R O K EN M IS A LIG N ED 19 / 0/ 19 / 1 0 1 0/ 0 0/ 0 0/ 0 22/ 0/ 22/ 1 0 1 42/ 20/ 22/ 3 2 1 C H R O M O R H IN O R R H EA 0/ 0 0/ 0 0/ 0 1/ 1 H EA D : MASS 0/ 0 0/ 0 0/ 0 0/ 0 CHROM ODACRYORRHEA 19 / 1 0/ 0 3/ 1 4/ 2 D R IE D , R ED P ER IN A S A L SU BSTANC E 0/ 0 0/ 0 0/ 0 1/ 1 BOTH FOREPAW S: D R IED , R ED SUBSTANCE 0/ 0 0/ 0 0/ 0 1/ 1 L E F T H IN D P A W : S W O LLEN 0/ 0 0/ 0 18 / 1 0/ 0 L E F T H IN D P A W O R LO W ER M I D L IN E : SC AB 0/ 0 6/ 1 4/ 1 0/ 0 L E F T H IN D P A W : A B R A S IO N 0/ 0 0/ 0 3/ 1 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L I N IC A L O B S E R V A T IO N D A T A W ER E R E S T R IC T E D T O T H E N U M B ER O F R A T S W ITH O B S E R V A T IO N S . M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N , a . R e s t r ic t e d t o r a t s w ith a c o n firm e d m a tin g d a te . V 30 640/ 29 0 15 / 15 / 0/ 2 2 0 28/ 2 21/ 13 / 21/ 1 1 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) T A B LE C l (P A G E 3 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 177 DOSAGE GROUP D O S A G E (M G /K G /D AY) LA C T A T IO N : I I I I I I IV 0 1 3 10 V 30 M AXIM U M P O S S IB L E IN C ID E N C E 602/ 28 583/ 27 638/ 29 638/ 29 6 1 7 / 29 M O R T A LIT Y S A C R IFIC ED a lb lc 0 0 0 LO C A LIZE D A LO P E C IA : TO TAL LIM B S U N D ER S ID E H EA D 34/ 34/ 0/ 0/ 3 3 0 0 49/ 42/ 22/ 0/ 3 3 1 0 2/ 2 2/ 2 0/ 0 0/ 0 22/ 22/ 0/ 0/ 1 1 0 0 30/ 23/ 0/ 7/ 4 3 0 1 R IG H T OR BO TH EA R S : SW O LLEN 27/ 2 19 / 1 0/ 0 32/ 3 49/ 3 IN C IS O R S : TO TAL M IS S IN G /B R O K EN M IS A LIG N ED 22/ 0/ 22/ 1 0 1 0/ 0 0/ 0 0/ 0 22/ 16 / 22/ 1 1 1 3 1/ 9/ 22/ 2 1 1 16 / 16 / 14 / 1 1 1 CHROM ODACRYORRHEA 22/ 1 0/ 0 0/ 0 4/ 1 10/ 1 H EA D OR R IG H T A X IL L A : MASS 0/ 0 0/ 0 0/ 0 3/ 1 4/ 1 H EA D : SCAB 0/ 0 0/ 0 0/ 0 0/ 0 7/ 1 S O FT OR LIQ U ID FEC ES 8/ 5 4/ 2 2/ 1 6/ 2 0/ 0 T R A U M A T IZED C O R N EA 0/ 0 0/ 0 19 / 1 0/ 0 0/ 0 R IG H T E Y E : SW OLLEN 0/ 0 0/ 0 10/ 1 0/ 0 0/ 0 T E A T : SW OLLEN 0/ 0 0/ 0 2/ 1 0/ 0 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L I N IC A L O B S E R V A T IO N D A T A W ER E R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H O B S E R V A T IO N S . M A XIM U M P O S S IB L E IN C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . T h e l i t t e r s fro m dam s 13 8 2 2 i n G ro u p I a n d 13 8 5 2 i n G ro u p I I w e re m ix e d t o g e t h e r . B o th dam s a n d l i t t e r s b e c a u s e i t w as n o t p o s s ib le t o i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e d . b . Dam 13 8 2 2 w as s a c r ific e d o n d a y 8 o f la c t a t io n . c . Dam 13 8 5 2 w as s a c r ific e d on d a y 1 1 o f la c t a t io n . w ere s a c r ific e 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) T A B LE C2 (P A G E 1 ) : B O D Y W EIG H TS - P R E C O H A B IT A T I ON - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 178 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 30 30 B O D Y W EIG H T (G) DAY 1 M EANS.D . 147.8 7.3 148.0 5.7 DAY 8 M EANS.D . 1 7 7 .7 9.1 175.3 7.3 DAY 15 M EANS.D . 202.4 12.2 199.2 11.1 DAY 22 M EANS.D . 218.5 15.0 214.5 14 .1 DAY 29 M EANS.D . 234.5 18.5 228.0 15.5 D A Y 36 M EANS.D . 243.7 18.2 236.7 16.6 D A Y 43 M EANS.D . 252.8 20.9 245.9 16 .1 D A Y 50 M EANS.D . 262.8 20.4 255.8 17.6 DAY 57 M EAN+S.D . 268.9 22.4 261.3 17.4 D A Y 64 DAY 70b M EANS.D . M EANS.D . 274.4 22.2 276.8 22.7 ( 29] a 268.5 18.2 [ 29] a 271.8 18.1 t 29] a DAY [] a. b. = DAY O F STUDY = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s v a lu e s f o r r a t s t h a t w e re m o rib u n d L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . s a c rific e d . III 3 30 14 9.3 + 6.5 18 1.3 + 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 + 2 7 .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 + 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 30 148.9 6.7 178.8 + 7.0 2 0 2 .7 8.2 2 17.4 + 9.6 233.0 10.2 238.9 10.1 250.1 11.1 258.8 1 1 . 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) T A B L E C3 (P A G E 1) : B O D Y W EIG H T C H A N G ES - P R E C O H A B IT A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 179 DOSAGE GROUP D O S A G E (M G /K G /D A Y) RATS TES TED N I 0 30 II 1 30 B O D Y W EIG H T C H A N G E (G) DAYS 1 - 8 M EANS. D . +30.0 7.5 +27.3 5.2 DAYS 8 - 15 M E A N S .D . +24.6 6.0 +23.9 5.4 D AYS 15 - 22 M EANS. D . +16.1 5.5 +15.3 + 5.2 D AYS 22 - 29 M EANS.D . +16.0 7.0 +13.5 4.0 D A YS 29 - 36 M EAN+S. D . +9.2 6.9 +8.8 5.4 D A YS 36 - 43 M EANS. D . +9.1 5.3 +9.1 5.3 D A Y S 43 - 50 D A Y S 50 - 5 7 M EANS. D . M EANS. D . + 1 0 . 0 5 .8 + 6 . 1 5 .7 +9.9 4.5 +5.5 4.4 D A YS 5 7 - 64 D A Y S 64 - 70 b DAYS 1 - 70b M EANS.D . M EAN+S.D . M EAN+S. D . +5.5 5.8 +2.6 5.4 [ 29] a + 1 2 9 . 3 2 1 . 7 [ 29] a +6.4 4.9 [ 29] a + 3 .3 + 3.6 ( 29] a + 1 2 4 .1 1 7 . 1 [ 29] a DAYS = DAYS O F STUDY t ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s f o r r a t s th a t w e re m o rib u n d s a c r ific e d . b . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . 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 0+ 1 3 8 . 2 4 . 1 IV 10 30 +31.2 4.8 +25.3 5.8 + 1 7 .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 + 1 3 4 . 9 1 8 . 7 V 30 30 +3 0 . 0 4 . 1 +23.8 + 4 .7 +14.7 + 4.8 +15.6 + 4 .1 +6.0 + 4 .9 * +11.1 + 4 .6 +8.7 5 .1 +5.2 + 3.8 +3.5 + 5.9 +4.3 + 5.5 0+ 1 2 3 . + 1 3 . 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) T A B L E C4 (P A G E 1) : M A T ER N A L B O D Y W EIG H TS - G E S T A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 180 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TESTED N 29a 29a P R EG N A N T N 28 27 IN C LU D ED IN A N A LYS ES N 28 27 M A T E R N A L B O D Y W EIG H T (G) DAY 0 M E A N S .D . 280.3 24.2 272.0 19.2 DAY 7 M EANS.D . 310.3 24.9 299.6 21.8 DAY 10 M EANS.D . 320.6 25.5 310.5 22.6 DAY 14 M EANS.D . 3 37.7 26.3 324.7 + 22.2 DAY 18 DAY 21 M E A N S .D . M EANS.D . 377.4 + 29.3 [ 27] c 405.4 46.0 [ 27] d 3 71.6 26.8 389.0 51.5 DAY [] a. b. c. d. * = D AY O F G ES T A T IO N = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s r a t s t h a t w e re m o rib u n d s a c r ific e d p r i o r t o c o h a b ita tio n . E x c lu d e s r a t s t h a t d id n o t h a v e a c o n firm e d m a tin g d a te . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d . E x c lu d e s v a lu e s fo r r a ts th a t d e liv e r e d . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . 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 2 7b 279.7 22.7 309.6 22.2 322.7 23.7 337.3 24.4 378.8 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 1 9 .7 * 363.3 2 5 .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) T A B L E C5 (P A G E 1 ) : M A T ER N A L B O D Y W EIG H T C H AN G ES - G E S T A T IO N - SUM M ARY - P G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 181 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 29a 29a P R EG N A N T N 28 27 IN C LU D ED IN A N A LYS ES N 28 27 M ATERNAL BODY W E IG H T C H A N G E (G) DAYS 0 - 7 M EANS.D . +30.0 9.3 +27.6 7 .1 DAYS 7 - 10 M EANS.D . +10.3 6.0 +10.9 6.3 DAYS 10 - 14 M EAN+S.D . + 1 7 .1 6.2 +14.2 4.3 D AYS 14 - 18 DAYS 18 - 21 DAYS 0 - 21 M EANS. D . M EAN+S. D . M EANS.D . +39.1 11.2 [ 27] c +29.5 31.6 [ 26]C ,d + 1 2 6 . 0 3 3 . 2 ( 27] d +46.9 8.9 +17.4 38.2 + 1 1 7 . 1 40.8 D AYS = D AYS O F G ES T A T IO N [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s r a t s th a t w e re m o rib u n d s a c r ific e d b . E x c lu d e s r a ts th a t d id n o t h a ve a c o n firm e d c . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d . d . E x c lu d e s v a lu e s fo r r a ts th a t d e liv e r e d . p r io r to c o h a b ita tio n . m a tin g d a te . III 3 30 30 29b IV 10 30 29 27b +30.1 + 9.0 +11.8 5.3 +17.9 5.4 +43.0 12.1 +28.3 24.6 +131.2+ 29.4 +29.9 10.4 + 13.1 + 5.2 +14.6 6.2 +41.5 9.3 +36.6 1 2 . 0 [ 26] d + 1 3 4 . 8 2 0 .5 ( 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 + 1 1 1 . 5 3 8 . 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) T A B L E C 6 (P A G E 1 ) : M A TER N A L B O D Y W EIG H TS - L A C T A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 0 13 RATS TES TED N 2 9a 29a 30 P R EG N A N T N 28 2 7 30 D E LIV E R E D i A L IT T E R N 28 27 29 M A T E R N A L B O D Y W E IG H T (G) DAY 1 M E A N S .D . 313.1 24.7 303.2 19.8 321.2 28.8 DAY 5 M EANS.D . 322.8 28.6 310.2 22.0 327.3 29.1 DAY 8 DAY 11 DAY 15 DAY 22 M EANS.D . M EANS.D . M EANS. D . M EANS.D . 341.0 26.3 [ 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 2 3 .6 [ 26] C 337.7 27.6 [ 25] b 351.4 31.2 [ 28] b 357.7 28.9 351.4 23.0 DAY (] a. b. c. = DAY OF = NUM BER E x c lu d e s E x c lu d e s E x c lu d e s LA C T A T IO N O F V ALU ES AVERAGED r a t s t h a t w e re m o rib u n d s a c r if ic e d p r i o r t o c o h a b ita tio n . v a lu e s th a t w ere n o t re c o rd e d . v a lu e s f o r r a ts th a t w ere s a c r ific e d o r s a c r ific e d due to no s u rv iv in g pups. IV 10 30 29 29 312.2 24.1 318.8 25.4 339.8 28.2 [ 21]b 345.2 24.9 349.9 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 1 7 .7 [ 28] C ARGUS 418-020 Page 182 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C 7 (P A G E 1 ) : M A T ER N A L B O D Y W EIG H T C H A N G ES - L A C T A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 183 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 RATS TESTED N 29a 29a 30 P R EG N A N T N 28 2 7 30 D ELIV E R E D A L IT T E R N 28 27 29 IN C LU D ED IN A N A LYS ES N 28 27 29 M ATERNAL BODY W EIG H T C H A N G E (G) DAYS 1 - 5 M EANS.D . +9.7 11.8 +7.0 14.5 +6.1 11.0 DAYS 5 - 8 DAYS 8 - 1 1 DAYS 1 1 - 1 5 DAYS 1 - 1 5 DAYS 15 - 22 DAYS 1 - 2 2 M EANS.D . M E A N S .D . M EANS.D . M EAN+S.D . M EANS.D . M EANS.D . +12.4 + 1 3 . 1 [ 24] C +14.9 1 2 .9 [ 21]b,c +4.3 + 15.9 [ 25]b,c +41.8 1 4 .5 [ 27] b -9.4 25.2 [ 27] b +32.4 2 3 .0 [ 27] b +16.0 10.6 ( 23] c +9.8 14.9 t 18]b ,c +8.5 19.3 [ 22]b ,c +42.8 17.5 [ 26] b -5.8 22.5 ( 26] b +37.0 2 1 .7 t 26] b +14.1 1 0 . 7 [ 25] C +9.6 13.2 [ 24] C +6.0 1 6 .1 [ 28] C +36.5 13.0 -6.3 16.5 +30.2 19.4 D AYS = DAYS O F LA C T A T IO N [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s fo r r a ts th a t b . E x c lu d e s v a lu e s fo r r a ts th a t c . Ex c lu d e s v a lu e s th a t w ere n o t w e re m o rib u n d s a c r ific e d p r i o r to w ere s a c r ific e d o r s a c r ific e d due re c o rd e d . c o h a b ita tio n . to no s u rv iv in g pups. 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 [ 24] C +9.1 15.2 C 24] C +12.6 1 3 . 4 t 27] C +42.9 1 7 . 2 +0.8 16.8 +43.7 1 5 . 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) T A B L E C 8 (P A G E 1 ) : A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - P R E C O H A B IT A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 184 DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TES TED N I 0 30 II III 13 30 30 IV 10 30 V 30 30 F E E D C O N S U M P TIO N (G /D A Y ) DAYS 1 - 8 DAYS 8 - 15 D AYS 15 - 22 D A YS 22 - 29 D A YS 29 - 36 D A Y S 36 - 43 D A Y S 43 - 50 D A YS 50 - 5 7 D A Y S 5 7 - 64 D AYS 64 - 70 c DAYS 1 - 70c M EANS.D . M EAN+S.D . M EAN+S.D . M EANS.D . M EANS.D . M EANS.D . M EANS.D . M EANS.D . M EANS.D . M EAN+S.D . M EAN+S.D . 18.8 1.8 20.8 2 .4 21.5 [ 28] a 21.3 + [ 28] a 21.4 2.0 2.2 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 [ 2 7 ] a,,b 21.3 1.6 [ 2 7 ] a , rb 19.2 [ 29] a 21.0 [ 29] a 21.2 ( 29] a 20.7 2.1 2 .9 2.3 2.2 21.0 1.8 21.5 [ 29] a 21.7 [ 29] a 21.2 1.9 1.8 2.0 21.1 [ 29]b 21.1 [ 29]b 21.0 [ 29]b 1.6 2.3 1.7 19.9 1.4 21.8 [ 29] a 21.8 [ 29] a 22.3 2 .7 2.2 2.8 21.8 [ 29] a 22.6 2.1 2.7 22.8 + [ 29] a 22.2 [ 27] a 22.1 2.5 2.2 1.8 21.4 2.0 21.9 2.0 19.7 1.7 21.7 2.4 22.2 + [ 29] a 22.1 ( 29] a 22.0 [ 29] a 22.2 [ 29] a 22.5 [ 28] a 22.2 [ 29] a 21.8 ( 29] a 21.2 [ 29] a 21.8 [ 29] a 1.9 2.9 2.3 2.2 2.4 2.8 2.2 2.4 1.9 19.6 [ 29] a 21.2 1.5 1.8 20.9 [ 25] a 21.2 [ 28] a 21.0 [ 29] a 21.4 + [ 29] a 22.0 1.6 1.6 1.9 1.8 3 .0 21.2 + [ 28] a 20.5 2 .3 1 .7 * 20.1 2.0 21.0 1.5 DAYS = DAYS O F STUDY [ ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d o r a p p e a re d in c o r r e c tly b . E x c lu d e s v a lu e s f o r r a t s th a t w e re m o rib u n d s a c r if ic e d . c . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . re c o rd e d , as w e ll as th o se a s s o c ia te d w ith s p illa g e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C9 (P A G E 1 ) : R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - P R E C O H A B IT A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 185 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III IV V 0 1 3 10 30 RATS TES TED N 30 30 30 30 30 F E E D C O N S U M P TIO N (G /K G /D A Y ) DAYS 1 - 8 D AYS 8 - 15 D AYS 15 - 22 D A Y S 22 - 29 D A YS 29 - 36 D A YS 36 - 43 D A Y S 43 - 50 D A Y S 50 - 5 7 D A Y S 5 7 - 64 D A Y S 64 - 70 c DAYS 1 - 70c M E A N + S .D . M EANS.D . M EANS. D . M EANS. D . M EANS.D . M E A N S .D . M EANS.D . M EANS. D . M EAN+S.D . M EANS.D . M EAN+S.D . 115.6 9.4 110.0 14.4 102.4 [ 28] a 94.3 [ 28] a 89.3 8.4 8.9 5.8 86.9 + 6.9 [ 29] a 87.8 7.2 [ 27] a 79.6 6.4 [ 28] a 81.1 9.2 ( 27] a 76.6 5.4 [ 27] a,,b 91.1 4 .1 [ 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 [ 29] a 86.7 ( 29] a 82.1 6.4 5.3 6.2 79.7 [ 29] b 78.1 [ 29] b 92.2 + [ 29]b 5.0 7.8 5.4 120.4 6.5 112.8 13.5 [ 29] a 101.3 7.6 ( 29] a 96.0 9.1 89.2 [ 29] a 88.7 4.8 7.2 86.0 + [ 29] a 80.7 [ 27] a 78.9 6.2 5.8 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 [ 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 [ 29] a 111.2 8.0 8.9 100.0 6.0 [ 25] a 94.1 6.4 [ 28] a 89.2 8.0 [ 29] a 87.5 5.6 [ 29] a 86.3 10.3 81.0 [ 28] a 77.3 7.0 4 .8 74.3 5.7 91.0 4.7 DAYS = DAYS O F STUDY [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d o r a p p e a re d in c o r r e c tly re c o rd e d , as w e ll as th o s e a s s o c ia te d w ith s p illa g e . b . E x c lu d e s v a lu e s f o r r a t s th a t w e re m o rib u n d s a c r if ic e d . c . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C IO (P A G E 1) : M A T ER N A L A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - G E S T A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 186 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 29a 29a PREGNANT N 28 27 IN C LU D ED IN A N A LYS ES N 28 27 M ATERNAL FEED C O N S U M P TIO N (G /D A Y ) DAYS 0 - 7 DAYS 7 - 1 0 M EANS.D . M EANS. D . 25.9 3.2 [ 27] c 27.0 3 .7 25.7 25.7 2.4 2.5 DAYS 1 0 - 1 4 D AYS 14 - 18 DAYS 1 8 - 2 1 DAYS 0 - 2 1 M EANS.D . M EANS.D . M EANS. D . M EANS.D . 27.6 3.5 26.1 2.8 23.6 [ 25] d 26.1 [ 25] d 2.4 2.6 25.8 2.4* [ 26] C 26.8 2.7 [ 26] C 23.2 3 .1 t 23] d 25.6 1.9 [ 23] d D AYS = D AYS O F G ES T A T IO N [ ] = NUM BER O F V A LU ES AV ER A G ED a . E x c lu d e s r a t s th a t w e re m o rib u n d s a c r if ic e d p r io r t o c o h a b ita tio n . b . E x c lu d e s r a t s t h a t d id n o t h a v e a c o n firm e d m a tin g d a te . c . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e . d . E x c lu d e s v a lu e s fo r r a ts th a t d e liv e r e d . * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . III 3 30 30 2 9b 26.0 3 .1 [ 26] C 28.0 2.9 28.4 3.5 [ 28] C 27.3 3 .1 24.5 [ 28] d 26.7 [ 28] d 2.8 2.3 IV 10 30 29 27b 25.0 2.5 26.8 [ 26] c 26.2 ( 26] c 26.1 [ 26] c 23.5 [ 26] d 25.6 [ 26] d 2.8 3.3 2.5 3.6 2.2 V 30 30 29 28b 24.1 2.3 [ 27] c 25.5 2.5 25.4 3 . 0* 25.6 3 .7 23.0 [ 27] d 24.6 [ 27] d 3.9 2 . 2* PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C l l (P A G E 1 ) : M A T ER N A L R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - G E S T A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 187 DOSAGE GROUP D O S A G E (M G /K G /D A Y) I II III 0 13 RATS TES TED N 29a 29a 30 P R EG N A N T N 28 2 7 30 IN C LU D ED IN A N A LYS ES N 28 27 29b M ATERNAL FEED C O N S U M P TIO N (G /K G /D A Y ) DAYS 0 - 7 DAYS 7 - 1 0 M EANS.D . M EANS.D . 87.5 [ 27]c 85.4 9.5 8.3 90.1 84.5 8.3 7.0 87.0 [ 26] c 87.7 7.6 7.1 DAYS 1 0 - 1 4 DAYS 1 4 - 1 8 D AYS 18 - 2 1 DAYS 0 - 2 1 M EAN+S.D . M E A N S .D . M EANS.D . M EANS.D . 84.0 7.7 1 2 . 2 6.2 [ 27] C 59.7 8.5 [ 24] c, d 77.0 5.5 ( 25] d 81.5 [ 26] C 77.1 t 26] C 59.9 [ 23] d 77.3 [ 23] d 7.3 7.7 7.7 5.7 84.4 8.0 [ 28] C 7 5 . 1 8.6 61.3 ( 28] d 77.7 ( 28] d 6.0 4.4 D AYS = DAYS O F G ES T A T IO N [ ] = NUM BER O F V A LU ES AVER AG ED a . E x c lu d e s r a t s t h a t w e re m o rib u n d s a c r ific e d p r io r to c o h a b ita tio n . b . E x c lu d e s r a t s t h a t d id n o t h a v e a c o n firm e d m a tin g d a te . c . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d , as w e ll as th o s e a s s o c ia te d d . E x c lu d e s v a lu e s fo r ra ts th a t d e liv e re d . w ith s p illa g e . 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 ( 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 [ 27] d 76.0 [ 27] d 9.2 5.3 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) T A B L E C 12 (P A G E 1 ) : M A T ER N A L A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - L A C T A T IO N - SUM M ARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 188 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III IV 0 1 3 10 V 30 RATS TESTED N 29a 29a 30 30 30 P R EG N A N T N 28 2 7 30 29 29 D ELIV E R E D A L IT T E R N 28 27 29 29 29 IN C LU D ED IN A N A LY S ES N 28 27 29 29 28b M A T ER N A L F E E D C O N S U M P TIO N (G /D A Y ) DAYS 1 - 5 DAYS 5 - 8 DAYS 8 - 1 1 DAYS 11 - 15d DAYS 1 - 15d M E A N S .D . M E A N S .D . M EANS. D . M EANS.D . M E A N S .D . 31.8 6.4 [ 25] c 51.2 8.6 [ 26]b,c 61.8 10.6 [ 25]b ,c 69.4 1 1 . 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 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 D AYS = DAYS O F LA C T A T IO N [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s r a t s t h a t w e re m o rib u n d s a c r if ic e d p r io r to c o h a b ita tio n . b . Ex c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d o r s a c r ific e d due to no s u r v iv in g p u p s . c . Ex c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e . d . B ecause i t is presum ed th a t th e pu ps b e g in to consum e m a te rn a l fe e d a f t e r d a y 15 o f la c ta tio n , w ere n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . m a te rn a l fe e d c o n s u m p tio n v a lu e s PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 13 (P A G E 1 ) : M A T ER N A L R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - L A C T A T IO N - SUMMARY - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 189 DOSAGE GROUP D O S A G E (M G /K G /D A Y) RATS TES TED N I 0 29a II 1 29a III 3 30 IV 10 30 V 30 30 P R EG N A N T N 28 27 30 29 29 D E LIV E R E D A L IT T E R N 28 27 29 29 29 IN C LU D ED IN A N A LYS ES N 28 27 29 29 28b M ATERNAL FEED C O N S U M P TIO N (G /K G /D A Y ) DAYS 1 - 5 DAYS 5 - 8 DAYS 8 - 1 1 DAYS 11 - 15d DAYS 1 - 15d M EANS.D . M EANS.D . M E A N + S .D . M EANS.D . M EANS.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 [ 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 D AYS = DAYS O F LA C T A T IO N [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s r a t s t h a t w e re m o rib u n d s a c r ific e d p r io r t o c o h a b ita tio n . b . E x c lu d e s v a lu e s f o r r a ts th a t w ere s a c r ific e d o r s a c r ific e d due to n o s u r v iv in g p u p s . c . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d , as w e ll as th o s e a s s o c ia te d w ith s p illa g e . d . B e cau se i t is presum ed th a t th e pups b e g in to consum e m a te rn a l fe e d a f t e r d a y 15 o f la c ta tio n , w ere n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . m a te rn a l fe e d c o n s u m p tio n v a lu e s PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C 14 (P A G E 1) : M A TIN G AN D F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - SUMMARY - P G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 190 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 ES TR O U S C Y C LIN G O B S ER V A TIO N S P R EC O H A B IT A T IO N ES TR O U S C Y C LIN G RATS EV ALU ATED N 2 9a 29a ESTROUS STAGES/ 21 DAYS M EAN+S. D . 5 . 2 + 1.0 5 .2 + 0 .6 R A T S W IT H 6 O R M ORE C O N S EC U T IV E D AYS O F D IES T R U S N 2 0 R A T S W IT H 6 O R M ORE C O N S EC U T IV E DAYS O F ESTRUS N 0 0 ESTROU S STAG E A T S A C R IFIC E RATS EV ALU ATED N 28b 28b D IES T R U S P R O ES TR U S ESTRUS M ETESTRUS N7 N 21 N0 N0 9 16 2 1 a . E x c lu d e s r a t s t h a t w e re m o rib u n d s a c r ific e d p r io r t o c o h a b ita tio n . b . E x c lu d e s v a lu e s fo r r a ts th a t d id n o t have a v a lu e re c o rd e d . 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) T A B L E C 14 (P A G E 2 ) : M A TIN G AN D F E R T I L I T Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - SUMMARY - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 191 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 01 3 R A TS IN C O H A B IT A T IO N N 29a 29a 30 D A YS IN C O H A B IT A T IO N b M EAN+S. D . 3 . 3 + 2.6 1.9 + 1.2 * 2.4 + 1 .7 [ 29] RATS TH AT M ATED N (% ) 29(100.0) 29(100.0) 30(100.0) F E R T IL IT Y IN D EX C N /N (% ) 2 8 / 29 ( 96.6) 2 7/ 29 ( 93.1) 3 0/ 30 (1 0 0 . 0 ) R A T S W IT H C O N FIR M ED M A TIN G D A T ES N 29 29 29 R A TS M A TIN G DAYS 1 -7 DAYS 8-14 d N (% ) N (%) 27 ( 93.1) 2( 6.9) 29(100.0) 0 ( 0 .0) 28 ( 96.6) M 3.4) RATS PREGNANT/RATS IN C O H A B IT A T IO N N /N (% ) 2 8 / 29 ( 96.6) 2 7/ 29 ( 93.1) 3 0 / 30 (1 0 0 . 0 ) ( ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s r a t s th a t w e re m o rib u n d s a c r if ic e d p r io r to c o h a b ita tio n . b . R e s t r ic t e d t o r a ts w ith a c o n firm e d m a tin g d a te an d r a ts th a t d id n o t c. Num ber o f p re g n a n c ie s /n u m b e r o f r a t s th a t m a te d . d . R e s t r ic t e d to r a ts w ith a c o n firm e d m a tin g d a te . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . m a te . IV 10 30 3 . 1 + 2.4 [ 28] 29 ( 9 6 .7 ) 29 / 29 (1 0 0 . 0 ) 27 27(100.0) 0 ( 0 .0) 29 / 30 ( 96.7) V 30 30 2.6 + 1.4 [ 29] 30(100.0) 2 9 / 30 ( 96.7) 29 29(100.0) 0 ( 0 .0) 2 9 / 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) T A B LE C 15 (P A G E 1) : N EC R O P S Y O B S ER V A TIO N S - SUM M ARY - P G E N E R A T IO N FE M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV 0 1 3 10 V 30 R A TS EX A M IN ED a N 30 30 30 30 30 M O R IB U N D S A C R IF IC E D N lb lc 0 0 0 S A C R IFIC ED d N le I f 0 0 0 APPEARED NORMAL N 29e 29f 29 30 30 K ID N EY S : L E F T , P E L V IS , M ARKED D IL A T IO N N 0 0 1 0 0 L E F T FO R ELIM B : U LN A AND R A D IU S , B ROK EN N 0 lc 0 0 0 a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le C24) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . R a t 13 8 0 4 was m o rib u n d s a c r ific e d on d a y 68 o f s tu d y . c . R a t 13 83 6 w as m o rib u n d s a c r ific e d o n d a y 59 o f s tu d y . d . T h e l i t t e r s fro m dam s 13 8 2 2 in G ro u p I a n d 13 8 5 2 in G ro u p I I w e re m ix e d t o g e t h e r . B o th dam s a n d l i t t e r s w e re s a c r if ic e d b e c a u s e i t w as n o t p o s s ib le to id e n t i f y to w h ic h l i t t e r th e p u p s b e lo n g e d . e . R a t 13822 was s a c r ific e d on d a y 8 o f la c ta tio n . f . R a t 13852 was s a c r ific e d on d a y 1 1 o f la c ta tio n . ARGUS 418-020 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) T A B L E C 16 (P A G E 1) : T E R M IN A L B O D Y W EIG H T S A N D O R G A N W EIG H T S - SUM M ARY - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 193 DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV 0 1 3 10 RATS TESTED N 30 30 30 29 a P R EG N A N T N 28 2 7 30 29 IN C LU D ED IN A N A LYS ES N 2 7b 26b 29c 29 T E R M IN A L B O D Y W EIG H T M EANS.D . 345.0 29.1 339.5 23.6 351.4 23.0 342.1 26.1 P IT U IT A R Y B R A IN M EANS. D . M EANS.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 LIV E R M EANS.D . 18.69 2.49 17.97 + 2.13 17.85 + 1.78 17.25 + 1.94 K ID N EY L E F T M EANS. D . 1.57 0.16 1.58 + 0.14 1.58 0.18 1.52 0.14 K ID N E Y R IG H T M EANS.D . 1.57 + 0.18 1.61 0.14 1.62 + 0.16 1.55 + 0.13 ADRENAL LEFT M EANS.D . 0.045 0.010 0.051 + 0.009 0.048 0.010 0.046 0.007 A D R EN A L R IG H T M E A N + S .D . 0.045 0.007 0.046 0.008 0.043 0.006 0.042 + 0.009 S P LEEN M EANS. D . 0.67 0.10 0.69 + 0.09 0 .71 0.11 0.69 + 0.09 C E R V IX M EANS.D . 0.22 0.12 0.19 0.05 0.20 + 0.08 0.20 0.10 OVARY LEFT M EANS.D . 0.052 + 0.011 0.055 0.016 0.054 0.014 0.049 + 0.010 O V A R Y R IG H T M EANS.D . 0.053 0.011 0.057 0.018 0.057 0.013 0.054 + 0.012 U TER U S N O N -G R A V ID M EAN+S.D . 0.52 + 0.14 0.59 + 0.21 0.53 + 0.15 0.58 + 0.19 [ ] = NUM BER O F V A LU ES A V ER A G ED A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . a . E x c lu d e s r a t 1 3 9 0 0 , w h ic h d id n o t h a v e o rg a n w e ig h t v a lu e s re c o rd e d . b . E x c lu d e s v a lu e s f o r r a t s t h a t w e re s a c r if ic e d , m o rib u n d s a c r ific e d o r s a c r ific e d du e t o n o s u r v iv in g p u p s . c . E x c lu d e s dam 1 3 8 6 2 , w h ic h w as p re g n a n t b u t d id n o t d e liv e r a l i t t e r . d . E x c lu d e s v a lu e s th a t a p p e a re d in c o r r e c tly re c o rd e d . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . V 30 30 29 28b 345.0 1 7 .7 0.016 0.006 [ 27] d 2 .1 7 0.11 18.08 1 .7 1 1.44 0 . 10** 1.49 0 . 10* 0.046 0.010 0.042 0.010 [ 27] d 0.72 0.10 0 .1 7 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) T A B L E C 1 7 ( P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T - S U M M ARY - P G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 194 DOSAGE GROUP D O S AG E (M G /K G /D AY) I I I I I I IV 0 1 3 10 V 30 RATS TES TED N 30 30 30 29a 30 P R EG N A N T N 28 27 30 29 29 IN C LU D ED IN A N A LYS ES N 27b 26b 29c 29 28b T E R M IN A L B O D Y W EIG H T M EANS.D . 345.0 2 9 .1 339.5 + 23.6 351.4 + 23.0 342.1 26.1 345.0 + 1 7 .7 P IT U IT A R Y d B R A IN M EANS.D . M E A N S .D . 5.311 + 1.260 [ 26] e 0.648 0.057 5.506 1.457 0.654 + 0.054 4.933 + 1.064 0.634 + 0.050 4.674 2.089 0.653 0.053 4.547 1.735 [ 27] e 0.630 0.034 LIV E R M EANS.D . 5.405 + 0.425 5.284 + 0.422 5.088 + 0 .4 8 1* 5.047 0.455** 5.244 0.461 K ID N EY L E F T M EANS. D . 0.455 + 0.042 0.465 0.041 0.449 + 0.040 0.443 0.032 0.418 0.032** K ID N E Y R IG H T M EANS.D . 0.456 + 0.044 0.474 + 0.042 0.461 + 0.037 0.454 0.032 0.431 + 0.029* ADRENAL L E FT d M EANS.D . 13.162 2.855 14.963 2.401 13.614 + 2.787 13.438 2.221 13.312 3.037 A D R EN A L R IG H T d S P LEEN C ER V IX M EANS.D . M EANS. D . M EANS.D . 13.042 2.341 0.195 + 0.026 0.063 0.031 13.642 2.274 0.204 + 0.026 0.057 + 0.014 12.230 + 1.775 0.203 i 0.029 0.058 + 0.026 12.418 + 2.418 0.200 0.023 0.058 + 0.027 12.042 2.869 [ 27] e 0.207 0.028 0.049 0.017 OVARY LE FT d M EANS.D . 15.227 3.484 16.053 4.570 15.333 + 4.080 14.289 3.173 15.446 + 4.566 O VAR Y R IG H T d M EANS.D . 15.4 17 2.965 16.886 + 5.250 16.271 + 3.379 15.903 3.306 14.108 3.631 U TER U S N O N -G R A V ID M EAN+S. D . 0.154 0.043 0 .175 0.063 0.151 + 0.044 0.170 0.049 0.146 0.033 [ ] = NUM BER O F V A LU ES AV ER A G ED A L L W EIG H TS W ERE R EC O R D ED I N GRAM S (G ) . R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . a . E x c lu d e s r a t 1 3 9 0 0 , w h ic h d id n o t h a ve o rg a n w e ig h t v a lu e s re c o rd e d . b . E x c lu d e s v a lu e s f o r r a t s th a t w e re s a c r if ic e d , m o rib u n d s a c r ific e d o r s a c r if ic e d du e t o n o s u r v iv in g p u p s . c . E x c lu d e s dam 1 3 8 6 2 , w h ic h was p re g n a n t b u t d id n o t d e liv e r a l i t t e r . d . V a lu e was m u ltip lie d b y 1000. e . E x c lu d e s v a lu e s th a t ap p e a re d in c o r r e c tly re c o rd e d . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S ig n if ic a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 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) T A B L E C l 8 ( P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - S U M M ARY - P G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 195 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV V 10 3 0 RATS TES TED N 30 30 30 29a 30 P R EG N A N T N 28 2 7 30 29 29 IN C LU D ED IN A N A LYS ES B R A IN W EIG H T P IT U IT A R Y LIV E R N M EAN+S. D . M EANS. D . M EANS.D . 27b 2.22 0 . 1 3 0 . 8 2 0.20 [ 26] d 839.90 101.30 26b 2.21 + 0 . 1 4 0.85 + 0.23 814.22 + 93.64 29C 2.22 + 0 . 1 3 0.78 0.16 806.07 98.78 29 2.22 0 . 0 8 0.71 + 0.27 776.69 90.72 28b 2 .1 7 0.11 0.72 0.28 [ 27] d 834.10 80.85 K ID N EY L E F T M EAN+S.D . 70.57 + 7.47 71.66 + 7.89 71.24 + 8.32 68.35 + 6 .1 7 66.42 4.29* K ID N E Y R IG H T ADRENAL LE FT A D R EN A L R IG H T S P LEEN M EANS. D . M EANS. D . M EANS.D . M EAN+S.D . 70.80 7.55 2.03 0.42 2.01 0 . 3 3 30.28 3.63 73.06 7.36 2.31 + 0.44 2.10 + 0 . 3 9 31.47 + 4.70 73.00 7.24 2.14 0.43 1.94 0.31 32.14 + 5.27 69.80 6.03 2.06 0.30 1 .9 1 0.38 30.94 + 3.74 68.59 2.11 4.86 0 .48 1.92 0.46 [ 27] d 33.18 4.83 C ER V IX M E A N S .D . 9.76 5.09 8.80 2.28 9.21 3.79 9.00 + 4 .3 7 7.90 + 2.68 OVARY LEFT M EANS. D . 2.35 0.49 2.48 0.74 2.43 + 0.65 2.19 + 0.46 2.46 0.76 O VA R Y R IG H T M EANS.D . 2.40 0.55 2.58 + 0.78 2.58 + 0.57 2.45 0.54 2.25 0.59 U TER U S N O N -G R A V ID M EANS.D . 23.74 6.45 26.97 + 10.31 23.93 + 6.55 26.16 + 8.39 23.15 5.23 [ ] = NUM BER O F V A LU ES AV ER AG ED A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . R A T IO S (% ) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 0 0 . a . E x c lu d e s r a t 1 3 9 0 0 , w h ic h d id n o t h a ve o rg a n w e ig h t v a lu e s re c o rd e d . b . E x c lu d e s v a lu e s f o r r a t s t h a t w e re s a c r if ic e d , m o rib u n d s a c r if ic e d o r s a c r ific e d du e t o n o s u r v iv in g p u p s . c . E x c lu d e s dam 1 3 8 6 2 , w h ic h was p re g n a n t b u t d id n o t d e liv e r a l i t t e r . d . E x c lu d e s v a lu e s th a t ap p e a re d in c o r r e c tly re c o rd e d . * S ig n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 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) T A B LE C l 9 (P A G E 1 ) : N A TU R A L D E L IV E R Y O B S ER V A TIO N S - SUMMARY - P G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 196 DOSAGE GROUP D O S A G E (M G /K G /D AY) R ATS A S S IG N ED TO N ATU R AL D E LIV E R Y N I 0 29a II 1 2 9a III 3 30 IV 10 30 V 30 30 P R EG N A N T N(%) 28 ( 96.6 ) 27( 93.1) 30 ( 1 0 0 .0 ) 29 { 9 6 .7 ) 29 ( 9 6 . 7 ) D E LIV E R E D A L IT T E R N (%) 28(100.0) 27 (100.0) 29 ( 9 6 .7 ) 29(100.0) 29(100.0) D U R A T IO N O F G E S T A T IO N b M EA N S . D . IM P LA N T A T IO N S IT E S P ER D E LIV E R E D L IT T E R N M EANS. D . 22.6 428 15.3 0.5 1.9 22.5 421 15.6 0.5 2 .1 22.8 442 15.2 + 0.5 2.3 22.6 [ 27] C 453 15.6 0.6 2.0 22.1 [ 28] C 445 15.3 i : DAM S W IT H S T IL L B O R N PU PS N(%) 3 ( 10.7) 4( 14.8) 5( 1 7 .2 ) 3 ( 10.3) 4 ( 13.8) DAM S W IT H N O L IV E B O R N PU PS N( %) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) G ES T A T IO N IN D E X d % N/N 100.0 28/ 28 100.0 27/ 27 96.7 2 9 / 30 100.0 29 / 29 100.0 2 9 / 29 DAM S W IT H A L L P U P S D Y IN G DAYS 1 -4 POSTPARTUM N (%) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) K 3.4) DAM S W IT H A L L PU P S D Y IN G DAYS 5 - 2 1 POSTPARTUM N(%) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 { 0 .0) [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s r a t s th a t w e re m o rib u n d s a c r if ic e d p r i o r to c o h a b ita tio n . b . C a lc u la te d a s th e tim e ( in d a y s ) e la p s e d b e tw e e n c o n firm e d m a tin g ( a r b i t r a r i l y d e fin e d as d a y 0) an d th e tim e th e f i r s t pup was d e liv e re d . c . E x c lu d e s v a lu e s f o r r a t s t h a t d id n o t h a v e a c o n firm e d m a tin g d a te . d . Num ber o f r a ts w ith liv e o ffs p rin g /n u m b e r o f p re g n a n t r a t s . (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) T A B LE C20 (P A G E 1 ) : L IT T E R O B S ER V A TIO N S (N A T U R A LLY D E L IV E R E D PU PS) - SUMMARY - P G EN ER A T IO N FE M A LE R A TS ARGUS 418-020 Page 197 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 01 3 D E L IV E R E D L IT T E R S W IT H O N E OR M ORE LIV EB O R N PUPS N 28 27 29 PUPS D E LIV E R E D (TO T A L) N M EANS.D . 402 14.4 2 .1 395 14.6 2.2 393 13.6 3.6 LIV EB O R N M E A N S .D . N(%) 14.2 2.2 397( 98.8) 14.2 2.6 384 ( 9 7 .2 ) 13 .4 + 3.6 388 ( 98.7) S T ILLB O R N M EAN+S. D . N {% ) 0 .1 0 .3 3( 0.7) 0 .4 1 .4 10( 2.5) 0 .2 0 .4 5( 1.3) UNKNOW N V IT A L STATUS N 2 1 0 PUPS FOUND D EA D OR PRESUM ED C A N N IB A LIZE D DAY DAYS DAYS DAYS DAYS 1 2 -5 6-8 9-15 16-22 V IA B IL IT Y IN D EX C LA C T A T IO N IN D E X d N / N (%) N / N (%) N / N (%) N / N (%) N / N (%) % N/N % N/N 2/397 ( 7/395 ( 1/388 ( 0/375 ( 0/375 ( 0.5) 1.8) 0.2) 0 .0 )a 0 .0 )a 97.7 388/397 99.7 375/376a 2/384 ( 6/382( 2/376 ( 1/362 ( 0/361 ( 0.5) 1.6) 0.5) 0 .3 )b 0 .0)b 98.2 377/384 98.9 3 61/365 b 3/388 { 7/385 ( 5/378 ( 1/373 ( 1/372 ( 0.8) 1.8) 1 .3 )* 0.3) 0.3) 97.4 378/388 98.1* 371/378 D A Y (S ) = D A Y (S ) POSTPARTUM a . E x c lu d e s l i t t e r 1 3 8 2 2 ; a l l pu ps w ere s a c r ific e d due to s a c r ific e o f dam . b . E x c lu d e s l i t t e r 13 8 5 2 ; a l l p u ps w ere s a c r ific e d due to s a c r ific e o f dam . c . Num ber o f l i v e p u p s on d a y 5 p o stp a rtu m /N u m b e r o f liv e b o r n p u ps on d a y 1 p o s tp a rtu m . d . Num ber o f l i v e p u ps on d a y 22 p o stp a rtu m /N u m b e r o f l i v e p u ps o n d a y5 p o s tp a rtu m . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S ig n if ic a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . 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 ( 5/400 ( 2/395 ( 3/393 ( 0/390 ( 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 3/388 ( 11/385 ( 10/374 ( 2/364 ( 0/362 ( 0.8) 2.8) 2 .7 ) ** 0.5) 0.0) 96.9 376/388 9 6 .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) T A B LE C20 (P A G E 2 ) : L IT T E R O B S ER V A TIO N S (N A T U R A LLY D E L IV E R E D PUPS) - SUMMARY - P G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page 198 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 0 13 D E L IV E R E D L IT T E R S W IT H O N E O R M ORE LIV EB O R N PUPS N 28 27 29 S U R V IV IN G P U P S / LIT T E R a DAY 1 b M E A N + S .D . 14.2 2.2 14.2 2.6 13.4 + 3.6 DAY 5 M EAN+S.D . 13.8 2 .1 13.9 2.5 13.0 + 3.4 DAY 8 DAY 15 D AY 22 M EANS.D . M EAN+S.D . M EANS. D . 1 3 . 9 + 2.0 [ 27] C 13.9 + 2.0 [ 27] c 13.9 2.0 [ 27] C 13.8 2.5 13.9 2.5 [ 26] C 13.9 2.5 [ 26] C 1 2 .9 3.4 12.8 3.3 12.8 + 3.4 PER C EN T M ALE PUPS PER NUM BER O F PUPS S EX ED DAY 1 b M EANS.D . 46.9 13.2 52.2 13.6 48.6 + 17.5 DAY 5 8D A Y DAY 15 D A Y 22 M E A N S .D . M EANS. D . M EAN+S.D . M EANS.D . 47.0 13.9 47.8 13.4 [ 27] c 47.8 13.4 ( 27] C 47.8 13.4 [ 27] c 53.1 13.3 53.0 13.3 52.6 13.2 [ 26] C 52.6 + 13.2 [ 26] C 49.1 + 17.6 49.3 + 17.4 49.2 + 17.5 49.2 17.4 DAY [] a. b. c. d. = D AY POSTPARTUM = NUM BER O F V A LU ES A V ER AG ED A ve ra g e num ber o f liv e pups p e r l i t t e r , in c lu d in g l i t t e r s In c lu d e s pups b o rn a liv e , fo u n d dead on d a y 1 p o s tp a rtu m . E x c lu d e s l i t t e r s in w h ic h th e dam w as s a c r if ic e d . E x c lu d e s l i t t e r 1 3 9 4 7 , w h ic h h a d n o s u r v iv in g p u p s on d a y w ith 1 of no s u rv iv in g la c ta tio n . pups. IV 10 29 13.8 3.0 13.6 + 2.8 13.6 2.8 13.4 2.8 13.4 + 2.8 V 30 29 13.4 3.3 12.9 3 .7 12.6 3.6 12.5 3.6 12.5 3.6 4 7 . 1 + 10.2 4 7 . 1 + 10.2 4 7 . 3 + 10.1 4 7 . 4 + 10.1 4 7 . 4 + 10.1 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) T A B LE C20 (P A G E 3 ) : L IT T E R O B S ER V A TIO N S (N A T U R A LLY D E L IV E R E D PUPS) - SUMMARY - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 199 DOSAGE GROUP D O S AG E (M G /K G /D AY) I II III 013 D E L IV E R E D L IT T E R S W IT H O N E OR M ORE LIV EB O R N PUPS N 28 27 29 L IV E L IT T E R S I Z E A T W EIG H IN G DAY 1 M EANS. D . 1 4 .1 2.2 14.1 2.7 13.3 3.6 DAY 5 M EANS.D . 13.8 2.1 13.9 + 2.5 13.0 3.4 DAY 8 DAY 15 D A Y 22 M E A N S .D . M E A N S .D . M EANS.D . 13.9 2.0 [ 27] b 13.9 2.0 [ 27] b 13.9 2.0 [ 27] b 13.8 2.5 13.9 2.5 ( 26] b 13.9 2.5 [ 26] b 12.9 3.4 12.8 + 3.3 12.8 + 3.4 P U P W E IG H T / L IT T E R (GRAM S) DAY 1 M E A N S .D . 6 .3 0 .5 6 .0 0 . 4 * 6.2 + 0.5 DAY 5 M EANS.D . 9 .4 1 .3 8.8 0.8 9 .5 1 .5 DAY 8 DAY 15 DAY 22 M EANS. D . M EANS. D . M EANS. D . 13.3 2.0 [ 27] b 25.0 4.0 [ 27] b 37.4 6.5 ( 27] b 1 2 .7 1.3 24.2 2.8 [ 26] b 36.7 5.5 [ 26] b 13.5 + 2.2 26.4 4 .7 39.7 8.3 DAY = DAY POSTPARTUM [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s l i t t e r 1 3 9 4 7 , w h ic h h a d n o s u r v iv in g p u ps on d a y 1 o f la c t a t io n . b . E x c lu d e s l i t t e r s in w h ic h th e dam w as s a c r ific e d . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . 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 + 4.0 38.8 6.1 V 30 29 1 3 . 8 + 2.5 [ 28] a 13.4 2.8 [ 28] a 1 3 .0 + 2.7 [ 28] a 12.9 2.8 [ 28] a 12.9 2.8 [ 28] a 5.7 0.5** [ 28] a 8 .5 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 (A P FO ) IN R A TS (S P O N S O R ' S S TU D Y NU M B ER: T - 6 8 8 9 . 6 ) T A B L E C 2 1 (P A G E 1 ) : C L IN IC A L O B S ER V A TIO N S ! FROM B IR T H TO D A Y 22 PO STPAR TU M - SUMMARY - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 200 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) L IT T E R S E X A M IN E D (N ) I I I I I I IV 0 1 3 10 28 2 7 29 29 T R A N S IE N T C L IN IC A L O B S ER V A TIO N S : a T O T A L F R E Q U E N C Y (D A Y S X P U P S ) / L IT T E R S W IT H O B S E R V A T IO N S COLD TO TOUCH N /N 22/5 5/4 29/5 3/2 B R U IS E b N /N 0/0 0/0 0/0 6/1 NO M ILK IN STOM ACH U M B ILIC A L H ER N IA P A LE L E F T FO R ELIM B OR M OUTH: MASS N /N N /N N /N N /N 1/1 0/0 0/0 0/0 0/0 2/1 0/0 2/1 0/0 0/0 0/0 0/0 3 /2 1/1 1/1 0/0 NO T N ES T IN G BAC K: SCAB R ED P E R IA N A L SUBSTANC E N O T N U R S IN G N /N N /N N /N N /N 3 /1 0/0 0/0 3 /1 0/0 0/0 0/0 0/0 0/0 0/0 1/1 0/0 1/1 1/1 0/0 0/0 P E R S IS T E N T C L IN IC A L O B S ER V A TIO N S : a T O T A L F R E Q U E N C Y (D A Y S X P U P S ) / L IT T E R S W IT H O B S E R V A T IO N S T IP O F T A I L M IS S IN G N /N 0/0 18/1 2/1 22/1 L E F T E Y E : T R A U M A T IZED C O R N EA N /N 0/0 0/0 0/0 2/1 T IP O F T A IL BLACK N /N 0/0 0/0 20/1 0/0 H IN D L IM B S R O T A T E D IN W AR D N /N 0/0 22/1 0/0 0/0 NO T A IL PRESENT N /N 0/0 22/1 0/0 0/0 S T A T IS T IC A L A N A LY S ES W ERE R ES T R IC T ED a . T a b u la tio n re s tr ic te d to ad ve rse b . Lo c a te d on th e h e a d , b a c k , c h e st * * S ig n ific a n t ly d if f e r e n t fro m th e T O T H E N U M B ER O F L IT T E R S W IT H O B S E R V A T IO N S . o b s e rv a tio n s ; a l l o th e r p u ps a p p e a re d n o rm a l. a n d /o r lo w e r m id lin e . v e h ic le c o n tro l g ro u p v a lu e ( p < 0 . 0 1 ) . 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-6889.6) T A B L E C22 (P A G E 1 ) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - SUM M ARY - F I G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) I ii III IV 0l 3 10 V 30 L IT T E R S EX A M IN ED N 28 27 28 28 29 T O T A L PUPS S T ILLB O R N OR FO U N D D EA D a ,b S T ILLB O R N FOUND DEAD N6 N3 N3 8 10 15 75 8 17 46 4 11 NO M ILK IN STOM ACH c N (%) 2 ( 66.7) 2 ( 28.6) 0 ( 0 .0) 2 ( 50.0) 5 ( 45.4) PU PS S A C R IF IC E D A N D N E C R O P S IE D ON DAYS 8 , 1 1 AN D 22 POSTPARTUM b L IT T E R S EV A LU A TED PUPS EV A LU A TED N 28 N 163 27 156 28 148 28 16 1 28 145 APPEARED NORM AL L IT T E R IN C ID EN C E PUP IN C ID EN C E N (%) N (%) 28(100.0) 163(100.0) 27(100.0) 156(100.0) 28 (1 0 0 . 0 ) 148(100.0) 28(100.0) 161(100.0) 27( 96.4) 144 ( 99.3) K ID N EY S : R IG H T , P E L V IS , M ODERATE L IT T E R IN C ID EN C E PUP IN C ID EN C E D ILA T IO N N (%) N (%) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 1( 3.6) K 0.7) a . R e s t r ic t e d t o p u p s i n w h ic h c o m p le te n e c ro p s ie s w e re p e rfo rm e d . C o m p le te n e c ro p s ie s w e re n o t p e rfo rm e d o n p u p s i n w h ic h a u to ly s is o r c a n n ib a liz a tio n p re c lu d e d e v a lu a tio n . b . R e fe r to th e in d iv id u a l pu p c lin ic a l o b s e rv a tio n s ta b le (T a b le C39) fo r e x te r n a l c lin ic a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . c . A n a ly s is r e s t r ic t e d to p u p s fo u n d d e a d and n e c ro p s ie d . ARGUS 418-020 oo oo oo o o o o o o 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) T A B L E C23 (P A G E 1 ) : P U P O R G A N W EIG H TS - SUM M ARY - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 202 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) L IT T E R S EX A M IN ED N I 0 27 II III 13 26 28 IV 10 28 V 30 28 T E R M IN A L B O D Y W EIG H T W E IG H T / LIT T ER M ALE PUPS FEM A LE PUPS B R A IN M EAN+S.D . M EAN+S. D . M EAN+S. D . 36.84 + 6.61 [ 25] a 38.26 + 6.52 [ 24]a,b 35.63 + 7 .1 1 [ 25] a 35.52 + 5.41 [ 22]a 36.82 + 5.08 t 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 3 7.78 + 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 [ 21]a,c W E IG H T / LIT T ER M EAN+S.D . 1.40 + 0.10 1.43 + 0.10 1.42 + 0.11 1.40 + 0.09 1.38 + 0.12 M ALE PUPS FEM A LE PUPS S P LEEN M EAN+S.D . M E A N + S .D . 1.42 + 0.11 ( 26] b 1.38 + 0.12 1.45 + 0.12 1 .4 1 + 0.10 1.45 + 0.13 [ 24] b 1.40 + 0.11 [ 26] c 1.42 + 0.12 1.38 + 0.09 1.40 + 0.13 [ 26] b 1.36 + 0.11 [ 27] C W E IG H T /LIT T ER M EAN+S.D . 0.14 + 0.05 0.12 + 0.03 0.13 + 0.05 0.14 + 0.04 0.12 + 0.04 M ALE PUPS FEM A LE PUPS THYM US M EAN+S.D . M EAN+S.D . 0.15 + 0.06 ( 26] b 0.13 + 0.05 0.12 + 0.04 0.12 + 0.04 0.13 + 0.06 [ 24] b 0.13 + 0.04 [ 26] C 0.13 + 0.05 0.14 + 0.05 0 .1 1 + 0.04 [ 26] b 0.12 + 0.04 [ 27] c W E IG H T /LIT T ER M EAN+S.D . 0.16 + 0.05 0.16 + 0.04 0.14 + 0.05 0 .1 7 + 0.05 0.14 + 0.05 M ALE PUPS FEM A LE PUPS M E A N + S .D . M EAN+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 .1 7 + 0.05 0.16 + 0.05 0.14 + 0.05 [ 26] b 0.14 + 0.05 [ 27] c A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s f o r p u p s in w h ic h th e te r m in a l b o d y w e ig h t c o u ld n o t b e d e te rm in e d b e c a u s e p u p o r ap pea red in c o rre c tly re c o rd e d . b . E x c lu d e s v a lu e s f o r l i t t e r ( s ) t h a t h a d n o m a le p u p s e x a m in e d . c . E x c lu d e s v a lu e s f o r l i t t e r ( s ) th a t h a d n o fe m a le p u p s e xa m in e d . id e n tific a tio n was n o t record e 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) T A B L E C23 (P A G E 2 ) : PU P O RG AN W EIG H TS - SUM M ARY - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 203 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) L IT T E R S EX A M IN ED N I 0 27 II III 13 26 28 IV 10 28 V 30 28 IN C LU D ED IN A N A LY S ES N 25a R A T IO S (% ) O F B R A IN T O T E R M IN A L B O D Y W E IG H T 22a 26a 24a 22a W E IG H T /LIT T ER M EAN+S.D . 3.93 + 0.64 4 .0 7 + 0.43 3 . 7 7 + 0.61 3.88 + 0.48 4 .1 1 + 0.62 M ALE PUPS FEM A LE PUPS M EAN+S.D . M EAN+S.D . 3.83 + 0.63 [ 24] b 4.02 + 0.70 R A T IO S (% ) O F S P L E E N T O T E R M IN A L B O D Y W E IG H T 3.95 + 0.36 4.18 + 0.59 3 . 7 5 + 0.56 [ 22]b 3.84 + 0.65 [ 24]c 3.82 + 0.50 3.94 + 0.58 4.00 + 0.51 [ 21]b 4.23 + 0.86 [ 21] c W E IG H T /LIT T ER M EAN+S.D . 0.38 + 0 .1 1 0.33 + 0.07 0.33 + 0.10 0.36 + 0.09 0.33 + 0.06 M ALE PUPS FEM A LE PUPS M EAN+S.D . M E A N + S .D . 0.40 + 0.13 ( 24] b 0.37 + 0.11 R A T IO S (% ) O F T H Y M U S T O T E R M IN A L B O D Y W E IG H T 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 .3 1 + 0.08 [ 21]b 0.34 + 0.07 [ 21] c W E IG H T /LIT T ER M EAN+S.D . 0.44 + 0.12 0.42 + 0.07 0.36 + 0.09* 0.45 + 0.12 0.39 + 0.09 M ALE PUPS FEM A LE PUPS M EAN+S.D . M E A N + S .D . 0.42 + 0 .1 1 ( 24] b 0.46 + 0.16 0.42 + 0.09 0.42 + 0.10 0.35 + 0.09 [ 22]b 0.37 + 0.10 t 24]C 0.46 + 0.13 0.45 + 0.13 0.37 + 0.11 [ 21]b 0.41 + 0.10 [ 21]C A LL [] a. b. c. * W EIG H T S W ERE R EC O R D ED IN GRAM S (G ) . = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s v a lu e s f o r p u p s in w h ic h th e te r m in a l b o d y w e ig h t c o u ld o r ap peared in c o rre c tly re c o rd e d . E x c lu d e s v a lu e s f o r l i t t e r ( s ) t h a t h a d n o m a le p u p s e x a m in e d . E x c lu d e s v a lu e s f o r l i t t e r ( s ) th a t h a d n o fe m a le p u p s e xa m in e d . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . not R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . be d e te rm in e d b e ca u se p u p id e n t ific a t io n w as n o t re c o rd e 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) T A B L E C23 (P A G E 3) : P U P O R G A N W EIG H TS - SUM M ARY - F I G E N E R A T IO N PU P S M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) L IT T E R S EX A M IN ED N R A T IO S (% ) O F S P L E E N T O B R A IN W E IG H T W EIG H T /LIT T ER M EAN+S.D . M ALE PUPS M EAN+S. D . FEM ALE PUPS M EAN+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 R A T IO S (% ) O F T H Y M U S T O B R A IN W E IG H T W EIG H T /LIT T ER M EAN+S. D . M ALE PUPS M EAN+S.D . FEM ALE PUPS M E A N + S .D . 1 1 .1 7 + 3.28 11.02 + 3.45 [ 26] a 11.46 + 3.69 10.80 + 2.35 10.95 + 2.60 10.66 + 3.07 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . ( ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s f o r l i t t e r ( s ) t h a t h a d n o m a le p u p s e x a m in e d . b . E x c lu d e s v a lu e s f o r l i t t e r ( s ) th a t h ad n o fe m a le p u ps e xa m in e d . III 3 28 IV 10 28 V 30 28 8.98 + 3 .17 8.62 + 3.75 [ 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 [ 24] a 9.92 + 2.82 [ 26] b 12.23 + 3 .71 11.53 + 3.45 9.46 + 3.22 ( 26] a 10.06 + 3.02 [ 27]b R A T IO S (% ) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 0 0 . 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) T A B LE C24 (P A G E 1 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 205 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 13 8 0 1 13 8 0 2 13 8 0 3 13 8 0 4 13 8 0 5 13 8 0 6 1380 7 13 8 0 8 13 8 0 9 13 8 10 13 8 11 13 8 12 13 8 13 13 8 14 13 8 15 13 8 16 DS ( DS ( DG ( DL ( DL ( DL ( 4 8 - 56) 59- 72) 0- 20) 1- 22) 5) 14 ) DS ( DS ( DS ( DS ( DS ( DS ( 68 ) 68 ) 68 ) 68 ) 68 ) 68 ) DS ( 15 - 17) DL ( 20- 21) DS ( 3 7- 45) DS ( DG ( 8 - 71) 0) DL ( 18 - 22 ) DL ( 9) L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA a CHROM ODACRYORRHEA a P A LA TE : BROKEN a SW OLLEN SNOUT IN C IS O R S : M IS A LIG N ED M O R IB U N D S A C R IF IC E D NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R IG H T E A R : SW O LLEN a NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES a DS = DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C24 (P A G E 2) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 206 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 13 8 17 13 8 18 13 8 19 13 8 2 0 13 8 2 1 13 8 2 2 13 8 2 3 13 8 2 4 13 8 2 5 13 8 2 6 13 8 2 7 13 8 2 8 13 8 2 9 13 8 3 0 DL ( DL ( 12 ) 14 ) DG ( DG ( DL ( DL ( DL ( DS ( DS ( DL ( 3- 21) 3- 21) 1- 22) 1- 22) 11- 12) 15 - 16) 2 2 - 26) 8) DL ( DG ( DL ( 14 ) 4- 21) 1- 22) DG ( 3 - 6 ) D L ( 13 - 2 2 ) NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N ED a S O FT OR LIQ U ID FEC ES L E F T F O R E L IM B : S C A B ( 0 .5 CM X 0 .5 CM) R IG H T F O R E L IM B : S C A B ( 0 .2 CM X 0 .2 CM) S A C R IFIC ED b NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES BOTH EA R S : SW OLLEN BOTH EA R S : SW OLLEN a NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S DS = DAY OF STUDY DG = D A Y O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . b . T h e l i t t e r s fro m dam s 13 822 in G ro u p I a n d 138 5 2 in G ro u p I I w e re m ixe d t o g e t h e r . b e c a u s e i t w as n o t p o s s ib le t o i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e d . B o th dams an d l i t t e r s w e re s a c r ific e 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) T A B LE C24 (P A G E 3) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N FEM A LE R ATS DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 1383 1 13 8 3 2 13833 13834 13 8 3 5 13 8 3 6 1383 7 13 8 3 8 13839 13840 138 41 13 8 4 2 13 8 4 3 13 8 4 4 13845 13 8 4 6 13 8 4 7 DS ( 4 0 - 45) DS( DS ( DS ( DL ( 5 7- 59) 59 ) 59 ) 1 7 - 21) DS ( DG ( DL ( 3201- 71) 21) 22) DL ( 12 ) DS ( 1 - 5) DS ( 7) IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L E F T FO R ELIM B AND FOREPAW : L E F T FO R ELIM B : FRAC TURED M O R IB U N D S A C R IF IC E D L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA SW OLLEN a a DS : DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N 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) T A B LE C24 (P A G E 4 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FE M A LE R A TS DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 13 8 4 8 13 8 4 9 13 8 5 0 13 8 5 1 13 8 5 2 13853 13 8 5 4 13 8 5 5 13 8 5 6 13 8 5 7 13858 13 8 5 9 13860 DL ( 11 ) DG ( DL ( DL ( DL ( 16 - 21 ) 4 - 22) 8) 12 - 13) DS ( DS ( DG ( DG ( DL ( DL ( 30- 32) 59- 73) 0 - 13) 20 ) 1- 22) 8- 22) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S A C R IFIC ED b NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S LO W ER M I D L I N E : S C A B ( 0 .5 CM X R IG H T E A R : S W O LLEN a SO FT OR LIQ U ID FEC ES SO FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES L O C A LIZ E D A L O P E C IA : U N D ER S ID E L O C A LIZ E D A L O P E C IA : U N D ER S ID E L O C A LIZ E D A L O P E C IA : U N D ER S ID E L O C A LIZ E D A L O P E C IA : U N D ER S ID E L O C A L IZ E D A L O P E C IA : LIM B S a 0 .2 a CM) DS = DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . b . T h e l i t t e r s fro m dam s 13 8 2 2 in G ro u p I a n d 13 8 5 2 i n G ro u p I I w e re m ix e d t o g e t h e r . b e c a u s e i t was n o t p o s s ib le to i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e d . B o th dams an d l i t t e r s w e re s a c r ific e d 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) T A B LE C24 (P A G E 5 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N FEM A LE R ATS DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 13 8 6 1 13 8 6 2 13 8 6 3 13 8 6 4 13 8 6 5 13 8 6 6 13 8 6 7 13 8 6 8 13 8 6 9 13 8 70 138 71 13 8 72 13 8 73 13 8 74 DS ( 77-10 9 ) DS ( DS ( DG ( DG ( DG ( DG ( DL ( DL ( 5) 73 ) 0- 17) 4- 6) 7 - 10) 1 1- 17) 4 - 13) 4 - 22) DL ( 7- 8) DL ( 22 ) NO A D V ER S E FIN D IN G S BOTH EA R S : SW OLLEN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA L E F T H IN D P A W : S W O LLEN L E F T H IN D P A W : S W O LLEN L E F T H IN D P A W : A B R A S IO N ( 0 .3 CM X L E F T H IN D P A W : S C A B ( 0 .3 CM X 0 .2 L O C A L IZ E D A L O P E C IA : LIM B S R IG H T E Y E : SW OLLEN T R A U M A T IZED C O R N EA a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S T E A T : SW OLLEN NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S a 0 .2 CM) CM) DS = DAY O F STUDY DG = D A Y O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N ARGUS 418-020 Page 209 PROTOC OL 418 - 0 2 0 : O R A L (G A V A G E) T W O -G E N E R A T IO N (O N E L I T T E R P E R G E N E R A T IO N ) R E P R O D U C T IO N S T U D Y O F AM M O N IU M P E R F L U O R O O C T A N O A T E (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 .6 ) T A B LE C24 (P A G E 6 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 13 8 75 13 8 76 13 8 77 13 8 78 13 8 79 13 8 8 0 1388 1 13 8 8 2 13 8 8 3 13 8 8 4 13 8 8 5 13 8 8 6 13 8 8 7 13 8 8 8 13 8 8 9 13 8 9 0 D S ( 8 - 9) DG ( DS ( DS ( DG ( DG ( DL ( DL ( 75568- 0017- 21) 73 ) 73 ) 2) 21) 22) 22) DL ( DS ( DL ( 1 4 - 15) 2 - 3) 22 ) C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R IG H T E A R : SW O LLEN IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED IN C IS O R S : M IS A LIG N E D a IN C IS O R S : M IS S IN G /B R O K EN a NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S DS = DAY OF STUDY DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N 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) T A B LE C24 (P A G E 7) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page 211 DOSAGE GROUP IV 10 M G/KG/DAY RAT # D ES C R IP T IO N 13 8 9 1 13 8 9 2 13 8 9 3 13 8 9 4 13 8 9 5 13 8 9 6 13 8 9 7 13 8 9 8 13 8 9 9 13 9 0 0 1390 1 13 9 0 2 13 9 0 3 DG ( DG ( DL ( 2) 3 - 20) 1 - 9) DL ( DG ( DS ( DS ( DS ( DG ( DG ( DL ( DL ( DS ( DG ( DG ( DL ( 12 - 14) 19 - 20) 3 7- 49) 58- 71) 58- 71) 0- 2) 0- 21) 1- 22) 19 - 22) 7) 11 ) 7 - 21) 1- 22) DL ( 22 ) NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S R IG H T A X I L L A : M ASS ( 2 .5 CM IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED IN C IS O R S : M IS A LIG N ED a CHROM ODACRYORRHEA a C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA R IG H T E A R : SW OLLEN R IG H T E A R : SW OLLEN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R IG H T E A R : SW OLLEN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S X 1 .0 CM X 1 .0 CM) DS = DAY O F STUDY DG = D A Y O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D A Y O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C24 (P A G E 8 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - P G EN ER A T IO N FE M A LE R ATS DOSAGE GROUP IV 10 M G/KG/DAY RAT # D ES C R IP T IO N 13 9 0 4 13 9 0 5 13 9 0 6 1390 7 13 9 0 8 13 9 0 9 13 9 10 13 9 11 13 9 12 13 9 13 13 9 14 13 9 15 13 9 16 139 17 13 9 18 13 9 19 13 9 2 0 DL ( 5) DS ( DL ( DG ( DG ( DL ( 8 7 - 95) 1 2 - 16) 14 ) 14 ) 14 - 22) DG ( DL ( 5- 21) 1- 22) DS ( 2 2 - 28) S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S BOTH EARS : SW OLLEN S O FT OR LIQ U ID FEC ES D R IE D , R ED P ER IN A S A L SUBSTANCE BOTH FOREPAW S: D R IED , RED SUBSTANCE R IG H T E A R : SW OLLEN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S B A C K : NUM EROUS SCABS NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S DS = DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N 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) T A B LE C24 (P A G E 9 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 13 9 2 1 13 9 2 2 13 9 2 3 13924 13 9 2 5 13926 13 9 2 7 13 9 2 8 13 9 2 9 13 9 3 0 13 931 13 9 3 2 13 9 3 3 13 9 3 4 13 9 3 5 DS ( 24 ) DG ( DL ( D L( 7 - 21) 1- 22) 6- 10) DG ( 1 2 - 2 1 ) DL ( 1- 10) DS ( 46 - 54) DG ( 4 - 8 ) DG ( 14 ) DG ( 19 - 21) D L ( 1 - 4) D L ( 5- 11) D L ( 1 2 - 18) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S UNGROOM ED CO AT NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R IG H T E A R : S W O LLEN R IG H T E A R : S W O LLEN a R IG H T E A R : S W O LLEN NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN L O C A L IZ E D A L O P E C IA : LIM B S C H R O M O R H IN O R R H EA H E A D : M ASS ( 0 .7 CM X 0 .5 CM X 0 .3 CM) H E A D : M A S S ( 0 .7 CM X 0 .5 CM X 0 .3 CM) H E A D : S C A B ( D ID N O T E X C E E D 0 .5 CM X 0 .5 LO C A LIZE D A LO P E C IA : H EAD CM) DS = DAY OF STUDY DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N 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) T A B LE C24 (P A G E 10 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N FE M A LE R ATS DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 13936 13 9 3 7 13 9 3 8 13939 13 9 4 0 13 9 4 1 13 9 4 2 13 943 13 9 4 4 13 9 4 5 13946 13 9 4 7 13 9 4 8 13949 13 9 5 0 DL ( 13 - 2 2 ) DS( 16 - 17) DL ( 12- 22) DG ( DL ( DL ( DS( DS( DS ( DG ( DG ( DL ( DL ( 9- 2 1 ) 1- 22) 1) 3 0 - 50) 53- 73) 53- 73) 0- 12) 0- 20) 7- 22) 9- 2 2 ) D L ( 8 - 9) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA a C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S BOTH E A R S : SW OLLEN BOTH EA R S : SW OLLEN a S A C R IFIC E D D U E TO NO S U R V IV IN G IN C IS O R S M IS A LIG N ED IN C IS O R S M IS S IN G /B R O K EN IN C IS O R S M IS A LIG N ED IN C IS O R S M IS S IN G /B R O K EN IN C IS O R S M IS A LIG N ED IN C IS O R S M IS S IN G /B R O K EN a IN C IS O R S M IS A LIG N ED a NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S PUPS DS = DAY OF STUDY DG = D A Y O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N 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) T A B L E C25 (P A G E 1) : B O D Y W EIG H TS - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 215 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP I 0 M G/KG/DAY 1380 1 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 1 154 154 155 141 155 149 145 140 154 145 152 136 155 147 152 138 156 143 134 144 151 148 154 142 160 147 153 145 153 149 183 177 187 173 182 186 181 168 194 177 178 167 177 186 171 164 179 174 187 170 186 175 186 175 188 188 176 175 173 177. 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 O F STUDY A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . L a s t v a lu e re c o rd e d b e fo re c o h a b ita tio n . b . R a t 1380 4 w as m o rib u n d s a c r ific e d o n d a y 68 o f s tu d y . 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. 70 a 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) T A B L E C25 (P A G E 2) : B O D Y W EIG H T S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 216 DAY 1 8 15 22 29 36 43 RAT # DOSAGE GROUP I I 1 M G/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 13 9 159 147 150 142 155 144 14 9 138 156 150 153 140 157 153 149 141 156 146 147 141 149 145 152 143 151 145 151 144 148 171 191 173 179 177 171 163 179 166 185 174 176 162 189 179 167 175 185 176 176 167 172 176 190 177 174 172 174 171 171 193 . 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 70 a 266. 273 . 283 . 283 . 260. 267. 267. 274 . 256. 268. M O R IB U N D S A C R IF IC E D O N D A Y 59 O F S T U D Y 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) T A B L E C25 (P A G E 3) : B O D Y W EIG H TS - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 217 1 8 22D A Y 15 29 36 43 RAT # DOSAGE GROUP I I I 3 M G/KG/DAY 13 8 6 1 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 130 161 149 149 141 161 149 146 145 154 148 154 142 156 143 155 144 149 144 155 14 6 158 152 150 147 155 144 153 148 150 15 7 193 177 181 181 194 176 173 178 180 185 182 174 200 174 192 185 179 176 188 173 190 179 188 183 184 174 181 183 178 177. 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. 70 a 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) T A B L E C25 (P A G E 4 ) : B O D Y W EIG H T S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 218 DAY RAT # 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 8 15 DOSAGE GROUP IV 136 160 1 7 8 . 160 192 2 1 5 . 155 192 225. 152 186 214 . 141 176 208. 157 191 215 . 151 192 225. 2201 5 9 1 9 1 . 140 165 18 5 . 2101 5 5 1 8 4 . 150 174 1 9 7 . 145 1 7 1 196. 140 173 19 8. 151 174 185. 14 9 188 207. 153 193 2 1 6 . 140 167 190. 2121 5 5 1 8 8 . 2001 4 7 1 7 7 . 151 186 219 . 2021 4 5 1 7 7 . 2111 5 9 1 8 9 . 142 173 199. 2121 5 3 1 8 3 . 148 182 204 . 156 19 1 2 15 . 146 176 2 18 . 154 182 206. 143 16 7 19 6 . 150 179 19 9 . 22 190. 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 . 29 36 43 10 M G / K G / D A Y 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. 70 a 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) T A B L E C25 (P A G E 5) : B O D Y W EIG H T S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 219 1 8 22D A Y 15 29 36 43 RAT # DOSAGE GROUP V 30 M G/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 141 174 203 . 224 . 240. 244 . 258. 164 191 204. 219. 237. 239. 249. 2021 4 6 178 . 216. 228. 238. 246. 2211 5 0 1 8 0 2 0 3 . . 237. 243 . 247. 212 2201 3 8 169 189. 199. . . 228. 158 190 216. 228. 237. 238. 256. 153 181 207. 232. 250. 246. 265. 2001 5 2 1 8 3 . 216. 231. 245. 247. 2201 4 0 163 185. 198. 214. . 224. 2221 6 0 1 9 1 . 233 . 247. 253 . 265. 147 178 205. 207. 231. 238. 251. 147 169 195. 213 . 223 . 224. 241. 2121 3 9 1 7 3 1 9 5 . . 227. 223 . 236. 156 186 206. 215. 233 . 247. 255. 149 181 207. 217. 234. 239. 255. 2101 5 5 1 8 8 . 225. 239. 245. 258. 211 2221 3 7 167 189. 199. . . 236. 2201 4 5 1 7 4 1 9 9 . . 232. 235. 251. 148 185 218. 230. 249. 250. 265. 2101 4 8 1 8 5 . 230. 245 . 254 . 263 . 146 181 204. 224 . 250. 258. 265. 149 176 195. 209. 224. 235. 246. 148 179 194. 207. 231. 235. 251. 2021 5 2 1 7 3 . 217. 235. 234 . 242 . 148 178 206. 229. 241. 248. 259. 200 2101 5 2 1 7 8 . . 225. 233 . 241. 2011 4 4 1 7 9 . 218. 230. 234 . 240. 159 182 208. 223 . 232. 249. 260. 142 173 205. 217. 236. 244 . 261. 2001 5 3 1 8 0 . 214. 228. 235. 241. DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. 50 270. 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. 57 276. 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. 64 279. 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 . 70 a 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) T A B L E C26 (P A G E 1 ) : M A T ER N A L B O D Y W EIG H TS - PR ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 220 PREGNANCY STATUS DAY 0 7 10 1 4 1 8 21 RAT # DOSAGE GROUP I 0 M G/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 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 238. 306. 319. M O R IB U N D 278 . 267. 306. 272 . 276. 300. 264 . 275. 279. 290. 324 . 238. 241. 266. 261. 292 . 268. 292 . 302 . 299. 290. 290. 311. 274 . 252 . 243 . 276. 289. 352 . 372 . 348. 356. S A C R IFIC ED ON 324 . 334. 305. 313 . 324 . 330. 293 . 298. 297. 308. 340. 350. 297. 301. 295. 307. 306. 328. 316. 325. 345. 366. 271. 284 . 270. 281. 297. 312. 291. 300. 299. 319. 306. 308. 327. 330 . 327. 342 . 339. 350. 313 . 327. 326. 325. 338. 339. 315. 320. 286. 291. 262 . 273 . DAY 310. 380. 378. 68 O F 352. 334 . 354 . 317. 322. 365. 305. 328. 348. 336. 378. 295. 292 . 332 . 312 . 322 . 336. 354 . 359. 368. 342. 343 . 370. 330. 305. 293 . 310 . 418 . 421. STUDY 396. 379. 408. 361. a 407. 304 . 362 . 381. 360. 411. 338. 340. 376. 360. 362 . 374 . 385. 385. 407. 385. 405. 414 . 370. 349. 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 . = PREGNANT N P = N O T PR EG N AN T (VALU ES DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was not recorded. EXCLUD ED FR O M A V ER A G ES ) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C26 (P A G E 2 ) : M A T ER N A L B O D Y W EIG H TS - P R ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 221 P R EG N A N C Y STATUS DAY 0 7 10 1 4 1 8 21 RAT # DOSAGE GROUP I I 1 M G/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 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 283 . 294 . 271. 275. 272 . M O R IB U N D 244. 303 . 258. 260. 278. 262 . 224 . 287. 245. 253 . 271. 295. 298. 276. 259. 282. 273 . 289. 276. 292. 278 . 270. 246. 248 . 323 . 337. 324 . 332. 291. 298. 298. 305. 296. 318 . S A C R IFIC ED ON 275. 280. 333 . 344 . 292 . 304 . 282 . 288. 298. 309. 284 . 289. 247. 258. 304. 312. 274 . 290. 285. 296. 297 . 303 . 333 . 341. 334 . 341. 286. 320. 267. 270. 308. 324. 306. 316. 328. 342. 310 . 326. 321. 332 . 303 . 310. 293 . 296. 268. 278. 278. 282 . DAY 354 . 348. 306. 315. 329. 59 O F 303 . 366. 314. 286. 322. 303 . 282. 322. 307. 311. 313 . 354 . 359. 331. 270. 335. 330. 353 . 337. 348. 329. 306. 294 . 297 . 403 . 390. 358. 352 . 380. STUDY 341. 428. 356. 282 . 374 . 353 . 312. 379. 352. 359. 370. 408. 389. 377 . 276. 390. 381. 410. 386. 398. 365. 356. 342. 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). 25 287. 278. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C26 (P A G E 3) : M A T ER N A L B O D Y W EIG H TS - PR ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 222 P R EG N A N C Y STATUS DAY 0 7 10 14 18 2 1 RAT # DOSAGE GROUP I l l 3 M G/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 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 234. 257. 265. D ID NOT D E LIV E R A LIT T E R 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). 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) T A B L E C26 (P A G E 4 ) : M A T ER N A L B O D Y W EIG H T S - PR ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 223 P R EG N A N C Y STATUS DAY 0 7 10 RAT # DOSAGE GROUP IV 14 18 10 M G / K G / D A Y 21 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 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 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. M A TIN G N O T C O N FIR M ED 274. 310. 321. 277. 305. 320. 293 . 309. 327. 254. 299. 314 . 289. 327. 338. N O C O N FIR M ED M A TIN G D A T E 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 C O N FIR M ED M A TIN G D A T E 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. 372 . 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) T A B L E C26 (P A G E 5 ) : M A T ER N A L B O D Y W EIG H T S - P R ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 224 PREGNANCY STATUS DAY 0 7 10 1 4 1 8 21 RAT # DOSAGE GROUP V 30 M G /KG /D AY 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 13 941 P 13942 P 13943 P 13944 P 13 945 P 13946 P 13 947 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. N O C O N FIR M ED M A T IN G D A T E 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 . 299. 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) T A B L E C 2 7 (P A G E 1 ) : M A T ER N A L B O D Y W EIG H TS - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 225 DAM # DAY 1 5 DOSAGE GROUP I 8 11 1 5 0 M G/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 . 287. 302. 365. 376. 386. 346. 366. 372. M O R IB U N D S A C R IF IC E D ON 320. 336. 346. 302. 308. 337. 315. 344 . 369. 302 . 298. 316. 298. 316. 348. 355. 357. 382. NOT PREGNANT 299. 322 . 337. 316. 342 . 363 . 301. 313 . a 340. 332. 332. 285. 294 . 292. 272. 271. a 296. 303 . a 299. 314 . 331. 312 . 337. 343 . 304. 334. 352. 327. 342 . 330. 338. 348 . 336. 330. 342 . 351. 317. 318. 342. 328. 349. 341. 351. 347. 368. 306. 297. 328. 284 . 280. 279. 265. 265. a DAY 309 390 372 68 O F 352 a 376 a 345 389 322. 396. 402 . STUDY 370. 341. 376. 331. 354 . 394. 341 354. 390 349. 343 351. 356 367. 321 326. 293 314. 336 328. 327 321. 369 381. 364 344 . S A C R IFIC ED ON 364 353 . 379 400. 355 338. 356 380. 3 94 404 . 340 351. 324 312. 303 309. DAY 338. 367. 366. 348. 340. 367. 286. 355. 370. 326. 393 . 359. 370. 320. 302 . 376. 344 . 317. 328. 8 OF 339. 385. 350. 376. 377. 309. 301. 306. LA C T A T IO N 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) T A B L E C 2 7 (P A G E 2) : M A T ER N A L B O D Y W EIG H T S - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 226 DAY 1 5 8 11 1 5 22 DAM # DOSAGE GROUP I I 1 M G/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 342. 329. 373 . 293 . 307. 310. 294. 293 . 304. 304. 326. 336. M O R IB U N D S A C R IF IC E D O N 289. 293 . 307. 335. 331. 355. 301. 314 . 327. NOT PREGNANT 290. 320. 312. 293 . 306. 324 . 260. 276. 287. 292. 315. 332 . 283 . 277 . 298. 290. 292. 297. 289. 296. 314. 319. 335. 353 . 314 . 320. a 320. 296. 322 . NOT PREGNANT 322 . 301. 317. 296. 309. 322. 340. 358. 375. 317. 338. 356. 318. 342. 358. 305. 328. 335. 301. 288. 325. 282. 295. a 277. 268. a DAY 375. 368. 343 . 320. 336. 59 O F a 385. 335. 365. 380. 344 . 316. 360. STUDY 329. 382. 340. 332. 338. 299. 331. 305. 276. 322 . 385. 349. a 362 . 362 . 301. 361. 323 . 326. 338. 377. 319. 350. S A C R IFIC ED ON a 331. 372 . 379. 371. 379. 347. 386. 358. 337. a 314 . 320. 323 . 299. 294 . DAY 361. 357. 343 . 310. 318. 359. 375. 361. 347. 351. 317. 368. 352. 336. 314. 331. 336. 341. 11 OF 331. 381. 330. 367. 295. 338. 316. 293 . LA C T A T IO N 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) T A B L E C 2 7 (P A G E 3) : M A T ER N A L B O D Y W EIG H TS - LA C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 227 8 11D A Y 1 5 15 DAM # DOSAGE GROUP I I I 3 M G/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 . P R E G N A N T ;: D ID N O T 297. 320 . 312 . 310. 340. 332 . 368. 366. 293 . 302 . 304 . 308. 318. 337. 319. 320. 315. 313 . 308 . 322 . 301. 324 . 368. 379. 309. 306. 398. 413 . 373 . 376. 309. 312 . 308. 329. 368. 366 . 291. 298. 332 . 341. 303 . 322 . 316. 335. 323 . 336. 300. 299. 295. 309. 327. 303 . 333 . 326. 312 . 315. 285 . D E LIV E R 336. 311. 339. 392. 322 . a 349. 330. 343 . 335 . 334 . a 327. 427. a 335. 342. 366. 313 . a 343 . 325. 340 . 338 . 316. 306. 352 . 336. 276. A LIT T E R 335. 344 . 344 . 406. 328. 348. 361. 327. 323 . 344 . 355. 401. 332. 438. 388. 330. 337. 374. 321. 381. 347. 347. 351. 364. 341. 339. a 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) T A B L E C 2 7 (P A G E 4) : M A TER N A L B O D Y W EIG H TS - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 228 DAM # DAY 1 5 DOSAGE GROUP IV 8 11 1 5 10 M G / K G / D A Y 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. 336. 334 . 319. 330 . 332 . 350 . 301. 310 . 311. 329. 351. 338. 350. 369. 268. 284 . NOT PREGNANT; 303 . 313 . 304 . 301. 317. 339. 306. 316. 321. 338. 316. 317. 301. 308. 343 . 343 . 294. 317. 350. 361. 294. 276. 316. 324. 305. 321. 326. 340. 281. 293 . 356. 336. 312. 288. 290. 309 . 285. 287. 301. 315. 275. a 352 . 371. 339. 334. 359. 405. a M A TIN G N O T 329. 322 . 349. 342. 364. 337. 317. 343 . 331. 382. 297. 337. a a 316. a a 335. a a 285. 361. 380. 389. 352. 347. 368. 328. 288. C O N FIR M ED 348. 314 . 356. 359. 350. 359. 315. 359. 347. 371. 320. 351. 336. 365. 346. 379. 325. 342 . 330. 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) T A B L E C 2 7 (P A G E 5) : M A T E R N A L B O D Y W E IG H T S - L A C T A T I O N - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E R A T S ARGUS 418-020 Page 229 DAY 1 5 8 11 1 5 22 DAM # DOSAGE GROUP V 30 M G /K G /D A Y 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13 944 13945 13946 13947 13 948 13949 13950 311. 310. 320. 346. 368. 357. 274 . 304. 307. 318. 334. 352. 305. 287. 303 . a 325. 320. 291. 316. 327. 342 . 350. 341. 273 . 278. 298. 310. 311. 318. 324. 320. 338. 349. 366. 353 . 289. 293 . 298 . 308. 334 . 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 . S A C R IFIC ED DUE TO NO S U RVIVIN G PUPS ON DAY 1 OF LA C TA T IO N 267. 289. 322 . 338 . 346. 323 . 345. 342 . 359. 366. 374. 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) T A B LE C28 (PAGE 1) : F E E D CONSUMPTION V A LU ES - P R EC O H A B IT A T IO N - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 230 DAYS RAT # 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- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a DOSAGE GROUP I 0 MG/KG/DAY 100. 132. 133 . 148 . 111. 140. 133 . 142 . 131. 142. 125. 126 . 123 . 125. 147. 164. 121. 132 . 126. 143 . 116. 139. 131. 130. 143 . 140 . 138 . 114 . 137. 124 . 188. 161. 158. 148. 122. 143 . 148 . 158. 142 . 156. 133 . 130. 143 . 154. 156. 193 . 123 . 14 9. 137. 158. 137. 144 . 144 . 138 . 144 . 142 . 149. 127. 133 . 120. 126. 168. 154. 162. 154 . 147. 152. 158. 143 . 2 18 .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. 145. 174. 137. 123 . 141. 134 . b 13 6. 153 . 145. 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. 14 9 .c 15 8 .c 156. 162. 147. 145 . 148 . 151. 174 . 152 . 172. 216. 151. 175 . 130. 117. 144 . 138. 163 . 144 . b 150. 148 . 173 . 13 9. 179. 140. 153 . 126. 119. 137. 145 . M O RIBUND S A C R I F I C E D O N D A Y 68 O F S T U D Y 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 A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. Last value recorded before cohabitation. b. S p ille d feed precluded the ca lcu lation of th is va lue . c . V a lu e ap peared i n c o r r e c t l y re c orde d and was e xc lu d e d from group averages and s ta tis tic a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C28 (PAG E 2) : F E E D C O N S U M P TIO N V A L U E S - P R E C O H A B IT A T IO N - I N D I V I D U A L D A T A - P G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 231 DAYS 1- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a RAT # DOSAGE GROUP I I 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. 146. 134 . 145. 133 . 145. 158. 154 . 145. 142 . 125. 110. 134 . 117. 127. 136. 129. 136. 141. 160. 136. 142 . 139. 156. 131. 133 . 165. 176. 139. 149. 118. 125 . 109. 128. 153 . 149 . 134 . 149. 147. 203 . 124 . 120. 132 . 130. 135. 141. 139. 155. 139. b 111. 153 . 211. 146. 170 . b 133 . 147. 125. 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. 13 9. 124 . 149. 144 . 145. 151. 140 . 127. 123 . 136. 139. 14 9. 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 . 147. 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. 13 9. 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. M O RIBUND S A C R I F I C E D O N D A Y 59 O F S T U D Y 133 . 120. 158. 129. 151. 136. 141. 114. 141. 135. 129. 146. 102 . 112 . 166. 136. 147 . 130. 134 . 136. 144 . 106. 122. 122 . 168. 141. 170 . 130. 142. 118. 155. 154. 132 . 120. 151. 127 . 148. 129. 159. 134 . 175. 111. 154. 137. 149. 128. 145. 114. DAYS = DAYS OF STUDY A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. La s t value recorded before co h abitation . b . S p ille d feed precluded the c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C28 (P A G E 3) : F E E D C O N S U M P TIO N V A L U E S - P R E C O H A B IT A T IO N - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E R A TS ARGUS 418-020 Page 232 DAYS 1- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a RAT # DOSAGE GROUP I I I 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. 13 9. 149 . 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. 143 . 149. 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. 14 9. 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 A L L W EIGHTS WERE RECORDED I N GRAMS ( G ) . a. Last value recorded before cohabitation. b. S p ille d feed precluded the c a lc u la tio n of th is value. c . V a lu e ap p e a re d i n c o r r e c t l y re c o rd e d and was e xc lud e d from group averages and sta tistica l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C28 (PAGE 4 ) : F E ED CONSUMPTION V A LU ES - PRECO HAB ITATIO N - IN D IV ID U A L DATA - P G EN ERA T IO N FEM A LE RATS ARGUS 418-020 Page 233 DAYS RAT # 1- 8 8- 1 5 1 5 - 2 2 DOSAGE GROUP IV 2 2 - 29 2 9 - 36 36 - 43 10 M G / K G / D A Y 4 3 - 50 50- 57 5 7 - 64 64- 70a 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. 149. 139. 153 . 147. 131. 145. 125. 126. 129. 116. 156. 167. 121. 133 . 124 . 146. 13 9. 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. 147. 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. 13 9. 123 . 108 . 118 . 122. DAYS = DAYS OF STUDY A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. Last value recorded before cohabitation. b . S p ille d feed precluded the ca lcu la tio n of th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TA B LE C28 (PAGE 5 ) : F E ED CONSUMPTION V ALU ES - PRECOHAB ITATION - IN D IV ID U A L DATA - P G EN ERATIO N FEM ALE RATS ARGUS 418-020 Page 234 DAYS 1- 8 8- 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 4 3 - 5 0 5 0 - 5 7 5 7 - 6 4 6 4 - 7 0 a RAT # DOSAGE GROUP V 30 M G /K G /D A Y 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 13 949 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. 149. 152 . 14 9. 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 . 139. 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. 14 9. 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 . 14 9 . 176. 141. 129. 155. 161. 145. 148. 146. 191. 179. 126. 149. 141. 147. 132. 161. 140. 136. 138. 163 . 151. 143 . 125. 135. 145. 150. b 156. 167. 141. 163. 133 . 127. 151. 166. b 147. 150. 170 . 165. 126. 155. 140 . 154 . 13 7 . 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 A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. Last value recorded before co habitation . b. S p ille d feed precluded the c a lc u la tio n of c. Valu e was n o t recorded. th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C29 (PAGE 1) : M ATERNAL F E E D CONSUMPTION VALUES - PRESUMED G ES TA T IO N - IN D IV ID U A L DATA - P G EN ER A T IO N FEM ALE RATS ARGUS 418-020 Page 235 PREGNANCY STATUS DAYS 0 -7 7 -10 10 - 14 14 - 18 18 - 2 1 2 1 - 25 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 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 180. 221. 187. 82 . 103 . 93 . 113 . 135 . 118. 79. 119. 110. 82 . 73 . 71. M O R IB U N D S A C R I F I C E D ON D A Y 68 O F S T U D Y 208. 1229 7 . 1 3 4 . . 67. 207. 1108 1 . 1 1 5 . . 1 5 7 . 66. 1 0 3 . 102 . 157. 173 . 218 . 72 . 108. 116. 66. 8 4 . 9 1 . 1209 7 . 1 3 1 . . 84 . 79. 180 . 74 . 108. 67. 55. 160. 85. 119 . 113 . 79. 207. 183 . 92. 125. 1 1 7 . 7 9 . 102. 90. 76. 74 . 187. 164 . 95. 1 1 7 . 108. 7 2 . 102. 102. 63 . 71. a 6 7. 82. 94. 74 . 1021 7 3 . 76. . 97. 75. 164 . 81. 98. 113 . 83 . 1001 3 3 . 64. 92 . . 65. 172. 182. 76. 115. 91. 85. 1 1 4 . 103 . 65. 68. 180. 85. 118 . 106. 67. 197 . 176. 168. 89. 124. 108. 1127 8 . . 1 0 4 . 6 9 . 100. 102. 61. 62 . 64. 218 . 204 . 176. 153 . 96. 126. 119 . 80. 113 . 10 7. 72 . 96. 94. 68. 9 9 . 8 4 . 76. 66. 66. 58. 90. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUD ED 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) T A B L E C29 (P A G E 2) : M A T E R N A L F E E D C O N S U M P TIO N V A L U E S - PR ES UM ED G E S T A T IO N - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E R A T S ARGUS 418-020 Page 236 PREGNANCY STATUS DAYS 0 - 7 7 -1 0 10 - 14 14 - 18 18 - 2 1 2 1 - 25 RAT # 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 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 DOSAGE GROUP I I 1 MG/KG/DAY 215. 201. 185. 177. 221. 9 4 . 120. 102. 81. a 107. 1007 2 . . 114 . 70. 95. 99. 85. 115 . 113 . 74. 70. 81. 68. 75. M ORIBUND S A C R I F I C E D O N D A Y 59 O F S TU D Y 1121 7 0 . 7 0 . 9 9 . . 176. 184. 154 . 83 . 115. 125. 1117 9 . 1 0 7 . . 68. 88. 7 7 . 82. 71. 61. 162 . 156. 166. 73 . 105 . a 1007 1 . . 1 0 4 . 1007 2 . 107. . 58. 78. 69. 180. 180. 149. 90. 109. 115 . 8 0 . 112. 120. 1107 6 . 9 7 . . 51. 65. 68. 159. 177 . 202 . 59. 78. 99. 78. 96. 118 . 7 6 . 111. 88. 69. 86. 63 . 199. 80. 115 . 114 . 150. 180. 6 1 . 8 0 . 82 . 1028 0 . . 1 1 4 . 50. 70. 176. 189. 77. 106. 108. 1018 9 . 1 0 6 . . 85. 177. 84 . 105. 130 . 73 . 182. 79. 104. 107 . 69. 182. 74 . 99. 92 . 56. 171. 77. 93 . 98. 681 8 3 . . 94 . 94 . 63 . 68 881 6 0 . . . 89. 55. 79. 58. P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUD ED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION A L L W EIGHTS WERE RECORDED I N GRAMS ( G ) . a. S p ille d feed precluded the c a lc u la tio n o f th is va lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C29 (PAGE 3 ) : M ATERNAL F E E D CONSUMPTION V A LU ES - PRESUMED G ES T A T IO N - IN D IV ID U A L DATA - P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 237 PREGNANCY STATUS DAYS 0 -7 7 -1 0 10 - 1 4 1 4 - 1 8 1 8 - 2 1 2 1 - 2 5 RAT # 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 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 DOSAGE GROUP I I I 140. 76. a DID NOT DELIVER A LITTER 168. 8 2 . 111. a 89. 105. 224. 194 . 98. 125. 8 7 . 111. 178. 7 7 . 103 . a 84 . 118. 177. 93 . 128. 173 . 158. 173 . 157. 87. 128. 7 2 . 100. 8 7 . 112. 68. 7 7 . 194 . 9 1. 123 . 197. 93 . 123 . 193 . 92. 136. 204. 158. 99. 125. 7 0 . 101. 170. 202 . 83 . 91. 98. 128 . 159. 79. 94. 214 . 92 . 136. 178. 76. 107. 217. a 155. 176. 176. 79 . 103 . 8 9 . 120. 66. 9 7 . 8 0 . 120. 86. 120. 196. 80. 109. 208. 87. 123 . 3 MG/KG/DAY 113 . 66. 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. 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 EXC LUD ED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION A L L W EIGHTS WERE RECORDED IN GRAMS ( G ) . a. S p ille d feed precluded the c a lc u la tio n of th is 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) T A B L E C2 9 (PAGE 4) : M ATER NAL F E E D CONSUM PTION V A LU E S - PRESUMED G E S T A T IO N - IN D IV I D U A L DATA - P G E N E R A T IO N F E M A L E RATS ARGUS 418-020 Page 238 PREGNANCY STATUS DAYS 0 -7 7 - 1 0 1 0 - 1 4 14 - 18 18 - 2 1 2 1 - 25 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 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 139. 72 . 93 . 168. 72 . 104 . 167. 74 . 97. 207 . 202 . 186. a 130. 82. 108. 8 4 . 111. 172 . 82. 115 . 185. 99. a 153 . 69. 87. MATING NOT CONFIRMED 174 . 70. 105 . 165. 78. 91. 14 7 . 75. 99. 170. 81. 108. 207. 92. 125. NO CONFIRMED MATING DATE 164 . 74 . 94 . 193 . 94. 115 . 169. 74 . 90. 208. 163 . 97. 132. 8 1 . 88. 173 . 80. 106. 185 . 94. 115 . 170. 84. 114 . 174 . 175. 79. 99. 7 8 . 112. NO CONFIRMED MATING DATE 172 . 7 3 . 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 EX C LU D ED 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) T A B L E C2 9 (P A G E 5) : M A T E R N A L F E E D C O N S U M PTIO N V A L U E S - PRESUM ED G E S T A T I O N - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E R A T S ARGUS 418-020 Page 239 PREGNANCY STATUS DAYS 0 -7 7 -10 10 - 14 14 - 18 18 - 2 1 2 1 - 25 RAT # DOSAGE GROUP V 30 M G /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 13 93 9 P 13 940 P 13 941 P 13 942 P 13943 P 13944 P 13 945 P 13946 P 13 947 P 13 948 P 13949 P 13950 P 164 . 187 . 73 . 104 . 8 7 . 111. 196. 87. 95. 196. 78. 128. 140. 63 . 84. 176. 176. 82 . 116. 86. 1 0 3 . 181. 74 . 108. 135. 58. 84. 181. 82. 113 . 176. 74 . 106. 1 7 1 . 80. 75. 861 3 9 . 61. . NO CONFIRMED MATING DATE 1 5 7 . 7 2 . 92 . 165. 84. 119 . 134. 63 . 87. 149. 70. 94. 159. 76. 89. 169. 7 1 . 95. 171. 85. 108. 167. 185. 75. 106. 7 9 . 112. 183 . 184 . 84. 105. 88. 1 0 7 . 164 . 74 . 103 . 1 5 7 . 7 5 . 92 . 155. 72. 96. 177. a 83 . 116. 68. 9 5 . 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. 69. 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) T A B LE C30 (PAGE 1) : M ATERNAL F E E D CONSUMPTION V A LU ES - LA C T A T IO N - IN D IV ID U A L D ATA - P G EN ERA T IO N FEM A LE RATS ARGUS 418-020 Page 240 DAY 1 - 5 5 -8 8 - 1 1 11. - 1 3 1 3 - 1 5 a DAM # 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 DOSAGE GROUP I 0 MG/KG/DAY 86. 1 2 6 . 165. 171. 163 . 215. 152 . 187. 126. MORIBUND S A C R IFIC ED ON b b 207. 135. 178. 229. 161. 177. 208. 116. 144 . 188. 156. 156. b 117. 167. 226. NOT PREGNANT b 189. 198. 173 . 193 . 229. 130. 101. 166. 142. 214. 147. 148. 109. 165. 106. 122 . 134 . 169. 160. 180. 140. 148. 164. 138. 128. 151. 171. 214 . 220. b 122 . 145. 101. 141. S A C R IFIC ED ON 123 . 169. 153 . 210. 139. 131. 193 . 122. 117. 180. b 84 . 149. 184. 107 . 85. 156. 89. 148. 165. DAY DAY 112. 147. 109. 68 O F 128. 146. 134 . 142 . 148. 153 . 143 . 138. 141. STUDY 152 . 168. 156. 13 9. 140. 157. 132. 46. 164. 133 . 118. 125. 85. 69. 137. 134. 8 OF 96. 143 . 150. 119. 177. 138. 118. 87. 98. 300. 174. 160. b 136. 111. 89. 172. 166. LACTATION 144 . 170 . 157. 13 9. 172 . 148. 136. 141. DAY = DAY OF LACTATION A L L W EIGHTS WERE RECORDED I N GRAMS ( G ) . a. I t i s presumed t h a t th e pups b e g in to consume th e m ate rn al fe e d a f t e r day 15 o f l a c ta tio n . b. S p ille d feed precluded the c a lc u la tio n of th is va lue. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 0 (P A G E 2) : M A TER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 241 DAY 1 - 5 5 -8 8-11 1 1 - 13 13 - 15 a DAM # 13 8 3 1 13832 13833 13834 13835 13 8 3 6 13 8 3 7 13 8 3 8 13 8 3 9 13 8 4 0 138 41 13 8 4 2 13 8 4 3 13 8 4 4 13 8 4 5 13 8 4 6 13 8 4 7 13848 13 8 4 9 13 8 5 0 1385 1 13 8 5 2 13 8 5 3 13 8 5 4 13 8 5 5 13 8 5 6 1385 7 13 8 5 8 13 8 5 9 13 8 6 0 DOSAGE GROUP I I 1 M G/KG/DAY 154 . 204 . 222 . 153 . 16 5 . 10 7. 15 9 . 16 9 . 133 . 170 . 138 . 154 . 219 . 135 . 145 . 10 9 . 138 . 12 7. 171. 18 1. 212. 124 . 140 . 123 . 16 2. M O R IB U N D S A C R IF IC E D O N D A Y 59 O F S TU D Y 115 . 13 6 . 164 . 12 8 . 128 . 123 . 13 7. 16 8 . 16 7. b 183 . 15 8 . 77. 173 . 121. NOT PREGNANT 1 2 9 . 112. 13 1. 13 2. 15 1. 140 . 121. 16 2 . 143 . 128 . 16 8 . 19 0 . 152 . 174 . 139 . 123 . 112. 13 7. 13 1. b 10 7. 116 . 139 . 13 1. 172 . 14 2 . 138 . 117. 15 0 . 122. 104 . 133 . 103 . 119 . 178 . 140 . 152 . 221. 173 . 10 7. 13 5 . 120. 129 . 18 9 . 121. 152 . 117. 193 . 13 9 . 148 . NOT PREGNANT 100. 127 . S A C R IFIC ED ON DAY 1 1 O F 129 . 15 1. 194 . 13 9 . 138 . 147 . 16 8 . 172 . 103 . 118 . 15 8 . 14 5 . 12 7. 15 9 . 144 . 164 . 205. 121. 201. 149 . 115 . 148 . 16 0 . 15 4. 15 5 . 114 . 13 2 . 15 6 . 152 . 205. 102. 15 0 . 111. 146 . 13 4 . 103 . 132 . 15 4. 98. 144. LA C T A T IO N D A Y = D A Y O F LA C T A T IO N A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . a . I t is presu m ed th a t th e pu ps b e g in to consum e th e m a te rn a l fe e d a ft e r d a y 15 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C3 0 (P A G E 3) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 242 DAY 1 - 5 8 8 -1 15 - 1 1 - 13 13 - 15 a DAM # 13 8 6 1 13 8 6 2 13 8 6 3 13 8 6 4 13 8 6 5 13866 13 8 6 7 13 8 6 8 13 8 6 9 13 8 70 138 71 13 8 72 13 8 73 13 8 74 13 8 75 13 8 76 138 77 13 8 78 13 8 79 13 8 8 0 1388 1 13 8 8 2 13 8 8 3 13 8 8 4 13 8 8 5 13 8 8 6 13 8 8 7 13 8 8 8 13 8 8 9 13 8 9 0 DOSAGE GROUP I I I 3 M G/KG/DAY 93 . 121. P R EG N A N T; D ID NOT 15 1. 100. 114 . 178 . 126 . 129 . b 225. 148 . 133 . 13 1. 138 . 18 8 . 121. 10 9 . 114 . 117. 15 1. 15 1. 154 . 16 9 . 16 2. 18 8 . 209. 128 . 16 1. 126 . 15 5 . 119 . 15 9 . 152 . 15 7. 13 7. 152 . 135 . 122 . 12 7. 13 1. 19 8 . 194 . 16 5 . 18 1. 133 . 118 . 99. 8 7. 126 . 153 . 114 . 130 . 64 . 92 . 12 7. 173 . 15 4. 16 6 . 14 1. D E LIV E R 208. 144 . 133 . 276 . 148 . 216 . 171. 14 1. 148 . 16 6 . 19 9 . 232 . 19 6 . 19 7. 19 6 . 18 9 . 183 . 204 . 157 . 238. 246. 172 . 101. 19 6 . 174 . 18 1. 244 . 2 14 . 86. A LIT T E R 92. 111. 93 . 135 . 126 . 16 1. 14 0 . 111. 84. 14 1. 13 7. 16 1. 14 6 . 145 . 15 9 . 130 . 115 . 14 1. 127 . 15 5 . 12 4 . 14 1. 62. 128 . 128 . 140 . 16 7. 16 0 . 122. 116 . 117. 119 . 19 5 . 15 9 . 18 7. 15 9 . 122. 10 4. 15 7. b 16 7. 164 . 15 2. 177. 148 . 145 . 205. 119 . 16 7. 162 . 172 . 65. 95. 14 7. 13 7. 149 . 19 1. D AY = D AY O F LA C T A T IO N A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . a . I t is presu m ed th a t th e pu ps b e g in to consum e th e m a te rn a l fe e d a ft e r d a y 15 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C30 (P A G E 4 ) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 243 DAY 1 - 5 5 -8 8-11 1 1 - 13 13 - 15 a DAM # DOSAGE GROUP IV 10 M G/KG/DAY 1389 1 13 8 9 2 13 8 9 3 13 8 9 4 13 8 9 5 13 8 9 6 13 8 9 7 13 8 9 8 13 8 9 9 13 9 0 0 1390 1 13 9 0 2 13 9 0 3 13 9 0 4 13 9 0 5 13 9 0 6 1390 7 13 9 0 8 13 9 0 9 13 9 10 13 9 11 13 9 12 13 9 13 13 9 14 13 9 15 13 9 16 139 17 13 9 18 13 9 19 13920 b 13 8 . 13 2. 15 2. 13 0 . 15 0 . b 15 6 . b 203 . 128 . 101. 14 1. 13 6 . 133 . 157 . 13 0 . 134 . NOT PREGNANT; 12 7. 112 . 13 2 . 153 . 140 . 15 6 . 123 . b 133 . 15 9 . 139 . 15 8 . 149 . 176 . 94. 115 . 115 . 163 . 15 7. 183 . 76 . 10 7. 13 1. 15 7. 148 . 173 . 15 4. 217 . 13 7. 13 9 . b 19 1. 49. 10 7. 14 7. 102. 173 . 12 4 . 10 9 . 126 . 164 . 18 7. b 2 17. 2 2 7. 175 . 18 6 . 171. 133 . M A TIN G N O T 19 0 . 18 6 . 173 . 175 . 170 . 208. 16 0 . 13 6 . 16 7. 18 5 . 16 2. 18 4. 19 8 . 19 8 . 19 0 . 220. 116 . 19 4. 174 . 15 8 . 139 . 143 . 146 . 14 2 . 138 . 110. 153 . 136 . 9 1. C O N FIR M ED 129 . 129 . 10 5 . b 132 . 146 . 85. 92. 14 1. 90. 128 . 13 1. 143 . 138 . 13 1. 149 . 88. 13 7. 122 . 5 7. 124 . 15 5 . 15 1. 193 . 16 9 . 123 . 179 . 15 1. 118 . 16 5 . 164 . 15 8 . 16 1. 15 8 . 16 8 . 99. 99. 16 6 . 12 7. 13 7. 13 2 . 16 2. 15 6 . 16 8 . 15 8 . 99. 15 5 . 143 . 66. D AY = D AY O F LA C T A T IO N A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . a . I t is pre su m e d th a t th e p u ps b e g in to consum e th e m a te rn a l fe e d a f t e r d a y 15 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C30 (P A G E 5 ) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 244 DAY 1 - 5 5 -8 8-11 1 1 - 13 13 - 15 a DAM # 13 9 2 1 13 9 2 2 13 9 2 3 13 9 2 4 13 9 2 5 13 9 2 6 13 9 2 7 13928 13 9 2 9 13 9 3 0 13 9 3 1 13 9 3 2 13 9 3 3 13 9 3 4 13 9 3 5 13 9 3 6 13 9 3 7 13 9 3 8 13939 13 9 4 0 13 9 4 1 13 9 4 2 13 9 4 3 13 9 4 4 13 9 4 5 13 946 13 9 4 7 13 9 4 8 13 9 4 9 13950 DOSAGE GROUP V 30 M G /KG /D AY 10 8 . 120. 172 . 114 . 140 . 9 2 . 9 7 . 10 6 . 82 . 9 0 . 80. 116 . 174 . 95. 136 . 14 7. 122 . 149 . 135 . 19 9 . 14 7. 148 . 126 . 13 2 . 146 . 9 1. 112. 14 7. 123 . 164 . 12 7. 144 . 103 . 145 . 122. b 170 . 2 17. 152 . 171. NOT PREGNANT 121. 143 . 68. 9 8 . 15 8 . 126 . 119 . 94 . 138 . 111. 124 . 15 9 . 16 8 . 134 . 14 2 . b 9 4 . 1 1 8 . 103 . 18 0 . 89. 13 5 . 249. 15 1. b 203 . 10 8 . 110. 183 . 126 . 13 9 . 15 8 . 145 . 16 8 . 152 . 16 8 . 13 2. 122 . 153 . 15 8 . 92. 103 . 121. 123 . 16 7. 133 . 126 . 221. 16 6 . 115 . 13 8 . 135 . 133 . 16 2. 130 . 140 . 15 7. 153 . 16 6 . 19 8 . 201. 14 8 . 13 7. 14 1. 144 . 13 1. 128 . 16 6 . 118 . 12 7. 140 . 150 . 10 8 . 115 . 142 . 14 1. 16 8 . 184 . 14 7. 136 . 13 7. 13 1. 16 6 . 128 . 14 1. S A C R IFIC E D D U E T O NO S U R V IV IN G PUPS ON D AY 1 O F LA C T A T IO N 118 . 120. 88. 139 . 15 1. 12 7. 170 . 193 . 171. 126 . 129 . 126 . 15 1. 15 5 . 136 . D AY = D AY O F LA C T A T IO N A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . I t is presum ed th a t th e pups b e g in to consum e th e m a te rn a l fe e d a f t e r d a y 15 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C 3 1 (P A G E 1) : M A TIN G AN D F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 245 RAT # ESTROUS STAGES/ 21 DAYS DAYS IN C O H A B IT A T IO N M A TIN G STATUS M A TIN G DATE P R EG N A N C Y STATUS ESTROUS STAGE A T S A C R IFIC E GROUP I 0 M G/KG/DAY 1380 1 13 8 0 2 13 8 0 3 13 8 0 4 13 8 0 5 13 8 0 6 13 8 0 7 13 8 0 8 13 8 0 9 13 8 10 13 8 11 13 8 12 13 8 13 13 8 14 13 8 15 13 8 16 13 8 17 13 8 18 13 8 19 13 8 2 0 13 8 2 1 13 8 2 2 13 8 2 3 13 8 2 4 13 8 2 5 13 8 2 6 13 8 2 7 13 8 2 8 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 M O R IB U N D S A C R IF IC E D O N D A Y 68 O F S T U D Y 1M 1M 3M 1M 14 M 2M 1M 4M 4M 3M 4M 8M 3M 3M 2M 2M 4M 4M 4M 4M 4M 1M 4M 1M 1M 4M C C C C C C C C C C C C C C C C C C C Cccccccccc P PRO P PRO PD P PRO P PRO P PRO P PRO PD P PRO NP D PD PD P PRO P PRO PD P PRO P PRO P PRO P PRO P PRO Pc P PRO P PRO P PRO PD P PRO P PRO P PRO P PRO M= PRO a. b. c. M ATED C = C O N FIR M ED NC = N O T C O N FIR M ED P = P R EG N A N T = PROESTRUS E = ESTRUS M ET = M ETESTR U S D = D IES T R U S R a t 13 804 w as m o rib u n d s a c r if ic e d on d a y 68 o f s tu d y (d a y s t a tis t ic a l a n a ly s e s . S ix o r m ore c o n s e c u tiv e d a y s o f d ie s tr u s w e re o b s e rv e d . E s tro u s sta g e was n o t re c o rd e d . NP = NOT PREGNANT 19 o f e s tro u s e v a lu a tio n ) ; v a lu e s e x c lu d e d fro m gro up a vera g es and PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C 3 1 (P A G E 2) : M A TIN G AN D F E R T IL IT Y , ES TR O U S C Y C LIN G AND D AYS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 246 RAT # ESTROUS STAG ES/ 21 DAYS DAYS IN C O H A B IT A T IO N M A TIN G STATUS M A TIN G DATE P R EG N A N C Y STATUS ESTROUS STAGE A T S A C R IFIC E GROUP I I 1 M G/KG/DAY 13 8 3 1 13 8 3 2 13 8 3 3 13834 13 8 3 5 13 8 3 6 1383 7 13 8 3 8 13 8 3 9 13840 13 8 4 1 13 8 4 2 13 8 4 3 13 8 4 4 13 8 4 5 13 8 4 6 13 8 4 7 13 8 4 8 13 8 4 9 13 8 5 0 1385 1 13 8 5 2 13 8 5 3 13 8 5 4 13 8 5 5 13 8 5 6 13 8 5 7 13 8 5 8 13 8 5 9 13 8 6 0 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 3M 4M 2M 2M 2M M O R IB U N D S A C R IF IC E D O N D A Y 59 O F S TU D Y 1M 1M 2M 1M 1M 1M 14 M M 1M 1M 1M 4M 3M 1M 1M 1M 1M 1M 1M 1M 4M 31 M M 4M C C C C C C C C C C C C C C C C C C C C C Cc cccccc P PRO P PRO P PRO P PRO P PRO P PRO PD PD NP E P M ET PD P PRO PD PD PD P PRO P PRO P PRO P PRO bN P E P P PRO PD PD PD P PRO P PRO P PRO P PRO M = M ATED C = C O N FIR M ED NC = N O T C O N FIR M ED PRO = PROESTRUS E = ESTRUS M ET = M ETESTR U S a . R a t 138 3 6 w as m o rib u n d s a c r ific e d o n d a y 59 s t a t is t ic a l a n a ly s e s . b . E s tro u s s ta g e was n o t re c o rd e d . P = PREGNANT NP = NOT PREGNANT D = D IES T R U S o f s tu d y (d a y 1 1 o f e s tro u s e v a lu a tio n ); v a lu e s e x c lu d e d fro m gro up avera g es and PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C 3 1 (P A G E 3) : M A TIN G A N D F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D AYS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 247 RAT # ESTROUS STAGES/ 21 DAYS DAYS IN C O H A B IT A T IO N M A TIN G STATUS M A TIN G DATE GROUP I I I 1386 1 13 8 6 2 13 8 6 3 13 8 6 4 13 8 6 5 13 8 6 6 13 8 6 7 13 8 6 8 13 8 6 9 13 8 70 138 71 13 8 72 13 8 73 13 8 74 13 8 75 13 8 76 138 77 13 8 78 13 8 79 13 8 8 0 1388 1 13 8 8 2 13 8 8 3 13 8 8 4 13 8 8 5 13 8 8 6 13 8 8 7 13 8 8 8 13 8 8 9 13 8 9 0 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 3 M G/KG/DAY 1 14 2 5 1 2 4 4 4 1 2 4 8 2 1 1 3 1 1 1 1 3 1 4 1 1 4 1 1 4 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 C NC C C C C C C C C C C C C C C C C C C Cccccccccc M= PRO a. b. M ATED C = C O N FIR M ED N C = N O T C O N FIR M ED = PROESTRUS E = ESTRUS M ET = M ETESTRUS E s tro u s s ta g e was n o t re c o rd e d on d a y 19 o f S ix o r m ore c o n s e c u tiv e d a ys o f e s tru s w ere P = PREGNANT NP = D = D IES TR U S e s tro u s e v a lu a tio n . o b se rve d . NOT P R EG N A N T PREGNANCY STATUS 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 ESTROUS STAGE A T S A C R IFIC E D PRO PRO D D D PRO PRO PRO PRO PRO D D PRO D M ET D PRO E PRO D D PRO PRO PRO D D D PRO M ET PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 1 (P A G E 4) : M A TIN G A N D F E R T I L I T Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R ATS ARGUS 418-020 Page 248 RAT # ESTROUS STAGES/ 21 DAYS DAYS IN C O H A B IT A T IO N M A TIN G STATUS M A TIN G DATE GROUP IV 13 8 9 1 13 8 9 2 13 8 9 3 13 8 9 4 13 8 9 5 13 8 9 6 13 8 9 7 13 8 9 8 13 8 9 9 13 9 0 0 13 9 0 1 13 9 0 2 13 9 0 3 13 9 0 4 13 9 0 5 13 9 0 6 139 0 7 13 9 0 8 13 9 0 9 13 9 10 13 9 11 13 9 12 13 9 13 13 9 14 13 9 15 13 9 16 13 9 17 13 9 18 13 9 19 13 9 2 0 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 10 M G/KG/DAY 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 D ID M M M M M M M M M M M M M M M M M M M M NOT M ATE C C C C C C C C C - Cc cc c NC C C C Cc ccccc NC C Cc M= PRO a. b. M ATED C= = PROESTRUS S ix o r m ore S ix o r m ore C O N FIR M ED NC = N O T C O N FIR M ED P = PREGNANT E = ESTRUS M ET = M ETESTRU S D = D IES T R U S c o n s e c u tiv e d a ys o f e s tru s w ere o b s e rv e d . c o n s e c u tiv e d a ys o f d ie s tr u s w ere o b s e rv e d . NP = NOT PREGNANT PREGNANCY STATUS 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 ESTROUS STAGE A T S A C R IFIC E PRO PRO D M ET D PRO PRO D PRO E PRO D PRO D PRO PRO D D D PRO D PRO PRO PRO M ET 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-6889.6) T A B LE C 3 1 (P A G E 5) : M A TIN G AN D F E R T I L I T Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - P G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 249 RAT # ESTROUS STAG ES/ 21 DAYS DAYS IN C O H A B IT A T IO N M A TIN G STATUS GROUP V 13 9 2 1 13922 13923 13924 13 9 2 5 13 9 2 6 13 9 2 7 13 9 2 8 13 9 2 9 13 9 3 0 13 9 3 1 13 9 3 2 13933 13 9 3 4 13 9 3 5 13 9 3 6 13 9 3 7 13 9 3 8 13 9 3 9 13 9 4 0 13 9 4 1 13 9 4 2 13 9 4 3 13 9 4 4 13 9 4 5 13 9 4 6 13 9 4 7 13 9 4 8 13 9 4 9 13 9 5 0 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 30 M G /K G /D AY 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= PRO a. b. M ATED C = C O N FIR M ED NC = N O T C O N FIR M ED = PROESTRUS E = ESTRUS M ET = M ETESTRU S S ix o r m ore c o n s e c u tiv e d a ys o f e s tru s w e re E s tro u s sta g e was n o t re c o rd e d . P = PREGNANT D = D IES TR U S o b se rve d . M A TIN G DATE C C C C C C C C C C C C C NC C C C C C C C C Cc c c c c cc NP = NOT PREGNANT 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 P ESTROUS STAGE A T S A C R IFIC E 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) T A B L E C32 (P A G E 1 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 250 DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a I 0 221 3 8 0 1 DL P 114 A L L T IS S U ES A PPEAR ED N O RM AL. 13 8 0 2 D L 22 P 114 A L L T IS S U ES A PPEAR ED N O RM AL. 13 8 0 3 D L 22 P 116 A L L T IS S U ES A PPEAR ED N O RM AL. 13 8 0 4 D S 68 - 6 7 M O R IB U N D S A C R IF IC E D O N D A Y 68 O F S T U D Y . A L L T IS S U ES A PPEAR ED N O RM AL. 13 8 0 5 13 8 0 6 13 8 0 7 13 8 0 8 13 8 0 9 13 8 10 13 8 11 13 8 12 13 8 13 13 8 14 13 8 15 13 8 16 138 17 13 8 18 13 8 19 13 8 2 0 13 8 2 1 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 DG 25 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 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 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. DS = DAY OF STUDY DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N P = PREGNANT NP = NOT PREGNANT a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le C24) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C32 (P A G E 2 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a I 0 8 1011 3 8 2 2 DL P S A C R IF IC E D O N D A Y 8 O F L A C T A T IO N .b A L L T IS S U ES A P P EA R ED NORM AL. 13 8 2 3 13 8 2 4 13 8 2 5 13 8 2 6 13 8 2 7 13 8 2 8 13 8 2 9 13 8 3 0 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 P P P P P P P P 116 115 115 112 116 113 113 114 A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. DS = DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N P = PREGNANT NP = NOT PREGNANT a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le C24) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . Th e l i t t e r s fro m dam s 13 8 2 2 in G ro u p I a n d 13 8 5 2 i n G ro u p I I w e re m ix e d t o g e t h e r . B o th dam s a n d l i t t e r s w e re s a c r if ic e d b e c a u s e i t w as n o t p o s s ib le to i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e d . ARGUS 418-020 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.S) T A B LE C32 (P A G E 3 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G E N E R A T IO N FEM A LE R ATS ARGUS 418-020 Page 252 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y PREGNANCY D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a 13 8 3 1 13 8 3 2 13 8 3 3 13 8 3 4 13 8 3 5 D L 22 D L 22 D L 22 D L 22 D L 22 P P P P P 115 115 113 114 114 A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED APPEARED A P P EA R ED A P P EA R ED APPEARED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 8 3 6 13 8 3 7 13838 13 8 3 9 13 8 4 0 13 8 4 1 13 8 4 2 13 8 4 3 13 8 4 4 13845 13 8 4 6 13 8 4 7 13 8 4 8 13 8 4 9 13 8 5 0 1385 1 DS 59 " D L 22 D L 22 D L 22 DG 25 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 DG 25 P P P NP P P P P P P P P P P NP 59 112 113 113 95 113 113 115 112 113 113 113 115 114 112 95 M O R IB U N D S A C R IF IC E D O N D A Y 59 O F S T U D Y . L E F T FO R ELIM B : U LN A AND R A D IU S , B R O K EN . A L L O TH ER T IS S U ES A P P EA R ED N O R M AL. A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. DS = DAY O F STUDY DG = D A Y O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N P = PREGNANT NP = NOT PREGNANT a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le C24) f o r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C32 (P A G E 4 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a 13 8 5 2 D L 11 P 102 S A C R IF IC E D O N D A Y 1 1 O F L A C T A T IO N .b A L L T IS S U ES A PPEAR ED NORM AL. 13853 13 8 5 4 13 8 5 5 13 8 5 6 13 8 5 7 13 8 5 8 13 8 5 9 13 8 6 0 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 P P P P P P P P 112 113 113 113 115 112 115 114 A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. DS = DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N D L = D A Y O F LA C T A T IO N P = PREGNANT NP = NOT PREGNANT a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le C24) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . T h e l i t t e r s fro m dam s 13 8 2 2 in G ro u p I a n d 13 8 5 2 in G ro u p I I w e re m ixe d t o g e t h e r . B o th dam s a n d l i t t e r s w e re s a c r if ic e d b e c a u s e i t was n o t p o s s ib le t o i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e d . 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) T A B LE C32 (P A G E 5 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 254 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a III 3 13 8 6 1 13 8 6 2 13 8 6 3 13 8 6 4 13 8 6 5 13 8 6 6 13 8 6 7 13 8 6 8 13 8 6 9 13 8 70 138 71 13 8 72 13 8 73 13 8 74 13 8 75 13 8 76 13 8 77 13 8 78 13 8 79 13 8 8 0 1388 1 13 8 8 2 13 8 8 3 13 8 8 4 D L 22 DG 25 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 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 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. N O R M A L .b NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 8 8 5 D L 22 P 114 K ID N E Y S : L E F T , P E L V IS , M ARKED D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 13 8 8 6 13 8 8 7 13 8 8 8 13 8 8 9 13 8 9 0 D L 22 D L 22 D L 22 D L 22 D L 22 P P P P P 112 116 112 112 116 A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. DS = DAY O F STUDY DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N P = PREGNANT NP = NOT PREGNANT a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le C24) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . R a t 13862 h ad one im p la n ta tio n s it e p re s e n t. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C32 (P A G E 6 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF N EC R O P S Y PREGNANCY D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a ARGUS 418-020 Page 255 13 8 9 1 13 8 9 2 13 8 9 3 13 8 9 4 13 8 9 5 13 8 9 6 13 8 9 7 13 8 9 8 13 8 9 9 13 9 0 0 1390 1 13 9 0 2 13 9 0 3 13 9 0 4 13 9 0 5 13 9 0 6 13 9 0 7 13 9 0 8 13 9 0 9 13 9 10 139 11 13 9 12 13 9 13 13 9 14 13 9 15 13 9 16 139 17 13 9 18 13 9 19 13 9 2 0 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D S 10 9 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 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 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL 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) T A B LE C32 (P A G E 7 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a ARGUS 418-020 Page 256 13 9 2 1 13 9 2 2 13 9 2 3 13 9 2 4 13 9 2 5 13 9 2 6 13 9 2 7 13 9 2 8 13929 13 9 3 0 13 9 3 1 13 9 3 2 13 9 3 3 13 9 3 4 13 9 3 5 13 9 3 6 13 9 3 7 13 9 3 8 13 9 3 9 13 9 4 0 13 9 4 1 13 9 4 2 13 9 4 3 13 9 4 4 13 9 4 5 13 9 4 6 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 DG 25 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 22 D L 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 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 9 4 7 DL 1 P 93 S A C R IFIC E D D U E TO NO S U R V IV IN G ON D A Y 1 O F LA C T A T IO N . A L L T IS S U ES A P P EA R ED NO RM AL. 13 9 4 8 13 949 13 9 5 0 D L 22 D L 22 D L 22 P P P 115 113 114 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 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) T A B LE C33 (PAG E 1) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 257 RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. W T. R EL. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a DOSAGE GROUP I 0 M G/KG/DAY 1380 1 13 8 0 2 13 8 0 3 13 8 0 4 c 13 8 0 5 13806 13807 13808 13809 13810 13 8 11e 13 8 12 13813 13 8 14 13815 13 8 16 13817 13818 13819 13820 13821 13822f 13823 13824 13825 13 8 2 6 13827 13828 13 8 2 9 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 2 8 .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 1 7 .2 1 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 .6 1 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 .5 1 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 0.44 0.49 1.86 2.08 1.54 1.14 1.64 1.48 1.58 1.55 1 .3 1 1 .6 7 1 .3 1 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 12.3 0 12.07 15.00 19.62 16.43 10.42 1 8 .1 1 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (ORG AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000 . b . F ix e d w e ig h t. c . R a t 138 0 4 w as m o rib u n d s a c r if ic e d o n d a y 68 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . d . V a lu e a p p e a re d in c o r r e c t ly re c o rd e d an d was e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . e . R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . f . R a t 138 22 was s a c r ific e d o n d a y 8 o f la c ta tio n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C33 (P A G E 2) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 258 RAT T ER M IN A L BODY NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW OVARY LEFT ABS. R EL. W T. % TBW a OVARY R IG H T ABS. R EL. W T. % TBW a U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW DOSAGE GROUP I 0 M G/KG/DAY 13801 13802 13803 13804C 13805 13806 13807 13808 13809 13810 13 8 11d 13812 13813 13 8 14 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 0.049 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 17.75 12.81 16.67 12.93 14.41 10.90 18.88 10.70 16.76 1 4 .11 13.99 11.42 10.27 14.69 14.24 18.62 12.79 12.62 17.68 20.94 17.66 14.86 14.89 13.00 25.89 17.94 13.72 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 0.049 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 .7 7 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 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % T B W := ( O R G A N W E I G H T / T E R M I N A L B O D Y W E I G H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000. b . F ix e d w e ig h t. c . R a t 13 80 4 w as m o rib u n d s a c r ific e d o n d a y 68 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . d . R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . e . R a t 13822 w as s a c r ific e d on d a y 8 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C33 (P A G E 3) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 259 RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a DOSAGE GROUP I I 1 M G/KG/DAY 13831 13832 13833 13834 13835 13 8 3 6 b 13837 13838 13839 13840c 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851c 13 8 5 2 d 13853 13854 13855 13 8 5 6 13857 13 8 5 8 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 .1 7 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 1 7 .5 1 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 .5 1 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 .6 7 1 .5 1 1.57 1.38 1 .6 1 1.24 1.60 1.80 1.57 1.52 1 .8 1 1.73 1 .5 1 1.86 1 .6 7 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 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 0.049 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 13.30 13.72 16.03 12.90 18.55 13.65 13.33 15.24 22.19 14.81 12.3 0 16.58 13.35 14.88 10.51 15.41 11.61 1 7 .0 1 16.01 15.48 12.12 16.08 14.92 16.86 15.82 16.38 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000 . b . R a t 13 83 6 was m o rib u n d s a c r ific e d o n d a y 59 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . c . R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . d . R a t 13 8 5 2 w as s a c r ific e d o n d a y 1 1 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C33 (P A G E 4) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 260 RAT T ER M IN A L BO D Y NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW OVARY LEFT ABS. R EL. W T. % TBW a OVARY R IG H T ABS. R EL. W T. % TBW a U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW DOSAGE GROUP I I 1 M G/KG/DAY 13831 13832 13833 13834 13835 13 8 3 6 b 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 .. 0 4 0 0 .. 0 4 0 0 .. 0 5 2 0 .. 0 3 8 0 .. 0 4 6 0 .. 0 3 9 0 .. 0 4 2 0 . 055 0 .051 0 . 049 0 . 060 0 . 046 0 ,. 0 3 0 0 ,. 0 4 7 0 ,. 0 4 9 0 ,. 0 4 2 0 ,. 0 3 4 0 .046 0 ,. 0 3 5 0 .050 0 .039 0 .043 0 .061 0 .052 0 .048 0 .059 0 .036 0 .043 0 .050 0 .052 1 1 . 08 1 1 . 20 15. 16 1 2 . 26 1 4 . ,46 1 1 ., 7 0 14.,67 14.,13 1 7 .,29 1 3 . .10 9..46 1 2 .77 13..92 1 2 . 50 1 0 . 83 13..90 1 0 . 42 1 4 , .66 18,.43 13,.65 14,.54 16,.08 1 2 ,. 2 0 1 2 ,. 7 2 15,.82 17 .75 0 ., 7 4 0 ., 7 9 0 .. 7 2 0 .. 6 7 0 .. 6 4 0 .. 4 9 0 .. 8 1 0 .. 6 6 0 .. 8 2 0 ., 5 9 0 .. 6 5 0 .. 6 7 0 . 54 0 ,. 7 9 0 ,. 5 1 0 ,. 4 8 0 .71 0 .61 0 ,. 6 8 0 ,. 6 4 0 ,. 6 0 0 ,. 5 9 0 ,. 7 0 0 ,. 8 3 0 ,. 7 8 0 ,. 7 9 0 .69 0 ,. 7 1 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 .. 1 4 0 .. 1 4 0 . 24 0 .. 1 5 0 .. 2 1 0 . 34 0 . 29 0 .. 2 0 0 .. 2 1 0 ,. 3 5 0 ,. 1 8 0 ,. 2 2 0 ,. 1 9 0 ,. 1 5 0 ,. 1 7 0 ,. 1 4 0 ,. 2 4 0 ,. 2 1 0 ,. 1 0 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 .. 0 7 2 0 .051 0 .050 0 . 050 0 .. 0 3 7 0 .. 0 4 9 0 . 055 0 . 062 0 ,. 0 4 6 0 ,. 0 6 4 0 .066 0 ,. 0 7 7 0 .047 0 ,. 0 4 2 0 ,. 0 9 4 0 ,. 0 3 7 0 ,. 0 5 4 0 ,. 0 4 9 0 ,. 0 3 4 0 ,. 0 3 4 0 ,. 0 3 3 0 ,. 0 4 9 0 ,. 0 8 2 0 ,. 0 7 5 0 ,. 0 7 7 0 ,. 0 4 5 0 .032 0 ,. 0 5 3 0 ,. 0 4 6 0 ,. 0 5 3 19..94 14 . 28 14 . 58 16..13 1 1 . 64 15..32 1 6 , .53 1 2 ,. 7 4 1 9 , .02 2 1 ,. 9 4 1 4 , .83 1 1 ,. 4 1 26,.70 1 1 ,. 0 1 1 7 , .20 14,.80 1 0 ,. 1 2 9,. 9 7 2 4 ,. 7 7 1 9 , .68 2 3 ,. 3 3 1 2 ,. 2 6 1 0 ,. 8 5 1 5 , .68 1 4 ,. 5 6 18,.09 0 ,. 0 6 5 0 ,. 0 4 1 0 ,. 0 6 5 0 ,. 0 7 4 0 ,. 0 4 5 0 ,. 0 5 7 0 ,. 0 6 5 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 1 8 ,. 0 0 1 1 ,. 4 8 1 8 ,. 9 5 2 3 ,. 8 7 1 4 ,. 1 5 1 8 ,. 1 0 1 3 ,. 3 3 1 4 ,. 1 3 31,.99 1 4 ,. 2 4 1 7 , .98 13 .86 28,.98 1 0 ,. 7 1 19,.11 1 3 ,. 9 0 1 2 ,. 8 0 19,.35 1 1 ,. 1 8 1 1 ,. 2 9 2 0 ,. 0 0 1 4 ,. 9 9 1 3 ,. 9 0 18,.34 1 3 ,. 9 2 2 0 ,. 4 8 0 ,. 5 8 0 ,. 6 2 0 ,. 4 1 0 ,. 3 7 0 ,. 5 0 0 ,. 5 3 1 ,. 1 0 0 ,. 6 0 0 .48 0 ,. 5 9 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 ,. 4 7 0 .43 0 ,. 7 0 0 ,. 1 6 0 ,. 1 7 0 ,. 1 2 0 ,. 1 2 0 ,. 1 6 --... 0 ,. 3 1 0 ,. 1 6 0 ,. 1 3 -0 ,. 1 6 0 ,. 2 1 0 .. 2 0 0 ,. 1 4 0 ,. 0 9 0 ,. 1 9 0 ,. 2 3 0 .. 1 1 0 .13 0 ,. 2 5 ---- --. . . 0 .37 0 . 14 0 ,. 1 9 0 ,. 1 4 0 ,. 1 6 0 .. 1 4 0 ,. 1 4 0 ,. 2 4 A LL a. b. c. d. W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = O RG AN W EIG H T . R E L . % T B W == ( O R G A N W E I G H T / T E R M I N A L B O D Y W E I G H T ) V a lu e was m u ltip lie d b y 1000. R a t 13 83 6 w as m o rib u n d s a c r ific e d on d a y 59 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . R a t was n o t p r e g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t 13852 w as s a c r ific e d on d a y 1 1 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s and s t a t i s t i c a l a n a ly s e s . 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) T A B LE C33 (P A G E 5) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 261 RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a DOSAGE GROUP I I I 3 M G/KG/DAY 13861 13 8 6 2 b 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 .1 7 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 1 7 .3 1 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 .6 7 1.35 1.59 1.75 1.56 1 .7 7 1.62 2.03 1.65 1.48 1.64 1.70 1.58 1.88 1 .8 1 1 .7 7 1.69 1.52 1.60 1.47 1.63 1.37 1.60 1.58 1 .3 1 1 .6 1 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 14.3 3 17.35 11.81 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000 . b . R a t 13862 was p r e g n a n t, b u t d id n o t d e liv e r a l i t t e r ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 3 (P A G E 6 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 262 RAT T ER M IN A L BODY NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW OVARY LEFT ABS. R EL. W T. % TBW a OVARY R IG H T ABS. R EL. W T. % TBW a U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW DOSAGE GROUP I I I 3 M G/KG/DAY 13861 13 8 6 2 b 13863 13 8 6 4 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 ., 0 3 2 0 ., 0 3 2 0 ., 0 4 7 0 ., 0 3 7 0 ., 0 4 5 0 ., 0 4 3 0 ., 0 4 3 0 ., 0 5 0 0 ., 0 4 3 0 .. 0 4 3 0 ,. 0 4 8 0 .. 0 4 1 0 .. 0 5 5 0 .. 0 4 5 0 .. 0 4 6 0 .. 0 3 7 0 .. 0 5 0 0 ,. 0 3 9 0 .. 0 3 5 0 ,. 0 3 5 0 ,. 0 4 9 0 ,. 0 4 9 0 .038 0.038 0.040 0.037 0.030 0.050 0 .051 0 .049 1 0 ., 2 6 1 3 . ,35 1 1 ., 0 4 1 2 ., 7 5 1 0 ., 7 2 1 2 ., 8 4 1 4 ,. 0 4 1 2 . 04 1 1 .. 1 4 1 3 .. 1 1 1 1 . 82 15..90 1 2 . 23 1 2 . 85 9.. 2 7 13..05 1 1 . 08 1 0 .67 9,. 6 4 15.. 1 7 13,.80 1 1 ,. 1 1 1 0 ,. 3 3 1 1 ,. 9 0 1 1 ,. 4 9 9, . 6 8 14,.92 1 5 , .00 13,.46 0 ., 6 6 0 .. 8 0 0 ., 7 2 0 ., 6 0 0 ., 6 3 0 .. 8 5 0 ., 7 6 0 .. 6 4 0 .. 4 9 0 .. 9 0 0 .. 8 9 0 .. 6 9 1 .. 0 2 0 .. 7 2 0 ,. 5 6 0 .. 6 4 0 .. 7 5 0 .. 7 0 0 .. 6 9 0 .78 0 .. 6 5 0 ,. 6 0 0 .75 0 ,.66 0 .. 7 8 0 ,. 6 8 0 ,. 7 5 0 .. 7 2 0 ,. 7 0 0 ,. 6 8 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 .. 1 0 0 .. 5 1 0 .. 1 9 0 ., 1 2 0 .. 1 8 0 ., 2 3 0 .. 2 0 0 .. 1 2 0 .. 1 4 0 .. 3 5 0 .. 1 9 0 .. 1 6 0 .. 1 8 0 ,. 1 6 0 ,. 1 9 0 ,. 2 2 0 ,. 3 0 0 ,. 0 9 0 ,. 3 0 0 ,. 1 9 0 .. 1 2 0 ,. 1 2 0.25 0 .22 0 ,. 4 3 0. 1 7 0 ,. 2 9 0 ,. 4 0 0 ,. 1 6 0 ,. 1 7 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 .. 0 3 5 0 .. 0 4 0 0 .. 0 4 2 0 .. 0 4 5 0 ,. 0 4 7 0 .. 0 6 6 0 .. 0 6 4 0 ,. 0 4 6 0 .. 0 4 9 0 ,. 0 6 9 0 ,. 0 3 7 0 ,. 0 5 0 0 .. 0 7 4 0 ,. 0 5 6 0 ,. 0 5 4 0 ,. 0 6 1 0 ,. 0 4 6 0 .. 0 3 1 0 .077 0 . 045 0 . 049 0 ,. 0 5 6 0 .093 0 ,. 0 5 9 0 ,. 0 5 5 0 ,. 0 6 4 0 ,. 0 3 5 0 . 049 0. 039 0 .068 1 1 .. 2 2 1 1 . 93 13 .43 13 . 31 16..46 1 9 . .10 1 2 ,. 9 2 1 3 ,. 7 2 1 7 , .88 1 0 ,. 1 1 14,.41 2 1 ,. 3 9 1 5 , .22 15,.08 15,.29 1 2 ,. 0 1 8 .81 2 3 ,. 4 8 1 2 ,. 4 0 15,.17 15,. 7 7 27 .19 16,.03 16,.37 1 9 , .88 1 1 ,. 2 9 1 4 ,. 6 3 1 1 ,. 4 7 18 ,.68 0 .. 0 2 4 0 . 054 0 .. 0 5 0 0 .. 0 4 7 0 .. 0 5 1 0 .. 0 7 4 0 .. 0 5 3 0 .. 0 4 9 0 .. 0 5 8 0 .. 0 7 9 0 .. 0 5 9 0 .. 0 4 7 0 .. 0 6 8 0 .. 0 7 4 0 .. 0 5 8 0 .. 0 6 9 0 .. 0 5 1 0 .. 0 4 6 0 .. 0 8 7 0 .. 0 4 9 0 .. 0 5 3 0 .. 0 6 2 0 .. 0 6 0 0 ,. 0 7 8 0 .. 0 5 8 0 .. 0 5 3 0 .. 0 4 6 0 .. 0 4 9 0 .. 0 5 9 0 .. 0 5 2 7 .69 - -- 14 .20 14 .03 14 .45 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 .0 7 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 ,. 3 2 0 .83 0 ,. 5 4 0 .47 0 .. 5 1 0 .. 4 8 0 .. 5 0 0 ,. 4 6 0 ,. 3 8 0 ,. 7 2 0 ,. 4 0 0 ,. 4 4 0 ,. 4 4 0 ,. 3 9 0 ,. 5 6 0 ,. 6 9 0 ,. 6 2 0 .. 6 6 0 .. 5 0 0 .. 7 8 0 .. 2 0 0 ,. 7 6 0 ,. 5 2 c 0 ,. 4 4 0 .. 5 9 0 .. 7 3 0 .. 7 7 0 .. 6 7 0 .. 3 1 0 .. 5 7 0 .. 1 0 ---- 0. 15 0 . 14 0 .. 1 4 0 .. 1 2 0 .. 1 5 0 .. 1 3 0 .. 1 1 0 .. 1 9 0 .. 1 1 0 .. 1 3 0 .. 1 3 0 .. 1 0 0 .. 1 6 0 .. 1 7 0 .. 1 6 0 .. 1 9 0 .. 1 5 0 .. 2 1 0 .. 0 6 0 .. 2 1 0 .. 1 5 0 .. 1 2 0 .. 1 8 0 .. 2 3 0 .. 2 5 0 .. 2 0 0 .. 0 9 0 ., 1 6 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 1000. b . R a t 13862 was p re g n a n t, b u t d id n o t d e liv e r a l i t t e r ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . c . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e 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) T A B LE C33 (PAG E 7) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 263 RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a DOSAGE GROUP IV 10 M G/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 300. 366. 332 . 386. 334 . 376. 361. 395 . 320. 0.013 0.023 0.022 0.017 0.018 0.016 0.006 0.018 0.010 4.33 6.28 6.63 4.40 5.39 4.26 1.66 4.56 3.12 2.26 2.20 2.19 2.28 2 .1 7 2.16 2.15 2.27 2.19 0.75 0.60 0.66 0.59 0.65 0.57 0.60 0.57 0.68 15.62 21.99 16.27 16.90 17.85 18.63 17.38 22.41 18.65 5.21 6.01 4.90 4.38 5.34 4.95 4.81 5.67 5.83 1.36 1.75 1.42 1.83 1.46 1.60 1.73 1.60 1.57 0.45 0.48 0.43 0.47 0.44 0.42 0.48 0.40 0.49 1.34 1.83 1.47 1.8 1 1.56 1.64 1.75 1.69 1.62 0.45 0.50 0.44 0.47 0.47 0.44 0.48 0.43 0.51 0.048 0.047 0.038 0.058 0.041 0.045 0.043 0.060 0.042 16.00 12.84 11.44 15.02 12.28 11.97 11.91 15.19 13.12 13901 13 9 0 2 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13 9 15 13916 13917 13918 13919 13920 350. 311. 318. 354 . 351. 355 . 337. 366. 356. 353 . 327. 355. 317. 294 . 323 . 376. 327 . 302. 329. 349. 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 4.57 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 2.32 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 0.66 0.68 0.64 0.68 0.61 0.61 0.66 0.61 0.61 0.62 0.69 0.63 0 .7 1 0.78 0.65 0.64 0.71 0.74 0.70 0.65 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 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 1.51 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 0.43 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 0.43 0.40 0.47 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 .5 1 1.60 1.44 1.39 1.34 1.62 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 0.036 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 1 3 .7 1 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 a. b. W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000. R a t was n o t p re g n a n t; v a lu e s w ere n o t A B S . W T. re c o rd e d . = O RG AN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE C33 (P A G E 8) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 264 RAT T ER M IN A L BODY NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW OVARY LEFT ABS. R EL. W T. % TBW a OVARY R IG H T ABS. R EL. W T. % TBW a U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW DOSAGE GROUP IV 10 M G/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 1390 0b 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13 9 12 13913 13 9 14 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 .7 7 10 .18 10 .64 11 .91 18 .23 10 .62 11 .14 10 .93 9 .43 12 . 7 1 13 .96 10 .70 13 .35 10 .93 10 .67 13 .3 1 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. 1 4 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 1 1 . 67 15. 57 9. 94 1 2 . 18 16. 77 1 2 . 76 13 . 02 1 0 . 13 1 4 . 69 16. 57 1 1 . 90 1 0 . 06 1 3 . 56 1 6 . 24 1 2 . 39 18. 40 1 8 . 03 9. 27 1 7 . 85 1 5 . 60 1 1 . 27 19. 87 1 7 . 35 16. 72 8 . 78 1 8 . 65 1 5 . 23 1 7 . 02 1 2 . 89 0 ,. 0 4 4 0 ,. 0 5 4 0 ,. 0 5 0 0 ,. 0 8 6 0 ,. 0 5 4 0 ,. 0 4 8 0 ,. 0 4 1 0 ,. 0 5 7 0 . 046 0 ,. 0 6 1 0 ,. 0 5 8 0 ,. 0 5 8 0 ,. 0 6 5 0 ,. 0 7 4 0 . 048 0 ,. 0 6 6 0 ,. 0 6 5 0 ,. 0 5 7 0 ,. 0 5 2 0 ,. 0 2 8 0 ,. 0 5 3 0 ,. 0 5 9 0 ,. 0 5 3 0 .. 0 7 1 0 .. 0 5 0 0 .. 0 5 2 0 .. 0 4 9 0 ,. 0 3 8 0 ,. 0 3 8 14 .67 14 .75 15 .06 22 .28 16 .1 7 12 .76 11 .36 14 .43 14 .38 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 .6 1 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 ,. 1 2 0 ,. 1 4 0 ,. 1 4 0 ,. 1 4 0 ,. 1 4 0 ,. 1 1 0 ,. 1 6 0 ,. 1 6 0 ,. 1 8 0 ,. 1 4 0 ,. 1 6 0 ,. 1 1 0 ,. 3 0 0 ,. 1 5 0 ,. 1 3 0 .. 2 2 0 .. 2 3 0 ,. 2 1 0 .. 1 5 0 .. 2 1 0 .. 1 6 0 .. 1 4 0 .. 1 9 0 .. 1 6 0 .. 1 3 ALL a. b. W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . V a lu e was m u ltip lie d b y 1000 . R a t was n o t p re g n a n t; v a lu e s w ere n o t A B S . W T. re c o rd e d . := O R G A N W E I G H T , R E L . % T B W == ( O R G A N W E I G H T / T E R M I N A L B O D Y W E I G H T ) X 1 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) T A B LE C33 (P A G E 9) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 265 RAT T E R M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a DOSAGE GROUP V 30 M G /K G /D AY 13 9 2 1 13 9 2 2 13923 13924 13925 13926 13927 13928 13929b 13930 13931 13 9 3 2 13933 13 9 3 4 13935 13936 13937 13938 13939 13 940 13941 13942 13943 13944 13945 13946 13 9 47d 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. 0.019 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 1 7 .5 7 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 1 8 .1 7 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 .7 1 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 .3 1 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 .5 1 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 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e w as m u ltip lie d b y 1000. b . R a t was n o t p r e g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . c . V a lu e a p p e a re d in c o r r e c t ly re c o rd e d a n d was e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . d . R a t 1 3 9 4 7 was s a c r ific e d du e t o no s u r v iv in g p u ps on d a y 1 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a tis t ic a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C33 (P A G E 10 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 266 RAT T ER M IN A L BODY NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW OVARY LEFT ABS. R EL. W T. % TBW a OVARY R IG H T ABS. R EL. W T. % TBW a U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW DOSAGE GROUP V 30 M G /K G /D AY 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 13 949 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 0.041 0.041 0.045 0.033 0.049 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 . 810d 0.023 0.041 11.76 11.65 12.81 13.20 10.38 13.88 1 5 .7 1 9.78 -- 10.57 10.60 12.88 18.40 8.53 17 .6 1 12.61 10.13 14.28 10.60 11.05 15.40 1 0 .1 7 12.03 15.25 11.40 6.80 -- 250.77d 6.30 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 .7 1 15.22 11.48 15.95 15.29 1 7 .6 1 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 1 1.3 7 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 a. b. c. d. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) V a lu e was m u ltip lie d b y 1000. R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t 1 3 9 4 7 was s a c r ific e d due t o no s u r v iv in g pu ps on d a y 1 o f la c ta tio n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t is t ic a l a n a ly s e s . V a lu e a p p e a re d in c o r r e c tly re c o rd e d an d was e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . 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) T A B L E C 3 4 (P A G E 1 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 267 RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW DOSAGE GROUP I 0 M G/KG/DAY 13801 13802 13803 13 8 0 4 b 13805 13806 13807 13808 13809 13810 13 8 11d 13 8 12 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822e 13823 13824 13825 13826 13827 13 8 2 8 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 .3 1 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 7 7 1 .6 7 732.02 737.68 781.65 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 7 7 .2 7 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 .3 1 1 .6 7 1 .3 1 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 1.91 1.74 1.74 -- 1.71 2.72 2.34 2.03 2.02 2.25 -- 1.67 2.16 2.21 1.8 1 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 ALL a. b. c. d. e. W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . F ix e d w e ig h t. R a t 13 8 0 4 w as m o rib u n d s a c r if ic e d o n d a y 68 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . V a lu e a p p e a re d in c o r r e c tly re c o rd e d an d w as e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t w as n o t p r e g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . R a t 13 8 2 2 was s a c r ific e d on d a y 8 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 4 (P A G E 2 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 268 RAT NUM BER B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW OVARY LEFT ABS. R EL. W T. % BRW OVARY R IG H T ABS. R EL. W T. % BRW U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW DOSAGE GROUP I 0 M G/KG/DAY 13801 13802 13803 13 8 0 4 b 13805 13806 13807 13808 13809 13810 13811c 13 8 12 13 8 13 13 8 14 13815 13816 13817 13818 13819 13820 13821 13822d 13823 13824 13825 13826 13827 13 8 2 8 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 .3 1 2.30 2 .3 1 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 .6 7 2.38 1.83 2.73 -- 2.08 2.52 1.8 1 1.68 2.19 1.86 2 .7 7 1 .9 1 1.94 3.12 -- 3.09 2.94 2.37 2.53 2.04 3 .5 1 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 0.049 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 2.37 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 2 5 .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 a. b. c. d. W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G AN W E IG H T / B R A IN W EIG H T ) X 1 0 0 . F ix e d w e ig h t. R a t 13 80 4 was m o rib u n d s a c r ific e d on d a y 68 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t w as n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . R a t 13822 was s a c r ific e d on d a y 8 o f la c ta tio n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s and s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C34 (P A G E 3) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 269 RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW DOSAGE GROUP I I 1 M G/KG/DAY 13831 13832 13833 13834 13835 13836a 13837 13838 13839 13 8 4 0 b 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 1385 1b 13852c 13853 13854 13855 13856 13857 13858 13859 13 860 2.17 2.31 2.23 2.26 2.38 1.91 2.07 2.45 2.30 98 18 20 20 18 40 26 26 75 20 39 91 15 03 2.32 2.23 19 04 15 10 22 0.026 0.015 0.019 0.013 0.019 0.017 0.024 0.021 0.013 0.018 0.016 ,017 ,015 .023 .026 .013 .019 .018 .027 .020 .017 .017 .018 .014 .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 73 77 68 06 08 58 84 03 23 84 0.89 0.60 0.81 1.14 0.44 0.51 1.14 1.04 21.35 18.12 1 7 .5 1 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 14.25 983.87 784.42 785.20 722.12 841.18 975.36 774.28 862.17 832.11 856.82 638.64 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 28 75 62 41 86 56 64 51 67 57 79 19 32 64 70 39 43 29 60 58 57 75.12 64.07 66.37 58.41 7 3 .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 .5 1 1.57 1.38 1.61 1.24 1.60 1.80 1.57 1.52 1.8 1 1.73 1 .5 1 86 67 49 68 58 50 87 16 28 63 80 29 49 53 53 59 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 0.049 0.055 0.040 0.059 0.038 0.049 0.050 0.055 0.053 0.077 0.052 0.039 0.061 047 050 033 051 039 058 034 058 053 059 040 059 044 057 0.050 0.048 2.21 2.12 2.47 1 .7 7 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 .7 7 2.43 61 54 79 69 16 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 0.046 0.030 0.047 049 042 034 046 035 050 039 043 061 0.052 0.048 0.059 0.036 0.043 0.050 0.052 1.84 1.73 2.33 1.68 1.93 -- 2.03 2.24 2.22 75 09 36 16 04 86 50 63 59 09 00 24 15 69 76 00 2.38 2.34 ALL a. b. c. W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . A B S . W T. = O RG AN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . R a t 1 38 3 6 was m o rib u n d s a c r if ic e d o n d a y 59 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s and s t a t is t ic a l a n a ly s e s . R a t 13 8 5 2 was s a c r ific e d o n d a y 1 1 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C34 (P A G E 4) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G E N ER A T IO N FEM A LE RATS ARGUS 418-020 Page 270 RAT NUM BER B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW OVARY LEFT ABS. R EL. W T. % BRW OVARY R IG H T ABS. R EL. W T. % BRW U TER U S N O N - G R A V ID ABS. R EL. W T. % BRW DOSAGE GROUP I I 1 M G/KG/DAY 13831 13832 13833 13834 13835 13836a 13837 13838 13839 13 8 4 0 b 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 1385 1b 13852c 13853 13854 13855 13856 13857 13858 13859 13860 2.17 31 23 26 38 91 07 45 30 1.98 2.18 2.20 2.20 2.18 40 26 26 75 20 39 91 15 03 32 23 19 04 15 10 22 0.74 0.79 0.72 0.67 0.64 49 81 66 82 0.59 0.65 67 54 79 51 48 71 61 68 64 60 0.59 0.70 0.83 0.78 0.79 0.69 0 .7 1 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 2 1 . 25 2 1 ,. 2 4 31,.42 3 4 , .8 6 30,.9 1 26,.78 34.48 35.78 34.98 36.07 33.82 33.02 3 5 .7 1 27.93 0.14 0.14 0.24 0.15 21 34 29 20 21 0.35 0.18 22 19 15 0.17 0.14 0.24 0.21 10 20 27 24 22 29 16 22 21 22 13 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 21 24 21 1.55 2.66 2.53 2.00 03 50 14 93 92 64 39 80 54 42 4.04 3.23 3.45 ,05 .57 46 ,19 ,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 ,102 036 ,060 ,046 ,043 0.066 0.039 ,066 ,037 ,043 ,066 ,055 ,041 .062 .044 ,060 3.00 1 .7 7 2.91 3 .2 7 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 82 85 96 51 01 88 10 70 0.58 0.62 0.41 0.37 50 53 10 60 48 59 0.55 0.75 0.63 0.51 32 64 72 36 43 84 24 45 23 54 64 0.52 0.47 0.47 0.43 0.70 26.73 26.84 18.38 16.37 21.01 53 . 1 4 24 . 49 2 0 .87 25..23 3 4 ,. 0 9 28..64 23 . 39 1 3 ,. 3 3 28,.32 3 1 . .86 2 0 .57 19..54 35.. 1 5 60.59 23.28 28.70 23.74 23.04 21.86 20.48 31.53 ALL a. b. c. W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = O RGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T) X 1 0 0 . R a t 138 36 was m o rib u n d s a c r if ic e d on d a y 59 o f s tu d y ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . R a t 13852 was s a c r ific e d on d a y 1 1 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C34 (P A G E 5) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 271 RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW DOSAGE GROUP I I I 3 M G/KG/DAY 13861 13862a 13863 13 8 6 4 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 1 7 .3 1 17.66 18.85 1 7 .6 7 17.99 18.95 18.41 18.20 18.27 1 3 .7 7 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 69.81 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 6 1 .2 1 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 7 8 .7 7 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 7 1 .3 1 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 0.030 0.048 0.059 0.043 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 .7 7 2.32 1 .9 7 2.28 1.40 2.13 2.62 2.15 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 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 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = O RGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T)i X 1 0 0 . a . R a t 1 3 8 6 2 w a s p r e g n a n t , b u t d i d n o t d e l i v e r <i l i t t e r ; v a l u e s e x c l u d e d f r o m g r o u p a v e r a g e s a n d s t a t i s t i c a l a n a l y s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C34 (PAG E 6) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 272 RAT NUM BER B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW OVARY LEFT ABS. R EL. W T. % BRW OVARY R IG H T ABS. R EL. W T. % BRW U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW DOSAGE GROUP I I I 3 M G/KG/DAY 13861 13862a 13863 13 8 6 4 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 3 1.1 1 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 .1 1 8.50 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 0.049 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 .8 1 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 .7 7 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 a. b. W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = O RGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T) X 1 0 0 . R a t 13862 was p re g n a n t, b u t d id n o t d e liv e r a l i t t e r ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e 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) T A B LE C34 (PAG E 7) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 273 RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW DOSAGE GROUP IV 10 M G/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 2.26 2.20 2.19 2.28 2 .1 7 2.16 2.15 2.27 2.19 0.013 0.023 0.022 0.017 0.018 0.016 0.006 0.018 0.010 0.58 1.04 1.00 0.74 0.83 0.74 0.28 0.79 0.46 15.62 21.99 16.27 16.90 17.85 18.63 17.38 22.41 18.65 691.15 999.54 742.92 741.23 822.58 862.50 808.37 987.22 851.60 1.36 1.75 1.42 1.83 1.46 1.60 1.73 1.60 1.57 60.18 79.54 64.84 80.26 67.28 74.07 80.46 70.48 71.69 1.34 1.83 1 .4 7 1 .8 1 1.56 1.64 1.75 1.69 1.62 59.29 83.18 67.12 79.38 71.89 75.92 81.40 74.45 73.97 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 0.042 0.048 0.048 0.057 0.034 0.040 0.043 0.072 0.034 1.86 2.18 2.19 2.50 1.57 1.85 2.00 3 .1 7 1.55 13901 13 9 0 2 13 9 0 3 13904 13905 13906 13907 13908 13909 13910 13911 13 9 12 13913 13914 13915 13916 13917 13918 13919 13920 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 0.016 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 0.69 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 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 18.54 640.09 836.97 749.01 650.63 817.29 871.56 847.77 728.83 766.20 842.27 742.48 752.68 673.21 667.25 710.48 772.08 748.48 646.40 740.00 813.16 1 .5 1 1.38 1 .3 1 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 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 1.56 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 .5 1 1.60 1.44 1.39 1.34 1.62 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 0.036 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 0.039 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 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . a . R a t was n o t p re g n a n t; v a lu e s w ere n o t re c o rd e d . R E L . % BRW = (ORGAN W E IG H T / B R A IN W EIG H T) X 1 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) T A B L E C 3 4 (P A G E 8 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 274 RAT NUM BER B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW OVARY LEFT ABS. R EL. W T. % BRW OVARY R IG H T ABS. R EL. W T. % BRW U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW DOSAGE GROUP IV 10 M G/KG/DAY 13891 13892 13893 13894 13895 13896 13897 13898 13899 13 9 0 0 a 13901 13 9 0 2 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13 9 15 13916 13917 13918 13919 13920 2.26 2.20 2.19 2.28 2 .1 7 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 .7 1 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 3 5 .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 .4 1 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 -- 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 18.14 45.00 2 5 .11 45.18 18.43 23.61 22.79 24.67 20.09 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 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = ORGAN W EIG H T . a . R a t was n o t p re g n a n t; v a lu e s w ere n o t re c o rd e d . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 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) T A B L E C 3 4 (P A G E 9 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 275 RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW DOSAGE GROUP V 30 M G /KG /D AY 13921 13 9 2 2 13923 13924 13925 13926 13927 13928 13929a 13930 13 931 13 9 3 2 13933 13 9 3 4 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13 946 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 18 99 16 08 29 03 25 2.29 2.24 39 19 30 01 29 04 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 0.022 016 018 012 010 017 005 016 016 030 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 .73 90 .56 .48 ,74 .25 ,71 ,70 .34 ,71 .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 1 8 .1 7 824.46 755.09 932.09 992.89 716.51 937.44 898.55 823.04 923.66 915.79 942.66 861.81 694.44 844.71 7 8 7 .7 7 824.63 844.44 718.34 844.64 810.88 785.84 769.56 814.92 760.70 839.70 686.36 904.31 899.50 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 51 58 49 34 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 7 1 .0 1 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 51 46 65 37 45 53 57 33 11 36 55 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 0.042 051 045 039 053 053 029 056 039 048 045 030 034 056 051 032 048 044 046 037 2.23 1.76 1.95 2.51 1.89 3.24 3.33 2 .1 7 -- 1.74 2.01 34 26 80 55 31 43 2.49 70 14 88 37 48 79 23 57 2.00 2.20 1.83 0.042 0.041 0.041 0.045 0.033 0.049 0.052 0.036 0.033 0.037 0.039 046 060 029 056 044 031 049 037 039 059 035 042 052 039 024 040 8 10 b 023 041 1.80 1.90 1.91 2.13 1.56 2.24 2.51 1.56 -- 1.65 1.87 11 02 34 69 92 53 18 62 74 47 60 83 59 70 18 36.82b 1.10 2.03 ALL a. b. c. W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . A B S . W T. = O RGAN W EIG H T . R E L . % BRW = (O R G A N W E IG H T / B R A IN W EIG H T) X 1 0 0 . R a t was n o t p re g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . V a lu e a p p e a re d in c o r r e c t ly re c o rd e d a n d was e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t 13 9 4 7 w as s a c r ific e d d u e t o n o s u r v iv in g p u p s on d a y 1 o f la c t a t io n ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t is t ic a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C34 (P A G E 10 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A P G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 276 RAT NUM BER B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW OVARY LEFT ABS. R EL. W T. % BRW OVARY R IG H T ABS. R EL. W T. % BRW U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW DOSAGE GROUP V 30 M G /K G /D A Y 13921 13922 13923 13924 13925 13926 13927 13928 13929a 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13 940 13941 13 942 13 943 13944 13945 13946 13 9 4 7b 13 948 13 949 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 3 5 .7 1 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 1.8 1 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 1 9 .1 1 18.78 26.78 18.83 24.66 22.17 28.36 12.23 22.06 29.54 18.66 32.18 ALL a. b. W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % BRW = (O R G A N R a t was n o t p r e g n a n t; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t 1 3 9 4 7 was s a c r ific e d due t o n o s u r v iv in g pu ps on d a y 1 o f la c t a t io n ; v a lu e s e x c lu d e d s t a t is t ic a l a n a ly s e s . W E IG H T / B R A IN W EIG H T ) X 1 0 0 . fro m g ro u p a v e ra g e s an 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) T A B LE C35 (PAGE 1) : NATURAL D E L IV E R Y , IM PLAN TATIO N S IT E S , AND PUP V I A B I L I T Y AND SEX - IN D IV ID U A L D ATA - P G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 277 DOSAGE GROUP I 0 MG/KG/DAY RAT/ L IT T E R NUMBER DURATION OF G ES T A T IO N (DAYS) N LIT TER DELIVERED LIVE S TILL- TOTAL BORN BORN BORN N NN 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 9 0 9 22 01 4 1 4 02 3 1 6 1 6 68M O R I B U N D S A C R I F I C E D O N D A Y OF STUDY 02 3 1 3 1 3 22 01 7 1 7 22 01 7 1 7 22 12 1 1 3 02 3 1 3 1 3 12 3 14(1) 15 NOT PREGNANT 23 23 22 23 23 23 23 22 23 22 23 23 23 23 23 23 23 22 22 14 12 17 15 15 15 16 13 (1) 14 17 12 9 16 15 16 16 14 13 13 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 14 13 [1] 17 15 16 [1] 15 16 13 14 17 12 9 16 15 16 16 14 13 14 1 MF 45 86 6 10 67 6 11 89 66 94 58 95 57 11 6 10 5 5 10 87 88 48 59 89 39 45 88 2 13 88 10 6 59 85 76 NUMBER OF L IV E COM PLETION OF' DAY 58 MF MF PUPS AT POSTPARTUM 15 MF 22 MF 45 86 6 10 67 5 11 89 66 94 48 45 86 69 67 5 11 89 66 94 48 45 86 69 67 5 11 89 66 94 48 45 86 69 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 85 76 M = MALE F = FEMALE ( ) = NUMBER O F PUPS DYING PRIOR TO W EIGHING ON DAY 1 POSTPARTUM. [ ] = NUMBER O F PUPS IN WHICH C A N N IB A LIZ A T IO N AND/OR A U TO LYS IS PRECLUDED TH E D ETER M IN ATIO N OF V I A B I L I T Y , a . Dam 13822 was s a c r i f i c e d on d a y 8 o f l a c t a t i o n . TOTAL IM PLAN T A T IO N S 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) T A B L E C35 (P A G E 2) : N A T U R A L D E L I V E R Y , I M P L A N T A T I O N S I T E S , A N D PUP V I A B I L I T Y A N D S E X - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E RATS ARGUS 418-020 Page 278 DOSAGE GROUP I I 1 MG/KG/DAY RAT/ LITTER NUMBER DURATION OF G E S T A T IO N (DAYS) N LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN NNN 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 01 7 1 7 02 3 1 4 1 4 22 01 5 1 5 22 01 3 1 3 22 01 8 1 8 M ORIBU ND S A C R I F I C E D ON D A Y 59 O F S TU D Y 22 11 1 12 02 3 1 8 1 8 23 12 0 12 NOT PREGNANT 22 22 22 23 23 23 23 23 23 22 11( 1 ) 13 10 17 12 14 8 16 16 12 0 0 0 0 0 0 7 0 0 1 12 [ 1 ] 13 10 17 12 14 15 16 16 13 NOT PREGNANT 23 22 23 22 22 23 22 23 22 12 17 17 16 (1) 16 14 17 15 13 0 0 0 0 0 1 0 0 0 12 17 17 16 16 15 17 15 13 1 MF 13 4 10 4 69 49 6 12 56 7 11 66 55 67 55 6 11 75 77 44 12 4 11 5 66 84 10 7 11 6 96 97 4 10 98 69 94 NUMBER. O F L I V E COM PLETION OF' DAY 58 MF MF PUPS AT POSTPARTUM 15 MF 22 MF 13 4 10 4 68 49 6 10 56 7 10 66 13 4 10 4 68 49 6 10 56 7 10 66 13 4 10 4 68 49 6 10 56 7 10 66 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 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 55 57 55 6 10 75 76 44 12 4 11 5 66 -- 10 7 11 6 95 97 4 10 98 68 94 55 57 55 6 10 75 76 44 12 4 11 5 66 -- 10 7 11 6 95 97 4 10 98 68 94 M = MALE F = FEMALE ( ) = NUMBER O F PUPS DYING PRIOR TO W EIGHING ON DAY 1 POSTPARTUM. [ ] = NUMBER O F PUPS IN WHICH C A N N IB A L IZ A T IO N AND/OR A U TO LYS IS PRECLUDED TH E D ET ER M IN A TIO N OF V I A B I L I T Y , a . Dam 13852 was s a c r i f i c e d on d a y 1 1 o f l a c t a t i o n . TOTAL IM PLAN TA T IO N S 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) T A B L E C35 (P A G E 3) : N A T U R A L D E L I V E R Y , I M P L A N T A T I O N S I T E S , A N D PUP V I A B I L I T Y A N D S E X - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E R A TS ARGUS 418-020 Page 279 DOSAGE GROUP I I I 3 MG/KG/DAY RAT/ L IT T E R NUMBER DURATION OF G E S T A T IO N (DAYS) N LIT TER DELIVERED LIVE S TILL- TOTAL BORN BORN BORN NNN 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 10 0 10 PREGNANT; DID NOT DELIV ER A LIT T ER 23 16 0 16 23 6 1 7 22 01 7 ( 1 ) 17 02 3 1 8 1 8 12 3 1 5 1 6 22 01 6 1 6 02 3 1 6 1 6 23 8 0 8 22 01 5 1 5 02 3 1 7 1 7 02 3 1 7 1 7 02 3 1 7 1 7 02 3 1 6 1 6 12 3 14 (1) 15 12 3 1 3 1 4 02 3 9 9 2 3 11 0 11 02 3 1 3 1 3 22 11 0 11 22 01 6 1 6 02 3 15(1) 15 23 11 0 11 02 4 3 3 22 12 0 12 23 11 0 11 12 3 1 4 1 5 22 01 6 1 6 02 3 1 5 1 5 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 L IV E COMPLETION OF DAY 58 MF MF PUPS A T POSTPARTUM 15 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 W EIGHING ON DAY 1 POSTPARTUM. TOTAL IM PLA N T A T IO N S 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) T A B L E C35 (PAGE 4) : N A T U R A L D E L I V E R Y , IM P LA N T A T IO N S I T E S , AND PUP V I A B I L I T Y AND S E X - I N D IV I D U A L D A T A - P G E N E R A T IO N F E M A LE RATS ARGUS 418-020 Page 280 DOSAGE GROUP IV 10 MG/KG/DAY RAT/ L IT T E R NUMBER DURATION OF G E S T A T IO N (DAYS) N LIT T ER DELIVERED LIV E S TILL- TOTAL BORN BORN BORN N NN 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 11 5 1 6 22 01 5 1 5 02 3 1 4 1 4 22 01 5 1 5 23 12 0 12 23 12 0 12 02 3 1 7 1 7 22 11 0 1 1 NOT PREGNANT; MATING NOT CONFIRMED 02 3 1 6 1 6 02 3 1 5 1 5 02 3 1 4 1 4 02 3 1 4 1 4 02 3 1 6 1 6 2a 1 4 1 6 21 01 6 1 6 02 3 4 4 02 3 1 4 1 4 22 01 5 1 5 23 12 0 12 22 01 4 1 4 22 01 3 1 3 02 3 1 8 1 8 02 3 1 7 1 7 02 3 1 6 1 6 0a 7 7 02 3 1 4 1 4 22 01 4 1 4 02 3 1 6 1 6 1 MF 46 78 78 77 11 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 L IV E 1C O M P L E T I O N O F D A Y 58 MF MF PUPS AT POSTPARTUM 15 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 6 22 59 69 84 77 76 89 98 79 34 59 68 66 M = MALE F = FEMALE a . Dam d i d n o t h ave a c o n fir m e d m a tin g d a te , w h ic h p re c lu d e s th e c a l c u l a t i o n o f th e d u r a t i o n o f g e s t a t i o n . TOTAL IM PLAN T A T IO N S 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) T A B L E C35 (P A G E 5) : N A T U R A L D E L I V E R Y , I M P L A N T A T I O N S I T E S , A N D PU P V I A B I L I T Y A N D S E X - I N D I V I D U A L D A T A - P G E N E R A T I O N F E M A L E R A TS ARGUS 418-020 Page 281 DOSAGE GROUP V 30 M G/KG/DAY RAT/ L IT T E R NUMBER DURATION OF G ES T A T IO N (DAYS) N 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 13 945 13 946 13947b 13948 13 949 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 LIT TER DELIVERED LIV E S TILL- 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 11 3 69 88 77 69 94 11 5 25 48 95 56 -- 75 94 65 NUMBER OF L IV E 1C O M P L E T I O N O F D A Y 58 MF MF PUPS AT POSTPARTUM 15 MF 22 MF 96 4- 77 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 94 64 M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING PRIOR TO W EIGHING ON DAY 1 POSTPARTUM. a . Dam d i d n o t h ave a c o n firm e d m atin g d a te , w h ich p re c lu d e s th e c a l c u l a t i o n o f th e d u r a t io n o f g e s t a t i o n . b . Dam 1 3 9 4 7 was s a c r i f i c e d due t o no s u r v i v i n g pups on d a y 1 o f l a c t a t i o n . TOTAL IM PLAN T A T IO N S 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-6889.6) T A B L E C36 (PAG E 1) : PUP BODY W EIG H T L I T T E R A V ER A G ES FROM B IR T H TO DAY 22 POSTPARTUM - I N D I V I D U A L D A T A - F I G E N E R A T IO N L I T T E R S ARGUS 418-020 Page 282 MATERNAL DOSAGE GROUP I 0 MG/KG/DAY RAT/ L IT T E R 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 DAY 1 MF T DAY 5 MF T DAY 8 MF T DAY 15 MF T 5.5 5.3 5.4 8.8 8 . 5 6 . 9 6.2 6.6 12.1 11.2 10.87 . 4 7 . 0 7 . 1 1 1 . 3 M O R I B U N D S A C R I F I C E D O N D A Y 68 7 . 2 6.8 7 . 0 10.6 10.0 5.8 5 .7 5 .7 8 . 3 8.2 6 . 3 6.0 6.2 9 . 1 8.8 6 . 5 5 . 8 6.2 10.2 9 . 9 6 . 7 6.2 6 . 5 9.9 9.2 6 . 4 6.0 6.1 9 . 8 9 . 4 NOT PREGNANT 6.5 6.4 6.5 10 .5 10 .4 7 . 4 7 . 0 7 . 2 11.6 11.6 5.8 5.2 5.6 8.0 7 . 4 5.8 5.5 5 .7 8.2 7 . 9 6 . 5 6.1 6 . 3 8.9 8.4 6.8 6 . 4 6.6 9 . 3 8.6 6.2 5 . 5 5 . 8 7.4 7.0 6.3 5.5 5.8 6 . 7 6.2 6 . 4 9 .7 8.4 9.0 8 .7 5 .7 5.3 5.5 9.5 8.9 7 . 2 6 . 7 6.8 12.1 1 1 . 3 7 . 0 6 . 9 6 . 9 12.8 12.8 6.6 6.1 6 . 4 9 .7 8.9 6 .4 6.3 6.3 8.1 8.2 6.8 6.2 6 . 5 9.9 9.0 6 . 4 5 . 6 6.1 9.6 9 .1 6.6 6 . 3 6 . 4 8 .7 8.4 10.06 . 7 6 . 3 6 . 5 9 .5 5.5 5.3 5.4 8.0 7 . 8 8.6 1 3 . 2 1 1 .7 11.0 1 7 .5 1 5 .8 OF STUDY 1 0 .3 8.2 9 .0 10.0 1 5 .4 1 1 .9 12.2 1 4 .5 9 .7 13.9 9.6 1 4 .7 1 3 .2 16 .8 1 5 .4 14 .0 12.2 12.0 1 4 .3 1 3 .0 14 .0 13 .2 1 7 .2 1 5 .6 14 .6 12.1 12.1 14 .4 13 .6 14 .2 1 0 .4 11.6 7 .8 8.1 8.6 9 .0 7.2 8.8 8.8 9 .2 11.5 12.8 9.3 8.1 9.5 9 .4 8 .5 9 .8 7 .9 15.3 15 .0 15 .2 1 7 .2 11.1 11.2 11.5 12.6 11.0 1 3 .6 1 3 .5 1 7 .0 1 0 .5 1 0 .5 1 0 .9 12.0 9.8 1 2 .3 12.1 1 7 .1 10 .9 1 0 .9 11.1 1 2 .4 10 .5 12.8 12.6 14 .0 13 .0 13.5 SACRIFICED ON DAY 1 8 .8 1 3 .2 12.0 12. 9 18 .7 12.8 1 1 .9 12.2 18 .7 1 3 .0 1 1 .9 12.6 13.9 13.3 13 .6 1 2 . 5 12.0 12.2 1 1 . 9 11.1 11.6 1 1 . 4 11.6 1 1 . 5 2 9 .2 3 0 .8 2 3 .2 2 8 .7 3 0 .1 2 3 .0 28.9 3 0 .5 2 3 .1 28.8 2 4 .4 23 .1 29 .7 28.4 3 1.2 2 6 .4 2 4 .6 2 3 .0 2 9 .3 2 6 .5 2 9 .8 2 7 .5 2 4 .5 2 3 .0 2 9 .5 2 7 .8 30.3 2 7 .2 26.4 26.9 3 2 .2 22.8 21.0 20.0 3 1.1 2 1 .5 1 9 .8 1 7 .4 3 1.6 22.4 20.6 1 8 .3 23.9 2 2 .7 23.4 18.4 16 .9 1 7 .8 21.0 1 9 . 6 20.1 26.9 2 4 .7 25.5 26.3 25 .0 25.6 8 O F :L A C T A T I O N 33.2 32.9 33.0 25.8 2 4 .7 25.2 24.8 2 3 .7 23.9 20.0 1 8 . 2 1 9 . 1 26.2 2 5 .1 2 5 .7 25.4 24.5 24.8 23.8 2 1 .4 22.9 22.7 2 2.7 2 2 .7 DAY 22 MF T 4 5 .6 4 3 .9 4 2 .0 4 3 .6 4 1.9 4 0 .8 4 4.4 43 .0 4 1.3 4 5 .7 3 3 .9 2 5 .6 4 0 .9 3 6 .0 4 5 .6 4 1.4 3 4 .4 2 4 .8 4 0 .2 3 4 .2 4 2 .7 43 .4 3 4 .2 2 5 .2 4 0 .5 3 5 .5 4 3 .6 4 3 .3 4 3 .8 3 4 .0 3 2 .8 3 3 .1 3 8 .2 28.6 30.5 2 6 .8 4 0 .5 4 1.2 4 3 .3 3 2 .6 3 1.0 2 9 .3 3 7.0 2 6 .6 2 8 .9 2 9 .0 3 8 .5 4 2 .6 4 3 .5 3 3 .5 3 2.2 3 0 .6 3 7.7 2 7.8 2 9 .4 2 8 .2 3 9 .5 5 4 .0 4 0 .4 3 5 .5 3 2 .0 4 1.7 4 1 .3 4 1.2 3 5 .5 5 3 .3 3 9 .1 3 4.2 28 .7 3 9 .9 3 9 .3 3 7.5 3 5 .1 5 3 .6 3 9 .7 3 4 .3 3 0 .4 4 1.0 4 0 .0 3 9 .8 3 5 .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) T A B L E C36 (PA G E 2) : PUP BODY W EIG H T L I T T E R A V ER A G ES FROM B IR T H TO D A Y 22 POSTPARTUM - I N D IV I D U A L D A TA - F I G E N E R A T IO N L I T T E R S ARGUS 418-020 Page 283 MATERNAL DOSAGE GROUP I I 1 MG/KG/DAY RAT/ LITTER NUMBER 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 DAY 1 MF T DAY 5 MF T DAY 8 MF T 6.3 5.9 6.8 6 . 5 6.2 6 .7 9 . 4 8.6 9.9 9.8 5 .7 5.6 5.6 9.0 8 .7 6 . 3 5 . 9 6.0 10.0 9 . 5 6.0 5.4 5.6 8 . 7 8.2 MORIBUND S A C R IFIC ED ON 6.2 5 . 7 5 . 9 8 .5 6 . 5 5 . 8 6.1 9 .1 6.6 6 . 4 6 . 5 9 .4 D A Y 59 7 .8 8.2 10.1 NOT PREGNANT 5.9 5.6 5.8 9.4 9 .1 6.1 5 . 9 6.0 8 . 5 8.1 6 .7 5 .9 6.3 8.0 7 . 2 6.0 5 . 7 5 . 8 7.8 7.2 6 . 7 6.6 6 . 7 9 .7 9.8 6.1 5 . 6 5 . 8 9 . 2 8.6 10.15 . 7 5 . 9 5 . 8 1 0 . 5 6 . 7 6.2 6.6 9 . 4 9 . 0 6.2 5 . 9 6.1 8.2 7 . 7 5.9 5.5 5 .7 8 . 5 8.2 NOT PREGNANT 6 . 3 6.2 6 . 3 9.3 9.2 5.2 4 .6 5.0 7.8 7.6 6.1 6.0 6.1 9 . 4 9 . 0 5 .7 5.5 5.6 9.6 9.4 5 .7 5 .1 5.4 9 . 2 8.1 6.8 6 . 3 6 . 4 10.2 9 . 8 5.5 5.2 6.1 5 . 7 5.3 5 .9 7.8 7.5 8.6 8 . 3 5 .7 5 .7 5 .7 8.5 8 .4 9.2 1 3 .1 9.9 14 .2 8.8 12.8 9 .7 14.0 8.4 12.9 OF STUDY 8.1 12.6 8.6 1 3 . 3 9 .7 15.5 9 .2 8 .3 7 .6 7.4 9 .7 9 .0 1 0 .3 9 .3 8.1 8 .3 12. 7 1 2 .9 11.2 11.8 1 3 .8 12.6 1 5 .8 13 .7 1 1 .4 12.0 9.3 13.3 7 . 7 11.1 9.2 13.5 9.6 14 .3 8 .7 13.2 9.9 14 .9 7 . 6 11.1 8 . 4 12.6 8.5 1 1 .9 1 2 .3 13 .7 12.2 13 .7 12.2 1 1 .7 11.6 1 4 .3 1 2 .5 12.1 10.1 1 0 .5 14 .1 12.2 1 5 .0 1 3 .3 11.0 11.1 1 3 .6 10.8 12.6 1 4 .4 11.8 1 4 .4 11.2 11.8 12.2 1 2 .9 1 4 .0 1 2 .4 1 3 .8 1 2 .5 12.1 1 2 .3 1 4 .9 12.6 1 2 .4 10.6 11.0 1 3 .9 1 2 .4 1 5 .4 1 3 .6 11.3 11.5 1 3 .4 1 0 .9 1 3 .2 1 4 .4 12.6 1 4 .6 11.2 12.2 12.0 DAY 15 MF T DA Y 22 MF T 2 5 .1 2 5 .4 2 6 .2 2 6 .6 2 5 .4 2 4 .2 2 3 .9 2 5 .1 2 5 .6 2 3 .8 2 4 .9 2 5 .0 2 5 .6 2 5 .9 2 4 .4 3 4 .6 4 1 .8 4 3 .0 3 7 .3 3 5 .9 3 2 .6 3 9 .1 4 0 .0 3 5 .9 3 2 .8 3 4 .1 4 1.0 4 1 .3 36.3 3 4 .0 2 6 .4 2 5 .3 2 4 .7 2 5 .4 2 3 .3 2 2 .9 2 5 .8 2 4 .2 2 3 .8 3 9 .6 3 6 .7 3 6 .1 3 7.6 3 4 .0 3 3 .1 3 8 .5 3 5 .1 3 4 .6 2 3 .7 2 7.0 2 3 .7 2 1.7 2 7.8 2 3 .4 3 1.9 2 6 .0 21.2 2 5 .2 2 2 .5 2 4 .6 2 2 .7 19 .8 2 8 .8 22.2 3 1.3 2 5 .4 2 0 .5 2 4 .1 2 3 .1 2 5 .6 2 3 .2 2 0 .5 2 8 .2 22.8 3 1.6 2 5 .8 21.0 2 4 .6 4 1 .6 4 0 .5 3 4 .5 3 5 .4 4 3 .1 3 5 .3 5 4 .6 4 2 .6 2 6 .2 3 8 .0 3 9 .2 3 6 .6 3 2 .4 2 9 .1 4 3 .3 3 2.7 5 2 .3 3 9 .7 2 6 .0 3 4 .9 4 0 .4 3 8 .2 3 3 .4 3 1.4 4 3 .2 3 4 .1 5 3 .4 4 1.8 2 6 .2 3 6 .4 SACRIFICED ON DAY 2 1 . 9 20.2 21.2 20.0 1 8 . 2 1 9 . 3 28.4 28.0 28.2 21.0 1 8 . 8 20.0 2 7.4 2 3 .0 2 2 .7 2 3 .4 26.6 26.9 22.6 22.8 22.1 2 2 . 4 22.8 2 3 . 2 11 OF 3 2.7 2 9 .5 3 9 .2 3 3 .5 4 3 .0 3 3 .2 4 0 .4 3 6 .7 LACTATION 29.9 3 1.5 2 7.2 28.7 38.8 39.0 2 8 .7 3 1.4 40.6 4 1.3 33.6 33.4 39.2 3 9 .7 3 7.5 3 7.0 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) T A B L E C36 (P A G E 3) : P U P B O D Y W EIG H T L I T T E R A V E R A G E S FROM B I R T H T O D A Y 22 POSTPARTUM - I N D I V I D U A L D A T A - F I G E N E R A T I O N L I T T E R S ARGUS 418-020 Page 284 MATERNAL DOSAGE GROUP I I I 3 MG/KG/DAY RAT/ L IT T E R 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 MF T DAY 5 MF T 6 0. 5. 5 5. 9 9 . 8 9 . ,0 9 . ,6 PREGNANT; DID NOT DELIV ER A LIT T ER 6 0. 5. 5 5.,7 .1 29 . ,3 9. 9. 6. 4 6. 4 6., 4 11., 4 11.. 3 11., 4 5 . ,4 5. 4 5 . ,4 8 8 8., 4 .. 5 .. 4 6. 6 6. 2 6..3 8 8 8.. 9 .. 5 .. 7 6 ,0. 5. 9 5..9 6..5 6..8 6.. 7 5.,7 .65 . 4 5. 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 .67 . . 9 7 ,.5 7. ,6 .65 . , 7 5. 4 5. 7 ..7 7 ..5 7 . 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 89 . 5 . 9 9 . 3 6.8 6. 6 6. 7 10,. 3 10. 3 10. 3 6. 5 6..1 6. 3 .8 89 , . 9 9 . 4 .87 . 4 7 ., 4 7 . 4 1 3 . 9 1 3 . 7 1 3 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 .65 5. 3 5 .5 8. 7 7 .8 8. 3 6. 5 5 . , 9 5 . 9 9 . 5 9 .1 9 .1 DAY 8 MF T 21 4 . 12. 9 1 4 .,0 1 3 .,8 1 8 .,3 11.. 5 10..8 9 . .6 1 3 .. 5 10..8 1 3 .,2 12..2 11..2 12.. 5 1 7 , .2 12. 5 15.,7 13 .5 1 4 ,.8 15,.7 15 ,.5 1 5 ,.4 14 .4 1 4 .6 12 .0 1 9 .0 13 .9 1 6 .0 11.2 12. 5 1 3 .6 1 3 .,6 1 8 .,5 11.,6 10.. 4 9 . ,6 12., 7 10..6 1 3 .,1 11. 8 10.. 7 1 3 ..2 1 4 .. 7 12.. 5 1 5 . .0 12..0 1 5 ..4 1 6 . .0 15 ..3 1 4 ..5 1 3 ,.1 1 4 ,.8 11,. 1 1 8 ,.5 13 .4 1 5 , .1 10 .8 11,.8 12,.6 1 3 ., 7 1 8 ..4 11..6 10..6 9 . .6 1 3 ..1 10.. 7 1 3 .,1 11.. 9 11.,0 12..8 1 5 ..5 12,. 5 1 5 ..4 12..8 15 ..3 1 5 . .8 15 ,.4 1 5 , .0 1 4 .0 1 4 ,. 7 11,.6 18 .9 13 .7 15 .7 10. 9 12,.2 12 . 7 DAY 15 MF T .8 ,02 6 . 2 6 . 2 6 . . 7 22..0 3 8 . .8 1 9 . .0 22..2 20..8 2 6 , .0 20. 7 2 7 .,9 19 .. 7 21. 4 23 .3 3 2 . .1 2 5 ..4 3 0 . .1 3 0 , .0 3 1 , .2 3 1 , .8 2 9 .6 29 .3 2 7 .2 2 7 .2 2 8 .2 33 .8 2 5 .8 3 2 .2 2 5 .1 26 .3 26 .9 22 ..0 3 8 ..2 1 8 . .6 21.. 4 21..2 2 5 ..9 1 8 . .0 2 8 . ,0 1 9 . ,0 20.,2 24 ..5 2 8 . .2 2 4 . .0 2 9 . .0 2 7 . .0 3 2 ..0 3 1 . .2 3 0 . .2 2 9 ,.3 2 6 . .2 2 7,.5 26,.4 3 2 , .0 24 .4 3 0 , .2 22 . 3 24.. 7 2 4 , .8 22..0 3 8 . .6 1 8 . .8 21..8 20.. 9 2 5 ..9 19 ..3 2 7 .,9 1 9 . ,2 20..8 2 3 .. 9 29..4 24.,7 2 9 . .6 2 8 , .6 3 1..9 3 1..5 29..7 29,.3 26,.9 2 7 ,.3 2 7 ,.4 3 3 ,.2 2 5 , .2 31,.7 22 . 7 25..7 2 4 . .9 DA Y 22 MF T .6 .63 4 . 33 . 3 4 .. 4 3 2 ,.1 5 9 , .6 2 9 ,.9 3 5 ,.1 29 .4 3 4 ,. 4 3 1 ,.9 3 9 , .6 2 8 ,.0 3 1 .0 3 5 .1 50,.7 3 7 .3 4 8 .2 4 6 .2 4 8 .8 48 .4 48 .3 39 .7 4 1 .6 46 .3 4 3 .2 53 .5 42 .9 5 0 .8 36 .4 3 5 .6 4 3 .1 3 1 ..4 6 0 . .6 2 9 . .0 3 1..7 2 9 . .1 33 .9 27.. 7 40.. 1 28 .3 28..7 35,.4 44 .5 3 7..4 4 5 ..9 4 1 . .6 4 8 ,. 4 48..7 4 7 ,. 9 3 8 , .1 3 9 . .2 46 .4 39 .5 53 .5 4 0 .2 47 .3 30 .7 3 2 .2 3 8 , .1 3 1 . .6 6 0 . .0 2 9 ..4 3 3 .,2 2 9 ..3 3 4 . .1 2 9 , .6 4 0 . ,0 2 8 .,2 2 9 ..9 3 5 . ,2 4 6 ..4 3 7 ..3 4 7 . .1 4 4 ..1 4 8 . .5 4 8 , .6 4 8 . .2 3 9 . .0 4 0 . .8 4 6 ,.3 4 1 ,.5 5 3 ,. 5 4 1 , .8 49,.9 3 1 ,.5 3 4 ,.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) T A B L E C3 6 (PAG E 4) : PUP BO DY W E IG H T L I T T E R A V E R A G E S FROM B IR T H T O D A Y 22 POSTPARTUM - I N D I V I D U A L D A T A - F I G E N E R A T I O N L I T T E R S ARGUS 418-020 Page 285 MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY RAT/ L IT T E R NUMBER 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 DAY 1 MF T DAY 5 MF T 6. 9 6. 8 6.. 9 11..1 10..8 10.. 9 8 .65 . 5 . 5 , . 7 9. .0 8..6 8..8 6.. 7 6.,1 6. 4 10.. 4 9 . .8 10..1 6 6.. 7 5 . , 9 .3 8..6 7 , .6 8..1 5..5 5.,4 5 .5 8.07 . . 9 . 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 8.. 9 . 4 8..6 6 6.2 10.0.. 4 5 . . 9 , . 9..4 9..7 1N O T P R E G N A N T ; M A T I N G N O T C O N F I R M E D 6.. 3 5 , . 9 6,.1 7 ..8 7 . .0 7 . . 3 6 6 6.. 7 .. 7 ,. 7 .29 . . 9 9, 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 .65 . . 7 5 , . 4 5 , 8..6 8,.2 8,. 4 7 . .2 7 , .0 7 , .1 11,.2 11,.2 11..2 .65 . 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 .69 , . 7 9 . 4 9 5,.9 5,.4 5 .7 8. 7 8,.0 8,. 3 6,.1 5 , . 7 5 . 9 10,. 4 9 .8 10,.1 .85 . . 9 5 , . 7 5 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 .69 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 1 5 ..4 1 3 ..0 1 4 ..9 12..6 12..0 1 4 . .8 14 .3 12,.0 13 ..5 1 5 ..3 12.. 4 13 .,9 11.,1 12.. 4 1 4 . .2 1 4 , .1 10.. 9 12,. 7 15 ..3 12.. 7 1 4 ..4 11..8 12..1 1 4 ..5 1 4 . .2 11.. 4 1 3 . .1 10,. 5 13 . 7 1 4 . .6 11..6 1 4 ..3 1 5 , .1 12,. 4 16,.7 12,.8 14 ,.9 12,. 5 12,.6 1 5 , .1 12,.0 12,.0 1 3 ,.2 1 3 ,. 7 15,.7 11,. 9 10,. 3 9,.3 12,. 7 1 4 ,.4 10,.0 1 3 . .2 1 4 , .8 12..1 1 6 . .4 12,. 5 1 4 ,.9 12,.0 11,. 5 1 4 ,. 3 11,. 7 11,.8 12,.1 1 3 , .1 1 4 , .6 10,.6 10,.0 9..9 1 3 . .2 1 4 ,.5 11..0 1 3 . .6 1 5 . .0 12,. 3 16 ,.5 12..6 1 4 ,.9 12,. 4 12,.0 1 4 ,.8 11..8 11,. 9 12,.6 13 ,.3 1 5 . .0 11,.2 10,.1 DAY 15 MF T 3 0 ..5 25 .4 2 6 . .9 25..7 24 .9 2 6 . .5 2 9 . .8 22. 3 21.. 7 2 9 . .2 2 4 . .5 2 5 . .6 2 3 ..1 2 6 . .0 24., 7 2 8 ..3 20., 7 20..1 29..7 2 4 ..9 2 6 . .2 2 4 .,3 2 5 . .2 2 5 .,5 2 9 . .1 21.. 4 21..0 22..2 2 6 , .6 2 6 . .0 1 9 . .6 2 5 ,.3 30..5 1 8 , .6 3 6 ,.3 2 4 . .2 22,.1 2 6 , .6 2 5 , .8 2 9 , .1 2 3 ,. 5 22..1 2 7 , .6 2 8 , .1 2 9 , .0 2 4 , .0 16 ..9 1 9 . ,8 2 3 .. 9 2 5 . .6 1 7 ..3 2 3 .. 9 3 0 ..3 1 8 . .2 3 6 , .0 23 .5 23 .4 2 5 , .6 24 .4 2 8 . .6 22. 9 21. 3 24 .3 2 7 ..3 2 7 . .1 21..8 1 5 . .2 20.. 9 2 5 . .2 25..7 1 8 . .8 2 4 ..3 3 0 ..4 18 ..5 3 6 . .1 2 3 ,. 7 22.. 9 2 6 . .2 2 5 . .1 2 8 ..9 2 3 ..2 21.. 7 25..7 2 7 . .6 2 7 . .8 22.. 7 1 6 . .1 DAY 22 MF T 4 8 . .6 3 9 , .2 4 3 ..0 38..5 38..4 4 2 . .2 4 6 . .8 29..9 3 4 . .8 4 5 . .8 3 7 . .0 4 1 . .0 3 4 ,. 9 3 9 . .2 3 8 . .1 4 3 ..0 2 7 ..5 32 .5 46,.9 3 8 ,.0 4 1 ,.9 3 6 .6 3 8 ,.6 3 9 , .8 4 4 ,. 9 2 8 , .6 3 3 ,.8 3 1..7 4 2 . .4 4 0 . .3 3 5 , .1 3 8 . .0 4 8 . .3 2 7 ,.9 55,.4 39,.4 3 6 . .8 4 2,.4 39,.5 45 .4 3 2 ..5 3 6 . .2 44 .4 4 3 ..9 4 4 ..6 3 9 . .0 3 1 . .8 28..7 3 9 . .2 4 1 , .0 3 1 ..5 3 7 ,.4 4 8 . .1 2 7 . .0 5 5 . .0 3 8 ..3 3 7 ..5 4 1 . .1 3 7 . .8 4 3 ..2 3 1 ..9 3 4 , .2 3 9 . .0 4 3 .. 5 4 0 . .8 35..7 3 0 . .0 3 0 ,.1 40,.7 4 0 , .8 3 3 ,.8 3 7 . .6 4 8 , .2 2 7 , .6 5 5 , .2 3 8 ,. 7 3 7 , .2 4 2 ,.0 3 8 ,. 7 4 4 ,. 4 3 2 ,.2 3 5 ,.3 4 1 ,.4 4 3 ., 7 4 2 ..2 3 7 . ,1 3 0 ..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) T A B L E C36 (P A G E 5) : PU P B O D Y W E IG H T L I T T E R A V E R A G E S FROM B I R T H T O D A Y 22 PO S TPAR TU M - I N D I V I D U A L D A T A - F I G E N E R A T I O N L I T T E R S ARGUS 418-020 Page 286 MATERNAL DOSAGE GROUP V 30 M G /K G /D A Y RAT/ LITTER NUMBER 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 13 946 13 947 13 948 13949 13950 DAY 1 MF T DAY 5 MF T DAY 8 MF T DAY 15 MF T 6 . 3 5 . 6 6.1 4.3 4 .0 6.0 5 . 6 4 .2 5.8 5.8 5.8 6.0 5 . 5 5.8 5 .7 5.5 5.2 5.4 5 .7 5.4 5.6 6 .9 6 .4 6.6 NOT PREGNANT 5 .7 5.2 5.4 5.2 5.0 5 .1 6.1 5 . 6 5 . 9 6.6 6.0 6.2 5.3 5.3 5.3 5.6 5.4 5.5 5.8 5.4 5 .7 7 . 3 6.8 7 . 0 5.6 5.4 5.4 5.6 5.5 5.5 5 .7 5.4 6.2 5 . 9 5 .5 6.1 5.8 5.4 5.6 7 . 2 6 . 7 6.8 5.8 5.5 5.6 5.5 5 .7 5.6 6 .5 6 .1 6.3 SACRIFICED DUE TO 5.9 5.5 5 .7 5.6 5.4 6.0 5 . 5 5.5 5.8 8 .7 7 .6 8.3 6 .7 -- 6 .7 8 . 4 8.2 8 . 3 8 . 5 8.0 8 . 3 7.9 7.4 7 .7 7.3 7.2 7.2 8 . 9 8.1 8 . 4 9 .1 8.5 8 .7 6.6 6.1 6 . 4 6.2 6.0 6.1 8 . 7 8.0 8 . 4 9 .4 9.0 9 .1 6 . 5 6 . 9 6.8 8 . 9 8 . 4 8.6 9.6 9.2 9.6 11.2 10.6 1 0 . 9 7 .1 7 .1 8.6 8 . 3 7 .1 8 .4 9 .1 8.4 8 .7 9 .7 9 .1 9.5 9.3 8.9 9 .2 12.6 1 1 . 4 1 1 . 7 7 .0 6.5 6 .7 9.4 9.6 9.5 10 .2 9.4 9.8 NO SURVIVING PUPS 8.8 8.1 8.6 9 . 2 8.8 9 . 1 9 .2 9.0 9 .1 11.8 9 .0 11.1 1 2 .3 1 0 .4 11.0 11.5 13 .1 9 .8 7 .1 1 2 .5 12.0 7 .9 1 2 .4 1 3 .6 1 5 .3 10.1 1 3 .0 1 2 .4 1 3 .6 1 3 .4 18 .7 10.2 1 3 .9 15 .0 ON DAY 12.8 1 3 .3 1 3 .4 10.2 -- 10.8 11.1 1 0 .5 10.8 11.3 11.6 11.1 9.0 1 0 .9 11.8 1 0 .5 1 0 .9 11.4 12.0 2 3 .8 22.2 21.0 2 2 .4 2 0 .3 2 3 .3 1 5 .3 2 6 .9 9 .0 6.8 11.5 11.6 9 .4 7 .0 12.0 1 1 .7 19 .2 1 7 .2 2 3 .0 1 7 .2 9 .7 9.4 15 .4 1 1 . 5 12.0 22.0 13.3 13.6 2 5 .1 14.4 1 4 .7 1 0 . 3 10.2 2 6 .0 1 7 .0 12.4 1 2 .7 2 5 .6 11.3 1 1 .7 2 3 .4 13.0 13.4 2 4 .7 13.0 13.2 2 4 .1 16 .4 9 .2 1 7 .1 9 .5 3 6 .5 22.2 14 .0 13.9 25 .7 14.0 14 .4 3 0 .0 1 OF LACTATION 1 1 .4 12.3 12.6 1 3 . 1 2 6 .4 2 7 .8 13.3 13 .4 2 8 .2 2 0 .4 -- 19 .4 20 .7 2 0 .4 2 3 .0 1 4 .3 2 5 .0 1 8 .8 16 .6 22.2 1 7 .2 20.0 2 0 .7 2 3 .9 2 4 .2 17 .1 2 4 .2 2 1 .3 22.8 2 3 .4 3 5 .8 2 1.5 2 5 .3 2 7 .8 2 5 .1 2 7 .2 2 7.2 2 2 .3 22.2 20.2 2 1.7 2 0 .4 2 3 .2 14 .8 2 5 .5 19 .1 16 .9 22.6 1 7 .2 19 .6 2 1 .3 2 4 .9 2 4 .9 1 7 .0 2 4 .8 22.2 2 4 .1 2 3 .9 3 6 .0 2 1.7 2 5 .5 2 8 .8 2 6 .0 2 7.6 2 7.8 DA Y 22 MF T 4 0 .0 39.0 3 2 .6 3 3 .0 33 .2 3 2 .8 2 4 .8 4 1.6 3 3 .3 -- 3 0 .2 2 9 .9 3 2 .8 3 2 .0 2 3 .2 3 8 .3 3 7.1 3 9 .0 3 1.4 3 1.7 3 3 .0 3 2 .5 2 3 .9 3 9 .2 2 4 .8 2 6 .1 33 .4 28 .5 29 .4 33 .6 4 1.2 4 1.7 2 7 .0 4 1.4 32 .2 3 9 .4 36.3 5 7 .4 3 7 .3 39.3 44 .8 2 3 .2 25 .7 3 2 .6 2 7 .6 3 2 .5 3 2 .0 3 7 .3 4 0 .4 2 7 .6 3 9 .9 2 9 .1 3 5 .1 3 5 .5 5 4 .1 3 4 .8 3 9 .4 4 2 .4 2 4 .1 2 5 .9 3 3 .0 2 7 .9 3 2 .3 3 2 .8 4 0 .4 4 0 .9 2 7.3 4 0 .6 3 0 .3 3 8 .1 3 6 .0 5 5 .0 3 5 .5 3 9 .4 4 3 .5 43 .2 42 .2 45 .2 4 0 .8 4 0 .1 4 4 .7 4 2 .3 4 1.6 4 5 .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) T A B L E C37 (PAGE 1 ) : PUP BODY W EIGHTS FROM B IR T H TO DAY 22 POSTPARTUM - IN D IV ID U A L DATA - F I G E N E R A T IO N PUPS ARGUS 418-020 Page 287 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 1 3 1 4 1 5 1 6 RAT/ LITTER # M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY 1P O S T P A R T U M D A Y 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 5.3 5 .1 6.8 6.6 6.17 . 0 7 . 1 6 . 7 7 . 0 7 . 1 6 . 7 7 . 0 5 . 8 5 . 9 6 . 7 5 . 9 6.6 6.0 8.0 6.8 6.67 . 6 7 . 6 8 . 7 5 . 4 8 . 3 7 . 8 7 . 2 6 . 4 7 . 4 7 . 7 5 . 6 M O R IB U N D S A C R IF IC E D O N D A Y 68 O F S TU D Y 7 . 1 6.5 6 .9 7 .4 7 .4 7 .8 6 .7 6.0 6.25 . 9 5 . 6 5 . 9 5 . 1 5 . 5 6 . 7 6.8 6.1 6.2 6.1 6.0 6 . 4 6.6 6.67 . 1 6.5 5.9 6.4 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 M S 5 . 9 6.1 7 . 3 6 . 7 7 . 3 6 . 7 6 . 7 5 . 1 6.0 5 . 8 5 . 4 5 . 5 6.1 5 . 5 6.1 5 . 5 6.0 6 . 5 6.2 6.0 6.0 6.6 6 . 4 5 . 4 5 . 4 6.85 . 7 5 . 4 5.8 5.8 5.2 6.6 6 . 9 6 . 4 6.2 6.2 5 . 8 6.1 6 . 5 5 . 6 5 . 6 6 . 4 5 . 7 5 . 9 F D 1 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 6.25 . 7 5 . 9 5 . 9 5 . 8 5.4 5.4 6.0 6.15 . 7 5 . 9 5.4 5.6 5 .9 6.26 . 5 6 . 4 6 . 9 6 .7 6.3 6.3 6.8 6.67 . 2 7 . 0 6 . 9 7 . 1 6.9 6.15 . 9 6 . 3 5 . 6 6 . 4 6 . 4 6 . 4 6.0 6.2 6 . 3 6.6 M D 1 5 . 6 5 . 5 6.2 6.17 . 2 6 . 4 7 . 1 6 . 5 5 .7 6.0 6.05 . 9 5 . 7 5 . 4 5.6 5.4 6.67 . 1 7 . 5 7 . 1 7 .2 6.9 6.5 6 . 5 6 . 7 6.2 6.2 6 . 3 7 .2 6 .9 7 .6 6.9 6.4 5 . 8 6.2 5 . 3 6.1 5 . 8 6.25 . 7 5 . 3 5 . 5 5 . 3 6.0 5 . 8 6.2 6 . 4 5 . 8 6.0 6 . 4 6 . 3 7 . 1 5 . 7 6.2 5 . 5 5 . 8 5 . 5 5 . 1 5.3 5.4 5 .7 5 .7 5.9 6 . 3 6.2 5 . 7 6.6 6 . 4 5.3 5.2 5.6 5.5 4 .9 6.66 . 7 6 . 4 6 . 7 6 .5 6.6 6 . 7 UU 4 .8 5.4 5.5 5.5 5.6 5.9 5.4 6 . 3 6.0 6.2 U U 6 . 5 6.0 6 . 5 5 .1 5.5 5.8 5 .4 4 .9 6.1 6 . 4 5.8 5.0 5.4 5.3 7 .5 6.9 6 .7 7 .0 7 .0 6 .7 6.4 7 .0 6.6 6.67 . 0 6 . 3 7 . 0 6 . 9 6 . 3 6 . 4 6.2 6 . 5 6 . 3 6 . 7 6.2 6.0 6.6 5 . 7 6.2 6.27 . 3 6 . 4 6 . 7 6 . 7 7 . 4 7 . 2 6.1 6.26 . 9 6 . 5 6 . 4 6 . 3 6 . 5 5 . 8 6.8 6.67 . 1 6 . 3 6 . 5 6 . 5 6 . 3 6 . 5 6 .7 6 .7 6.3 6 .7 6.5 7 .3 6.5 6 .7 7.2 6 . 3 6.2 5 . 9 6.8 5 . 6 5 . 4 6.1 6 . 5 5 . 7 6.6 6.1 7 . 0 6.1 6.1 6 . 5 6 . 3 6 . 4 6.8 6.2 6.0 5 . 8 6 . 3 5 . 9 6.0 6.17 . 1 6 . 5 6.3 3 .4 6.5 5 .5 6 . 7 5 . 6 6.6 6.1 5 . 9 6 . 5 6.0 5 . 9 6.6 6 . 3 6 . 5 5 . 7 5 . 4 5 . 4 5 .3 5 . 4 5 . 8 5 .3 MS 5.4 5 .2 5.5 5 .1 4 .7 5 .7 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (PRES U M ED C A N N IB A L IZ E D ) , X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "SEC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R RED . 17 6.0 5 .8 4 .0 5 .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) T A B L E C 3 7 (P A G E 2) : P U P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 288 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 1 3 1 4 1 5 1 6 R AT/ L IT T E R # 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 M ATERNAL DOSAGE GROUP I I 6.65 . 9 6 . 3 6 .5 7 . 0 6.6 7 . 0 6.6 6.16 . 3 5 . 8 5 . 8 6.66 . 4 6 . 7 5 . 6 6.05 . 7 6 . 5 5.8 M O R IB U N D S A C R IF IC E D ON 6.2 5 . 6 6 . 3 6 . 3 6.2 6 . 4 6 . 5 6.6 6.66 . 9 6 . 3 6 .3 NOT PREGNANT 5.9 5.8 5.5 6.5 6.15 . 8 6 . 7 5.8 6 . 5 6.8 6 . 4 6.6 6 . 4 5 . 8 6.0 6.2 6.8 6 . 9 6 . 9 6 . 9 6.05 . 9 6 . 3 6 .4 6.06 . 4 5 . 3 M S 6.8 6.6 6 . 9 6 . 3 6 . 7 6.1 6.1 5 . 4 6.05 . 9 5 . 9 5 . 9 NOT PREGNANT 6.5 5.5 7 .0 6.2 4 .9 5.2 5.2 5.3 6 . 3 6.8 5 . 9 6.2 5.8 4 .8 5.8 5 .7 6.05 . 8 5 . 8 5 .7 6 . 7 6.8 6.6 7 . 2 5 .7 5.0 5.5 6.0 6 . 3 5 . 8 5 . 4 6.2 5 . 5 5.5 6.3 5 .7 5 .9 7 .5 5 .2 6.2 6.0 D A Y 59 6 .4 7 .1 7 .0 5 .9 6.2 7.0 6.0 6 .3 5.8 MS 6.6 6 .5 6.1 6 .5 5 .1 5 .9 6.2 5.5 5 .9 5 .6 6.0 5 .7 6 .9 6.3 7 . 1 6.6 5.2 5.5 6.4 5.2 6.1 4 . 2 O F STUDY 5 .1 5.6 6.3 6 .4 6.5 6 .4 5.8 6.0 5 .7 5.8 6.8 6.2 MS 6 .7 6 .4 5.8 6.2 4 .8 6 .4 6.0 5 .4 6 .7 5 .6 6 .3 6.0 5 .9 6 .7 5 .2 5.3 6.6 6 .3 MS 7 .0 5.8 5.0 6 .7 5 .4 6.3 5 .6 5 .2 5.8 5 .1 5.5 5 .8 1 M G/KG/DAY 6 . 4 6.1 6 . 7 6.8 6.2 6 . 7 5 . 6 6.1 5 . 8 5 . 5 6.8 5 . 6 5.8 5.5 5 .7 5 . 8 6.2 6.2 5 . 7 6.1 5 . 6 5 . 8 6.6 6 . 5 5.6 5 .7 6.1 5 .7 6.5 6.1 5 .2 6 .4 6.8 5 .4 5 .7 5 .7 5.8 5.5 6 .7 5.8 5 .7 6 .3 5.6 5.5 4 .9 5.5 6 .5 5 .7 6 .5 5 .9 6.1 6.6 6.3 6.0 6.1 6.0 6.6 5.5 5 .1 6.1 6 . 4 5 .1 5 .9 5.9 5.9 5 .1 6.3 5.4 4 .7 6.0 6 . 5 6 . 4 5 . 2 6.2 5 . 3 5.8 5.3 5 .7 5.8 5.4 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 1P O S T P A R T U M D A Y 6.1 5 . 6 6 . 4 6.1 6.5 6.5 5.8 5.4 5.6 5 .4 4 .4 5.2 5.4 5.6 6.3 5.9 6.5 5 .7 5.8 6.1 6 . 3 5 . 5 5 . 9 6.1 FS FS FS 6.1 6 . 4 6 . 4 5 . 9 6.0 5 . 6 FS 5.5 5 .9 6.1 3 .7 6.6 5.5 5.0 6 .5 5 .1 5 .7 5 .9 4 .5 6.3 5 .4 4 .4 6 .7 5.0 5.5 5.0 5 .9 6.1 5 .4 FS 5.0 5 .9 4 .9 5 .6 FD 1 5.5 5.6 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EA N L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (P R ES U M ED C A N N IB A L IZ E D ) , X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R R ED . 17 5 .4 5 .6 5 .9 5 .7 4 .9 6.1 5.0 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) T A B L E C37 (PA GE 3) : PU P B O D Y WEIGHTS FROM B I R T H T O D A Y 22 PO ST PAR TUM - I N D I V I D U A L D A T A - F I G E N E R A T I O N PUPS ARGUS 418-020 Page 289 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 RAT/ LITTER # MATERNAL DOSAGE GROUP I I I 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 PREGNANT; 5 .7 6.5 7.1 6.8 5.3 5.6 6.2 6.5 5.5 6.4 7.0 6.4 5.1 6.0 7.4 6.5 6.5 7.3 7.7 7.0 6.6 5.3 5.3 6.7 7.2 6.9 6.3 6.4 7.0 5.7 6.5 6.1 5.7 5.6 6.2 7.5 5.9 5.7 5.9 7.8 6.6 6.6 7.1 7.3 7.4 7.4 6.9 5.6 6.3 6.6 8.0 5.9 6.4 6.1 5.7 6.1 5.8 DID NOT 6.0 5.9 4.3 6.5 6.1 6.1 7.0 7.2 6.3 5.8 7 .1 7.4 6.3 6.1 7.2 7.5 6.7 7.4 7.1 6.1 7.5 6.5 7.4 6.7 6.5 6.0 5.7 5.6 6.2 6.2 DELIVER A 5 .7 6.3 5.8 6.4 5.6 5.7 6.3 6 .7 6.2 5.8 5.7 5.5 6.2 6.2 6.6 6.2 6.6 5.6 6.0 6.9 5.0 6.8 7.3 7.3 6.7 6.3 6.4 5.9 6.9 5.4 6.2 6.3 4.7 7.2 6.1 6.9 6.5 7.7 7.5 6.6 6.6 5.9 6.1 7.0 6.3 5.9 5.7 5.4 6.0 6.1 6.8 6.1 5.9 5.4 6.0 LITTER 5.8 6.4 5.1 6.8 5.1 5.5 6.1 6.1 5.7 5.6 6.6 6.6 5.7 6.6 7.0 6.6 7.5 7.2 6.7 6.0 6.6 6.4 6.5 6.1 6.0 5.7 5.9 6.0 6.2 6.1 FS 5.9 7.4 6.3 5.8 7.1 6.5 6.0 6.0 6.5 6.4 6.1 6.5 7.1 7.3 6.8 6.7 6.0 5.5 7.3 6.6 5.9 MD 1 6.5 5.6 5.7 6.4 7.0 6.2 5.7 6.5 6.4 6.5 6.2 6.0 7.4 6.1 6.9 5.9 6.1 6.3 5.0 6.4 5.9 6.1 5.7 6.1 5.8 6.3 6.1 5.0 5.2 5.1 3.5 4.9 6.1 6.5 5.5 6.7 6.3 5.7 6.1 6.5 6.3 6.7 6.1 7.4 6.2 5.5 5.4 5.5 5.9 6.2 6.6 5.7 6.1 5.3 6.0 5.9 5.3 5.4 6.2 MS 5.7 6.1 6.0 6.4 5.5 6.4 5.9 6.1 6.5 7.2 6.3 6.1 5.7 7.2 6.4 6.0 6.0 6.6 5.7 6.7 5.5 5.7 6.1 5.6 5.3 5.7 6.3 5.6 6.0 6.9 5.7 5.6 6.7 7.0 6.8 6.4 4.8 7.2 6.3 6.2 6.1 6.4 5.3 6.0 5.6 5.8 6.2 6.0 5.1 6.0 6.0 6.0 6.3 5.8 5.6 6.1 6.7 6.0 5.0 6.1 6.4 6.1 5.3 5.7 5.8 5.4 6.2 5.8 5.0 6.1 6.0 5.0 5.5 7.0 5.5 6.5 6.2 6.3 6.3 6.6 6.6 5.7 6.3 5.7 5.7 5.6 6.4 5.8 5.7 6.0 5.5 6.1 5.7 5.6 6.1 4 .7 6.3 4.7 5.0 5.7 5.6 6.7 6.7 6.2 6.3 FS FD 1 FS 5.3 5.6 6.7 FD 1 5.7 5.2 6.0 FS 4.9 5.5 5.5 5.1 6.1 6.3 5.5 6.1 5.2 6.2 6.2 6.4 4.4 5.2 A L L W E I G H T S W E R E R E C O R D E D I N GRAMS (G) . MEAN L IT T E R WEIGHTS INCLUDE ONLY WEIGHTS OF LIV E PUPS. FIRST LETTER -- M-MALE, F-FEM ALE, U-SEX UNDETERMINABLE SECOND LE T T E R -- A - A L I V E , S-STILLBORN, U-UNCERTAIN, D -D IED , M-MISSING (PRESUMED CANNIBALIZED), X - S A C R I F I C E D DUE TO S A C R I F I C E O F DAM NUMBER FOLLOWING "SECOND LETTER " INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 17 4.8 6.2 5.7 6.2 4.5 18 5.9 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) T A B L E C3 7 ( PA GE 4) : PUP BO D Y W E IG H T S FROM B I R T H T O D A Y 22 POSTPARTUM - I N D I V I D U A L D A T A - F I G E N E R A T I O N PUPS ARGUS 418-020 Page 290 PUP # 1 2 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 .1 7 .0 6 .5 5. 7 5. 9 7. 4 6 .3 6 .4 NOT 6 .4 6 .5 6 .3 7. 4 6 .7 5. 7 5.9 7. 5 5 .6 5. 3 6 .5 5. 9 6 .2 6 .0 6 .3 6 .5 6 .3 6 .6 6 .2 7. 1 6 .9 5. 8 6 .5 7 .2 6 .. 9 5 .. 9 6 .. 8 5 , .8 7. 2 5. 8 6 .2 6 .9 MS 5. 8 6 .7 6 .3 7. 2 5. 6 6 .5 6 .4 6 .2 7. 0 5..4 7 . .1 5. 1 6 .9 5. 6 7 .3 4 .2 6 .5 7. 3 7 , .0 6 .6 6 .8 6 .7 6 .8 6 .. 8 6 .3 6 .8 6 .0 6 .4 6 ,. 3 6 .4 6 .0 6 .6 PREGNANT; MATING NOT CONFIRMED 6 .0 6 .. 4 6 .4 6 .5 6 .7 6 .6 7 . .1 6 .7 6 .6 7. 4 6 .5 6 .7 7. 3 6 .8 7. 0 7. 1 5..9 6 .8 7. 2 7. 1 6 .0 6 .7 4 , .6 5. .8 7. 3 6 .7 6 .0 6 .0 5. 1 6 .7 5. 8 5,.9 5.8 5. 5 6 .1 6.9 5,.9 8 .1 5. 9 6 .2 5, .8 6 ,. 3 5 .1 6 .7 5 .4 6 .7 5. 2 5. 5 6 .5 6 .5 6 .7 6 .6 6 .5 6 .7 5 ,. 7 5. 1 6 .0 6 .5 6 .3 6 .. 0 6 .1 5. 9 6 .0 5. 6 5,.3 6 .1 5. 9 5. 9 6 .5 6 .1 5. 5 6 .6 5. 8 6 .1 7. 0 6 .8 6 .6 6 .4 6 .0 6 .1 6 .1 5. 6 6 .9 6 .3 6 .0 6 .4 6 .5 6 .1 6 .3 6 .5 5. 6 6 .6 6 .0 6 .5 6 ,. 6 6 .6 4. 9 6 .4 6 .8 5. 6 7. 3 7 .7 5. 5 6.9 7. 2 5. 6 6 .3 5. 7 6 .1 6 .7 6.5 5.6 MS 5. 1 5. 8 5. 7 6 .3 5. 7 6 .2 6 .7 5. 8 6 .1 6 .1 5. 5 6 .3 6 .2 6 .5 5 .7 5 .5 5 .9 5 .8 6 .7 6 .5 6 .5 6 .0 5.7 7 .4 7 .4 7 .1 5 .0 MS 5 .5 5 .5 6 .0 6 .7 5 .5 6 .4 5 .6 6 .8 5 .8 6 .7 5 .9 5 .9 6 ,. 7 6 ,. 1 5 . .6 4 ,. 4 6 ,. 3 6 ,. 1 5 -. 8 5 .7 5, . 9 6 .. 2 6 .4 7 , .0 6 ,. 4 4 .. 8 6 ,. 3 5,.5 5 .4 5..5 6 .3 5, .2 5,.3 6 ,. 3 6 .0 5 .7 6 .4 5 .8 5.. 7 6 ,.8 5,.5 5, .6 6 .. 0 5 , .2 6 ,. 0 6 ,. 3 6 ,. 3 5, .6 5. .6 6 ..2 6 .3 6 ,. 1 5., 7 5. .6 5, .6 5,.9 6 .. 0 6 .4 5..4 5 ,. 9 6 ,. 0 5,.4 5,.9 6 ,. 3 4 ,. 9 6 ., 4 7 , .0 5..4 6 .. 0 6 .5 5,.9 6 .3 6 .2 5 .8 5 .9 5 ,. 3 6 ,. 9 5,.3 6 ,. 5 5,.3 6 .2 5 .7 5 .9 6 .. 0 5, .8 5,.3 5 .9 6 .2 5,.9 5 .8 5 .8 6 .6 6 .. 0 5,.4 6 .2 6 .3 5,.3 5 .9 6 .9 5 .4 6 ,. 2 6 ,. 5 6 ,. 5 6 ,. 2 5 , .1 6 .0 4 .. 8 5 .5 5.. 7 6 .4 5. . 4 5, . 4 5 .5 5 .9 5 .9 6 .1 5 .4 6 .. 1 5,.3 6 ,. 6 6 .2 5,.3 6 .2 6 ..2 6 ,. 4 7..3 6 .. 2 4..9 6 ,. 5 5,.3 5,.5 5., 7 5,.4 5,.3 6 ,. 0 5,.9 5,.4 5, .6 5, .8 5., 7 6 ,. 1 6 ,. 9 6 ,. 0 5. .6 5, . 5 5..9 6 .. 9 6 ,. 7 6 .3 5,.3 5..3 5. .6 5. .0 6 .. 1 5..5 5..4 6 ,. 1 6 .3 5.. 7 6 ,. 6 6 .. 1 5,. 1 6 ,. 6 5. .2 5,. 7 5.. 9 6 ., 6 6 .3 6 .4 5 .5 5..5 5..7 5..9 6 .. 1 6 ., 6 FS 6.0 6.3 5.6 5.8 5.3 5.2 6.2 5.8 6.1 A L L W E I G H T S WERE R E C O R D E D I N GRAMS (G) . MEAN L IT T E R WEIGHTS INCLUDE ONLY WEIGHTS OF L IV E PUPS. FIR ST LETTER -- M-MALE, F-FEM ALE, U-SEX UNDETERMINABLE SECOND L E T T E R -- A -A L IV E , S-STILLBOR N , U-UNCERTAIN, D -D IED , M-MISSING (PRESUMED C AN N IBALIZED), X - S A C R I F I C E D DUE TO S A C R I F I C E O F 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) T A B L E C 3 7 ( P A G E 5) : P U P B O D Y W E I G H T S FROM B I R T H T O D A Y 22 P O S T P A R T U M - I N D I V I D U A L D A T A - F I G E N E R A T I O N P U P S ARGUS 418-020 Page 291 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 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 13 941 13 942 13943 13944 13 945 13946 13947 13 948 13 949 13950 6.5 3.9 5.3 6.0 4 .1 6.0 6.0 4.4 6.3 6.0 6.8 5.4 6.1 6.9 NOT 5.4 5.2 6.4 6.1 6.3 5.8 5.3 6.1 6.3 5.7 5.7 6.8 6.6 PREGNANT 5.5 5.0 5.6 5.5 5.6 6.6 6.6 6.2 5.7 5.1 5.6 5.7 6.2 5.9 7.5 7.8 5.8 6.0 5.6 6.0 5.7 5.2 5.2 6.7 6.0 7.7 5.8 6.6 5.8 5.6 5.5 5.6 6.7 6.6 SACRIFICED 6.6 5.2 5.5 5.4 5.8 6.2 6.6 5.1 5.9 6.1 6.9 5.3 5.9 5.6 5.6 5.6 6.1 6.0 5.8 6.4 DUE TO 6.1 5.2 6.2 6.5 4 .7 6.5 5.2 4 .7 5.5 6.0 7.3 6.1 4.5 5.9 5.9 5.5 5.0 5.4 6.5 5.8 MD 1 6.3 5.4 6.4 5.0 6.1 7.1 7.5 MD 1 5.8 5.5 5.6 5.5 5.6 6.4 6.5 4.3 5.3 5.9 4.9 5.8 5.9 6.8 5.8 5.6 6.1 5 .7 5.3 4.9 6.2 6.3 6.0 6.9 6 .7 6.5 5.2 5.9 5.3 5.4 5.6 5.4 6.4 6.0 6.4 7.2 7.4 6.9 5.6 5.6 5.4 5 .1 5.8 5.3 6.0 5.9 5.6 6.3 6.2 6.3 5.0 6.2 6.2 7.0 7.0 5.9 6.0 5.5 5.5 5.5 5.5 5.4 6.4 6.2 6.0 NO SURVIVING PUPS 6.1 5.6 6.3 5.5 6.3 5.8 6.0 5.8 5.7 6.0 5.4 5.9 6.0 4.4 5.9 6.6 6.2 5.4 5.4 5.8 5 .7 5.3 6.1 7.3 6.7 5.2 5.5 5.2 5.9 6.2 5.2 7.0 6.1 5.7 7.7 6.1 5.4 5.6 5.3 5.6 5.9 6.1 ON DAY 1 OF 5 .7 5.3 5.4 5.2 MS 5 . 3 6.2 3.8 6.2 6.0 6.0 MS 5.7 6.0 5.5 5.8 6.4 5.3 4.8 5.5 7.2 5.9 4 .7 5.3 5.8 4.8 5.7 6.1 7.2 5.4 5.4 4.8 6.6 5.2 5.3 5.1 5.6 5.4 5.5 5.3 5.4 7.4 5.0 5.7 5.4 6.3 5.6 6.1 5.5 5.4 5.4 6.1 6.4 LACTATION 5.7 5.4 6.0 5.3 5.5 5.2 6.2 5.5 6.3 5.8 5.2 4.4 6.0 5.5 5.2 5.6 5.6 5.2 4.9 4.2 7.1 5.7 4.7 5.7 5.9 6.1 5.2 5.8 6.2 5.6 5.3 6.0 6.2 5.3 5.7 5.5 5.0 5.5 5.9 4.9 4.5 5.7 5.6 5.4 5.3 5.4 6.4 5.3 5.3 5.3 6.0 5.4 5.5 5.8 5.3 5.4 5.6 5.0 5.6 5.8 5.5 5.3 5.1 6.1 4.4 5.2 5.9 6.4 5.6 5.1 5.8 6.6 5.6 5.9 5.8 5.4 5.4 5.7 5.6 FS 5.6 5.9 6.1 5.3 6.0 6.7 5.2 5.1 5.6 5.4 5.3 4.9 6.2 5.3 5.5 5.2 FS 5.3 5.6 FS 5.4 5.8 5.7 5.6 6.0 5.4 5.1 4.4 5.9 6.7 5.3 FS 5.5 5.6 5.4 5.4 6.6 5.7 5.3 5.3 5.2 5.1 5.1 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . M EA N L I T T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A L E , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 7 (P A G E 6 ) : PU P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 292 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I 0 M G/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 12.0 12.4 12.5 12.2 11.3 9.6 9.4 11.8 M O R IB U N D S A C R IF IC E D O N 10.2 10.3 11.7 10.1 7 . 7 8 .7 8.2 8 .7 9.5 9.4 9.2 9.0 10.7 10.5 9.4 10.4 9.7 10.2 9.8 10.6 10.3 10.3 9.9 8.9 NOT PREGNANT 10.6 9.6 9.1 10.7 12.6 12.4 11.5 1 1 .7 7.8 8.3 7.6 8.4 8 .7 8.4 8.6 7.9 9.0 9 .1 8.5 9.4 9.3 9.2 9.3 9 .7 7.3 7.8 7.3 7.9 10.4 9.4 9 .1 9.9 9.3 8.6 9.9 8.4 10 .7 9.7 9.6 8.9 11.6 12.1 12.5 11.7 1 3 .1 13.3 12.0 12.6 10.2 9.6 9.8 9.9 8.3 7.9 9.0 7.6 9.9 8.5 10.6 10.2 9.8 8.9 9 .7 9.5 9 .1 8.0 8 .7 8.9 10.1 8.9 9.7 10.3 8.4 7 .7 7.9 8.3 7.9 8.5 9.2 12.2 12.2 11.4 11.4 14.1 10.7 D AY 68 O F STUDY 10.6 10.8 9.8 8 . 3 MM 3 9.3 9.0 8.6 9.2 10.6 9.3 MS 9.6 10.4 10.2 MD 3 MS 8.4 10.7 9.6 7.9 7.6 8.6 9.4 7.8 MD 1 8.7 8.8 11.4 13.3 9.5 8.2 10.2 10.4 8.6 9.8 7.4 10.1 10.4 8.2 8.3 8.9 8.4 7.6 8.8 9.5 8.9 11.3 12.4 9.2 9.0 10.1 9.4 9.1 10.2 8.3 10.6 10.9 8.1 7.6 8.5 9.7 6.4 9.2 8.5 9.9 11.1 12.8 8.5 8.6 9.8 9.4 8.5 9.9 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 1 2 .7 11.0 7.3 9.8 9.7 8.4 10.8 MS 8.5 11.9 7.1 10.1 8.1 9.6 10.7 9.6 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 10.7 10.7 9.9 8.4 8.6 9.6 9.3 9.2 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 8.5 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 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . M EAN L IT T E R W EIG H TS IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . 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) T A B L E C 3 7 (P A G E 7) : P U P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 293 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 R A T/ L IT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY POSTPARTUM DAY 5 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 9.6 9.0 9.6 9 .7 10.2 10.6 10.7 9.7 9.2 8.6 9.4 8.1 9.0 10.3 10.6 10.1 9.4 8.7 8.6 8.2 M O R IB U N D S A C R IF IC E D O N 8.5 9.2 8.5 8.0 9.9 9.5 8.8 8.3 10 .4 10.3 9.3 8 .7 NOT PREGNANT 8 .7 10.4 9.9 9 .1 8 .7 7.9 6.9 9 .7 7.9 7.6 8.3 8.0 7.3 7.9 6.9 7.3 10.6 9.6 9.2 8.5 8.9 10.1 8.9 8.3 10.6 9.9 10 .7 MS 9.8 10.2 9.5 8.5 8.9 8.2 8.4 7 . 7 8.9 8.1 8.4 8.5 NOT PREGNANT 8.5 9.4 9.3 9.8 7.8 8.5 7 .7 8.1 8.5 9.0 9.4 8 .7 10.0 9.5 10.2 9.7 8 .7 8.6 9.0 9 .7 9.7 10 .7 10.3 10.3 7 .4 7.9 7.5 8.6 9.0 8.2 8.8 8.8 8.9 9.1 8.0 8.2 9.8 8.6 9.5 8.0 10 .4 10.4 9.8 9.0 9.3 10.3 10.1 9.4 9.1 8.3 8.6 D A Y 59 O F S TU D Y 8.1 8.9 10.0 8.0 8.9 7.4 8.0 9.4 9.0 8.9 9.8 8.4 8.7 10.2 9.5 MS 8.6 7.8 8.7 9.7 7.9 7.2 8.5 9.9 9.6 MS 8.8 8.3 8.6 9.5 7.7 6.5 8.3 10.0 9.5 MS 10.2 8.3 7.6 10.2 7.2 9.5 10.1 9.3 10.0 8.3 8.1 8.3 10.0 7.0 9.4 7.6 9.7 9.4 8.0 8.4 8.7 8.3 8.5 10.1 9.1 8.9 9.8 8.0 8.6 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 9.0 9.1 8.3 FM 3 7.5 8.0 8.1 8.0 9.0 8.0 8.2 7.0 FM 2 FS 8.8 8.1 6.7 FS 9.0 7.6 7.0 9.3 7.5 7.9 7.2 7.2 9.6 8.8 8.0 9.9 FD 5 FD 1 8.5 7.5 8.9 9.2 FS 7.8 7.4 6.9 8.2 8.7 8.6 FD 3 8.7 8.0 7.4 8.7 6.8 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . M EA N L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 8 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 294 PUP # 1 2 3 4 56 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY POSTPARTUM D AY 5 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 10.5 10.2 PR EG N A N T; 9.4 9.0 1 0 .7 12.4 9.2 9.2 10.2 6.1 9.9 7.6 9.3 8.8 7.6 8.9 10.8 10.1 10.0 9.6 10.5 11.2 12.1 11.6 9 .1 9.6 10.3 14.3 10.0 8.1 7.4 8.3 8.7 9.2 7.5 7.6 5.7 12.4 8.9 10.4 9.3 9.3 11.5 12.3 11.5 8.6 11.5 10.3 13.5 9.0 11.0 9.0 7.8 9.5 11.0 9.5 8.9 10.1 10.6 10.4 8.3 D ID NO T D E LIV E R A 9.2 9.1 10.0 12.2 10.4 12.1 7.9 8.6 6.5 8.1 9.3 9.2 6.9 7 .1 7.3 8.9 9.8 9.3 8.5 8 .7 9.3 8.4 8.5 7.5 7.4 8 . 0 MD 3 7 .9 7.4 8.0 9.4 9 .1 10.2 11.5 11.9 11.7 8 .7 9.0 9.3 10.1 10.3 10.0 10.6 9.8 10.3 11.1 11.3 10.4 12.2 11.9 11.5 9 .7 13.0 12.2 11.4 8.9 10.4 9.8 9.9 9.2 10.6 11.2 9.9 9.8 1 3 .7 10.6 9.9 9.1 9.4 8.8 1 0 .7 11.5 11.1 9.0 9.5 8.5 9.3 8.7 8.6 8.4 9.7 9.0 9.4 LIT T E R 9.7 10.5 8.7 9.0 6.9 8.6 7.3 10.4 8.6 7.6 9.0 10.3 9.6 10.6 9.4 11.3 11.6 12.5 11.9 9.5 9.3 7.9 9.5 11.2 8.6 8.1 9.5 8.7 8.8 FS 8.6 8.8 7.1 10.1 8.3 10.0 7.9 7.7 7.3 8.5 9.0 10.3 9.3 9.2 11.3 11.7 10.5 10.0 10.2 9.1 9.7 10.9 8.3 8.7 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 8.3 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 8.1 7.3 8.4 7.5 7.7 8.3 6.5 9.3 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 1 FD 3 FS 7.6 9.1 8.3 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPAR TU M T H E E V E N T O C C U R R ED . 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) T A B L E C3 7 (P A G E 9) : PU P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 295 PU P # 1 2 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY POSTPARTUM D AY 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 1 0 ..0 9..4 1 0 .,8 1 0 ..8 9..4 1 0 ..6 1 1 .. 3 8 ..8 1 0 .. 1 NOT 7 ,. 8 1 0 .. 1 1 0 ,. 3 1 0 .. 0 1 1 .3 1 0 .. 8 9..1 11 .7 8 .7 8 ,. 5 9,.3 8 ,. 2 9. .6 7,.9 9 .6 9 .4 9 .7 9 .6 9 .3 7 .3 1 1 .. 5 1 1 ,.2 1 1 . 6 M S 1 0 .. 9 8 ..8 8 .. 6 9. 2 9. 4 9. .1 1 0 .. 4 9. , 4 9 . 9 1 1 . 1 1 1 ..2 7 . ,6 8 .9 8 .0 8 .0 8 .. 6 9..3 9. .6 7..9 10.7 6 .9 10.6 6 .6 11.1 8 .. 7 9. .2 9 . . 4 1 0 ,. 2 9. 8 9 . 2 1 0 .. 9 9. .2 9, .8 9. 9 8 .4 7 . .6 9 . . 6 1 0 ,. 6 1 0 . 1 1 0 . 1 9..4 P R EG N A N T ; M A TIN G N O T C O N FIR M ED 8 .. 1 8 ,. 0 7. 8 8 .0 7 .7 9.. 7 9 . 1 1 0 . 5 9 . 7 9,. 7 1 1 . 3 1 1 ,. 6 1 0 . 4 1 0 . 6 1 1 ,. 8 9 . . 2 1 0 ,. 5 1 0 . 0 1 0 . 7 9, .6 1 0 .. 1 6 ,. 6 9. 7 1 1 . 0 8 ,. 5 1 0 .. 2 9 .3 1 0 . 7 8 . 8 MD 3 8 .. 8 8 .5 8 .3 9. 2 9. .0 1 0 . 7 12 .4 1 0 . 0 8 ,. 7 8 .2 9. 0 9. 0 8 .9 1 0 ,. 8 1 0 .2 10.6 9 . 3 1 0 ., 7 9, . 3 9 .9 9. 7 9 . 7 1 0 .. 0 7 , .8 9 .3 8 .8 9. 5 8 .. 2 1 0 ,. 2 1 0 . 0 1 0 . 8 1 0 . 9 1 0 . 5 8 .8 8 .2 9. 0 8 .8 8 .. 8 8 .3 9 .0 9. 2 9. 2 8 .. 2 8 .3 8 .9 7. 9 9. 4 9,.3 1 0 .2 1 0 .0 9. 5 1 0 . 2 8 .. 2 1 0 ,. 3 1 1 . 3 9. 6 1 0 . 6 1 0 .3 9 .7 9 .5 9. 9 9. 2 1 0 .3 9 .2 9 .0 8 .3 8.9 8 .9 10.8 8 .7 9. 8 MM 4 7. 5 9. 5 10.1 8 .7 8 .7 7. 1 10.5 11.2 9. 0 9. 7 MS 8 .5 8 .4 8 .5 10.2 9. 1 10.5 9. 8 9. 2 8.7 8 .8 10.3 9. 4 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 1 0 .4 9. 6 7. 8 11.6 9. 0 9. 5 8 .2 9. 9 9. 4 8 .7 1 0 ..2 9..3 9..9 8 .. 6 9. .8 1 0 .3 9..3 8 ,. 8 8 ,. 8 7 , .1 9, .0 1 0 ,. 8 9, .6 8 ,. 4 9, . 9 8 ,. 1 7,.9 9 .8 9, . 5 8 ,. 3 1 0 ,. 6 8 ,. 1 8 .2 8 .3 8 ,. 8 9 .1 8 .2 1 0 .. 2 8 ,. 4 9. .6 7..4 5. ,1 1 0 .5 1 0 .. 1 8 .9 1 0 .. 8 7 . .2 9,.5 1 1 ,. 4 9, .1 1 1 .. 0 1 0 .. 8 9, .2 9,, 1 9, . 9 9, .6 8 ,. 5 1 0 .3 8 ,. 4 9, .1 8 ,. 5 9,. 7 7,.9 8 .. 8 1 1 ,. 2 8 .9 9. .1 8 .5 7 , .2 9., 7 8 .. 6 8 ,. 1 9. . 4 6 .. 8 9,.5 1 1 .7 9. .2 8 ,. 1 9. . 5 7..7 8 ,. 6 1 0 .3 9. .6 8 .. 6 8.7 8 .3 8 ,. 8 7,.4 9..3 8 .. 2 8 .. 6 8 ,. 5 1 1 ,. 1 8 .. 2 8 ,. 0 1 0 ,. 4 8 ,. 5 7,.7 6 .0 9 .5 1 0 ,. 6 9, .2 9, .1 1 0 ,. 0 8 ,. 6 8 ,. 9 1 0 ,. 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 1 0 ,. 4 9, .6 8 ,. 6 9,.3 8 ,. 6 8 ,. 8 1 0 ,. 4 6 ,. 8 8 ,. 7 8 ,. 9 9, .1 7 ,. 4 1 0 .. 1 8 .9 8 .. 8 7..9 9. .0 4.,9 7 , ,2 7,,7 6 .. 3 9. .2 1 0 .. 3 8 .. 6 7.,7 7..9 8 ..2 8 .. 9 1 1 ..2 8 .. 3 8 .. 1 8 .. 6 7 . ,6 9., 7 8 .,8 7 . ,0 8 .6 1 0 ,. 9 8 ,. 6 FS 8 .9 8.2 7 ,. 4 8 ,. 6 6.9 9, .0 8 ,. 6 8 ,. 6 9.7 10.2 7.7 9, .2 8 ,. 9 9, .1 7 ,. 4 7.9 8.6 8.7 8 .. 0 F D 3 FD 3 8 .. 8 8 .. 4 FM 3 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EAN L I T T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 10 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 296 PUP # 1 2 34 56 7 8 91 1 0 1 1 1 2 1 3 1 4 1 5 1 6 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP V 30 M G /KG /D AY 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 F M 2 F M 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 1 0 . 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 1 0 . 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 10.6 10.9 7. 0 7 .4 8 .8 8 .5 11.5 6 .5 8 .5 9. 3 1 0 .2 11.4 7. 6 8 .9 8.9 10 . 0 11.1 7 .4 8 .9 8 .9 10.1 1 1 .2 6 .7 8 .4 9. 2 9. 9 11.1 7. 0 8 .6 8 .4 10.3 9. 6 7. 6 9. 5 6 ,. 6 1 0 ,. 0 1 0 ,. 7 MD 2 7 .8 8 .2 10.7 11.5 6 .8 9. 0 8 .4 7. 5 11.6 7. 6 8 .3 8 .8 10.3 9. 0 12 . 1 6 .9 9. 4 10.6 9. 5 13 . 1 6 .6 8 .8 10.6 9. 7 11.7 7. 6 8 .9 8 .6 9. 8 13 . 8 MM 5 8 .9 9. 9 10.1 9. 2 5. 3 9. 7 9. 7 9. 8 11.9 6 .6 9. 5 9. 7 9. 4 10.3 6 .3 9 .1 9 .7 6 .8 8 .0 8 .5 10.1 5 .7 7. 5 8 .1 7. 9 9. 0 6 .2 9. 1 9. 5 9. 8 9. 3 9. 5 9. 4 9. 2 9 .6 9. 6 9. 8 1 1 .2 9. 6 1 0 . 0 9. 9 1 0 . 4 9. 4 9. 6 9 .0 9. 2 9. 5 S A C R I F I C E D D U E T O N O S U R V I V I N G P U P S O N D A Y :L O F L A C T A T I O N 9. 6 8 .3 8 ., 5 8 .7 9. 6 9. 2 8 .1 7 .6 8 .3 7. 7 9. 0 10.2 10.0 8 .2 9. 6 9., 5 8 .9 9. 6 8 .6 8 .9 9. 1 8 .7 9. 3 MS 9 .1 1 0 .0 9. 6 8 .6 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 1 0 ,. 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 8 .3 9. 1 6 .4 7 .8 7. 1 7. 7 8.9 7. 2 7. 8 7. 6 6 .8 5. 9 8 .4 6 .1 FM 2 7. 5 8 .3 10.1 10.6 6 .8 9. 2 8.9 FS 9. 6 7. 3 9. 3 11.0 7. 1 FS 8 .1 9. 1 9. 8 FS 7 . ,8 9. ,0 8 ., 7 6 ., 6 7 , .0 8.7 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S (G ) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A L E , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTU M T H E E V E N T O C C U R R ED , 1 7 18 8 .. 8 6 ,. 1 F M 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) T A B L E C 3 7 (P A G E 1 1 ) : P U P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 297 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY POSTPARTUM D AY 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 17.2 18 .1 18.2 17.8 16.3 15.3 16.0 19.9 M O R IB U N D S A C R IF IC E D O N 16.5 16.0 14.9 14 .7 12.6 11.3 10.6 1 1 . 7 13.0 12.6 10.9 13.0 14.2 15.2 15.0 15.7 15 .1 13.9 14.0 14.2 14.2 15.3 13.7 15.5 NOT PREGNANT 16.0 15.9 14.6 15.4 17.5 18 .1 17.4 14.6 11.3 10.8 10.9 11.5 12.0 12.6 10.0 11.9 11.6 11.2 11.4 11.2 12.6 12.9 13 .1 12.5 10.6 11.2 9.1 11.3 13 .1 14.2 14.0 13.2 14.5 13.4 11.9 13.4 13.0 13.8 14.4 15.5 MX 8 MX 8 MX 8 F X 8 18.4 19.3 19.3 18.0 12.9 14.2 14.9 13 .7 12.0 11.9 12.6 11.8 13.3 13.6 9.7 13.8 14.5 13.3 13.7 13.9 13.0 12.8 13.0 12.9 11.8 11.6 10.3 12.1 11.8 12.0 11.1 1 2 . 5 13.2 12.3 12.8 17.5 16.1 17.1 13.3 13.9 17.2 D A Y 68! O F STU D Y 14 .7 15.4 13.7 1 3 . 1 MM 3 1 2 . 3 11.6 11.6 12.9 13.4 13.4 MS 13.2 12.4 14.8 MD 3 MS 1 4 . 8 15.8 18.5 9.1 11.5 10.8 13.0 12.0 MD 1 14.1 14.2 FX 8 18.8 13.2 12.0 14.6 14.6 11.0 12.2 10.4 14.6 17.0 12.1 10.9 10.6 12.9 11.4 12.0 13.0 12.9 FX 8 18.6 10.8 12.1 13.4 15.2 12.8 12.6 10.4 14.1 16.9 10.5 11.3 11.7 11.8 10.9 1 2 .9 13.8 15.2 FX 8 18.4 13.5 11.8 13.3 13.6 12.7 11.5 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 1 3 .1 1 3 .1 11.2 MM 2 10.5 10.7 12.2 1 6 .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 1 2 .7 12.3 10.9 11.7 1 7 .7 14.9 18.0 17.0 15.3 16.0 16.2 14.2 14.4 12.0 13.3 14.0 12.9 14.4 15.0 11.7 10.8 15.0 11.7 15.4 1 5 .1 11.6 11.8 14.7 13.4 14.0 11.8 10.6 13.0 15.5 17.0 11.7 11.4 11.3 12.6 11.4 10.4 12.3 12.1 FX 8 14.8 18.0 11.2 9.2 10.6 12.3 8.6 13.4 11.5 13.9 FX 8 14.3 UU 11.7 10.3 11.8 11.9 9.6 12.0 11.5 13.6 15.6 8.0 10.3 11.0 12.0 9.7 10.3 12.8 12.9 11.4 13.4 1 4 .1 12.0 10.6 11.1 13.1 13.1 12.2 12.7 13.5 12.1 11.1 13.4 10.8 12.5 13.1 12.6 11.1 11.1 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 1 3 .7 11.2 11.0 UU FD 2 12.0 12.6 12.0 13.5 1 2 .7 1 2 .7 FM 2 13.4 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . M EAN L IT T E R W EIG H TS IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L IV E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . 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) T A B L E C 3 7 (P A G E 12 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 298 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY POSTPARTUM DAY 8 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 13.2 13.4 13.8 12.7 13.8 13.2 15.2 14.6 12.9 1 3 .1 14.0 12.0 12.9 14.5 14.5 14.2 12.6 1 2 .7 12.9 13.4 M O R IB U N D S A C R IF IC E D O N 13.4 11.8 13.1 12.2 14.8 11.9 13.0 13.6 13.9 16.2 16.4 15.0 NOT PREGNANT 1 2 .7 1 3 .7 1 4 .1 11.8 1 4 .1 12.6 12.0 14.3 11.1 11.7 10.4 11.0 13.8 10.9 12.3 10.5 14.0 14.5 11.9 13.9 12.4 13.2 12.3 12.1 16 .1 16.0 15.0 MS 14 .7 14.8 13.4 14.0 12.4 11.6 12.0 11.2 12.4 11.8 12.1 11.7 NOT PREGNANT 13.8 13.6 13.6 13.2 12.5 13.5 11.3 14.4 10.8 13.2 10.6 14.7 14.9 14.6 15.6 12.1 12.8 13 .1 14.6 12.5 13.9 15 .1 14.8 15.7 10.2 11.7 10.4 11.0 13.3 13.2 12.6 11.6 12.3 12.0 12.0 11.9 14.0 14 .1 12.5 13.5 13.0 15 .1 12.9 11.8 11.6 13.6 13.1 1 4 .1 13.2 12.5 11.6 D A Y 59i O F S T U D Y 12.6 11.8 10.7 12.8 13.2 13.9 15 .7 15.9 1 4 .7 11.4 11.7 11.9 10.7 1 3 .1 13.3 MS 12.8 12.2 11.8 10.7 MD 7 9.4 12.3 14.6 11.9 MS 15.0 9.6 12.0 12.4 12.9 12.0 12.2 14.5 13.3 MS 1 3 .1 12.3 10.8 13.2 10.8 13.5 14.0 14.6 13.3 9.5 12.4 11.9 14.7 11.5 13.5 14.5 1 2 .7 13.9 11.7 12.7 12.3 12.2 11.2 13.2 14.8 13.3 13.6 11.1 11.7 12.2 12.3 14.3 1 2 .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 1 3 .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 1 2 .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 11.2 FM 3 12.2 1 2 .7 11.8 13.0 11.3 8.6 FS 13.4 11.5 13.6 10.1 10.5 12.3 FD 5 10.7 FS 11.0 1 2 .7 11.7 14.2 FD 1 12.5 11.8 11.1 FD 3 11.1 FD 8 12.2 12.0 10.8 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G ) . M EA N L I T T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 7 (P A G E 13 ) : PU P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 299 PUP # 1 2 3 4 56 7 8 9 1 0 1 1 1 2 13 14 15 16 1 7 18 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY POSTPARTUM D AY 8 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 15.3 12.1 P R EG N A N T; 14.5 12.8 16.8 19.8 9.5 11.8 9.7 10.6 11.1 10 .7 13.8 14.3 10.4 11.1 13.3 13.0 13.1 11.4 10.6 13.3 16.6 12.7 15.2 12.5 14.1 16.4 16.0 15.8 14.3 14.6 8.6 19.4 14.0 16.9 10.9 12.3 13.6 10.0 11.5 17.5 12.3 15.0 12.9 15.6 18.0 16.6 15.8 14.4 15.9 1 2 .7 18.7 13.8 16.0 11.6 13.4 13.4 12.2 1 5 .7 14.0 D ID NO T D E L IV E R A 13 .7 14.2 14.0 17.3 19.4 19.3 11.8 12.4 12.2 9.9 1 2 .7 10.8 10.1 8.0 9.4 13.8 14.6 11.9 11.8 14.6 12.2 12.4 13.7 17.5 14.0 15.5 14.4 16.2 13.3 16.3 13.0 14.4 14.0 11.1 18.5 13.7 15.5 11.1 13.2 13.5 11.1 12.4 11.9 11.1 9.9 16.3 14.4 15.3 15.3 15.4 16.1 16.2 1 6 .7 1 5 .1 14.2 12.8 1 4 .7 15.3 10.7 11.3 10.9 11.0 15.1 MD 3 11.5 13.5 18.0 12.6 15.9 12.9 15.0 15.3 16.2 14.7 1 5 .1 12.3 12.5 13.9 15.6 11.5 12.5 12.7 15.4 LIT T E R 13.4 17.7 12.3 11.7 9.1 12.3 9.8 14.5 12.0 11.6 15.5 15.8 12.7 16.4 14.1 16.0 15.3 15.7 16.5 14.8 14.5 14.3 13.9 16.0 10.7 11.5 12.9 14.4 13.3 FS 10.6 10.0 9.0 14.0 10.7 11.5 12.3 11.2 13.9 14.8 12.2 16.4 12.7 13.7 16.2 13.0 15.3 15.1 16.4 12.7 13.4 15.7 10.9 12.5 14.0 14.8 15.2 14.0 13.8 MD 1 11.3 MD 7 13.4 10.2 10.6 11.5 11.1 8.8 11.9 8.9 1 4 .7 13.1 16.4 15.6 15.1 14.9 12.7 14.4 12.3 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 1 2 .9 12.6 13.2 16.9 10.6 13.3 12.3 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 1 2 .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 1 4 .7 11.8 16.0 6.9 14.2 14.6 11.2 11.6 1 3 .1 13.4 13.0 10.8 9.9 13.1 10.8 12.0 10.7 1 5 .1 15.7 14.1 15.5 12.5 15.2 15.9 16.1 11.1 10.8 12.0 13.8 1 2 .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 1 5 .1 14.8 10.7 11.1 13.2 14.7 11.7 9.2 9.3 12.8 10.6 FM 7 11.2 13.1 14.3 13.9 FS FS 12.1 14.1 10.7 11.7 13.6 1 3 .8 FM 3 9.6 11.1 8.7 12.9 1 0 .7 13.0 11.2 FD 6 12.2 FD 4 10.5 9.3 FD 4 11.3 13.6 14.6 11.8 FD 1 11.1 13.5 14.8 11.0 8.7 FM 4 FD 2 10.7 FD 1 FD 3 FS 12.5 7.4 11.8 FD 8 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S (G ) . M EAN L IT T E R W EIG H T S IN C L U D E O N LY W EIG H T S O F L IV E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L IV E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 7 (P A G E 1 4 ) : PU P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 P O S TPA R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 300 PUP # 1 2 34 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 R AT/ LIT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/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 12.8 14.5 1 5 .1 12.8 13.3 15.6 12.1 13.5 NOT 10.7 13.6 15.2 12.5 1 6 .1 14.3 10.8 16.4 1 2 .9 15.8 12.3 1 3 .1 15.0 12.2 11.3 13.5 13.4 1 6 .7 11.3 9.3 1 3 . 8 1 6 . 3 1 6 . 3 MS 1 5 . 4 13.1 12.3 13.9 13.0 13.7 15.5 15.4 16.5 14.3 15 .1 12.5 11.1 13.0 11.5 12.5 10.2 14.6 8.3 1 1 .7 1 3 .7 15.6 14.5 15.4 15.4 13 .1 14 .1 14 .7 14.3 14.4 12.9 13 .7 10.3 11.8 11.8 13.4 14.3 13.4 13.5 13.6 12.6 P R EG N A N T ; M A TIN G N O T C O N FIR M ED 9.9 10 .7 10.3 10.3 11.3 13.6 12.7 14.4 14.6 14.0 16.0 14.9 12.3 15.3 11.1 11.0 10.2 12.6 11.3 7.9 9.8 16.8 13.3 15.5 12.5 1 6 . 4 1 5 . 0 1 5 . 8 1 4 . 0 MD 3 11.8 13.6 12.2 13.4 1 3 .1 17.0 14.5 18.2 13 .1 13.5 12.5 11.9 1 1 .7 15.8 15.3 15.4 13 .7 13.2 1 2 .7 12.2 11.8 13.2 13.4 11.9 12.6 13.4 11.0 13.8 15.7 13.7 15.6 15.6 15.3 13 .1 13.0 11.3 11.8 13.2 13.3 10.8 11.3 12.0 12.3 14.4 12.0 14.6 12.9 12.1 1 2 .9 1 4 .7 13 .2 14 .6 1 3 .1 14.5 15.0 16 .1 16 .1 15 .1 12.4 12.4 11.5 1 1 .7 12.2 10.9 10.3 11.1 11.2 8 .7 15.9 12.2 13.0 MM 4 13.9 15.2 13.2 11.0 13.4 10.2 13.2 12.8 12.4 11.6 MS 11.8 13.2 14.0 12.7 12.4 1 5 .1 11.4 11.7 12.9 11.4 14.5 11.7 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 11.6 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 1 3 .1 11.9 9.2 14.3 15.0 9.9 1 2 .7 9.1 13.0 14.4 8.8 11.2 15.2 12.1 1 2 .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 1 5 .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 1 3 .1 12.5 11.3 13.0 1 5 .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 1 2 .7 15.5 11.9 12.6 11.4 12.6 12.1 14.4 11.1 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 10.7 9.1 13.4 13.2 14.4 11.0 15.0 10.9 10.8 12.6 10.0 FS 11.4 FD 3 10.6 11.3 FD 8 12.7 12.3 11.5 10.8 1 0 .7 11.5 FM 3 FD 3 A L L W EIG H T S W ER E R EC O R D ED I N GRAM S (G) . M EA N L I T T E R W EIG H T S IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (PRES U M ED C A N N IB A L IZ E D ) , X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC ON D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R RED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 15 ) : PU P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TPA R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 301 1 2 6 8 10 11 12P U P # 345 7 9 13 14 15 16 1 7 18 R AT/ L IT T E R # 13 9 2 1 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 13 946 13 947 13 948 13 949 13950 M ATERNAL DOSAGE GROUP V 30 M G /K G /D A Y 8P O S T P A R T U M D A Y 13.4 8.3 1 2 .7 8.0 12.81 3 . 3 1 3 . 5 1 2 . 7 1 2 . 9 MM 6 9.7 10.7 13.6 13.2 9.2 11.3 12.5 9.4 10.2 12.6 9.7 11.3 10.3 12.9 7.2 10.8 11.0 9.0 11.3 12.1 14.1 9.5 11.4 12.8 9.4 11.2 12.5 12.9 MM 2 11.0 13.0 12.9 12.1 11.9 MD 8 MD 1 11.2 11.3 8.3 10.0 11.7 MD 3 MD 1 12.2 12.6 10.9 11.4 10.8 13.4 FM 2 10.7 10.4 12.2 11.9 10.8 11.7 FM 2 11.5 12.4 7.8 MS 10.7 10.5 10.8 12.9 12.5 10.4 11.7 11.6 NOT PREGNANT 9 . 8 10.8 10.6 7.2 12. 9 12.0 7.8 11.7 6.9 12.4 10.7 8.0 12.0 5.3 11.6 12.0 MM 4 13.4 9.7 7.7 13.8 13.0 9.9 12.3 9.8 7.5 12.2 12.1 10.3 11.6 10.0 8.0 12.1 12.1 7.3 12.8 7.2 MD 8 12.1 12.3 11.0 13.3 10.4 MD 6 12.6 12.0 8.2 12.9 MD 8 6.4 11.8 12.3 11.1 12.0 8.5 6.8 11.4 11.2 10.2 10.5 11.5 14.3 14.6 15.0 12.3 11.5 14.5 13.0 14 .7 14 .1 15.4 11.1 13.3 13.3 14.1 12.0 17.4 10.3 16.2 10.3 13.7 11.8 12.1 14.1 20.0 11.1 15.4 9.6 13.7 12.4 12.3 14.8 18.0 9.1 15.3 9.5 13.4 12.3 1 3 .7 14.0 17.4 MM 5 14.7 10.1 12.1 11.6 14.3 1 3 .1 15.2 11.3 14.7 9.0 12.3 12.7 14.1 9.0 13.7 9.2 15.5 11.0 12.6 10.5 14.5 14.3 17.8 11.0 15.2 MD 2 12.7 12.5 14.1 13.3 6.0 1 5 .1 9.8 12. 9 11.6 13.4 14.5 9.4 13.5 9.8 12.4 12.0 13.5 14.5 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 S A C R IFIC ED 13.6 11.4 12.6 1 4 . 5 13.3 13.0 D U E TO NO S U R V IV IN G PUPS ON D A Y 1 O F LA C T A T IO N 1 3 . 6 1 3 . 9 12.0 11.6 1 3 . 9 1 1 . 4 1 0 . 4 11.8 13.0 14.8 13.4 12. 9 13.6 14.3 13.0 12.4 12.7 MS 13.0 13.0 14.0 14.8 12.5 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 1 3 .1 11.1 FD 6 FM 5 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . M EAN L IT T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L IV E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L IV E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 16 ) : P U P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 302 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 R A T/ LIT T E R # M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY POSTPARTUM D A Y 15 13801 13802 13803 13804 13805 13806 13 8 0 7. 13808 13809 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 28.6 30.0 29.2 29.0 31.6 30.8 31.4 29.8 27.0 23.0 23.6 21.3 M O R IB U N D S A C R IF IC E D O N 28.3 29.4 28.5 27.5 26.1 23.1 23.3 25.3 24.7 24.3 24.3 25.1 30.5 30.6 29.2 27.4 27.8 29.2 26.1 30.0 3 1.7 29.6 32.1 31.2 NOT PREGNANT 28.2 28.6 26.0 26.6 33.9 31.4 32.7 33.2 22.6 23.8 23.3 25.3 21.6 20.6 21.3 20.8 21.6 20.6 19.2 19.5 25.5 23.3 23.9 22.0 20.8 17.6 20.4 18.8 22.1 22.3 20.4 1 9 .1 26.9 26.1 26.3 28.2 28.7 26.0 27.5 22.6 MX 8 MX 8 MX 8 F X 8 32.3 32.4 34.3 33.6 25.8 27.0 28.9 20.3 24.8 24.7 23.8 24.1 22.3 21.5 20.5 16.4 27.9 23.9 25.7 27.4 25.6 21.8 25.3 28.0 25.2 25.0 23.3 23.8 23.1 23.2 22.7 24.2 2 7.6 30.3 2 9 .1 31.4 33.1 30.6 21.1 2 3 .1 22.6 D A Y 68! O F STU D Y 28.9 29.9 26.8 2 4 . 3 MM 3 2 3 . 6 22.8 22.4 23.2 3 1 .1 29.3 MS 29.0 28.2 27.2 MD 3 MS 2 9 . 2 26.7 29.7 24.6 21.9 19.2 24.9 20.6 MD 1 26.8 30.9 FX 8 32.3 25.3 22.6 21.9 23.3 26.5 23.0 21.6 27.8 33.0 24.9 19.8 15.5 24.1 16.5 18 .1 24.9 24.5 FX 8 34.6 26.2 24.5 19.3 26.2 20.0 23.6 22.8 27.7 30.9 21.9 20.5 16.3 24.0 15.5 18.6 24.8 24.4 FX 8 31.8 23.8 25.2 23.2 27.1 24.4 24.3 21.4 28.0 28.1 24.4 28.6 31.0 23.2 27.7 FM 7 26.0 22.8 17.7 30.6 28.7 31.8 29.6 27.1 25.2 29.2 29.1 29.1 25.5 25.4 23.1 30.9 26.3 29.9 2 7 .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 26.2 30.7 18.3 19.9 16.2 21.8 16.6 20.3 24.9 2 3 .1 FX 8 33.0 25.1 24.8 16.0 MM 2 22.3 20.5 23.0 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 29.0 22.8 27.8 25.6 23.2 29.1 25.0 31.3 25.0 23.9 23.1 28.0 27.8 2 7 .1 25.7 32.6 20.7 22.6 16.8 23.1 17.8 20.1 26.7 2 7 .1 FX 8 26.9 31.2 22.5 19.1 15.6 23.1 1 6 .1 20.8 22.0 22.9 FX 8 23.3 2 1 .7 16.9 25.8 27.3 20.0 22.8 26.8 24.8 18.9 25.6 24.4 18.6 2 1 .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 2 5 .1 23.9 20.4 FM 2 25.4 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M E A N L I T T E R W E I G H T S I N C L U D E O N L Y W E I G H T S O F L I V E :P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (P R ES U M ED C A N N IB A L IZ E D ) , X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . 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) T A B L E C3 7 (P A G E 1 7 ) : P U P B O D Y W EIG H T S FRO M B IR T H T O D A Y 22 P O S TPA R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 303 PUP # 1 2 3 4 56 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY POSTPARTUM D A Y 15 13831 13832 13833 13 8 3 4 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 13 8 6 0 26.3 25.4 23.0 2 7 .1 25.9 2 4 .1 26.0 26.4 26.5 25.8 25.7 25.0 27.6 26.4 25.6 26.9 24.6 24.0 27.4 26.4 M O R IB U N D S A C R IF IC E D ON 27.2 25.7 27.3 25.1 25.4 24.3 24.8 23.8 24.5 26.4 24 .7 24.3 NOT PREGNANT 23.9 26.1 20.1 24.7 25.8 23.8 29.6 26.5 24.4 22.7 23.7 24.0 19.6 25.6 22.9 20.2 29.6 27.5 30.0 27.9 23.4 22.8 23.9 23.4 29.9 32.2 33.0 MS 24 .1 24.0 25.6 24.9 22.6 20.8 20.2 21.5 24.9 25.9 25 .1 25.2 NOT PREGNANT M X11 M X11 M X11 M X11 21.1 21.3 22.6 19.6 24.5 21.0 24.5 20.7 29.2 30.8 29 .1 28.8 22.9 20.1 23.0 21.0 27.4 27.3 26.7 28.2 25.5 2 1 .7 24.5 23.6 22.0 23.6 23.7 22.4 24.2 24.0 22.2 24.8 24.8 26.5 26.2 22.6 25.8 24.9 26.2 27.9 25.9 25.8 25.5 26.1 26.2 2 4 .1 25.6 D A Y 5S1 O F S T U D Y 26.6 2 7 .7 25.8 28.1 25.7 25.1 24.2 24.2 23.6 23.5 29.5 23.9 22.0 28.7 25.2 MS 29.4 20.5 24.9 25.1 MD 7 22.1 20.0 22.7 24.1 MS 27.8 21.2 25.0 17.5 23.0 25.0 21.6 28.3 20.7 MS 25.6 19.7 23.6 M X11 18.9 19.2 28.6 20.6 26.5 24.9 22.3 23.5 M X11 23.3 20.9 27.3 19.4 24.4 24.2 22.2 23.7 M X11 21.2 18.6 28.5 20.5 27.4 21.8 19.5 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 M X11 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 3 0 .1 21.3 31.6 24.3 22.5 22.8 FX 11 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 FX 11 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 FX 11 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 3 1 .7 25.7 21.0 23.5 FX 11 19.1 16.5 27.0 22.5 29.6 19.1 22.0 21.0 2 3 .1 2 3 .1 24.9 24.5 22.5 25.9 25.9 1 7 .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 21.9 FM 3 26.2 22.0 24.6 23.2 18.3 17.6 FS 27.9 21.1 25.8 19.2 19.0 18.7 FD 5 20.2 FS 21.3 FD 11 18.7 18.5 FD 1 17.3 24.7 27.7 FD 3 23.9 FD 8 18.7 19.0 23.7 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A L E , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 18 ) : PU P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 304 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY POSTPARTUM D A Y 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 PR EG N A N T; 2 1 .7 22.6 40.5 40.3 18 .1 20.2 23.2 26.8 21.7 20.2 27.2 27.3 21.4 20.2 29.1 26.7 19 .1 18.5 2 2 .9 22.4 19.9 23.9 31.8 31.8 24.4 24.4 31.2 31.8 29.8 29.9 30.4 32.0 32.6 32.5 30.7 29.8 29.8 3 1.1 27.8 27.5 28.1 23.6 32.3 29.1 33.1 34.6 25.5 27.5 31.4 31.7 25.3 24.9 25.8 25.7 26.9 25.6 24.8 26.9 25.6 D ID NOT D E L IV E R A 22.2 2 1 .7 21.6 36.3 38.2 3 8 .1 17.2 19.6 18.9 21.0 24.7 21.5 21.8 22.2 17.9 25.1 2 7.7 29.5 19.6 22.1 19.5 25.4 30.8 25.7 21.0 20.2 MD 3 20.3 20.3 22.6 29.6 20.1 25.8 32.2 32.3 32.4 25.9 27.5 28.9 30.8 28.7 29.2 29.8 32.5 30.0 33.8 32.8 3 1.7 32.0 31.6 28.8 32.0 29.7 30.2 30.1 28.6 27.9 25.1 27.2 25.9 30.6 24.7 28.3 30.8 26.1 23 .1 32.0 25.7 26.0 25.2 31.8 31.2 34.0 22.0 2 1 .7 23.8 24.8 24.9 25.8 25.4 24.3 26.5 24.5 LIT T E R 19.8 38.2 19.5 14.4 20.2 20.5 21.1 3 1 .1 20.2 23.2 26.3 25.9 18.9 28.8 29.1 32.6 33.0 32.4 28.5 29.4 29.6 28.0 25.4 33.8 2 1 .7 28.7 12.8 28.6 22.1 FS 19.7 23.9 21.3 24.1 21.3 30.3 18.8 20.1 24.4 29.9 28.9 30.1 28.9 30.0 31.0 28.0 28.4 24.6 25.2 30.2 25.4 32.6 21.4 27.0 22.4 28.1 22.5 MD 1 M D15 MD 7 26.4 20.8 24.4 18.4 21.2 16.3 29.0 24.4 29.7 27.3 3 1 .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 2 7 .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 2 1 .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 26.6 2 1 .7 19.8 26.7 22.3 2 3 .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 1 7 .7 20.3 17.2 FM 4 FD 2 FD 8 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EA N L IT T E R W EIG H TS IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 7 (P A G E 1 9 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 305 PUP # 1 2 34 56 7 8 9 10 11 12 13 14 15 16 1 7 18 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY POSTPARTUM D AY 15 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13 9 0 4 13905 13 9 0 6 13907 13908 13909 13910 13911 13 9 12 13913 13 9 14 13 9 15 13916 13917 13918 13919 13920 31.0 27.8 27.5 26.3 28.6 27.9 30.2 22.1 22.7 NOT 21.9 26.9 27.8 20.8 23.9 32.2 18.7 35.1 25.0 23.6 28.9 25.9 30.7 22.1 22.5 29.3 28.2 31.9 22.8 17.3 3 2 . 3 3 0 . 0 2 8 . 7 MS 2 9 . 3 26.1 24.0 26.8 23.0 24.6 26.5 28.6 25.3 29.1 25 .7 26 .1 24.0 25.0 28.6 24.0 28.3 12 .7 22.4 28.2 28.6 23.9 25.8 27.5 27.5 23.6 30.8 27.9 30.0 32.2 28.0 18.2 21.6 25.3 21.1 23.5 22.4 21.8 22.6 20.8 20.0 P R E G N A N T ; M A TIN G N O T C O N FIR M ED 23 .1 20.0 23.8 23.1 21.9 27.8 26.6 24.9 26.1 28.6 26.4 26.8 22.8 21.8 25.6 20.2 21.5 15.2 22.1 20.4 28.2 27.5 2 7.1 19 .7 2 1 .7 3 1 . 2 3 0 . 1 2 8 . 4 3 0 . 6 MD 3 1 7 .7 18.0 16.0 20.7 18.3 37.5 3 3.1 38.8 24 .7 23.3 23.1 24.9 25.2 20.0 23.8 22.0 22.1 21.0 2 7 .7 25.6 27.3 27.0 26.0 26.1 24.2 25.6 24.2 25.9 29.3 28.4 2 7 .7 29.9 28.3 25.2 20.1 25.1 22.5 21.8 19.3 24.8 21.6 22.4 22.6 24.7 26.3 25.4 27.5 30.4 25.8 30.2 28.2 25.8 30.0 30.3 26.5 27.2 29.2 26.4 24.4 24.9 23.1 23.4 25.2 17.9 17.4 14.1 17.5 17.4 29.7 25.3 25.9 MM 4 24.1 24.4 26.9 24.4 19.1 21.7 25.7 28.0 17.8 23.7 MS 19.5 23.3 22.1 24.2 29.0 29.6 25.7 22.7 29.5 25.1 28.4 22.3 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 1 8 .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 2 7 .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 1 6 .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 1 5 .1 25.4 24.3 23.4 26.2 25.0 27.6 25.4 FS 19 .1 18.4 23.0 FD 3 19.0 24.4 22.9 18.5 25.2 31.6 18.6 20.0 20.3 27.0 32.2 17.0 FD 7 25.9 FD 8 19.9 24.8 22.5 24.1 25.5 23.8 22.2 23.4 22.8 20.9 25.8 24.3 21.3 24.9 23.2 21.9 24.3 24.7 FD 9 FD 9 FD 3 FM 3 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . M EA N L I T T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPAR TU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 20 ) : PU P B O D Y W EIG H T S FROM B IR T H T O D A Y 22 P O S TPA R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 306 PUP # 1 2 3 4 56 7 8 9 1 0 1 1 12 13 14 15 16 1 7 18 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP V 30 M G /K G /D A Y POSTPARTUM D AY 15 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13 938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13 9 5 0 2 6 . 3 1 6 . 4 2 8 . 0 2 6 . 7 2 5 . 6 2 6 . 4 2 6 . 9 1 3 . 7 MM 6 2 4 . 7 2 3 . 0 2 3 . 8 2 3 . 8 1 8 . 3 MM 2 MD 1 MD 1 F M 2 F M 2 21.3 20.8 21.1 21.9 20.7 21.0 20.0 19.5 20.0 20.7 22.8 23.9 21.1 24.5 20.6 25.3 17.8 20.9 23.5 23.2 18.3 21.1 18.8 25.3 13.9 24.5 14 .7 15.2 21.0 22.5 2 4 . 9 2 3 . 9 2 3 . 8 2 3 . 8 2 4 . 1 2 2 . 3 2 3 . 8 1 9 . 9 MS 2 2 . 9 15.9 15.6 15 .1 13.8 1 7 .1 14.5 15.0 15.3 14.3 16.5 2 6 . 7 2 6 . 8 2 7 . 7 2 6 . 4 MD 8 MD 3 2 6 . 8 2 5 . 8 2 4 . 6 2 4 . 7 NOT PREGNANT 2 0 . 6 1 9 . 4 2 0 . 4 1 3 . 9 1 9 . 6 2 0 . 8 1 9 . 1 2 0 . 2 MD 8 1 9 . 3 1 8 . 2 1 9 . 9 1 5 . 9 1 1 . 9 1 9 . 8 1 7 . 2 MD 8 MD 6 1 7 . 2 1 6 . 7 23.4 22.0 23.6 2 2 .7 22.8 23.9 2 2 .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 1 5 . 4 M M 12 MM 4 2 4 . 2 2 0 . 9 2 3 . 1 2 5 . 4 1 5 . 1 2 1 . 0 1 4 . 5 22.0 20.7 24.1 1 9 .7 22.1 22.8 22.6 20.2 14.9 21.8 26.5 2 7 .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 2 2 .9 24.5 21.8 1 7 . 5 1 6 . 9 1 4 . 3 1 8 . 8 1 7 . 5 1 7 . 9 1 6 . 3 MD 2 1 6 . 8 1 7 . 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 2 1.9 23.7 23.0 21.6 21.1 19.8 2 5 .7 2 5 .7 24.2 25.8 23.4 24.0 24.9 2 2 .9 25.4 19 .9 23.2 22.8 26.2 2 8 .1 25.0 24.5 25.9 26.5 25.8 20.8 3 7 .1 35.9 36.8 40.5 36.6 31.0 34.3 2 0 . 4 2 4 . 1 2 2 . 1 MM 5 2 1 . 6 2 4 . 3 2 0 . 7 2 4 . 9 2 0 . 9 1 6 . 5 25.2 25.3 25.3 26.3 26.4 25.4 25.0 25.9 26.4 2 4 .1 31.8 30.4 29.8 29.3 28.6 28.4 28.2 2 7 .7 27.9 27.6 S A C R I F I C E D D U E T O N O S U R V I V I N G P U P S O N D A Y 1 ID F L A C T A T I O N 2 7 .1 28.1 27.9 27.6 24.6 25.5 24.4 25.4 24.9 2 7 .1 27.0 28.2 27.0 28.2 27.4 2 7.1 27.8 28.4 29.4 27.5 2 8 . 9 2 8 . 6 2 8 . 4 3 0 . 3 2 5 . 7 2 7 . 5 MS 2 6 . 9 2 6 . 1 2 7 . 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 2 3 .1 27.3 29.0 25.6 10.0 20.1 22.6 23.7 23.1 14.7 23.6 19.1 24.4 22.4 24.6 13.7 27.6 16.5 17.5 23.3 17.7 18 .1 22.5 22.9 22.7 1 7 .7 24.9 22.7 24.2 23.6 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 FM 10 24.3 25.3 FM 3 27.3 FD 2 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 2 3 .1 FD 6 FM 5 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . M EAN L IT T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L IV E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L IV E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 7 (P A G E 2 1 ) : P U P B O D Y W EIG H TS FRO M B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 307 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY POSTPARTUM D A Y 22 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 13811 13 8 12 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 45.0 44.6 47.5 45.2 44.3 45.4 43.0 43 .1 43.9 40.0 40.7 40.6 M O R IB U N D S A C R IF IC E D ON 4 8 .1 44.9 46.6 46.3 3 2 .7 35.4 32.1 35.0 2 7.4 26.4 26.8 20.1 40.9 4 1 .1 42.8 36.6 32.2 38.5 36.9 35.9 48.3 45.4 43.4 4 5 .1 NOT PREGNANT 43.2 42.0 41.4 44.7 43.9 40.1 44.2 45.2 3 7 .1 31.8 36.4 35.3 36.2 33.4 32.8 33.8 32.8 32.2 31.8 34.4 36.0 36.2 39.9 37.9 3 1.9 24.3 2 7 .1 31.8 3 1 .7 29.1 30.6 30.6 27.2 25.0 26.1 27.8 36.4 43.0 48.9 40.6 MX 8 MX 8 MX 8 F X 8 5 7.2 53.3 52.0 53.4 3 1 .7 4 9.1 40.5 43.7 3 6.1 34.9 29.1 35.9 26.4 34.9 32.0 2 7 .7 42.5 40.3 39.8 45.0 39.3 35.8 47.0 42.2 42.8 42.0 45.5 40.6 38.5 34.6 35.3 36.7 40.6 42.5 44.3 46.5 40.5 44.7 48.3 38.8 4 2 .1 D A Y 681 O F S TU D Y 45.3 43.2 41.0 3 4 . 4 MM 3 3 4 . 2 25.4 26.5 26.2 39.5 44.4 MS 34.6 36.5 37.3 MD 3 MS 4 3 . 5 41.9 45.8 38.8 32.2 34.4 41.0 28.1 MD 1 27.7 35.0 FX 8 52.9 40.7 34.6 31.8 37.9 42.0 39.0 35.0 42.5 44.0 35.5 33.5 25.6 37.5 31.2 30.0 20.8 36.9 FX 8 53.0 41.7 32.7 33.3 42.4 40.8 38.2 33.2 44.9 39.5 32.7 3 1 .7 32.5 36.7 28.9 29.8 23.4 44.7 FX 8 54.1 37.0 36.1 35.2 42.9 4 1 .1 40.8 35.4 46.3 43.5 36.9 44.1 37.3 44.5 41.3 FM 7 44.9 42.5 43.0 32.4 26.1 39.8 35.3 41.2 38.3 33.4 24.8 42.2 37.3 45.3 45.2 36.4 23.5 36.4 34.5 41.4 39.0 32.8 26.0 3 7.7 36.2 43.1 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 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 39.6 40.6 34.1 32.4 27.3 39.7 26.0 29.9 36.4 40.6 FX 8 33.3 3 1 .1 28.8 4 1 .1 32.5 42.4 35.8 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 4 1 .7 42.4 46.6 36.5 28.4 2 7 .1 38.2 26.5 29.6 34.2 39.2 FX 8 4 1 .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 3 7 .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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M E A N L I T T E R W E I G H T S I N C L U D E O N L Y W E I G H T S O F L I V E :P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC ON D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E EV EN T O C C U R RED . 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) T A B LE C 3 7 (P A G E 2 2) : P U P B O D Y W EIG H TS FROM B IR T H TO D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 308 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY POSTPARTUM D A Y 22 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13 8 4 4 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13 8 5 8 13859 13860 39.4 36.2 30.8 33.6 40.3 45.0 43.3 42.3 50.2 40.0 40.9 43.0 36.2 40.5 34.5 38.0 36.7 35.2 36.9 33.0 M O R IB U N D S A C R IF IC E D O N 37.8 39.4 4 1 .1 38.5 36.0 4 1.6 37.8 33.3 37.0 36.1 32.6 37.5 NOT PREGNANT 46.5 45.2 36.3 38.8 37.2 43.4 39.0 43.4 35.1 33.2 35.3 34.6 42.9 32.0 33.6 34.5 45.3 33.8 4 5 .1 4 2.7 36.2 37.2 35.7 31.2 55.0 51.4 55.4 MS 39.3 43.8 43.3 40.9 27.5 26.5 2 3 .7 25.3 37.4 3 7 .7 38.4 39.0 NOT PREGNANT M X11 M X11 M X11 M X11 33.4 37.8 32.2 32.9 30.1 26.5 35.2 28.8 40.2 38.9 34.0 42.0 32.9 31.6 29.8 38.6 39.6 4 4 .1 43.9 44.2 30.5 35.3 33.8 33.2 37.4 40.3 39.6 40.1 33.9 36.6 39.5 37.3 34.3 32.1 41.4 45.2 46.0 37.6 40.5 43.7 39.1 37.3 34.0 31.8 35.7 37.8 34.4 D A Y 59 O F S TU D Y 4 1 .1 36.1 41.6 37.6 32.8 38.0 34.0 39.3 40.0 41.4 39.4 34.3 37.3 42.7 35.1 MS 43.2 26.3 37.3 37.0 MD 7 33.7 32.0 48.4 35.3 MS 43.1 28.1 38.5 33.0 34.2 30.1 30.1 43.6 36.3 MS 42.7 25.5 33.8 M X11 31.4 29.6 39.5 32.7 42.7 35.2 43.4 37.5 M X11 35.0 29.5 38.8 33.6 41.2 32.7 41.5 35.4 M X11 33.7 29.6 39.3 33.0 38.6 31.3 40.1 36.1 33.6 35.3 38.8 3 7.7 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 M X11 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 FX 11 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 3 7 .1 33.5 26.5 40.4 28.8 52.7 45.0 28.4 34.6 FX 11 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 FX 11 32.8 29.7 36.7 3 1.1 39.8 30.6 38.5 38.3 33.1 44.0 36.0 36.7 3 1.1 FS 34.7 33.0 UU 3 7.7 34.8 42.8 33.7 52.5 43.1 29.6 3 3 .8 FX 11 34.1 30.3 39.9 25.6 38.4 30.7 38.3 35.9 36.5 37.0 40.0 3 7.7 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 4 1 .1 23.6 28.1 29.0 40.8 36.0 38.3 35.7 40.7 32.6 28.7 FM 3 35.7 31.0 36.0 34.6 27.8 28.4 FS 38.4 24.9 38.6 25.3 27.5 25.4 FD 5 31.8 FS 36.4 FD 11 27.1 27.3 FD 1 23.6 36.2 36.7 FD 3 3 7 .7 FD 8 30.0 27.1 32.3 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . M EA N L IT T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 23 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 P O S TPA R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 309 P U P # 1 2 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY POSTPARTUM D AY 22 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 32.8 33.1 PR EG N A N T; 32.2 30.8 57.8 60.2 26.9 29.5 18 .1 35.8 26.2 30.2 37.6 33.8 27.0 33.3 41.6 37.7 26.9 26.1 30.7 34.1 39.1 24.5 4 9 .1 50.0 4 1.2 33.0 49.0 50.3 48.5 47.2 48.9 48.8 48.7 50.2 45.0 40.0 41.4 40.1 37.6 44.0 43.6 47.3 36.4 51.3 55.5 51.5 43.9 38.8 4 7 .7 49.9 36.3 36.5 35.4 34.4 4 3 .1 39.0 32.0 36.5 36.2 D ID NOT D E LIV E R A 32.5 32.1 33.0 6 1 .1 59.3 61.5 30.9 30.4 28.5 36.3 39.3 33.8 28.0 29.4 29.9 26.6 37.4 34.5 29.7 31.7 33.7 36.3 44.6 3 7 .7 3 2 . 3 2 6 .8 MD 3 27.8 29.5 29.8 29.8 35.3 3 1.0 48.5 51.3 54.7 35.3 28.9 38.1 4 7.2 50.2 47.0 43.9 45.8 46.7 52.3 51.8 42.4 48.0 46.1 48.8 4 4 .8 4 7 . 6 4 9 . 9 39.1 39.1 3 7.7 3 7.4 39.3 42.2 48.0 41.9 45.9 42.3 43.5 39.9 53.5 40.3 44.3 42.4 52.4 5 1.7 53.8 31.4 30.7 29.7 32.2 34.1 35.8 20.4 3 1.1 42.3 36.8 LIT T E R 30.3 59.8 31.9 43.5 31.2 35.6 33.0 44.4 31.4 30.8 39.5 44.0 37.3 45.3 45.6 48.0 48.8 52.6 40.9 43.9 44.4 46.1 47.9 50.4 29.6 3 4 .1 40.5 36.0 33.9 FS 31.4 39.1 30.9 34.3 34.8 42.3 23.6 32.2 41.9 43.4 44.4 48.1 46.0 52.3 51.6 4 7 .1 40.8 46.3 52.9 27.4 42.6 50.0 30.2 36.9 42.5 33.8 34.3 MD 1 M D15 MD 7 35.2 23.2 35.5 29.9 33.7 39.4 42.5 40.1 4 1 .1 42.2 46.7 47.9 52.8 37.2 43.3 48.0 43.1 40.6 50.7 31.3 38.9 38.8 32.0 30.5 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 38.2 41.9 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 2 7 .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 FD 2 0 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 30.7 34.0 28.2 32.1 33.9 FM 7 30.1 34.0 42.2 33.5 FS FS 37.3 47.6 32.5 32.3 38.9 31.5 30.8 38.3 31.6 35.6 22.7 FD 4 30.0 34.3 42.6 42.9 FD 1 45.1 FD 1 FS 32.4 44.0 FM 3 31.5 32.4 FD 6 35.0 FD 4 26.7 37.2 45.1 35.0 FD 3 29.6 29.8 35.8 27.1 FM 4 FD 2 FD 8 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . M E A N L I T T E R W E I G H T S I N C L U D E O N L Y W E I G H T S O F L I V E :P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (P R ES U M ED C A N N IB A L IZ E D ) , X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 7 (P A G E 2 4 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 310 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY POSTPARTUM D A Y 22 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13 9 0 3 13 9 0 4 13 9 0 5 13906 13907 13 9 0 8 13909 13910 13911 13 9 12 13913 13 9 14 13915 13916 13917 13 9 18 13 9 19 . 13920 47.8 36.8 44.1 40.2 40.1 44.5 44.9 23.7 32.4 NOT 28.3 39.7 39.6 28.1 38.4 49.8 26.7 51.3 36.1 32.3 39.0 39.3 43.2 29.3 27.8 40.7 41.3 46.7 38.2 26.9 5 1 . 6 4 9 . 0 4 6 . 0 MS 4 7 . 2 38.7 35.3 4 1 .1 44.3 39.5 39.1 46.4 46 .1 42.2 42.5 36.9 35.9 46.0 34.9 36.9 30.3 33.0 22.7 41.0 42.2 4 1 .7 39.8 44.3 40.7 37.6 48.6 48.5 48.8 44.4 45.6 33.2 27.9 28.9 32.9 29.0 3 5.1 34.4 32.8 3 7 .1 36.9 P R E G N A N T ; M A T IN G N O T C O N FIR M ED 30.6 35.5 29.3 30.7 34.7 43.3 42.2 44.3 41.9 41.5 40.4 38.8 42.3 42.0 40.9 31.3 38.9 35.6 36.9 36.2 2 9 . 2 4 4 . 2 4 2 . 3 3 6 . 1 4 4 .8 4 7 . 4 5 0 . 3 4 8 . 1 4 5 . 9 MD 3 30.9 23.2 26.4 30.4 28.3 59.5 59.5 50.5 42.5 37.3 4 1.4 39.8 38.4 39.5 36.0 36.2 35.8 40.9 43.4 43.4 40.3 42.5 46.3 35.7 39.7 43.6 40.0 38.4 4 4 .8 4 6 . 2 4 4 . 1 4 6 . 9 4 7 . 0 35.9 29.8 34.4 29.3 33.3 39.5 31.8 36.6 37.0 34.9 47.2 43.2 39.7 49.3 46.0 44.3 46.2 40.8 48.0 41.5 40.0 45.3 46.3 44.8 40.5 39.6 40.0 39.6 38.1 38.4 32.5 32.3 33.6 32.6 33.1 44.1 38.5 40.9 MM 4 43.6 40.6 41.0 33.6 32.5 32.7 43.7 36.4 34.0 36.6 MS 25.7 39.1 36.6 41.3 39.9 45.9 33.4 41.6 44.9 43.6 3 7.1 30.2 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 4 3 .1 29.7 32.2 45.5 37.8 38.7 37.0 43.8 3 7 .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 4 1 .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 4 3 .1 25.4 3 1 .7 25.9 40.2 44.1 36.3 33.5 48.3 26.9 3 7 .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 3 1 .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 3 7.1 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 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 35.0 37.4 32.2 34.9 38.9 32.7 29.3 41.6 41.3 37.4 FD 9 FD 9 FD 3 FD 3 32.1 33.3 FM 3 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPAR TU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C 3 7 (P A G E 25 ) : PU P B O D Y W EIG H TS FRO M B IR T H TO D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 311 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP V 30 M G /K G /D A Y POSTPARTUM D AY 22 13921 13922 13923 13 9 2 4 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13 940 13 941 13942 13943 13944 13945 13 946 13947 13948 13949 13 9 5 0 4 1 . 8 2 7 . 6 2 3 . 2 4 6 . 1 4 7 . 0 4 5 . 6 4 6 . 5 4 2 . 1 MM 6 4 0 . 7 4 2 . 0 4 0 . 9 4 0 . 4 3 2 . 8 MM 2 MD 1 MD 1 F M 2 F M 2 31.5 33.4 33.5 33.0 3 1.9 3 1.6 33.6 29.6 28.4 29.4 33.5 32.3 30.2 29.8 28.6 34.5 34.3 34.3 37.2 35.4 32.9 31.0 40.8 40.8 31.0 23.0 24.0 36.7 26.2 37.2 3 4 . 6 3 3 . 2 3 3 . 3 3 0 . 0 3 2 . 3 3 4 . 4 3 0 . 9 3 4 . 0 MS 3 2 . 3 25.3 2 7 .1 23.9 22.3 24.0 25.4 25.7 18.9 20.6 2 4 .7 4 2 . 1 4 0 . 7 4 0 . 3 4 3 . 1 MD 8 MD 3 4 3 . 2 3 6 . 8 3 4 . 7 3 8 . 2 NOT PREGNANT 1 9 . 3 2 4 . 2 2 5 . 6 2 6 . 4 2 7 . 3 2 5 . 2 2 5 . 1 2 5 . 3 MD 8 2 5 . 2 1 9 . 9 2 8 . 3 2 4 . 9 2 9 . 3 2 6 . 3 2 7 . 7 MD 8 MD 6 2 5 . 2 2 6 . 2 31.3 33.4 34.9 36.5 31.5 33.1 33.6 32.7 31.0 32.7 27.9 26.7 25.5 29.6 32.6 27.5 26.7 27.6 24.6 29.8 2 9 . 4 M M 12 MM 4 2 4 . 9 2 7 . 3 3 5 . 7 2 6 . 8 3 3 . 3 3 3 . 9 3 5 . 2 31.6 30.7 36.1 34.3 36.3 33.4 32.9 30.4 21.5 33.4 38.2 45.2 38.0 37.6 4 4 .1 38.5 44.3 42.4 42.6 39.4 40.0 41.2 44.9 43.5 4 1.5 39.0 40.0 42.8 38.6 40.4 2 1 . 7 2 8 . 0 2 9 . 2 2 5 . 3 2 8 . 9 3 0 . 0 2 6 . 1 MD 2 3 1 . 4 2 5 . 9 4 2 .1 42.4 38.4 40.1 38.1 44.3 44.3 4 1 .1 37.6 4 1.6 35.7 34.0 30.0 30.2 31.0 32.0 26.8 28.7 26.2 27.3 4 2.1 38.5 36.8 38.5 39.8 42.4 41.4 39.6 35.9 31.9 4 0.7 24.3 35.7 32.6 38.9 39.3 38.0 35.5 34.3 40.0 57.5 57.2 46.9 6 1.7 51.9 53.6 56.4 3 5 . 1 3 9 . 7 3 7 . 2 MM 5 2 7 . 9 3 4 . 1 3 6 . 5 3 4 . 7 3 7 . 3 3 8 . 3 3 7.6 3 8 .7 4 1 .5 3 8 .7 39.0 3 9 .7 39.5 39.3 40.0 40.0 43.2 4 4 .1 46.2 44.5 45.8 40.9 43.1 4 1 .7 43.1 42.3 S A C R I F I C E D D U E T O N O S U R V I V I N G P U P S O N D A Y 1 ID F L A C T A T I O N 48.4 40.2 4 6 .1 43.4 44.8 39.9 39.9 4 1 .7 3 7 .1 4 1.9 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 4 5 . 4 4 4 . 7 4 2 . 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 40.6 30.7 30.7 32.8 28.7 22.5 40.7 30.3 32.3 34.7 31.9 22.5 36.6 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 25.2 FD 6 33.1 27.6 33.7 33.5 40.4 38.1 26.0 38.5 31.0 3 7 .1 36.1 FM 10 37.0 42.8 FM 3 39.9 FD 2 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 32.6 32.8 25.3 38.8 FD 7 37.6 20.5 FM 2 24.3 FM 6 34.7 39.9 26.0 FS 32.1 29.5 40.1 35.4 27.9 FD 6 FM 5 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . M EAN L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L IV E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R R ED . ARGUS 418-021 Page 312 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C38 (P A G E 1) : PU P V IT A L S TA TU S AN D S EX FROM B IR T H TO D A Y 22 PO STPARTU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 2 1 22 23 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY 13801 13802 13 8 0 3 13 8 0 4 13805 13806 13807 13808 13809 13 8 10 13811 13812 13 8 13 13 8 14 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 MA MA MA MA F A F A F A F A F A MA MA M A MA MA MA MA MA 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 FM 7 F A F A M O R IB U N D S A C R IF IC E !1 O N D A Y 68 O F S T U D Y MA MA MA MA MA MA F A F A F A F A F A F A M A M A M A M A M A MM 3 F A F A F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A MA MA MA MA MA MA MS F A F A F A F A F A MA MA MA MA MA MA MA MA MA F A F A F A M A M A M A M A MD 3 M S F A F A F A F A F A F A NOT PREGNANT MA MA MA MA MA MA MA MA MA F A F A F A MA MA MA MA MA F A F A F A F A F A F A F A MA MA MA MA MA MA MA MA MA MA MA F A MA MA MA MA MA MA MA MA MA MA F A F A MA MA MA MA MA F A F A F A F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A M A M A M A M A MD 1 F A F A F A F A F A F A F A MA MA MA MA MA F A F A F A F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A MX 8 MX 8 MX 8 F X 8 F X 8 F X 8 F X 8 F X 8 F X 8 F X 8 F X 8 F X 8 MA MA MA MA F A F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A MA MA F A F A F A F A F A F A F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A M A M A M A M A M A M A M A M A MM 2 M A F A F A MA MA MA MA MA F A F A F A F A F A F A F A MA MA MA MA MA MA MA MA F A F A F A F A MA MA MA MA MA MA MA M S F A F A F A F A FA FA FA FA FA FA FA FA FA UU 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 F A FD 1 FA F A F A F A FM 2 FA FA FA FA UU F A FD 2 F A FM 4 FD 2 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPAR TU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 8 (P A G E 2) : P U P V IT A L S T A T U S A N D S E X FRO M B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 313 PUP # 1 2 34 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 2 0 2 1 22 23 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY 13 8 3 1 13 8 3 2 13 8 3 3 13 8 3 4 13 8 3 5 13 8 3 6 13 8 3 7 13 8 3 8 13 8 3 9 13 8 4 0 138 41 13 8 4 2 13843 13 8 4 4 13 8 4 5 13 8 4 6 13 8 4 7 13 8 4 8 13 8 4 9 13 8 5 0 1385 1 13 8 5 2 13 8 5 3 13 8 5 4 13 8 5 5 13 8 5 6 13 8 5 7 13 8 5 8 13 8 5 9 13 860 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A F A MA MA MA MA F A F A F A F A MA MA MA MA MA MA F A F A M O R IB U N D S A C R IF IC E D O N D A Y 59 O F S TU D Y MA MA MA MA MA F A F A F A MA MA MA MA MA MA MA F A MA MA MA MA MA MA F A F A NOT PREGNANT MA MA MA MA MA F A F A F A M A M A M A M A M A MD 7 F A F A MA MA MA MA MA F A F A F A MA MA MA MA MA MA F A F A MA MA MA MA MA MA MA F A MA MA MA MA MA MA MA F A MA MA MA M S M S M S M S MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A F A NOT PREGNANT M X11 M X11 M X11 M X11 M X11 M X11 M X11 M X11 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 F A F A F A F A MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A F A MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA MA MA FA FX 11 MA MA MA MA FA MA FA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA MA MA FA FX 11 MA MA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FD FA FA FA FA FA MA MA FA FX 11 FA MA FA FA FA FA FA FA MA FA FA FA FA FS FA FA UU FA FA FA FA FA MA FA FA FX 11 FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA F A FM 3 FA FA FA FA F A FD 3 FD 2 F A F A F A F A F A FD 4 FA F A F A F A F A FD 8 F A FM 2 FS FS FA FA FA FA FS FS FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 5 FD 1 FA FA FA FA FS FA FA FA F A FD 11 FA FA FA F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NU M B ER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R R ED . ARGUS 418-021 Page 314 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C3 8 (P A G E 3) : PU P V IT A L S TA TU S AN D S EX FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY 13 8 6 1 13 8 6 2 13 8 6 3 13 8 6 4 13 8 6 5 13 8 6 6 13 8 6 7 13 8 6 8 13 8 6 9 13 870 13 8 71 13 8 72 13 8 73 13 8 74 13 8 75 13 8 76 138 77 13 8 78 13 8 79 13 8 8 0 1388 1 13 8 8 2 13 8 8 3 13 8 8 4 13 8 8 5 13 8 8 6 13 8 8 7 13 8 8 8 13 8 8 9 13 8 9 0 MA MA P R EG N A N T; 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 F A MA MA MA MA MA MA D ID NO T D E L IV E R A L IT T E R MA MA MA F A F A F A MA MA F A F A F S M A M A M A M A M A MD 1 M A M A M A M A M A M D15 M A M A M A M A M A MD 7 M A M A M A MA MA M A MA MA MA MA MA F A FA F A F A FA FA F A M A M A MD 3 F A F A F A MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A F A F A M A MA M A MA MA M A M A M A M A MA MA F A MA MA MA MA MA F A FA FA FA FA FA FA M A MA M A MA F A F A M A M A M A MA M A MA M A M A MA MA F A F A MA MA MA MA MA MA MA MA MA MA MA F A MA MA MA MA F A F A FA M A M A MA MA MA F A M A MA MA MA MA MA FA FA FA FA FA FA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA MD 6 FA FA FA MA FA FA FA FA FA FA FA MA FA MA FA FA FA FA FA MA 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 FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 6 FA FA F A FD 4 FA F A FD F A FD 2 0 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 FA FA FA FA F A F A FD 3 F A FD 1 FA FA FA FA FA FA FA FA FA FA FS FA FA FA F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (P R ES U M ED C A N N IB A L IZ E D ) , X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C38 (P A G E 4) : PU P V IT A L S TA T U S AN D S EX FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 315 P U P # 1 2 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 2 2 23 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY 1389 1 13 8 9 2 13 8 9 3 13 8 9 4 13 8 9 5 13 8 9 6 13 8 9 7 13 8 9 8 13 8 9 9 13 9 0 0 13 9 0 1 13 9 0 2 13 9 0 3 13 9 0 4 13 9 0 5 13 9 0 6 1390 7 13 9 0 8 13 9 0 9 13 9 10 139 11 13 9 12 13 9 13 13 9 14 13 9 15 13 9 16 139 17 13 9 18 13 9 19 13 9 2 0 MA MA MA MA MA MA MA MA MA NOT 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 P R EG N A N T; MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A 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 MS F A F A MA MA MA MA MA MA MA MA M A M A M A MM 4 MA MA MA MA MA MA F A F A MA MA MA F A MA MA MA MA MA MA MA F A M A T IN G N O T C O N FIR M ED MA MA MA MA MA MA MA MA MA F A F A F A MA MA MA MA MA MA F A F A M A M A MD 3 M S MA MA MA MA FA MA MA F A F A MA MA MA F A 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 FA FA FA MA MA F A F A MA MA MA F A M A M A M A MD 9 FA FA FA FA MA FA FA FA FA FA FA FA MA FA MS MA FA FA MA FA FA MA MA FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA MA FA FA MA FA FA FA FA FA FA MA 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 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 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 FS F A F A F A F A FD 3 FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 7 FA FA FA F A FD 8 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FM FA FA FA FA FA F A FD 9 FD 9 FD 3 F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE SEC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E TO S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C38 (P A G E 5) : PU P V IT A L S TA T U S AN D S E X FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 316 P U P # 1 2 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 2 0 2 1 22 23 R A T/ LIT T E R # M ATERNAL DOSAGE GROUP V 30 M G /K G /D A Y 139 21 13 9 2 2 13 9 2 3 13 9 2 4 13 9 2 5 13 9 2 6 139 27 13 9 2 8 13 9 2 9 13 9 3 0 139 3 1 13 9 3 2 13 9 3 3 13 9 3 4 13 9 3 5 13 9 3 6 1393 7 13 9 3 8 13 9 3 9 13 940 13 9 41 13 9 4 2 13 9 4 3 13 9 4 4 13 9 4 5 13 946 13 9 4 7 13 9 4 8 13 9 4 9 13 950 MA MA MA MA MA MA MA MA NOT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FD 1 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA P R EG N A N T MA MA MA MA MA MA MA MA M M 12 MM 4 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A MA MA MA MA MA MA MA MA MA MA MA MA MA MA M A MM 2 MA MA MA MA MA MA MA MA MA MA M A MD 8 MA MA MA MA FA MA MA MA MA MA MA MA MA FA MM 5 MA MA MA MA MA MA FA MA MA MA MA MA MA MA MA FA FA MA MA MA MA MA MA MA MA MA MD 1 MA MA MA MA MA MD 3 MA MA MA FA FA MA MA MA MA MA MA MA MA FA FA MA FA MA MA MA MA MD 1 MA MA FA MA MA FA MA MD 8 MA FA FA MA MA FA MA MA FA MA MA FA FA MA FA MA MA MS MA FM 2 FA MA FA MA FA FA MA MD 6 MA FA FA FA MA FA MD 2 FA FA MA MA FA MA FA FA MA FA MM 6 FM 2 FA MA FA MS FA FA MD 8 FA FA FA FA FA MA FA FA FA FA MA MA FA MA FA FA MA 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 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 7 FA FA FA FA FA FA FA FA MA FA FA FA FA FA MA FA FA FA FA F A FD 6 FD 6 FM 2 FA FA FA FA FA F A F A F A FM 6 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 F S FA FA FA FA FA FA FA F A FM 10 FA FA FA FA FA F A FM 3 FA FA F A FD 2 FA FS FS F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - A - A L I V E , S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ), X -S A C R IF IC E D D U E T O S A C R IF IC E O F DAM NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C3 9 (P A G E 1) : C L IN IC A L O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 317 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D A Y) LIT T E R NUM BER D A Y (S) POSTPARTUM O B S ER V A TIO N S a I 0 1380 7 5 3 /17 PU PS: COLD TO TO U C H ; NOT N E S T IN G ; N O T N U R S IN G . 13 8 17 1 1/15 PU PS: C O LD TO TO U C H ; NO M ILK IN STOM ACH. 13 8 2 0 5 1/14 PU PS: COLD TO TO U C H . 13824 2 16 /16 PU PS: COLD TO TO U C H . 13 8 2 7 1 1/16 PU PS: COLD TO TO U C H . II 1 13833 8, 9 1 / 1 4 PU PS : U M B ILIC A L H E R N IA . 1383 7 1 1/12 PU PS: COLD TO TO U C H . 13 8 3 9 1-22 4 1/12 PUPS: 1/12 PUPS: N O T A I L P R E S E N T b ; H IN D LIM B S R O T A T E D IN W A R D . COLD TO TO U C H . 13 8 4 9 3 1/16 PU PS: COLD TO TO U C H . 13 8 5 0 1 5 -2 2 2/13 PUPS: 1/12 PUPS: COLD TO TO U C H . T IP O F T A IL M IS S IN G . 13 8 5 2 5- 6 1 / 1 2 P U P S : L E F T F O R E L IM B , M ASS ( 0 .3 CM I N D I A M E T E R ) . N IP P L E EX A M IN A T IO N S FO R A L L M A LE PUPS A P P EA R ED N O R M A L. a . T a b u la tio n r e s tr ic te d to a d ve rse o b s e rv a tio n s ; a l l b . O b s e rv a tio n c o n firm e d a t n e c ro p s y . o th e r pups a p p e a re d n o rm a l. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C39 (P A G E 2) : C L IN IC A L O B S ER V A T IO N S FROM B IR T H TO D A Y 22 PO STPARTU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 318 M ATERNAL DOSAGE GROUP M A T ER N A L D O SAG E (M G /K G /D AY) LIT T E R NUM BER D A Y (S) POSTPARTUM O B S ER V A TIO N S a III 3 13 8 6 8 1 16 /16 PU PS: COLD TO TO U C H . 13 8 73 7 1/16 PU PS: COLD TO TO U C H . 13 8 77 3 1/13 PU PS: COLD TO TO U C H . 13 8 78 1 9/ 9 PU PS: COLD TO TO U C H . 1388 7 13 8 8 8 1-20 21,22 12 1/11 PUPS: 1/11 PUPS: T IP OF T A IL BLAC K . T I P O F T A I L M IS S IN G .b 1 / 14 P U P S : R ED P ER IA N A L S U B S TA N C E. 13 8 8 9 7 2 /16 PU PS: COLD TO TO U C H . IV 10 13 8 9 4 1- 4 1 / 1 4 P U P S : T IP O F T A IL M IS S IN G . 5 -22 1/13 P U PS : T IP O F T A IL M IS S IN G . 13 8 9 5 1- 6 1 / 1 5 P U P S : B R U IS E , B A C K ( D ID N O T E X C E E D 2 .0 CM X 1 .0 C M ). 13 8 9 8 5 1/16 PU PS: COLD TO TO U C H . 13 9 0 5 21,22 1 / 1 6 P U P S : L E F T E Y E , T R A U M A T IZ E D C O R N E A .b 13 9 0 6 7 1/13 P U PS : P A L E ; NO M ILK IN STOM ACH; N O T N E S T IN G . 13 9 12 5 1 / 1 4 P U P S : S C A B , B A C K ( 0 .2 CM I N D I A M E T E R ) . 12 1 / 1 4 P U P S : U M B ILIC A L H E R N IA . 13 9 14 1,2 1/18 PU PS: COLD TO TO U C H ; NO M ILK IN STOM ACH. N IP P L E EX A M IN A T IO N S FO R A L L M A LE PU PS A P P EA R ED N O R M A L. a . T a b u la tio n re s tr ic te d to a d ve rse o b s e rv a tio n s ; a l l b . O b s e rv a tio n c o n firm e d a t n e c ro p s y . o th e r pups a p p e a re d n o rm a l. P R O T O C O L 4 1 8 - 0 2 0 : ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C3 9 (P A G E 3) : C L IN IC A L O B S ER V A TIO N S FROM B IR T H T O D A Y 22 PO STPARTU M - IN D IV ID U A L D A TA - F I G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER D A Y (S) POSTPARTUM O B S ER V A TIO N S a ARGUS 418-020 Page 319 13 9 2 1 13 9 2 2 13 9 2 7 13 9 3 0 13 9 3 1 13 9 3 4 12-22 1 15 -19 4- 7 8- 9 1, 2 3 4 5 12-20 1 4 ,5 1,2 3 1/14 PUPS 1/ 9 PUPS 1/ 9 PUPS 1/16 PUPS 1/15 PUPS 18 /18 3 /18 18 /18 1/18 1/15 PUPS PUPS PUPS PUPS PUPS 1/15 PUPS 1/14 PUPS 1/15 PUPS 1/15 PUPS 13 9 4 4 9 1/11 PUPS 13 9 4 8 3 11/12 PUPS 4 11/11 PUPS N IP P L E EX A M IN A T IO N S FO R A L L M A LE PUPS A P P EA R ED N O R M A L. a . T a b u la tio n r e s tr ic te d to a d ve rs e o b s e rv a tio n s ; a l l o th e r pups a p p e a re d n o rm a l. M O U T H , M ASS ( D ID N O T E X C E E D 0 .2 CM X 0 .3 CM X 0 .1 C M ). COLD TO TO UCH. U M B ILIC A L H ER N IA . B A C K , B R U IS E (D ID N O T E X C E E D 1 .0 CM X 0 .5 CM) B A C K , B R U IS E ( 0 .2 CM I N D I A M E T E R ) . COLD TO TOUCH. COLD TO TOUCH. COLD TO TOUCH. B A C K , B R U IS E ( 0 .5 U M B ILIC A L H ER N IA . CM I N D IA M ET ER ). NO M ILK IN STOM ACH. B A C K , B R U IS E ( 1 .0 CM X 0 .5 C M ) . H E A D , B R U IS E ( 0 .5 CM I N D I A M E T E R ) , B A C K , B R U IS E ( 2 .0 CM X 1 .0 C M ). H E A D A N D B A C K , B R U IS E ( 1 .0 CM I N D IA M E T E R ) , C H E S T A N D LO W ER M I D L IN E , B R U IS E ( 2 .5 CM X 1 .5 C M ); C O LD TO TO U C H . P A L E ; NO M ILK IN STOM ACH. COLD TO TO UCH . COLD TO TO UCH. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C40 (P A G E 1) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a ARGUS 418-020 Page 320 1380 1 13 8 0 2 13 8 0 3 13 8 0 5 13 8 0 6 13 8 0 7 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 0 8 1 1 PU P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 0 9 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 10 1 1 P U P : S T IL L B O R N ,. A L L T IS S U E S A P P E A R E D N O R M A L 1 PU P: FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED N O RM AL. 3 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED NORM AL 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 12 13 8 13 13 8 14 13 8 15 13 8 16 22 A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 13 8 17 2 1 PU P : FOUND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R T H ER E V A LU A T IO N . 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. C o m p le te n e c ro p s ie s w e re n o t p e rfo rm e d o n p u p s in w h ic h a u t o ly s is o r c a n n ib a liz a t io n p re c lu d e d e v a lu a t io n . R e fe r t o th e in d iv id u a l pup c lin ic a l o b s e rv a tio n s ta b le (T a b le C39) fo r e x te r n a l c lin ic a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE C40 (P A G E 2) : N EC R O P S Y O B S ER V A TIO N S FROM B IR T H TO D A Y 22 POSTPARTUM - IN D IV ID U A L D A TA - F I G EN ER A T IO N PUPS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A T IO N S a I ( C o n t .) 0 13 8 18 2 1 PUP : FOUND D EA D . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 19 1 1 PUP : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER TIS S U ES A P P EA R ED N O RM AL. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 2 0 13 8 2 1 13 8 2 2 13 8 2 3 13 8 2 4 13 8 2 5 13826 13 8 2 7 13 8 2 8 13829 22 22 8b 22 22 22 22 22 22 22 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 8 3 0 1 1 P U P : ,S T I L L B O R N ,. A L L T I S S U E S A P P E A R E D N O R M A L . 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. a . C o m p le te n e c ro p s ie s w e re n o t p e rfo rm e d o n p u p s in w h ic h a u t o ly s is o r c a n n ib a liz a t io n p re c lu d e d e v a lu a t io n . R e fe r t o th e in d iv id u a l pu p c lin ic a l o b s e rv a tio n s ta b le (T a b le C39) fo r e x te r n a l c lin ic a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . T h e l i t t e r s fro m dam s 13 8 2 2 i n G ro u p I a n d 13 8 5 2 in G ro u p I I w e re m ix e d t o g e t h e r . B o th dam s a n d l i t t e r s w e re s a c r if ic e d b e c a u s e i t was n o t p o s s ib le t o i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e d . 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) T A B LE C40 (P A G E 3) : N EC R O P S Y O B S ER V A TIO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A TA - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 322 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a II 221 1 3 8 3 1 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13832 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13833 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13834 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13835 2 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . 3 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 3 7 1 1 P U P : S T ILLB O R N . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 3 8 13 8 3 9 13 8 4 1 4 1 PU P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 4 2 13 8 4 3 13 8 4 4 13845 13 8 4 6 7 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 8 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 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) T A B LE C40 (P A G E 4) : N EC R O P S Y O B S ER V A TIO N S FROM B IR T H TO D A Y 22 POSTPARTUM - IN D IV ID U A L D A TA - F I G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A T ER N A L D O S A G E (M G /K G /D AY) I I ( C o n t .) 1 LIT T E R NUM BER 13 8 4 7 13 8 4 8 13 8 4 9 DAY POSTPARTUM 1 22 22 22 O B S ER V A TIO N S a 7 P U P S : S T ILLB O R N . A U T O LY S IS P R EC LU D ED EV A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. FURTH ER A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. ARGUS 418-020 Page 323 13 8 5 0 1 1 P U P : S T ILLB O R N . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 5 2 13 8 5 3 13 8 5 4 l i b A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 5 5 1 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N ORM AL. 5 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N ORM AL. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13856 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1385 7 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 5 8 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13859 1 1 1 P U P : FOUND D EA D . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 8 6 0 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . a . C o m p le te n e c ro p s ie s w e re n o t p e rfo rm e d o n p u p s i n w h ic h a u t o ly s is o r c a n n ib a liz a t io n p re c lu d e d e v a lu a t io n . R e fe r t o th e in d iv id u a l pup c lin ic a l o b s e rv a tio n s ta b le (T a b le C39) fo r e x te rn a l c lin ic a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . T h e l i t t e r s fro m dam s 13 8 2 2 in G ro u p I a n d 13 8 5 2 in G ro u p I I w e re m ix e d t o g e t h e r . B o th dam s a n d l i t t e r s w e re s a c r if ic e d b e c a u s e i t was n o t p o s s ib le t o i d e n t i f y t o w h ic h l i t t e r th e p u p s b e lo n g e 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) T A B L E C40 (P A G E 5) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 324 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D A Y) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a III 13 8 6 1 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 6 3 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 6 4 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 6 5 1 1 P U P : FOUND D EA D . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13866 8 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . 15 1 P U P : FO U N D D E A D . NO M ILK IN STOM ACH . A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 6 7 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED N O RM AL. 6 1 P U P : FOU ND D E A D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LU D ED FU R TH ER EV A LU A T IO N . 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. 7 1 P U P : FOU ND D E A D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 6 8 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13869 13 8 70 4 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 138 71 3 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. 4 1 P U P : FOU ND D E A D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LU D ED FU R TH ER EV A LU A T IO N . 20 1 P U P : F O U N D D E A D . N O M I L K I N S T O M A C H . A U T O L Y S I S PR EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 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) T A B L E C40 (P A G E 6 ) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 325 M ATERNAL DOSAGE GROUP M A TER N A L D O S AG E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a I I I (C o n t.) 13 8 72 13 8 73 13 8 74 13 8 75 13 8 76 13 8 77 13 8 78 13 8 79 13 8 8 0 1388 1 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 2 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LUD ED FU R TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED NO RM AL. 1 PU P: FOUND D EA D . A L L T IS S U ES A P P EA R ED NORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED N ORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 8 2 13 8 8 3 13 8 8 4 13 8 8 6 13 8 8 7 13 8 8 8 13 8 8 9 13 8 9 0 3 1 P U P : FOUND D EA D . A U T O LY S IS P R EC LU D ED FUR TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1 1 PU P: FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 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) T A B LE C40 (P A G E 7) : N EC R O P S Y O B S ER V A TIO N S FROM B IR T H TO D AY 22 POSTPARTUM - IN D IV ID U A L D A TA - F I G E N E R A T IO N PUPS ARGUS 418-020 Page 326 M ATERNAL DOSAGE GROUP M A TER N A L D O S AG E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a IV 10 11 3 8 9 1 1 P U P : S T I L L B O R N ., A L L T I S S U E S A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 9 2 1 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13893 13 8 9 4 13 8 9 5 13 8 9 6 13 8 9 7 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 8 9 8 13 8 9 9 3 1 P U P : FOUND D EA D . A L L T IS S U ES AP P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1390 1 13 9 0 2 13 9 0 3 13 9 0 4 13 9 0 5 13 9 0 6 13 9 0 7 7 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 1 2 PU PS : S T ILLB O R N . A L L TIS S U ES AP P EA R ED N O RM AL. 3 1 P U P : FOU ND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LU D ED FUR TH ER EV A LU A T IO N . 8 1 P U P : FOU N D D E A D . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 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) T A B L E C40 (P A G E 8) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A TA - F I G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O SAG E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a I V (C o n t .) 10 13 9 0 9 13 9 10 13 9 11 13 9 12 13 9 13 13 9 14 13 9 15 13 9 16 139 17 13 9 18 13 9 19 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 9 2 0 3 1 PUP : FOUND D EA D . A L L T IS S U ES A P P EA R ED N O RM AL. 9 2 P U PS : FOUND D EA D . A U T O LY S IS PR EC LU D ED FU R TH ER EV A LU A T IO N . 1 PUP : FOUND D EA D . NO M ILK IN STOM ACH. A L L OTHER T IS S U ES A P P EA R ED NORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . a . C o m p le te n e c ro p s ie s w e re n o t p e rfo rm e d o n p u p s in w h ic h a u t o ly s is o r c a n n ib a liz a t io n p re c lu d e d e v a lu a t io n . R e fe r t o th e in d iv id u a l pup c lin ic a l o b s e rv a tio n s ta b le (T a b le C39) fo r e x te r n a l c lin ic a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E C40 (P A G E 9) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 328 M ATERNAL DOSAGE GROUP M A T ER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a V 223 0 1 3 9 2 1 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 9 2 2 1 2 PU PS: FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 9 2 3 13 9 2 4 13 9 2 5 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13926 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 9 2 7 7 1 PU P : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER TIS S U ES A P P EA R ED N O RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13928 13 9 3 0 13 9 3 1 13 9 3 2 13 9 3 3 3 1 P U P : FOU ND D EA D . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 8 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LUD ED FUR TH ER EV A LU A T IO N . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 6 1 P U P : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED N O RM AL. 8 1 PU P: FOUND D EA D . A L L TIS S U ES A P P EA R ED N ORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 6 2 PU PS: FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED N O RM AL. 1 P U P : FOU ND D EA D . NO M ILK IN STOM ACH. A U T O LY S IS PR EC LUD ED FUR TH ER EV A LU A T IO N . 8 1 P U P : FOUND D EA D . A L L TIS S U ES A P P EA R ED N ORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 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) T A B L E C40 (P A G E 10 ) : N EC R O P S Y O B S ER V A T IO N S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 329 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D A Y) LIT T E R NUM BER DAY POSTPARTUM O B S ER V A TIO N S a V ( C o n t .) 30 13 9 3 4 13 9 3 5 13 9 3 6 13 9 3 7 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13 9 3 8 2 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 9 3 9 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NO RM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 9 4 0 22 A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 13 9 4 1 1 1 P U P : S T ILLB O R N . A L L T IS S U ES A PPEA R ED NORM AL. 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 13 9 4 2 13 9 4 3 13 9 4 4 13 9 4 5 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 13946 22 1 P U P : K ID N E Y S , R IG H T , P E L V IS , M O DERATE D IL A T IO N . A L L O TH ER T IS S U ES AP P EA R ED NORM AL. A L L O TH ER PUPS APPEAR ED NORM AL. 13 9 4 7 1 1 PU P : FOUND D EA D . NO M ILK IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 13 9 4 8 13 9 4 9 13 9 5 0 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 3 PU PS: S T ILLB O R N . A L L TIS S U ES A PPEA R ED NORM AL 2 1 PU P: FOUND D EA D . A L L TIS S U ES APPEAR ED NORM AL 22 A L L P U P S E X A M I N E D A P P E A R E D N O R M A L . 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) T A B L E C 4 1 (P A G E 1 ) : PU P O R G AN W EIG H T S - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU P S ARGUS 418-020 Page 330 M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY RAT/ L IT T E R NUM BER 1380 1 13 8 0 2 13 8 0 3 13 8 0 4 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 B R A IN MF T S P LEEN MF T THYM US MF T 1 .6 7 1.58 1.35 1.53 1.48 1.43 1.60 1.53 1.39 0 . 2 7 0.21 0 . 2 4 0.10 0 . 1 5 0.12 0.11 0 . 1 3 0.12 0.21 0.19 0.17 M O R IB U N D S A C R IF IC E D O N D A Y 68 O F S TU D Y 1 .3 1 1.45 1.20 1 .4 1 1.26 1.43 0.19 0.11 0.12 0 . 1 4 0.15 0.13 0.26 0.13 1.27 1.45 1.40 1.47 1.23 1.63 1 .4 1 1.40 1.25 1.54 1.40 1.44 0.09 0.18 0.14 0.17 0.06 0.21 0.12 0.17 0.08 0.20 0.13 0.17 0.07 0.22 0.11 0.21 NOT PREGNANT 1.36 1.29 1.32 0.11 0.10 0.10 0 . 0 8 1.38 1.38 1.48 1.33 1.43 1.36 0.13 0.13 0.14 0.08 0.14 0.10 0.14 0.15 1.36 1.20 1.59 1.34 1.16 1.54 1.35 1.18 1.56 0.05 0.17 0.14 0.05 0.14 0.13 0.05 0.16 0.14 0.13 0.13 0.12 1.30 1.25 1.38 1.35 1.43 1.26 1.45 1.4 1 S A C R IFIC ED 1.5 1 1.49 1.48 1 .4 1 1.28 1.36 1.34 1.43 ON DAY 1.50 1.44 0.08 0.06 0.07 0.20 0.12 0 . 1 6 0.12 0 . 0 8 0.10 0 . 0 7 0 . 1 7 0.12 8 O F :L A C T A T I O N 0 . 3 4 0.22 0 . 2 8 0 . 1 4 0.11 0.12 0.09 0.18 0.18 0.11 0.28 0.16 -- 1.37 1.37 -- 0.07 0.07 -- 1.36 1.57 1.39 1.25 1.56 1.45 1.30 1.56 1.42 0.14 0.17 0.25 0.14 0.14 0.20 0 . 1 8 0 . 1 6 0.20 0.13 0.15 0.18 1 .5 1 1.38 1.27 1.44 1.39 1.41 0.15 0.13 0.14 0.17 0.11 0.10 0.10 0 . 1 4 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 T E R M IN A L B O D Y W EIG H T MF T 44.6 43.0 a 42.5 41.3 a 43.6 42.2 a 46.6 3 2 .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 3 1.1 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 = M ALE F = FEM ALE T = TOTAL A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . a . P u p 's i d e n t i f i c a t i o n w as n o t r e c o r d e d ; th e re fo re , te rm in a l b o d y w e ig h t c o u ld n o t be d e te rm in e 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) T A B L E C 4 1 (P A G E 2 ) : PU P O R G A N W EIG H TS - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 331 M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY RAT/ LIT T E R NUM BER 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13 8 5 2 13853 13854 13855 13856 13857 13858 13859 13 8 6 0 B R A IN MF T S P LEEN MF T THYM US MF T 1 .4 7 1.65 1 .5 1 1.47 1.49 1.49 1.47 1.57 1.50 0.11 0 . 1 4 0.12 0 . 1 5 0.12 0 . 1 4 0.12 0.12 0.12 0.12 0.14 0.17 1.52 1.52 1 .4 7 1.44 1.50 1.48 0.07 0.08 0.08 0.18 0.10 0 . 1 4 0.12 0.11 M O R IB U N D S A C R IF IC E D ON D A Y 59 O F S T U D Y 1.66 1.45 1.49 1.40 1.58 1.42 0.19 0.17 0.18 0.11 0 . 0 9 0.10 0.26 0.16 1.42 1.45 1.44 0.14 0.13 0.14 0.17 NOT PREGNANT 1.34 1.49 1.33 1.39 1.43 1.41 1.53 1.32 1.33 1.40 1.29 1.29 1.49 1.45 1.49 1.34 1.34 1.44 1.31 1.34 1.46 1.43 1 .5 1 1.33 0.15 0.17 0.11 0.12 0.11 0.16 0.21 0.11 0.15 0.12 0.11 0.06 0.16 0.08 0.21 0.04 0.15 0.14 0.11 0.09 0.14 0.12 0.21 0.08 0.15 0.14 0.13 0.15 0.13 0.17 0.21 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 S A C R IFIC E D ON D AY 1 1 OF LA C T A T IO N 1.53 1.11 1.53 1.40 1.45 1.36 1.40 1.10 1.53 1.30 1.54 1.36 1.46 1.10 1.53 1.35 1.50 1.36 0.13 0.15 0.08 0.10 0.06 0.11 0.14 0.04 0.08 0.07 0.15 0.11 0.14 0.10 0.08 0.08 0.10 0.11 0.17 0.18 0.20 0.10 0.22 0.11 1.52 1.44 1.50 1.37 1 .5 1 1.40 0.18 0 .17 0.18 0.16 0.10 0.10 0.10 0 . 1 9 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 T E R M IN A L B O D Y W EIG H T MF T 33.1 45.2 a 36.2 36.7 36.7 35.5 a 3 7.7 37.3 34.9 40.4 a 37.0 37.0 a 36.0 36.1 a 36.0 32.7 a 36.0 34.4 36.3 43.4 34.3 33.6 a 36.3 51.4 a 27.5 37.3 37.0 3 7 .7 30.1 27.8 a 31.0 50.4 a 23.6 33.8 36.6 40.6 32.2 30.7 a 33.6 50.9 a 25.6 35.6 37.8 30.1 40.2 32.9 39.6 33.2 37.4 35.4 27.5 23.8 37.0 25.6 41.8 30.7 40.7 38.7 32.6 27.0 38.6 29.2 40.7 32.0 39.0 37.0 M = M ALE F = FEM ALE T = TOTAL A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . P u p 's i d e n t i f i c a t i o n w as n o t r e c o r d e d o r a p p e a re d i n c o r r e c t l y d e te rm in e d . re c o rd e d ; th e re fo re , te rm in a l b o d y w e ig h t c o u ld n o t 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) T A B L E C 4 1 (P A G E 3) : PU P O R G AN W EIG H TS - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 332 M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY RAT/ LIT T E R NUM BER 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 B R A IN MF T S P LEEN MF T 1.34 -- 1.34 PR EG N AN T; D ID NOT 1.36 1.43 1.40 1.50 -- 1.50 1.48 1.28 1.42 1.13 1.45 1.20 1.34 1.28 1.3 1 1.4 1 1.45 1.43 1.23 1.35 1.29 -- 1.25 1.25 1.12 1 . 2 5 1 . 1 8 1.44 1.4 1 1.42 1.40 1.40 1.40 1.63 1.40 1.52 1.48 1.43 1.46 1.59 1.62 1.60 1.5 1 1.55 1.53 -- 1.54 1.54 1.64 1.53 1.58 1.58 1.39 1.48 1.45 1.39 1.42 1.45 1.50 1.48 1.4 7 1.39 1.43 1.51 1.31 1.41 b 1.4 7 1.45 1.46 1.62 1.55 1.58 -- 1.31 1.31 1.53 1.32 1.42 -- 1.37 1.37 0.08 -- 0.08 D E LIV E R A L IT T E R 0.11 0 . 1 1 0 . 1 1 0.28 0.12 0.12 0.05 0.08 0.09 -- 0.02 0.09 0.10 0.22 -- 0.14 0.06 0.12 0.11 0.10 0.10 0.08 0.10 0.12 0.16 0.28 0.13 0.09 0.08 0.10 0.10 0.10 0.05 0.10 0.11 0.19 0.13 0.13 0.13 0.11 0 . 2 3 0 . 1 7 0.16 0.14 0.15 -- 0.23 0.23 0.10 0 . 1 9 0 . 1 4 0.19 0.16 0.18 0.06 0.07 0.06 0.10 0 . 1 3 0.12 0.19 0.13 0.16 0.21 0 . 0 8 0 . 1 4 0.12 0.18 -- 0.15 -- 0.12 0.18 0.15 0.10 0.06 0.12 0.18 0.15 0.12 0.06 THYM US MF T 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 T E R M IN A L B O D Y W EIG H T MF T 36.2 ___ 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 3 7 .7 37.6 43.6 42.3 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 4 7 .7 42.9 37.2 44.5 48.0 27.4 33.6 59.3 29.5 a 29.0 a 31.8 36.3 28.0 29.9 35.4 46.2 41.5 46.2 44.2 51.8 46.9 47.8 37.4 41.0 45.8 34.8 40.3 49.9 -- 35.8 -- 40.6 45.3 25.9 32.1 38.8 40.4 47.6 25.9 34.0 38.8 M= A LL a. b. M ALE F = FEM ALE T = TOTAL W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . P u p 's i d e n t i f i c a t i o n w as n o t r e c o r d e d ; t h e r e f o r e , A l l pups w ere s e le c te d f o r c o n tin u e d o b s e rv a tio n . te rm in a l b o d y w e ig h t c o u ld n o t be d e te rm in e 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) T A B L E C 4 1 (P A G E 4) : P U P O R G A N W EIG H T S - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 333 M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY R AT/ L IT T E R NUM BER 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13 9 14 13915 13916 13917 13 9 18 13919 13920 B R A IN MF T S P LEEN MF T 1.60 1.53 1.56 0.17 1.44 1.51 1.48 0.19 1.52 1.40 1.37 1.41 1.44 1.40 0.17 0.10 1.54 1.52 1.39 1.46 1.46 1.49 0.16 0.12 1.44 1.37 1.36 1.28 1.40 1.32 0.16 0.10 1.33 1.30 1.32 0.07 N O T P R EG N A N T ; M A TIN G N O T 1.36 1.28 1.32 0.07 1.60 1.49 1.54 0.19 1.43 1.27 1.32 1.38 1.30 1.13 1.40 1.28 1.22 0.15 0.11 0.05 1.53 1.4 1 1.4 7 1.20 1 . 2 9 1 . 2 4 0.18 0.12 b 1.50 1.43 1.46 0.12 1.42 1.44 1.39 1.47 1.40 1.46 0.17 0.10 1.49 1.44 1.41 1.25 1.45 1.34 0.13 0.20 1.43 1.4 1 1.42 0.09 1.30 1.31 1.30 0.08 1.32 1.42 1.54 1.40 1.43 1.41 0.18 0.12 1.62 1.37 1.50 0.26 1.48 1.49 1.48 1.12 1 . 3 8 1 . 2 5 0.08 0.12 0 . 2 6 0.22 0.13 0.16 0.13 0.15 0.16 0.13 0.19 0.18 0 . 1 3 0.12 0.14 0.15 0.06 0.08 0.11 0 . 0 9 C O N FIR M ED 0.07 0.07 0.17 0.18 0.13 0.14 0 . 1 3 0.12 0.07 0.06 0 . 2 3 0.20 0.10 0.11 0.10 0.14 0.14 0.16 0.19 0.10 0.10 0.20 0.13 0.16 0.12 0.12 0.11 0.16 0.12 0.14 0.20 0.10 0.09 0.19 0.12 0.21 0.10 0.12 THYM US MF T 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 T E R M IN A L B O D Y W EIG H T MF T 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 3 1 .7 46.0 3 7.7 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 4 1 .7 41.0 42.2 37.9 25.3 M= A LL a. b. M ALE F = FEM ALE T = TOTAL W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . P u p 's i d e n t i f i c a t i o n w as n o t r e c o r d e d o r a p p e a re d d e te rm in e d . A l l p u p s w e re s e le c te d fo r c o n tin u e d o b s e rv a tio n . in c o rre c tly rec ord e d ; th e re fo re , te rm in a l b o d y w e ig h t c o u ld n o t 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) T A B L E C 4 1 (P A G E 5) : P U P O R G A N W EIG H T S - IN D IV ID U A L D A T A - F I G E N E R A T IO N PU PS ARGUS 418-020 Page 334 M ATERNAL DOSAGE GROUP V 30 M G/KG/DAY RAT/ LIT T E R NUM BER 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13 9 3 4 13935 13936 13937 13938 13939 13940 13941 13 942 13943 13944 13945 13946 13947 13948 13949 13950 B R A IN MF T S P LEEN MF T THYM US MF T T E R M IN A L B O D Y W EIG H T MF T 1.53 1.49 1.5 1 1.29 -- 1.29 1.52 1.4 1 1.46 1.49 1.43 1.46 1.35 1.40 1.38 1.39 1.35 1.37 1.19 1.16 1.18 1.46 1.39 1.42 NOT PREGNANT 1.28 1.33 1.30 1.13 1.15 1.14 1.32 1.30 1.3 1 1.17 1.19 1.18 -- 1.26 1.26 1.33 1.30 1.32 1.42 1.48 1.45 1.43 1.32 1.40 1.42 1.21 1 . 2 6 1.5 1 1.46 1.48 1 . 2 9 1.22 1 . 2 6 1.59 1.52 1.56 1.58 1.4 1 1.50 -- 1.56 1.56 1.39 1.35 1.37 1.4 1 1.35 1.38 1.35 1.26 1.30 S A C R IFIC ED DUE TO 1.46 1.38 1.42 1.52 1.45 1.48 1.64 1.48 1.56 0.16 0.12 0.10 0.09 0.11 0.11 0.06 0.16 0.14 -- 0.09 0.08 0.13 0.12 0.07 0.18 0 . 0 8 0.10 0.07 0.11 0.06 -- 0.07 0.14 0.10 0.12 0.05 0.07 0.15 0.15 0.11 0 . 1 3 0.09 0.06 0.16 0.15 0.04 0.06 0.19 0.13 0.18 0.15 -- 0.13 0.09 0.11 0.24 0.12 0.11 0.14 NO S U R V IV IN G 0.14 0.14 0.12 0.12 0.18 0.17 0.15 0.12 0.10 0.08 0.12 0.12 0.06 0.17 0.18 0.10 0.15 0.14 0.16 0.16 0.07 0.20 0.10 -- 0.13 0.15 0.17 0.16 0.06 0.18 0.14 0.10 0.14 0.14 0.16 0.16 0.06 0.19 0.09 0.07 0.12 0.06 0.09 0.05 0.06 0.06 0.10 0.10 0.12 0 . 0 8 0.08 0.12 0.06 0.06 -- 0.11 0.08 0.15 0.08 0.07 0.15 0.10 0.15 0.12 0.08 0.13 0.19 0.16 0.12 0.11 0.12 0 . 1 4 0.11 0.12 0.16 0.14 0.23 0.18 0.05 0.04 0.07 0.06 0.16 0.16 0.24 0.12 0.10 0.12 0.18 0.14 -- 0.16 0.12 0.16 0.13 0.12 0.20 0.18 0.14 0.17 0.16 0.13 0.20 0.17 0.13 0.16 PUPS ON DAY 1 O F LA C T A T IO N 0.14 0.12 0.18 0.18 0.19 0.28 0.15 0.18 0.21 0.16 0.18 0.24 46.1 32.8 a 34.5 32.9 34.0 23.9 a 25.3 24.9 31.5 a -- 34.3 38.0 39.0 29.2 38.4 30.0 41.4 a -- 35.1 a 43.2 43.4 40.9 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 3 2 .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 = M ALE F = FEM ALE T = TOTAL A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . a . P u p 's i d e n t i f i c a t i o n w as n o t r e c o r d e d o r a p p e a re d i n c o r r e c t l y d e te rm in e d . re c o rd e d ; th e re fo re , te rm in a l b o d y w e ig h t c o u ld n o t 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-6889.6) T A B LE D 1 (P A G E 1) : C L IN IC A L O B S ER V A TIO N S - SUM M ARY - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 336 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV V 10 3 0 M AXIM U M P O S S IB L E IN C ID E N C E M O R T A LIT Y FOUND DEAD a M O R IB U N D S A C R IF IC E D a AN N U LAR C O N S T R IC T IO N O F TH E T A IL C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N U R IN E -S T A IN E D A B D O M IN A L FU R EM A C IA T IO N CHROM ODACRYORRHEA D EC R EAS ED M OTOR A C T IV IT Y COLD TO TOUCH 4 5 6 3 / 60 3 2 1 44/ 4 12/ 9 25/ 4 11/ 1 0/ 0 22/ 3 1/ 1 1/ 1 4 5 4 7 / 60 3 3 0 122/ 11* 18 / 9 41/ 4 2/ 2 1/ 1 53/ 5 1/ 1 1/ 1 4 5 7 6 / 60 3 3 0 69/ 7 22/ 11 11/ 1 11 3 / 2/ 2 244/ 0/ 1/ 9 0 1 46 0 2/ 60 2 1 1 122/ 11* 10/ 4 73/ 5 6/ 1 15/ 3 * 55/ 4 1/ 1 21 3 / 4 4 7 3 / 60 7 6 1 212 1 4 / ** 2 6 / 12 101 2 4 / ** 40/ 9 ** 22/ 7 * * 61 7 1 / 12/ 5 * * 11/ 5 IN C IS O R S : TO TAL M IS A LIG N ED M IS S IN G /B R O K EN SCAB b SO FT OR LIQ U ID FEC ES 47/ 5 12/ 3 36/ 4 89/ 4 22/ 11 62/ 3 62/ 3 0/ 0 23 0 / 1 4 / 11 258/ 194/ 66/ 9 7 4 55/ 5 6/ 5 171/ 123/ 48/ 5 3 2 18 / 3 7/ 7 188/ 181/ 25/ 4 4 2 7/ 3 3/ 3 M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S x R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D1 4) f o r o b s e rv a tio n s f o r r a ts th a t w e re fo u n d d e a d o r m o rib u n d s a c rific e d . b . L o c a te d o n n e c k , h e a d , b a c k , m o u th , a n d b e h in d l e f t e a r . * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e (p<:0.05) . ** S i g n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 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) T A B LE D 1 (P A G E 2) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 337 DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV V 0 1 3 10 30 M A XIM U M P O S S IB L E IN C ID E N C E 4 5 6 3 / 60 4 5 4 7 / 60 4 5 7 6 / 60 4 6 0 2 / 60 4 4 7 3 / 60 M O R T A LIT Y FOUND DEAD a M O R IB U N D S A C R IF IC E D a 33 32 2 331 1 0 01 7 6 1 LO C A LIZE D A LO P E C IA : TO TA L LIM B S BACK H EA D 30/ 30/ 0/ 0/ 1 1 0 0 56/ 56/ 0/ 0/ 1 1 0 0 36/ 3 1/ 3/ 2/ 3 1 1 1 10/ 0/ 10/ 0/ 1 0 1 0 7/ 2 7/ 2 0/ 0 0/ 0 R IG H T OR BO TH E Y E ( S ) : C O R N EA L O P A C IT Y 0/ 0 14/ 1 0/ 0 0/ 0 2/ 2 R ALES 1/ 1 0/ 0 0/ 0 0/ 0 2/ 2 D EH Y D R A T IO N 0/ 0 0/ 0 0/ 0 19 / 2 14/ 1 LA C R IM A T IO N 0/ 0 0/ 0 34/ 1 0/ 0 6/ 1 R IG H T E Y E : SW O LLEN 0/ 0 0/ 0 0/ 0 0/ 0 6/ 1 SNOUT : SW OLLEN 3/ 1 2/ 1 32/ 2 6/ 1 4/ 1 P EN IS : R ED SUBSTANCE 0/ 0 0/ 0 0/ 0 1/ 1 4/ 1 EXC ES S S A LIV A T IO N R ED , D R IE D , S LIG H T P E R IN A S A L SUBSTANCE V O C A LIZA T IO N 4/ 4 0/ 0 1/ 1 2/ 2 0/ 0 1/ 1 3/ 3 3/ 2 0/ 0 1/ 1 1/ 1 0/ 0 1/ 1 1/ 1 1/ 1 BOTH EARS : SW OLLEN 0/ 0 0/ 0 8/ 3 2/ 2 0/ 0 M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S x R A T S )/ N U M B E R N /N = T O T A L NUM BER O F O B S ER V A TIO N S /N U M B ER O F R A TS a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s s a c rific e d . O F R A TS EX A M IN ED P ER G R O U P . W IT H O B S E R V A T IO N . ta b le (T a b le D 14 ) fo r o b s e rv a tio n s fo r ra ts th a t w ere fo u n d d e a d o r m o rib u n 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) T A B LE D 1 (P A G E 3 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N M A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV 0 1 3 10 V 30 M AXIM U M P O S S IB L E IN C ID E N C E 4 5 6 3 / 60 4 5 4 7 / 60 4 5 76 / 60 4 6 0 2 / 60 4 4 7 3 / 60 M O R T A LIT Y FOUND D EAD a M O R IB U N D S A C R IF IC E D a 3 332 2 331 1 001 7 6 1 T I P O F T A I L M IS S IN G 0/ 0 0/ 0 0/ 0 21/ 1 0/ 0 T IP O F T A IL BLACK 0/ 0 0/ 0 0/ 0 9/ 1 0/ 0 B A C K : U LC ER A T IO N 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 R E D , S LIG H T P ER IO R A L SUBSTANC E 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 P T O S IS 0/ 0 20/ 1 0/ 0 0/ 0 0/ 0 ENOPHTHALM OS 0/ 0 2/ 1 0/ 0 0/ 0 0/ 0 H E A D : A B R A S IO N 18 / 2 0/ 0 0/ 0 0/ 0 0/ 0 R IG H T E Y E : EN LA R G ED 102/ 1 0/ 0 0/ 0 0/ 0 0/ 0 M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . R e fe r t o th e in d iv id u a l c l i n i c a l o b s e rv a tio n s ta b le (T a b le D 14 ) f o r o b s e rv a tio n s f o r r a ts t h a t w e re fo u n d d e a d o r m o rib u n d s a c rific e d . 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) T A B L E D2 (P A G E 1 ) : B O D Y W EIG H TS - SUM M ARY - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S AG E (M G /K G /D AY) RATS TES TED N I 0 60 II III 13 60 60 IV V 10 30 60 60 B O D Y W EIG H T (G) DAY 1 M EANS. D . 4 2 .7 6.9 4 1 .0 6.8 43.8 9 .7 44.6 6.6 40.4 8.4 DAY 8 DAY 15 DAY 22 DAY 29 D A Y 36 D A Y 43 D A Y 50 M EANS.D . M EAN+S.D . M EANS.D . M EANS.D . M EANS. D . M EANS. D . M EAN+S.D . 75.2 11.7 t 59] a 124.1 1 5 .9 [ 59] a 183.9 20.4 ( 59] a 241.0 2 3 .1 [ 58] a 297.9 27.7 [ 47] a 342.4 28.8 [ 30] a 383.2 33.7 [ 30] a 72.3 9.8 [ 58] a 118.8 13.3 [ 58] a 175.6 1 7 . 9 [ 58] a 231.6 21.0 [ 58] a 288.2 28.3 [ 54] a 327.8 25.9 [ 30] a 359.7 26.8* [ 29] a 77.3 15.2 [ 58] a 126.9 20.7 [ 57] a 186.6 26.0 [ 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 1 5 .8 [ 59] a 181.4 21.8 [ 59] a 233.0 27.6 [ 59] a 280.1 40.0* [ 49] a 323.6 3 4.0* [ 30] a 355.3 4 0 .2 ** [ 30] a 69.6 1 2 .7 * [ 55] a 109.2 1 7 .6 * * [ 55] a 162.7 2 0 .4 ** [ 55] a 2 11.1 25.2** [ 55] a 250.8 3 3 .4 ** [ 48] a 291.3 3 2 .5 ** [ 30] a 318.3 3 5 .3 ** [ 30] a DAY [] a. * ** = D A Y P O S TW EA N IN G = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s v a lu e s f o r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . m a tu ra tio n , fo u n d d e a d o r m o rib u n d s a c r if ic e d . ARGUS 418-020 Page 339 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D2 (P A G E 2 ) : B O D Y W EIG H TS - SUM M ARY - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 340 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III IV V 0 1 3 10 30 RATS TES TED N 60 60 60 60 60 IN C LU D ED IN A N A LYS ES N 30a 29a 30a 30a 30a B O D Y W EIG H T (G) DAY 57 M EANS. D . 412.5 36.4 387.8 + 28.8* 398.7 33.0 380.1 + 4 3 .8 ** 338.5 3 6 .7 ** D A Y 64 M EANS.D . 443.9 40.9 416.4 + 32.8* 424.1 34.8 404.5 4 9 .3 ** 360.2 3 9 .4 ** DAY 70b M EANS.D . 463.7 + 44.2 434.6 + 39.2* 442.2 36.6 420.9 5 1 .1 * * 372.7 4 0 .7 ** P R EC O H A B IT A T IO N C M EAN+S.D . 488.1 + 46.5 463.3 46.4 468.2 + 39.9 443.8 5 3 .9 ** 391.0 4 2 .0 ** DAY 99d M EANS.D . 521.9 54.0 493.0 + 4 9 .4 * 497.4 + 40.9 469.5 5 7 .5 * * 409.8 4 1 . 1 * * DAY 106 M EANS.D . 539.0 + 55.5 504.6 52 .0* 506.9 45.4 * 481.8 6 0.8 ** 416.1 + 48.0** DAY 113 M EANS.D . 554.8 + 57.6 [ 28] a 513.4 53.6* 512.3 49.0* 488.7 6 1 .0 ** 428.0 4 0 .1 * * [ 29] a DAY [] a. b. c. d. * ** = D A Y P O S T W EA N IN G = NUM BER O F V A LU ES AV ER AG ED E x c lu d e s v a lu e s f o r r a ts th a t w e re s a c r ific e d fo llo w in g s e x u a l m a tu r a tio n , fo u n d d e a d o r m o rib u n d B e c a u s e b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly i n t e r v a ls , b a se d on e a ch r a t ' s d a y p o s tw e a n in g , w as th e la s t d a y o n w h ic h th e y o u n g e s t r a t s ( in t h is g ro u p ) h a d a b o d y w e ig h t v a lu e re c o rd e d . P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was be g u n fo r th e F I g e n e ra tio n r a t s w e re 92 to 106 d a ys o f a g e . F i r s t w e e k ly v a lu e re c o rd e d a f t e r c o h a b ita tio n . S ig n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . s a c rific e d . d a y 70 p o s tw e a n in g r a t s ; a t th a t tim e th e s e PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D3 (P A G E 1 ) : B O D Y W EIG H T C H AN G ES - SUM M ARY - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TESTED N I 0 60 II III 13 60 60 IV V 10 30 60 60 IN C LU D ED IN A N A LY S ES N 59a 58a 58a 59a 55a B O D Y W EIG H T C H A N G E (G) DAYS 1 - 8 M EANS.D . +32.3 7.0 +30.9 5.4 +33.0 7 .1 +31.8 5.9 +27.9 6 .4 ** DAYS 8 - 15 D AYS 15 - 22 DAYS 22 - 29 D AYS 29 - 36 D A YS 36 - 43 D A Y S 43 - 50 M EANS.D . M E A N S .D . M EANS.D . M EANS.D . M EANS. D . M EANS.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 t 30] a +40.8 9.8 [ 30] a +46.5 5.0 +56.8 7 .0 * +55.9 5.2 +57.0 17.0 [ 54] a +39.8 1 9 .1 [ 30] a +33.0 6 .3 * * [ 29] a +49.2 6.9 [ 57] a +59.7 7 .1 [ 57] a +56.6 5.6 [ 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 1 0 .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 1 2 .6 * * +40.7 1 3 .2 ** [ 48] a +35.4 7 . 7 * * [ 30] a +27.0 9 .6 ** [ 30] a D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e xu a l * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . m a tu ra tio n , fo u n d d e a d o r m o rib u n d s a c rific e d . ARGUS 418-020 Page 341 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D3 (P A G E 2 ) : B O D Y W EIG H T C H A N G ES - SUM M ARY - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 342 DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TES TED N I 0 60 II III 13 60 60 IV V 10 30 60 60 I N C L U D E D I N ,A N A L Y S E S N 30a 29a 30a 30a 30a B O D Y W EIG H T C H A N G E (G) D A Y S 50 - 5 7 M E A N S .D . +29.3 8.0 + 28.1 6.2 +27.3 13.1 +24.8 + 7 .3 * +20.2 9 .1 * * D A Y S 5 7 - 64 M EANS. D . +31.4 8.3 +28.6 6.8 +25.3 6 .4 * +24.4 + 12.3 +21.7 6 . 6** D A Y S 64 - 70 b DAY 1- P R EC O H A B IT A T IO N M E A N S .D . +19.8 6.2 M EANS.D . +445.1 + 4 4 . 1 +18.3 9 .1 +422.3 44.5 +18.2 5.3 +423.5 38.9 +16.4 8.2 +12.5 6 . 8* * +399.7 5 0 .8 ** +350.5 3 9 .1 * * DAYS 99c -106 M EANS.D . + 1 7 .1 33.5 +11.6 8.3 +9.6 12.4 +12.2 9.4 +6.3 26.5 DAYS 106 - 113 DAYS 1 -113 M EANS.D . M EANS.D . +10.1 37.3 [ 28] a + 5 1 1 . 6 5 5 .0 [ 28] a +8.8 10.0 + 4 7 2 .5 5 2 .3 * * +5.4 15.6 + 4 6 7 . 6 4 9 . 6 * * +7.0 8.1 +444.6 58 .3** +7.3 10.8 [ 29] a + 3 8 7 . 8 3 7 . 4 * * ( 29] a D A Y (S ) = D A Y (S ) P O S TW EA N IN G [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s f o r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n , fo u n d b . P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was begu n fo r r a t s w e re 92 t o 10 6 d a y s o f a g e . c . F i r s t w e e k ly v a lu e re c o rd e d a f t e r c o h a b ita tio n . * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . d e ad o r m o rib u n d s a c r if ic e d . th e F I g e n e ra tio n r a t s ; a t th a t tim e th e se PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D4 (P A G EI 1 ) : A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - SUM M ARY - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 343 DOSAGE GROUP D O S A G E (M G /K G /D A Y) RATS TES TED N I 0 60 II III 13 60 60 IV V 10 30 60 60 IN C LU D ED IN A N A LYS ES N 59a 58a 58a 59a 55a F E E D C O N S U M P TIO N (G /D A Y ) DAYS 1 - 8 D AYS 8 - 15 DAYS 15 - 22 D A YS 22 - 29 D A YS 29 - 36 D AYS 36 - 43 D A Y S 43 - 50 D A YS 50 - 5 7 D A Y S 5 7 - 64 DAYS 64 - 70 c DAYS 1 - 70c M EAN+S.D . M EANS.D . M EAN+S.D . M E A N S .D . M EANS. D . M EAN+S.D . M EANS.D . M EANS.D . M EANS.D . M EAN+S. D . M EANS.D . 10.5 1.5 18.1 [ 58] b 22.4 2.0 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 10.4 1.3 17.4 1.8 21.6 + 2.0 24.7 2 .2* 26.8 2 .1* [ 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 [ 27] a ,b 27.6 3.3 [ 28]a,b 23.7 1.7** [ 28]a,b 1 0 .8 2.4 18.2 2.9 [ 57] a 22.3 2.7 [ 57] a 25.3 3.6 [ 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 10.6 1.6 17.6 2.8 21.6 + 2.4 25.7 2.5 [ 58] b 28.4 4.0 [ 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 ( 30] a 27.7 3.8 [ 30] a 24.4 2.4 [ 30] a 9.3 1.7** 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 D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s f o r r a t s th a t w e re s a c r if ic e d fo llo w in g s e x u a l m a tu r a tio n , fo u n d d e a d o r m o rib u n d s a c r if ic e d . b . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e , w e t o r s o ile d fe e d . c . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly i n t e r v a ls , b a s e d on e a ch r a t ' s d a y p o s tw e a n in g , d a y s 6 4 - 7 0 p o s tw e a n in g th e la s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d f o r th e y o u n g e s t r a t s in t h is g ro u p . * S i g n ific a n t ly d iff e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S i g n if ic a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p ^ O . O l ) . was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D4 (P A G E 2) : A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - SUM M ARY - F I G E N E R A T IO N M A LE R A T S DOSAGE GROUP D O S AG E (M G /K G /D AY) I II III IV V 0 1 3 10 30 RATS TES TED N 60 60 60 60 60 IN C LU D ED IN A N A LY S ES N 30a 28a,b 29a, b 30a 29a,b F E E D C O N S U M P TIO N (G /D A Y ) D A Y S 99 - 1 0 6 M EANS.D . 28.7 2.9 27.7 3 .1 27.8 3 .1 28.5 3.3 26.9 3.6 DAYS106 -1 1 3 D A Y S 99 - 1 1 3 M E A N + S .D . M E A N S .D . 28.8 3.0 [ 24]b,c 28.8 3.0 [ 24]b ,c 27.6 27.6 3.2 2.9 27.2 27.5 + 4 .1 3.3 28.2 [ 28] b 28.2 [ 28] b 3 .1 3.0 26.9 3.4 [ 28]a,b 27.2 3 .1 ( 28]a,b D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n , b . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e , w et o r s o ile d fe e d . c . E x c lu d e s v a lu e s f o r r a t s t h a t w e re s a c r ific e d b e fo re d a y 113 p o s tw e a n in g . fo u n d d e a d o r m o rib u n d s a c r ific e d . 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) T A B L E D5 (P A G E1 1 ) : R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - SUM M ARY - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 345 DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TES TED N I 0 60 II III 13 60 60 IV V 10 30 60 60 IN C LU D ED IN A N A LYS ES N 59a 58a 58a 59a 55a F E E D C O N S U M P TIO N (G /K G /D A Y ) DAYS 1 - 8 M EANS. D . 179 .2 + 23.9 183.8 19.4 177.8 25.7 176.6 19.9 168.3 25.0* D A YS 8 - 15 D AYS 15 - 22 D A YS 22 - 29 D A YS 29 - 36 D A Y S 36 - 43 D A Y S 43 - 50 D A Y S 50 - 5 7 D A Y S 5 7 - 64 D AYS 64 - 70 c DAYS 1 - 70c M EANS.D . M EANS.D . M EAN+S. D . M EANS.D . M E A N S .D . M E A N S .D . M E A N S .D . M EAN+S. D . M EAN+S.D . M EANS.D . 182.9 19.5 [ 58] b 146.3 12.2 121.0 15.8 [ 58] a 104.6 7.6 [ 47] a 90.7 6.8 C 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 [ 54] a 91.3 7.7 [ 29] a , b 78.7 5.6 [ 29] a , b 75.8 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 [ 57] a 143.3 10.9 [ 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 [ 29] a , 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 6.4 [ 30] a 95.2 5.9* [ 30] a 18 1.0 25.6 149.4 1 7 .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** [ 30] a D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s f o r r a t s th a t w e re s a c r ific e d fo llo w in g s e x u a l m a tu r a tio n , fo u n d d e a d o r m o rib u n d s a c r if ic e d . b . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e , w et o r s o ile d fe e d . c . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly in t e r v a ls , b a s e d on e a c h r a t ' s d a y p o s tw e a n in g , d a y s 6 4 - 7 0 p o s tw e a n in g th e la s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e was re c o rd e d f o r th e y o u n g e s t r a ts in t h is g ro u p . * S i g n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . ** S i g n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 . 6 ) T A B L E D 5 ( P A G E 2 ) : R E L A T I V E F E E D i C O N S U M P T I O N V A L U E S ( G / K G / D A Y ) - S U M M A R Y - F I G E N E R A T I O N M A L E R A T S DOSAGE GROUP D O S A G E (M G /K G /D AY) RATS TESTED N I 0 60 II III 13 60 60 IV V 10 30 60 60 IN C LU D ED IN A N A LYS ES N 30a 28a,b 29a,b 30a 29a,b F E E D C O N S U M P TIO N (G /K G /D A Y ) D A Y S 99 - 1 0 6 DAYS106 -1 1 3 D A Y S 99 - 1 1 3 M EANS.D . M EANS.D . M EANS.D . 54.4 4.6 52.8 4.8 [ 24]b,c 53.7 4.4 [ 24]b,c 55.7 54.7 55.1 5.0 5.6 4.9 55.3 53.5 54.5 5.5 6.7 5.3 60.4 + 8 . 8** 58.0 [ 28] b 58.6 ( 28] b 5.0** 5 .0** 65.6 8 .1 ** 63.3 6 .5 ** [ 28]a,b 64.8 6 . 6** [ 28]a,b D A Y S = D A YS P O S TW EA N IN G [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e xu a l m a tu ra tio n , b . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e , w et o r s o ile d fe e d . c . E x c lu d e s v a lu e s f o r r a t s th a t w e re s a c r ific e d b e fo re d a y 113 p o s tw e a n in g . * * S ig n ific a n t ly d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . fo u n d d e a d o r m o rib u n d s a c rific e d . 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) T A B L E D 6 (P A G E 1) : S E X U A L M A T U R A T IO N - SUMMARY - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV 0 1 3 10 V 30 M ALE RATS N 60 60 60 60 60 IN C LU D ED IN A N A LYS ES N 5 2 a -d 58a 5 7a 58a 54a P R EP U T IA L S EP A R A T IO N e M EANS. D , 4 8 . 5 2 . .0 49. 5 2 .7 49.4 3.4 49.7 3 .1 52.2 3 .1 * * a . E x c lu d e s v a lu e s f o r r a t s t h a t w e re fo u n d de ad o r . m o rib u n d s a c r if ic e d . b . E x c lu d e s v a lu e s f o r r a ts in w h ic h t e s t in g was d is c o n tin u e d b e fo re th e r a t becam e s e x u a lly m a tu re . c . E x c lu d e s v a lu e s fo r r a ts th a t w ere n o t o b s e rv e d . d . E x c lu d e s v a lu e s fo r r a t 6555, w h ic h d id n o t h a ve p r e p u tia l s e p a ra tio n re c o rd e d on one d a y an d was s e p a ra te d th e fo llo w in g d a y . e . A ve ra g e d a y p o s tp a rtu m th a t th e p re p u ce was o b se rve d to be s e p a ra te d . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . 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-6889.6) T A B L E D 7 (P A G E 1 ) : M A TIN G AN D F E R T IL IT Y - SUM M ARY - F I G E N E R A T IO N M A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D A Y) I II III 0 13 R ATS IN C O H A B IT A T IO N N 30 29 30 D AYS IN C O H A B IT A T IO N a M EAN+S. D . 3 . 0 + 2.4 3.0 + 1 .1 2.4 + 1.2 RATS TH AT M ATED b N (%) 29( 96.7) 29(100.0) 30(100.0) F E R T IL IT Y IN D EX C N /N (% ) 2 8 / 29 ( 96.6) 2 8 / 29 ( 96.6) 2 8 / 30 ( 93.3) R A T S W IT H C O N FIR M ED M A TIN G D A T ES N 29 29 30 M A TED W IT H F E M A L E d DAYS 1 -7 N (%) 29(100.0) 29(100.0) 30(100.0) RATS PREGNANT/RATS IN C O H A B IT A T IO N N /N (% ) 2 8 / 30 ( 93.3) 28 / 29 ( 96.6) 2 8 / 30 ( 93.3) [ ] = NUM BER O F V A LU ES AV ER AG ED a . R e s t r ic t e d t o r a t s w ith a c o n firm e d m a tin g d a te an d r a t s th a t d id n o t m a te . b . In c lu d e s o n ly o n e m a tin g f o r e a c h m a le r a t . c . Num ber o f p re g n a n c ie s /n u m b e r o f r a ts th a t m a te d . d . R e s t r ic t e d t o r a t s w ith a c o n firm e d m a tin g d a te . IV 10 30 2 .7 + 1.6 30(100.0) 2 8 / 30 ( 93.3) 30 30 ( 1 0 0 . 0 ) 2 8 / 30 ( 93.3) V 30 30 2.5 + 1.2 30(100.0) 2 9 / 30 ( 96.7) 30 30 ( 1 0 0 . 0 ) 2 9 / 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) T A B LE D 8 (P A G E 1) : N EC R O P S Y O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 349 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III IV V 0 1 3 10 30 R A TS EX A M IN ED a N 60 60 60 60 60 M O R T A LIT Y a N3 3 3 2 7 FOUND D EAD N2 3 3 1 6 M O R IB U N D S A C R IF IC E D N1 0 0 11 APPEARED NORMAL N 59 58 53 44 * * 49** LU N G S : A L L LO B ES , M O TTLED DARK RED N 1 0 0 00 P R O S TA TE: SM ALL N0 1 0 0 0 T ES T ES : L E F T , FLA C C ID , SM ALL N 0 1 0 0 0 L E F T , LARG E N0 0 1 0 0 E P ID ID Y M ID ES : L E F T , SM ALL N0 1 0 0 0 LIV E R : L E F T L A T E R A L A N D /O R M ED IA N LO B ES , TAN AND/OR B LAC K OR W H ITE A R E A (S ) N0 0 6* 10** 9 ** LA R G E N0 0 0 0 1 K ID N EY S : R IG H T , P E L V IS , M ODERATE OR S LIG H T D IL A T IO N N0 0 0 4* * 1 a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te rn a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y an d fo r r a t s th a t w e re fo u n d d e a d o r m o rib u n d s a c r if ic e d . * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S ig n ific a n t ly d iff e r e n t fro m th e G ro u p I v a lu e ( p < 0 .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) T A B L E D 8 (P A G E 2 ) : N EC R O P S Y O B S ER V A TIO N S - SUM M ARY - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV V 0 1 3 10 30 R A TS EX A M IN ED a N 60 60 60 60 60 M O R T A LIT Y a N3 3 3 2 7 FOUND DEAD N2 3 3 1 6 M O R IB U N D S A C R IF IC E D N1 0 0 11 IN T E S T IN E S : D IS T E N D E D W IT H G A S N0 0 0 10 THYM US : SM ALL N0 0 0 10 STOM ACH: C A R D IA C R E G IO N , U LC ER A T IO N S N 0 0 0 10 SPLEEN : TA N A R EA EX T EN D ED IN T O TH E PARENCHYM A N0 0 0 10 SM ALL N0 0 0 0 1 a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D14) f o r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y a n d f o r r a t s t h a t w e re fo u n d d e a d o r m o rib u n d s a c r if ic e d . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . ARGUS 418-020 Page 350 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D9 (P A G E 1 ) : T E R M IN A L B O D Y W EIG H T S A N D O RG AN W EIG H TS - SUM M ARY - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 351 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 30 29 T E R M IN A L B O D Y W EIG H T M EANS.D . 559.9 59.8 527.2 54.8* E P ID ID Y M IS L E F T M EANS.D . 0.6854 0.0589 0.6626 0.0821 CAUDA E P ID ID Y M IS L E F T M EANS.D . 0.3333 0.0363 0 .3 177 0.0499 T E S T IS L E F T M EANS. D . 1.7456 0.1501 1.7058 0.1844 L E F T T E S T IS M IN U S T U N IC A A LB U G IN EA M EANS. D . 1.6129 0.1426 1.5455 0.2513 S EM IN A L V E S IC LE S W IT H F L U ID M EANS. D . 1.89 78 0.3480 2.0708 0.2430 S EM IN A L V E S IC LE S W IT H O U T F L U ID M EANS.D . 0.9878 0.1781 1.0380 0.1480 E P ID ID Y M IS R IG H T M EANS.D . 0.6982 0.0609 0.6870 0.0446 T E S T IS R IG H T M EAN+S. D . 1.7324 0.1389 1.72 2 7 0.1363 PROSTATE M EANS.D . 1.0374 0.2849 1.0825 0.2897 P IT U IT A R Y M EANS.D . 0.015 0.003 0 .0 17 0.006 B R A IN M EANS.D . 2.34 0.13 2.28 0.16 A LL a. * ** W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . E x c lu d e s v a lu e s fo r r a ts th a t had o rg a n s S ig n ific a n t ly d iff e r e n t fro m th e G ro u p I S ig n ific a n t ly d iff e r e n t fro m th e G ro u p I dam aged (w e ig h t v a lu e ( p < 0 .0 5 ) . v a lu e ( p < 0 .0 1 ) . affected). III 3 30 523.9 4 8 .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 6 3 .5** 0.6720 0.0589 0.3288 0.0395 1.7732 0.1254 V 30 29 437.6 4 1.6 * 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 1.0 70 1 0.1428 0.6881 0.0455 1.7 6 7 7 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 [ 28] a 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) T A B L E D9 (P A G E 2 ) : T E R M IN A L B O D Y W EIG H TS A N D O RG AN W EIG H TS - SUM M ARY - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 30 29 T E R M IN A L B O D Y W EIG H T M EANS. D . 559.9 59.8 527.2 + 54.8* L IV E R M EANS. D . 21.65 + 3.22 24.57 + 4 .0 4 ** K ID N EY L E F T M EANS.D . 2.21 0.20 2.35 0.26* K ID N E Y R IG H T M EANS.D . 2.24 0.21 2.34 0.28 ADRENAL LE FT M EANS.D . 0.032 + 0.006 0.032 0.008 A D R EN A L R IG H T S P LEEN M EANS.D . M E A N S .D . 0.030 0.007 [ 29] a 0.94 0.14 0.029 0.007 0.83 0 .1 5 * THYM US M E A N + S .D . 0.51 0.12 0.46 0.12 A LL a. * ** W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . E x c lu d e s v a lu e s fo r ra ts th a t had o rg an s S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I dam aged (w e ig h t v a lu e ( p < 0 . 0 5 ) . v a lu e ( p < 0 .0 1 ) . affected). III 3 30 523.9 4 8 .2* 28.24 4 .2 2 ** 2.46 0 .20* * 2.48 + 0 .2 4 ** 0.031 + 0.005 0.029 + 0.005 0.85 + 0 .14 * 0.44 + 0.15 IV 10 30 499.3 6 3 .5 ** 29.28 + 4 .0 9 ** 2.30 + 0.22 2.33 0.25 0.029 + 0.006 0.028 0.006 0.81 + 0.2 3 ** 0.38 0 . 11* * V 30 29 437.6 + 4 1.6 ** 2 9 . 7 4 + 3 b9 7 * * 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) T A B L E D IO ( P A G E 1 ) : R A T IO S (%) O F O R G A N W E IG H T T O T E R M I N A L B O D Y W E IG H T - S U M M A R Y - F I G E N E R A T IO N M A L E R A T S ARGUS 418-020 Page 353 DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV V 0 1 3 10 30 RATS TESTED N 30 29 30 30 29 T E R M IN A L B O D Y W EIG H T M EANS.D . 559.9 + 59.8 527.2 54.8* 523.9 + 4 8 .2* 499.3 6 3 .5 ** 437.6 + 4 1 .6 ** E P ID ID Y M IS L E F T M EANS.D . 0.123 + 0.014 0.127 0.018 0.130 0.016 0.136 + 0 .0 1 7 ** 0.149 + 0 .0 1 7 ** CAUDA E P ID ID Y M IS L E F T M EANS.D . 0.060 0.007 0.060 + 0.011 0.063 + 0.008 0.066 + 0 . 010* 0.072 + 0 . 010* * T E S T IS L E F T M EAN+S.D . 0.314 + 0.036 0.327 + 0.050 0.351 + 0 .0 6 1** 0.360 + 0 .0 4 8 ** 0.396 + 0 .0 4 4 ** L E F T T E S T IS M IN U S T U N IC A A LB U G IN EA M EANS.D . 0.290 0.034 0.296 0.057 0.324 0.057* 0.330 0 .0 4 7 ** 0.366 + 0 .0 4 1 ** S EM IN A L V E S IC LE S W IT H F L U ID M EANS. D . 0.339 + 0.061 0.396 0 .0 5 2 ** 0.377 0.049* 0.416 + 0.064** 0.436 + 0.0 82** S EM IN A L V E S IC LE S W IT H O U T F L U ID M EAN+S.D . 0.176 + 0.033 0.198 + 0.034* 0.196 + 0.028* 0.217 + 0.032** 0.218 0.046** E P ID ID Y M IS R IG H T M EANS.D . 0.126 + 0.014 0.131 + 0.011 0.130 + 0.013 0.140 + 0 .0 17** 0.152 + 0.0 18 ** T E S T IS R IG H T M EANS.D . 0.312 0.036 0.329 + 0.040 0.343 0.044* 0.358 0 .0 49 ** 0.401 + 0.050** PROSTATE P IT U IT A R Y a B R A IN M E A N S .D . M EANS. D . M EAN+S.D . 0.185 + 0.052 2.621 0.589 0.421 0.045 0.203 + 0.050 3.181 + 1.203 0.435 0.040 0.197 + 0.046 3.071 1.054 0.443 + 0.041 0.210 + 0.043 2.809 + 1.064 0.461 0.055** 0.199 0.039 3.041 1.421 ( 28] b 0.502 0 .0 4 3 ** A LL a. b. * ** W EIG H TS W ERE R EC O R D ED I N GRAM S (G) . V a lu e was m u ltip lie d b y 1000. E x c lu d e s v a lu e s fo r r a ts th a t had o rg a n s S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I S i g n ific a n t ly d i f f e r e n t fro m th e G ro u p I dam aged (w e ig h t v a lu e ( p < 0 .0 5 ) . v a lu e ( p < 0 . 0 1 ) . affected). R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 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) T A B L E D IO (P A G E 2 ) : R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T - SU M M ARY - F I G E N E R A T IO N M A L E R A T S DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV 0 1 3 10 V 30 RATS TES TED N 30 29 30 30 29 T E R M IN A L B O D Y W EIG H T M E A N S .D . 559.9 + 59.8 527.2 54.8* 523.9 48 .2 * 499.3 + 6 3 .5 ** 437.6 4 1 .6 ** LIV E R . M EANS.D . 3.860 0.324 4.648 0 .5 10 ** 5.408 + 0 .75 4 ** 5.895 0 .6 9 7** 6.787 + 0.550** K ID N EY L E F T M EANS.D . 0.396 0.031 0.446 0.0 42** 0.472 0.045** 0.464 + 0 .0 46 ** 0.465 0.038 ** K ID N E Y R IG H T M EANS. D . 0.402 0.034 0.446 0 .0 4 1** 0.474 + 0 .0 41** 0.469 0 .0 50 ** 0.467 + 0.036** ADRENAL LE FT a M EANS. D . 5.693 + 1 .1 2 4 6.016 + 1.402 5.999 1.124 5.837 + 1.282 6.332 + 1.366 A D R EN A L R IG H T a S P LEEN M EANS.D . M EANS.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 THYM US M EANS. D . 0.091 0.022 0.088 + 0.023 0.082 0.024 0.077 + 0.025 0.088 + 0.033 A LL a. b. * ** W EIG H TS W ERE R EC O R D ED I N GRAM S (G ) . V a lu e was m u ltip lie d b y 1000 . E x c lu d e s v a lu e s fo r r a ts th a t had org an s S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I dam aged (w e ig h t v a lu e ( p < 0 . 0 5 ) . v a lu e ( p < 0 . 0 1 ) . affected). R A T IO S ( %) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . 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) T A B L E D l l (P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - S U M M A R Y - F I G E N E R A T IO N M A L E R A T S ARGUS 418-020 Page 355 DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV 0 1 3 10 V 30 RATS TESTED N 30 29 30 30 29 B R A IN W EIG H T M EANS.D . 2.34 0.13 2.28 0.16 2 .3 1 0.12 2.28 + 0.10 2.18 0 .1 4 ** E P ID ID Y M IS L E F T M EANS.D . 29.33 2.23 29 .11 3.84 29.28 2.70 29.57 2.64 29.91 2.74 CAUDA E P ID ID Y M IS L E F T M EANS.D . 14.26 1.4 1 13.94 2.20 14.28 1.53 14.46 + 1 .7 1 14.60 1.74 T E S T IS L E F T M EANS. D . 7 4 .7 1 5.90 74.92 8.24 79.23 11.56 78.03 6.10 79.31 6.62* L E F T T E S T IS M IN U S T U N IC A A LB U G IN EA M EAN+S. D . 69.03 + 5.56 67.86 + 1 1.3 1 72.93 10.86 71.56 + 5.80 73.09 6.81 S EM IN A L V E S IC LE S W IT H F L U ID M EANS. D . 81.16 13.80 90.84 9.80 * 85.37 + 12.40 90.50 + 1 2 .9 6 * 87.40 16.74 S EM IN A L V E S IC LE S W IT H O U T F L U ID M EANS.D . 42.24 + 7.0 7 45.56 6.31 44.20 5.44 47.06 6.27 43.78 8.89 E P ID ID Y M IS R IG H T M EANS. D . 29.88 2.19 30.20 + 2.42 29.63 2.13 30.27 + 2.06 30.80 + 3.04 T E S T IS R IG H T M EANS. D . 74.15 5.37 75.66 6.05 77.4 3 6.43 77.76 + 5.38* 80.05 8 . 1 2 * * PROSTATE M EANS. D . 44.37 11.95 47.19 11.80 44.54 10.14 45.93 + 10.09 40.10 8.42 P IT U IT A R Y M EAN+S. D . 0.62 + 0.14 0.73 0.25 0.70 0.24 0.60 + 0.20 0.61 + 0.29 [ 28] a A LL a. * ** W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . E x c lu d e s v a lu e s fo r r a ts th a t had o rg an s S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I dam aged (w e ig h t v a lu e ( p < 0 . 0 5 ) . v a lu e ( p < 0 . 0 1 ) . affected). R A T IO S (% ) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 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) T A B L E D l l (P A G E 2 ) : R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - S U M M ARY - F I G E N E R A T IO N M A L E R A T S 1 1 1H O 1 DOSAGE GROUP D O S A G E (M G /K G /D AY) II III 13 IV 10 V 30 1 1 1 1 RATS TESTED N 30 29 30 30 29 B R A IN W EIG H T M EANS. D . 2.34 0.13 2.28 0.16 2 .3 1 0.12 2.28 0.10 2.18 0 .14 ** LIV E R M EANS.D . 9 27.17 135.62 1074.98 149.66** 1224.30 178 .78 ** 1285.40 159 .24** 1363.79 165.99** K ID N EY L E F T M EANS.D . 94.77 7.87 102.81 7.5 6 ** 106.56 9 .0 7 ** 100.98 7.9 3 * 93.27 9.95 K ID N E Y R IG H T M EAN+S.D . 95.87 9.05 102.62 7 .6 8 ** 107.40 1 0 . 20* * 102.29 9.81* 93.60 7.88 ADRENAL LEFT M EANS.D . 1.35 0.24 1.39 0.36 1.35 0.23 1.2 7 0.26 1.26 0.25 A D R EN A L R IG H T S P LEEN M EANS.D . M EANS.D . 1.28 0.28 ( 29] a 40.39 5.51 1.28 0.31 36.24 4.6 9 * 1.24 0.22 36.73 6.06* 1.24 0.24 35.91 10 .9 9 ** 1.17 0 . 2 6 34.21 5.76 ** THYM US M E A N + S .D . 21.84 5.64 20.35 5.61 19 .15 6.53 16.77 4.95** 17.78 6.93* A LL a. * ** W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . E x c lu d e s v a lu e s fo r r a ts th a t had o rg a n s S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I dam aged (w e ig h t v a lu e ( p < 0 . 0 5 ) . v a lu e ( p < 0 .0 1 ) . affected). R A T IO S (% ) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 0 0 . Page 356 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 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 NUMBER MOTILE MEANS.D. 250.1 71.1 266.4 95.2 271.6 74.2 258.9 73.0 257.2 86.6 MOTILE PERCENT MEANS.D . 83.1 8.8 83.7 6.8 83.9 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 28.4 64.6 40.4 TOTAL COUNT b MEAN+S.D . 301.3 77.8 318.4 108.6 324.4 87.4 315.2 88.9 321.8 104.1 ARGUS 418-020 Page 357 SPERM COUNT c MEAN+S.D. 135.6 67.8 162.0 110.4 144.6 79.0 136.3 62.0 115.7 57.5 SPERM DENSITY d MEAN+S.D. 1194.3 632.1 1423.7 922.5 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 MEAN+S.D. 45.3 13.1 40.4 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"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 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. 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) T A B LE . D 13 (P A G E 1) : CAUDA E P ID ID Y M A L SPERM M ORPH OLOGY - SUMMARY - F I G E N E R A T IO N M A LE R ATS DOSAGE GROUP D O S AG E (M G /K G /D AY) I II III 013 RATS TES TED N 30 29 30 IN C LU D ED IN A N A LY S ES N 30 28a 30 NORM AL M EANS.D . 195.3 1.9 195.2 2.6 194.9 2.0 DETAC H ED HEAD M EANS. D . 2 .7 1.6 3 .2 1 . 8 3 .0 1 .7 NO HEAD M EANS.D . 1 .4 1. 0 1 .4 1.2 1 .7 1.1 BROKEN FLA G ELLU M M E A N S .D . 0 .5 0 .7 0.0 0 . 2 * 0 .3 0 .5 NO HOOK M EANS.D . 0.0 0.0 0 . 1 0 .3 0.0 0.2 C O ILED FLA G ELLU M M EANS.D . 0.0 0.2 0.0 0.0 0 . 1 0 .3 BENT FLAG ELLU M M EAN+S. D . 0.0 0.0 0.0 0.0 0.0 0.0 BENT FLAG ELLU M T IP M EANS.D . 0.0 0.0 0.0 0.0 0.0 0.0 PERCENT ABNORM AL M EAN+S.D . 2 .4 0 .9 2 .4 1 .3 2.6 1.0 a . E x c lu d e s v a lu e s f o r r a t 1 0 8 2 , w h ic h h a d le s s th a n 200 sperm p e r 20 f i e l d s . * S i g n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . 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 0.2 0.0 0.2 0.0 0.0 2 .4 1 . 0 V 30 29 29 19 4 .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 ARGUS 418-020 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) T A B LE D 14 (P A G E 1) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN E R A T IO N M A LE RATS ARGUS 418-020 Page 360 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 1001 1002 1003 1004 1005 1006 10 0 7 10 0 8 1009 1010 1011 1012 10 13 10 14 10 15 10 16 1017 6553 6554 6555 1021 1022 10 2 3 1024 1025 10 2 6 DP ( 93DP ( 93DP ( 93- 94) 94) 9 7) D P(112-113) D P (114-118) DP ( DP ( 76 ) 24 ) DP ( DP ( DP ( DP ( DP ( DP ( 3) 4 - 7) 4 - 14) 2 2 - 32) 22- 32) 3 1- 35) DP ( DP ( DP ( DP ( DP ( 35353 72 735- 3 7) 3 7) 59) 34) 3 7) DP ( DP ( DP ( DP ( 25 ) 36 ) 17-118) 36 ) NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA SNOUT : SW OLLEN CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS A LIG N ED IN C IS O R S : M IS S IN G /B R O K EN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES A N N U LAR C O N S T R IC T IO N O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES SO FT OR LIQ U ID FEC ES U R IN E -S T A IN E D A B D O M IN A L FU R A N N U LAR C O N S T R IC T IO N O F T H E T A IL N E C K A N D H E A D : S C A B ( 0 . 4 CM I N D IA M E T E R ) A B D O M IN A L D IS T E N T IO N a NO A D V ER S E FIN D IN G S SNOUT : SW OLLEN IN C IS O R S : M IS S IN G /B R O K EN N E C K : S C A B ( 0 . 3 CM I N D IA M E T E R ) H E A D : S C A B ( 0 . 5 CM I N D IA M E T E R ) H E A D : A B R A S IO N ( 1 . 0 CM I N D IA M E T E R )a NO A D V ER S E FIN D IN G S FOUND DEAD C H R O M O R H IN O R R H EA R IG H T E Y E : EN LA R G ED a EX C ES S S A LIV A T IO N D P = D A Y P O S TW EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 2) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 361 DOSAGE GROUP I 0 M G/KG/DAY RAT # 10 2 7 1028 10 2 9 10 3 0 103 1 10 3 2 10 3 3 . 1034 10 3 5 10 3 6 10 3 7 10 3 8 10 3 9 10 4 0 10 41 10 4 2 1043 DP ( DP ( DP ( 8- 9 ) 2) 8- 1 6 ) DP ( 23 - 43) DP ( 2 - 4) DP ( 4) DP ( 4) DP ( 4) DP ( DP ( DP ( DP ( DP ( 8- 1 6 ) 35 ) 74 ) 2) 35 ) DP ( DP ( DP ( DP ( 34 ) 34 ) 42 ) 7 7 - 85) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 8) 15 - 24) 30- 3 1) 3 2- 46) 33- 34) 33- 40) 4 7 - 54) 5 9 - 85) 8 9 -118 ) D ES C R IP T IO N A B D O M IN A L D IS T E N T IO N S O FT OR LIQ U ID FEC ES A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S T R IC T IO N O F TH E T A IL C H R O M O R H IN O R R H EA a D EC R EA S ED M OTOR A C T IV IT Y COLD TO TOUCH M O R IB U N D S A C R IF IC E D NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N EX C ES S S A LIV A T IO N S O FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA EX C ES S S A LIV A T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA V O C A LIZA T IO N FOUND DEAD IN C IS O R S : M IS A LIG N ED NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES B A C K : S C A B ( D I D N O T E X C E E D 0 .5 CM I N D IA M E T E R ) H E A D : S C A B ( 0 .4 CM I N D IA M E T E R ) H E A D : A B R A S IO N ( 1 .0 CM I N D IA M E T E R ) CHROM ODACRYORRHEA IN C IS O R S : M IS S IN G /B R O K EN H E A D : S C AB ( 0 .8 CM I N D IA M E T E R ) B A C K : S C A B ( D ID N O T E X C E E D 1 .0 CM X 0 .5 CM) L O C A L IZ E D A L O P E C IA : LIM B S 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) T A B LE D 14 (P A G E 3) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 362 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 10 4 4 10 4 5 10 4 6 10 4 7 10 4 8 10 4 9 1050 10 5 1 10 5 2 1053 1054 1055 1056 10 5 7 10 5 8 1059 10 6 0 DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 33- 34) 34 ) 34 ) 34 ) 2) 9- 13) 42 ) 93- 94) 20 ) DP ( 29 ) DP ( 4) DP ( 18 - 28) DP ( 90 ) DP ( 90 ) DP ( 90- 97) DP ( 9 0 -10 9 ) D P (10 3 -10 9 ) DP ( 109 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA SO FT OR LIQ U ID FEC ES EXC ES S S A LIV A T IO N C H R O M O R H IN O R R H EA S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA A N N U LA R C O N S TR IC TIO N O F T H E C H R O M O R H IN O R R H EA R ALES CHROM ODACRYORRHEA IN C IS O R S : M IS S IN G /B R O K EN a CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N ED a NO A D V ER S E FIN D IN G S T A IL D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 4) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G E N E R A T IO N M ALE R ATS ARGUS 418-020 Page 363 DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 10 6 1 10 6 2 10 6 3 10 6 4 10 6 5 10 6 6 106 7 10 6 8 10 6 9 10 70 10 71 10 72 10 73 10 74 10 75 10 76 10 77 10 78 10 79 10 8 0 10 8 1 1082 10 8 3 1084 10 8 5 DP ( 2 8 - 36) D P (10 4 -10 5 ) DP ( 5) DP ( DP ( 5) 6) DP ( DP ( DP ( DP ( DP ( DP ( DP ( 3) 38 ) 26 - 36) 2 5 - 35) 29 ) 4 4 - 45) 27 ) DP ( 2 5 - 35) DP ( 37 ) DP ( 2 5 - 35) DP ( 37 ) DP ( 37 ) DP ( 25 - 35) DP ( 28 - 37) NO A D V ER S E FIN D IN G S A N N U LA R C O N S T R IC T IO N O F T H E T A IL CHROM ODACRYORRHEA C H R O M O R H IN O R R H EA a U R IN E -S T A IN E D A B D O M IN A L FU R FOUND D EAD NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA A N N U LA R C O N S T R IC T IO N O F T H E T A IL A N N U LA R C O N S T R IC T IO N O F T H E T A IL S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A N N U LA R C O N S T R IC T IO N O F TH E T A IL NO A D V ER S E FIN D IN G S V O C A LIZA T IO N NO A D V ER S E FIN D IN G S A N N U LA R C O N S T R IC T IO N O F TH E T A IL NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S EXC ES S S A LIV A T IO N A N N U LA R C O N S T R IC T IO N O F TH E T A IL H E A D : S C A B ( 0 .2 CM I N D IA M E T E R ) D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 5 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 364 DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 1086 10 8 7 1088 1089 1090 10 9 1 10 9 2 10 9 3 1094 10 9 5 10 9 6 10 9 7 10 9 8 10 9 9 DP ( 10 - 17) DP ( 80 ) DP ( 80- 81) DP ( 8 0 -115 ) DP ( 8 0 -119 ) D P (10 2 -10 3 ) DP ( 45 ) DP ( 25 - 38) DP ( 37 ) DP ( 37 ) DP ( DP ( DP ( DP ( 20 ) 3 2- 51) 4 2 - 51) 50 - 52) DP ( 3DP ( 24DP ( 35DP ( 50- 6) 25) 36) 5 1) DP ( DP ( DP ( DP ( DP ( 34 ) 34 ) 3 4 - 36) 3 4- 37) 3 4- 37) A B D O M IN A L D IS T E N T IO N C H R O M O R H IN O R R H EA SN O U T: SW OLLEN IN C IS O R S : M IS A LIG N E D CHROM ODACRYORRHEA a C H R O M O R H IN O R R H EA FOUND DEAD NO A D V ER S E FIN D IN G S R IG H T E Y E : C O R N EA L O P A C IT Y SO FT OR LIQ U ID FEC ES EXC ES S S A LIV A T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES P T O S IS AN N U LAR C O N S T R IC T IO N O F TH E CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA ENOPHTHALM OS C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SNOUT : SW OLLEN U R IN E -S T A IN E D A B D O M IN A L FU R C H R O M O R H IN O R R H EA CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N E D a T A IL D P = D A Y P O S TW EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 6) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 365 DOSAGE GROUP I I 1 M G/KG/DAY RAT # 1100 1101 1102 110 3 110 4 110 5 110 6 110 7 110 8 110 9 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 DP ( 36 ) 1D P ( ) 1D P ( ) 1D P ( ) 2D P ( ) 8D P ( - 18) DP ( 23 - 35) 8D P ( - 18) D P (10 0 -10 1) DP ( 23 - 33) D P (10 0 -10 1) DP ( 23 - 33) DP ( 5) DP ( 35 ) DP ( 34 ) DP ( 7- 17) DP ( 22- 41) DP ( 34 ) DP ( 6 4 -119 ) DP ( 2 2 - 34) DP ( DP ( DP ( DP ( 34 ) 100 ) 34 ) 6 4- 85) D ES C R IP T IO N NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S D EC R EA S ED M OTOR A C T IV IT Y C O LD TO TOUCH EM A C IA T IO N FOUND DEAD A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S TR IC TIO N O F T H E T A IL A B D O M IN A L D IS T E N T IO N S O FT OR LIQ U ID FEC ES A N N U LA R C O N S TR IC TIO N O F T H E T A IL C H R O M O R H IN O R R H EA A N N U LA R C O N S TR IC TIO N O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N H E A D A N D N E C K : S C A B (D ID N O T E X C E E D 0 .5 CM I N D IA M E T E R ) S O FT OR LIQ U ID FEC ES L O C A L IZ E D A L O P E C IA : LIM B S a A N N U LA R C O N S TR IC TIO N O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES IN C IS O R S : M IS A LIG N ED 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) T A B LE D 14 (P A G E 7) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 366 DOSAGE GROUP I I I 3 M G/KG/DAY . RAT # 1121 1122 112 3 112 4 112 5 112 6 112 7 112 8 112 9 113 0 113 1 113 2 113 3 113 4 113 5 DP ( 5) DP ( 38 ) DP ( 45 ) D P ( 6 2- 67) D P ( 9 7- 98) DP ( 9 7-110 ) DP ( 9 7-118 ) D P (10 0 -118 ) DP ( 118 ) D P ( 5 - 9) DP ( 25 - 35) DP ( 2 7 - 38) DP ( 35- 38) DP ( 25 - 28) DP ( 2 7 - 54) DP ( 25 - 35) DP ( 25 - 35) DP ( 6 4- 69) 2D P ( ) D P ( 4 - 5) DP ( 50 ) DP ( 3 0 - 81) DP ( 3 0 -118 ) DP ( 37 ) DP ( 44- 77) DP ( 8 2 -118 ) DP ( 37 ) DP ( 25 - 35) D ES C R IP T IO N FOUND DEAD SO FT OR LIQ U ID FEC ES A N N U LA R C O N S T R IC T IO N S O F T H E T A IL B A C K : S C A B (D ID N O T E X C E E D 0 .5 CM IN D IA M E T E R ) C H R O M O R H IN O R R H EA CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N E D a SN O U T: SW OLLEN a CHROM ODACRYORRHEA a NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA A N N U LA R C O N S T R IC T IO N S O F T H E T A IL H E A D : S C A B S ( D ID N O T E X C E E D 0 .5 CM I N D IA M E T E R )a N E C K : S C A B ( 2 .0 CM X 0 .5 C M )a B A C K : S C A B ( 0 .4 CM I N D IA M E T E R ) B E H IN D L E F T E A R : S C A B (D ID N O T E X C E E D 0 .5 CM I N D IA M E T E R ) A N N U LA R C O N S T R IC T IO N S O F T H E T A IL A N N U LA R C O N S T R IC T IO N S O F T H E T A IL IN C IS O R S : M IS S IN G /B R O K EN FOUND DEAD C H R O M O R H IN O R R H EA R ED , D R IE D , S LIG H T P ER IN A S A L SUBSTANC E IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA a C H R O M O R H IN O R R H EA LA C R IM A T IO N IN C IS O R S : M IS S IN G /B R O K EN a C H R O M O R H IN O R R H EA A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S 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) T A B LE D 14 (P A G E 8) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 367 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 113 6 113 7 113 8 113 9 114 0 114 1 114 2 114 3 114 4 114 5 114 6 114 7 114 8 114 9 115 0 115 1 115 2 115 3 D P (10 7-119 ) D P (10 7-119 ) D P (10 7-119 ) D P (10 9 -110 ) DP ( 3) DP ( 9) DP ( DP ( DP ( DP ( DP ( 2) 2) 3) 3 - 15) 9 - 19) D P (10 1-10 3 ) DP ( 36 ) DP ( 36 ) DP ( 76 -10 3 ) D P { 9 1-10 3 ) D P (10 5 -110 ) D P (119 -12 0 ) DP ( 2 4 - 36) CHROM ODACRYORRHEA a SNOUT : SW OLLEN a IN C IS O R S : M IS S IN G /B R O K EN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA EM A C IA T IO N FOUND DEAD NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S EM A C IA T IO N COLD TO TOUCH C H R O M O R H IN O R R H EA U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S EXC ES S S A LIV A T IO N NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA CHROM ODACRYORRHEA CHROM ODACRYORRHEA a NO A D V ER S E FIN D IN G S A N N U LA R C O N S TR IC TIO N S O F T H E T A IL 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) T A B LE D 14 (P A G E 9 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 368 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 115 4 115 5 115 6 115 7 115 8 115 9 116 0 116 1 116 2 116 3 116 4 116 5 116 6 116 7 116 8 116 9 1170 1171 1172 1173 1174 DP ( 35 ) DP ( 59 - 62) D P ( 6 3- 65) DP ( 35 ) DP ( 59 ) DP ( 59 - 65) DP ( 92 ) D P (10 2 -119 ) D P ( 35 ) DP ( 2 3 - 33) DP ( 43- 44) DP ( 4 3 - 54) D P ( 6 3 - 93) DP ( 35 ) DP ( 1 - 4) DP ( 3 8 - 39) DP ( 24 ) DP ( 34 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R ED , S LIG H T P ER IO R A L SUBSTANC E B A C K : S C A B ( 0 .5 CM I N D IA M E T E R ) L O C A LIZE D A LO P E C IA : BACK C H R O M O R H IN O R R H EA CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA CHROM ODACRYORRHEA a NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES A N N U LA R C O N S T R IC T IO N S O F T H E T A IL CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S S O FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S R ED , D R IE D , S LIG H T P E R IN A S A L SU B STAN C E S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S 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) T A B LE D 14 (P A G E 1 0 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 1175 1176 1177 1178 1179 118 0 DP( 34 ) D P ( 56- 57) D P ( 56- 61) D P ( 5 6 -10 8 ) D P ( 5 6 -119 ) D P (10 9 -118 ) D P (117-119 ) D P ( 103 ) D P (10 3 -119 ) D P (10 3 -1 1 9 ) D P ( 18 - 20) D P ( 2 1- 22) DP( 30 ) EXC ES S S A LIV A T IO N C H R O M O R H IN O R R H EA SN O U T: SW OLLEN IN C IS O R S : M IS A LIG N E D CHROM ODACRYORRHEA a IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS A LIG N ED a C H R O M O R H IN O R R H EA CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N E D a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S H E A D : S C A B ( 0 .3 CM I N D IA M E T E R ) LO C A LIZE D A LO P E C IA : HEAD EXC ES S S A LIV A T IO N D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . ARGUS 418-020 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) T A B LE D 14 (P A G E 1 1 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 370 DOSAGE GROUP IV 10 M G/KG/DAY RAT # D ES C R IP T IO N 118 1 118 2 118 3 118 4 118 5 118 6 118 7 118 8 118 9 119 0 119 1 119 2 119 3 119 4 119 5 119 6 119 7 119 8 119 9 1200 DP ( DP ( DP ( DP ( DP ( 10- 2 0 ) 5) 10- 2 0 ) 25- 44) 25 - 33) DP ( 8 2- 83) DP ( 8 2 - 98) D P ( 102 ) DP ( 4 8 - 55) DP ( 8 1- 86) DP ( DP ( DP ( DP ( DP ( DP ( 8 4 -117) 2 4 - 26) 60 ) 6 1- 65) 66- 7 5 ) 87 ) 8D P ( - 16) DP ( 1 7 - 37) DP ( 24 ) DP ( 2 4 - 40) DP ( 25 - 40) DP ( 29 - 32) DP ( 29 - 40) DP ( 29- 40) DP ( 39- 40) DP ( 40 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S TR IC TIO N S O F T H E T A IL A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED S O FT OR LIQ U ID FEC ES IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN a M O U T H : S C A B (D ID N O T E X C E E D 0 .5 CM X 0 .5 CM) B A C K : U L C E R A T IO N ( 1 .0 CM X 0 .5 CM) B A C K : S C A B ( 1 .0 CM X 0 .5 CM) LO C A LIZE D A LO P E C IA : BACK P E N IS : RED SUBSTANCE NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S T IP O F T A IL BLACK T I P O F T A I L M IS S IN G a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA D EH Y D R A T IO N a A B D O M IN A L D IS T E N T IO N a U R IN E -S T A IN E D A B D O M IN A L FU R EM A C IA T IO N a COLD TO TOUCH U R IN E -S T A IN E D A B D O M IN A L FU R M O R IB U N D S A C R IF IC E D 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) T A B LE D 14 (P A G E 12 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 371 DOSAGE GROUP IV 10 M G /KG /D AY RAT # 1201 1202 12 0 3 12 0 4 1205 12 0 6 12 0 7 1208 12 0 9 1210 1211 1212 12 13 12 14 12 15 12 16 12 17 12 18 12 19 1220 1221 DP ( 36 ) DP ( 6 9 -118 ) DP ( 2 3 - 33) DP ( 4 1- 42) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 35 ) 47 ) 3) 3) 3) 4) 23 - 32) 64 ) DP ( 35- 36) DP ( DP ( DP ( 35 ) 35 ) 31 ) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 34 ) 34 ) 63- 64) 63- 68) 63- 68) 63- 68) 6 9 -118 ) 74 -118 ) D ES C R IP T IO N SO FT OR LIQ U ID FEC ES NO AD V ER S E FIN D IN G S IN C IS O R S : M IS A LIG N ED a A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S EX C ES S S A LIV A T IO N R ED , D R IE D , S LIG H T P ER IN A S A L SUBSTANCE D EC R EA S ED M OTOR A C T IV IT Y EM A C IA T IO N a COLD TO TOUCH FOUND DEAD H E A D : S C A B ( D ID N O T E X C E E D 0 .4 CM I N D IA M E T E R ) S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S D EH Y D R A T IO N a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA SO FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA S O FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA CHROM ODACRYORRHEA SNOUT : SW OLLEN IN C IS O R S : M IS A LIG N ED IN C IS O R S : M IS A LIG N ED a CHROM ODACRYORRHEA 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) T A B LE D 14 (P A G E 13 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 372 DOSAGE GROUP IV 10 M G/KG/DAY RAT # 1222 1223 1224 1225 1226 12 2 7 1228 1229 12 3 0 123 1 12 3 2 12 3 3 12 3 4 12 3 5 12 3 6 12 3 7 12 3 8 12 3 9 1240 DP ( 2 2 - 32) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 2- 6 ) 4 - 5) 7 - 24) 7 - 23) 2 2 - 34) 2 2 - 32) 48 - 49) 2 2 - 32) 2 2- 32) 8) 22 - 34) 6 1-119 ) DP ( 2 2 - 3 1) DP ( 80 ) D ES C R IP T IO N A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA EM A C IA T IO N A B D O M IN A L D IS T E N T IO N A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S TR IC TIO N S O F TH E T A IL A N N U LA R C O N S TR IC TIO N S O F TH E T A IL SO FT OR LIQ U ID FEC ES A N N U LA R C O N S TR IC TIO N S O F TH E T A IL A N N U LA R C O N S TR IC TIO N S O F TH E T A IL SO FT OR LIQ U ID FEC ES A N N U LA R C O N S TR IC TIO N S O F T H E T A IL BOTH EA R S : SW OLLEN a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 1 4 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G E N E R A T IO N M ALE R ATS ARGUS 418-020 Page 373 DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 12 4 1 12 4 2 1243 12 4 4 1245 12 4 6 1247 1248 1249 12 5 0 125 1 1252 1253 1254 DP ( 2 6 - 36) DP ( 26 - 34) DP ( 3 8 - 39) DP ( 2 5 - 26) DP ( 2 5 - 35) DP ( 5 - 7) 10D P ( - 18) DP ( 37 ) 10D P ( - 20) DP ( 25 - 34) 10D P ( - 20) DP ( 29 - 42) DP ( 37 ) D P ( 5 - 6) DP ( 25 - 38) DP ( 37 ) DP ( 37 ) DP ( 37 ) DP ( 37 ) DP ( 37 ) DP ( 38 ) DP ( 4) 10D P ( - 20) DP ( 2 5 - 35) A N N U LA R C O N S T R IC T IO N S O F T H E T A IL NO A D V ER S E FIN D IN G S A N N U LA R C O N S T R IC T IO N S O F T H E T A IL H E A D : S C A B ( 0 .2 CM I N D IA M E T E R )a NO A D V ER S E FIN D IN G S A N N U LA R C O N S T R IC T IO N S O F T H E T A IL A N N U LA R C O N S T R IC T IO N S O F T H E T A IL U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S TR IC TIO N S O F T H E T A IL A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S T R IC T IO N S O F T H E T A IL EXC ES S S A LIV A T IO N C H R O M O R H IN O R R H EA A N N U LA R C O N S T R IC T IO N S O F T H E T A IL C H R O M O R H IN O R R H EA V O C A LIZA T IO N A N N U LA R C O N S T R IC T IO N S O F T H E T A IL A N N U LA R C O N S T R IC T IO N S O F T H E T A IL R ALES EM A C IA T IO N C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S T R IC T IO N S O F T H E T A IL a D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 15 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 374 DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 12 5 5 1256 12 5 7 1258 1259 12 6 0 126 1 12 6 2 12 6 3 12 6 4 DP ( 36 ) DP ( 36 ) DP ( 67 ) DP ( 83 - 91) DP ( 84 ) DP ( 87 ) D P ( 9 2- 96) DP ( 93 ) DP ( 3 - 4) 8D P ( - 9) DP ( 2 4 - 34) 6D P ( ) DP ( 9 - 19) DP ( 3) DP ( 3) DP ( 3) DP ( 4) DP ( 2 4 - 37) 1D P ( ) 1D P ( ) 1D P ( ) 1D P ( ) 2D P ( ) 1D P ( ) 1D P ( ) 1D P { ) 1D P ( ) 2D P ( ) NO AD V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES SO FT OR LIQ U ID FEC ES P EN IS : R ED SUBSTANC E U R IN E -S T A IN E D A B D O M IN A L FU R P EN IS : R ED SUBSTANCE P EN IS : R ED SUBSTANCE UNGROOM ED C O AT P EN IS : R ED SUBSTANCE C H R O M O R H IN O R R H EA C H R O M O R H IN O R R H EA AN N U LAR C O N S T R IC T IO N S O F TH E T A IL C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N D EC R EA S ED M OTOR A C T IV IT Y COLD TO TOUCH U R IN E -S T A IN E D A B D O M IN A L FU R FOUND DEAD NO AD V ER S E FIN D IN G S A N N U LA R C O N S TR IC TIO N S O F T H E T A IL D EC R EA S ED M OTOR A C T IV IT Y BOTH E Y E S : C O R N EA L O P A C IT Y a EM A C IA T IO N a COLD TO TOUCH FOUND DEAD D EC R EA S ED M OTOR A C T IV IT Y BOTH E Y E S : C O R N EA L O P A C IT Y a EM A C IA T IO N COLD TO TOUCH FOUND DEAD a D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 16 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 375 DOSAGE GROUP V 30 M G/KG/DAY RAT # D ES C R IP T IO N 12 6 5 12 6 6 12 6 7 12 6 8 12 6 9 12 70 12 71 1272 1273 , 1274 1275 1276 12 77 12 78 DP ( 2 4- 34) DP ( 36- 39) DP ( 36 ) 11D P ( - 16) 11D P ( - 16) DP ( 36- 37) DP ( 49 ) DP ( 76 - 77) DP ( 26- 33) DP ( 26 - 39) DP ( 29 - 39) DP ( 3 2- 39) DP ( 3 2- 39) DP ( 3 3- 39) DP ( 39 ) DP ( 39 ) DP ( 5) DP ( 2 - 3) DP ( 3) DP ( 3) DP ( 3) DP ( 3) DP ( 4) DP ( 3 - 15) DP ( 5 - 7) 8D P ( - 16) DP ( 2 3 - 70) A N N U LA R C O N S TR IC TIO N S O F T H E T A IL A N N U LA R C O N S TR IC TIO N S O F T H E T A IL A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S LA C R IM A T IO N R IG H T E Y E : SW OLLEN A N N U LA R C O N S TR IC TIO N S O F T H E T A I L a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R ED , D R IE D , S LIG H T P ER IN A S A L SUBSTANC E CHROM ODACRYORRHEA C H R O M O R H IN O R R H EA DEHYDRATED a EM A C IA T IO N a D EC R EA S ED M OTOR A C T IV IT Y U R IN E -S T A IN E D A B D O M IN A L FU R a COLD TO TOUCH a CHROM ODACRYORRHEA a M O R IB U N D S A C R IF IC E D U R IN E -S T A IN E D A B D O M IN A L FU R C H R O M O R H IN O R R H EA a D EC R EA S ED M OTOR A C T IV IT Y EM A C IA T IO N a COLD TO TOUCH U R IN E -S T A IN E D A B D O M IN A L FU R a FOUND DEAD U R IN E -S T A IN E D A B D O M IN A L FU R EM A C IA T IO N A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S TR IC TIO N S O F T H E T A IL D P = D A Y P O S TW EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 14 (P A G E 1 7 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 376 DOSAGE GROUP V 30 M G /K G /D A Y RAT # 12 79 1280 128 1 12 8 2 12 8 3 12 8 4 12 8 5 12 8 6 12 8 7 1288 12 8 9 12 9 0 129 1 12 9 2 12 9 3 12 9 4 12 9 5 8D P ( - 18) DP ( 2 8 - 35) 2D P ( ) DP ( 3) DP ( 16 ) DP ( 18 - 21) DP ( 6 1- 69) DP ( 89 ) DP ( 89 ) DP ( 89- 91) DP ( 8 9 -119 ) D P (10 2 -10 4 ) D P (117-119 ) D P (118 -119 ) D P (118 -119 ) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 2 2 - 32) 7 - 23) 7 - 23) 9- 10) 59- 61) 7 - 23) 6 1- 64) 6 1-119 ) 6 1-119 ) 22- 23) DP ( 15 ) D ES C R IP T IO N A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S T R IC T IO N S O F T H E T A IL C H R O M O R H IN O R R H EA FOUND D EAD L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S IN C IS O R S : M IS A LIG N E D C H R O M O R H IN O R R H EA SO FT OR LIQ U ID FEC ES CHROM ODACRYORRHEA IN C IS O R S : M IS A LIG N ED a CHROM ODACRYORRHEA CHROM ODACRYORRHEA a IN C IS O R S : M IS S IN G /B R O K EN a L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A N N U LA R C O N S T R IC T IO N S O F T H E T A IL A B D O M IN A L D IS T E N T IO N A B D O M IN A L D IS T E N T IO N C H R O M O R H IN O R R H EA B A C K : S C A B (0 .3 CM I N D IA M E T E R ) A B D O M IN A L D IS T E N T IO N SN O U T: SW OLLEN CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N ED a N E C K : S C A B ( 0 .5 CM I N D IA M E T E R ) NO A D V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S 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) T A B LE D 14 (P A G E 18 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS DOSAGE GROUP V 30 M G /K G /D A Y RAT # D ES C R IP T IO N 12 9 6 12 9 7 12 9 8 12 9 9 13 0 0 D P ( 100 ) D P (10 0 -10 1) D P (10 0 -10 6 ) D P (10 0 -10 6 ) D P (10 3 -10 6 ) D P (10 4 -10 6 ) D P ( 10 7 ) D P ( 20 - 29) D P ( 20 - 29) D P ( 2 5 - 99) D P ( 25-117) DP( 67 ) D P ( 72 - 84) D P ( 9 1- 92) D P(111-117) R ALES C H R O M O R H IN O R R H EA CHROM ODACRYORRHEA a IN C IS O R S : M IS A LIG N ED a EM A C IA T IO N a U R IN E -S T A IN E D A B D O M IN A L FU R a FOUND DEAD NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A N N U LA R C O N S TR IC TIO N S O F T H E T A IL A N N U LA R C O N S TR IC TIO N S O F T H E T A IL IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA a IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN a D P = D A Y P O S T W EA N IN G a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . ARGUS 418-020 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) T A B L E D 15 (P A G E 1 ) : B O D Y W EIG H TS - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 378 RAT # 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 10 14 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 DOSAGE GROUP I 0 M G/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 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 . 105. 159. 69. 118 . 176 . 81. 133 . 198 . 1227 5 . . 1 7 8 . 74 . 133 . 192 . 67. 116 . 173 . 78. 124 . 181. 83. 138. 194 . 2128 7 . 1 4 8 . . 69. 116 . 169. 79. 132 . 188. 84. 123 . 175. 77. 116. 176. 88. 1 4 7 . 209. 2229 1 . 1 4 8 . . 2019 0 . 1 3 7 . . 80. 129. 192 . 57. 9 7. 152 . 80. 13 1. 185. 80. 128. 189. 2018 5 . 1 3 1 . . 2015 6 . 1 3 5 . . 57. 104. 164 . 62. 97. 153 . 66. 101. 1 6 3 . 69. 115 . 17 4 . 57. 106. 158. 62 . 107. 161. M O R IB U N D S A C R IF IC E D ON 76. 130. 198. 218. 281. 233 . 289. 264. 323 . 231. 292. 254. 319. 227. 286. 240. 293 . 250. 304 . 270. 338. 225. 279. 252 . 307. 230. 282. 236. 300. 274 . 328. 290. 350. 262. 322. 250. 200 . 300. 227. 238. 259. 318. 268. 338. 215. 269. FOUND DEAD ON D AY 220. 271. 235. 210. 286. 261. 208. 260. D A Y 4 P O S TW EA N IN G 255. 317. 337 368 364 334 387. 407. 408. 372. 350 320 354 359 336 394. 387. 401. 398. 365. 367 411. 319 368. 25 P O S TW EA N IN G 331 368. 298 329. 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. 70 a P R EC O H A B IT A T IO N b 487. 489. 487. 452 . 524 . 523 . 525. 487. 473 . 485. 500 . 459. 508 . 537. 542 . 497 . 435. 472 . 520. 483 . 559 . 524 . 466. 398. 500 . 420. DAY A LL a. b. = D A Y P O S T W EA N IN G W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . B e ca u se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a se d on e a ch r a t ' s d a y p o s tw e a n in g , w as th e l a s t d a y o n w h ic h th e y o u n g e s t r a t s ( in t h is g ro u p ) h a d a b o d y w e ig h t v a lu e re c o rd e d . P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was b e g u n f o r th e F I g e n e ra tio n r a t s w e re 92 to 106 d a ys o f a g e . d a y 70 p o s tw e a n in g r a t s ; a t t h a t tim e th e s e PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 15 (P A G E 2 ) : B O D Y W EIG H TS - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 379 RAT # DOSAGE GROUP I 0 M G/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 5 7 6 4 7 0 a P R E C O H A B I T A T I O N b 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 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. 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. 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 . 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 . 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. 315. 291. 249. 246. 267. 296. 262 . 275. 256. 257. 305. 307. 346. 322. 276. 333 . 335. 331. 329. 306. 306. 279. 364. 289. 299. 407. 319. 313 . 445 345 349 474 . 371. 372 . 491. 518. 385. 385. 395. 406. FO U N D 320. 297. DEAD ON 365. 332. DAY 4 2 :P O S T W E A N I N G 388 415. 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. 392 . 378. 344. 424 407 376 462 . 426. 395. 480 . 441. 415. 493 . 441. 415. DAY A LL a. b. = D A Y P O S TW EA N IN G W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . B e cau se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a se d on w as th e la s t d a y on w h ic h th e y o u n g e s t r a ts ( in t h is g ro u p ) h ad a b o d y P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was r a t s w e re 92 t o 10 6 d a y s o f a g e . ea ch r a t ' s d a y p o s tw e a n in g , w e ig h t v a lu e re c o rd e d . begun fo r th e F I g e n e ra tio n d a y 70 p o s tw e a n in g r a t s ; a t th a t tim e th e se PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (A P F O ) I N R A T S (S P O N S O R 'S 1 S T U D Y N U M B ER ; T - 6 8 8 9 . 6 ) T A B L E D 15 (P A G E 3 ) : B O D Y W EIG H TS - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 380 RAT # DOSAGE GROUP I 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 D A Y 78 507. 509. 510. 474 . 85 504 . 523 . 523 . 480 . 92 537. 542 . 547 . 503 . 99a 530. 554 . 558. 508. 10 6 547. 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. FO U N D D EA D O N D A Y 25 P O S TW EA N IN G 577. 491. 503 . 531. 534 . 562. 410 . 422 . 432 . 441. 568. M O R IB U N D S A C R IF IC E D O N D A Y 4 P O S TW EA N IN G 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 M G/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) T A B L E D 15 (P A G E 4) : B O D Y W EIG H T S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 381 RAT # DOSAGE GROUP I D A Y 78 85 92 99a 10 6 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. 389. 402. 533 . 413 . 404 . 546. 418. 423 . 547. 425 . 432 . 444 . 447. 509. FO U N D 450. 416. DEAD ON 464. 433 . DAY 42 P O S TW EA N IN G 489 496. 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. 0 M G/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) T A B L E D 15 (P A G E 5) : B O D Y W EIG H T S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 382 RAT # 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 DOSAGE GROUP I I DAY 1 8 15 22 2 9 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. 69. 73 . 71. FO U N D 59. 59. 51. 65. 59. 78. 69. 74 . 86. 71. 74 . 83 . 80. 86. 60. 78. 79. 72 . 66. 67 . 55 . 60. 83 . 81. 80. 64 . 112. 118. 122. DEAD ON 97. 101. 95. 109. 99. 125. 112. 124 . 137. 116. 128. 132 . 131. 148. 97. 128. 130. 116. 113 . 112. 95. 101. 132 . 134 . 127. 111. 166, 223 . 170, 159, 225. 220. D A Y 6 P O S TW EA N IN G 140, 185. 150, 203 . 145, 161, 146, 204 . 211. 201. 187 163, 245. 221. 186 241. 206 264 . 181 239. 190 242 . 195 258. 195 252 . 206 264. 150 205. 193 245 . 193 254 . 172 228. 1 6 5 220. 165 216. 146 190. 152 196. 194 258. 196 254 . 181 238. 1 5 2 201. 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. 1 M G/KG/DAY 43 50 301. 332. 317. 358. 299. 311. 296. 318. 365 . 335. 344 . 321. 353 . 390 . 57 360. 394. 357. 367. 343 . 378. 419. 64 385 422 379 400 355 406 446 70 a P R EC O H A B IT A T IO N b 400. 436. 438. 465. 394 . 397. 356. 438 . 464 . 422 . 439. 380. 477. 4 94 . 347. 372 . 350. 328. 322 . 282 . 361. 349. 288. 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. FO U N D 378. 328. DEAD ON 410. DAY 345 357. 4 5 :P O S T W E A N I N G 446 465 . 323 . 355. 387 400 . 329. 494 . 452 . DAY A LL a. b. = D A Y P O S TW EA N IN G W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . B e ca u se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly i n t e r v a l s , b a s e d on e a ch r a t ' s d a y p o s tw e a n in g , was th e la s t d a y on w h ic h th e y o u n g e s t r a t s (in t h is g ro u p ) h ad a b o d y w e ig h t v a lu e re c o rd e d . P re c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was begun fo r th e F I g e n e ra tio n r a ts w e re 92 t o 10 6 d a y s o f a g e . d a y 70 p o s tw e a n in g r a t s ; a t th a t tim e th e se PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 15 (P A G E 6) : B O D Y W EIG H TS - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A T S ARGUS 418-020 Page 383 RAT # DOSAGE GROUP I I 1 M G/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 5 7 6 4 7 0 a P R E C O H A B I T A T I O N b 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 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 . 70. 78. 73 . 71. 73 . 69. 66. 75. 76. 94. 92. 78. 71. FO U N D 57. 52. 75. 79. 72. 62 . 59. 87. 86. 84. 65. 67. 75. 84. 77. 74. 117. 126. 125. 111. 123 . 118. 108. 123 . 125. 142. 142. 135. 128 . DEAD ON 101. 92. 118 . 125. 120. 107 . 106. 137. 131. 134 . 102. 108. 118. 126. 120. 121. 178. 233 . 186. 246. 179. 242. 168. 226. 184. 244 . 178. 234. 165. 224. 178. 239. 187. 254 . 196. 248. 193 . 249. 195. 257. 190. 245 . D A Y 2 P O S TW EA N IN G 1 5 1 . 210. 136. 172 . 184. 220. 184 . 231. 170. 161. 223 . 212. 173 . 201. 202. 230. 266. 265. 194. 165. 257. 220 . 165. 224 . 177. 231. 188. 242 . 184. 232. 182. 239. 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. 334. 330. 336. 332. 335. 345. 276. 307. 298. 364 . 353 . 330. 346. 342. 372. 370. 386. 366. 359. 388 . 311. 337. 325. 396. 382 . 369. 372 . 378. 395. 402. 422. 390. 379. 418 . 348. 360. 343 . 426. 409. 399. 402 . 408. 419. 440 . 459. 412 . 402. 450 . 387. 381. 368 . 453 . 451. 424 . 432 . 432 . 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 A LL a. b. = D A Y P O S T W EA N IN G W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . B e ca u se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a se d on w as th e la s t d a y o n w h ic h th e y o u n g e s t r a t s ( in t h is g ro u p ) h a d a b o d y P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was r a t s w e re 92 t o 10 6 d a y s o f a g e . e a c h r a t ' s d a y p o s tw e a n in g , w e ig h t v a lu e re c o rd e d . begun fo r th e F I g e n e ra tio n d a y 70 p o s tw e a n in g r a t s ; a t t h a t tim e th e se PROTOCOL 418-020: O R A L (G A V A G E ) TW O-G E N E R A T IO N (O N E L I T T E R P E R G E N E R A T IO N ) R E P R O D U C T IO N S T U D Y O F AM M O N IU M P E R F L U O R O O C T A N O A T E (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 . 6 ) T A B L E D 15 (P A G E 7 ) : B O D Y W EIG H T S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 384 RAT # DOSAGE GROUP I I D AY 78 85 92 99a 10 6 1061 10 6 2 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. 6F O U N D D E A D O N D A Y P O S TW EA N IN G 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. FO U N D 480. 323 . DEAD ON 497. DAY 364. 386. 45 P O S TW EA N IN G 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 M G/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) T A B L E D 1 5 ( P A G E 8) : B O D Y W E I G H T S - I N D I V I D U A L D A T A - F I G E N E R A T I O N M A L E R A T S ARGUS 418-020 Page 385 RAT # DOSAGE GROUP I I 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. 500. 506. 438. 429. 509. 519. 440. 434 . 533 . 543 . 458. 454 . 554 . 566. 465. 471. 490. 503. 521. 535. FOUND DEAD ON DAY 2 POSTWEANING 432. 403 . 436. 407. 456. 419. 479. 429. 389. 513 . 496. 465 . 472 . 460. 396. 521. 499. 484 . 478 . 463 . 400 . 541. 518. 496 . 488. 486. 409. 545. 531. 511. 503 . 496. 494 . 573 . 582. 475 . 479. 551. 492 . 434 . 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) TA B LE D15 (PAGE 9 ): BODY WEIGHTS - IN D IV ID U A L DATA - F I GEN ERATIO N MALE RATS ARGUS 418-020 Page 386 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 DAY D O S A G E G R O U P :I l l 81 1 5 22 2 9 36 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. 53 . 56. 54. 46. FOUND 74. 78. 64. 56. 60. 58. 72. 62. FOUND 56. 72. 77 . 88. 87. 76. 80. 85. 78. 55 . 63 . 58. 67. 52 . 68. 85. 85. 94 . 96. 77. DEAD ON 120. 132. 112 . 99. 103 . 102 . 125. 102. DEAD ON 102. 117. 116. 142. 140. 129. 131. 140. 128. FOUND 109. 99. 110. 92 . 110. 136. 141. 144 . 145. 124. DAY 5 POSTWEANING 186. 247. 300. 195. 249. 309. 178. 239. 297. 154 . 208. 274 . 152 . 205. 269. 153 . 205. 258. 191. 248. 312 . 167. 228. 288. DAY 2 POSTWEANING 160. 226. 287. 179. 233 . 283 . 173 . 225. 280. 213 . 270. 340. 204. 266. 317. 184. 233 . 288. 197. 252 . 306. 204. 273 . 328. 192. 252 . 305. DEAD ON DAY 9 POSTWEANING 164 . 222. 281. 151. 203 . 256. 168. 225. 283 . 146. 163 . 191. 211. 248. 245. 196. 257. 313 . 194 . 250. 304. 198. 201. 251. 249. 299. 304. 182 . 234. 277. 3 MG/KG/DAY 43 50 337 345 376. 379. 303 325 344 318 367 338 326 327 322 298 276 335 338 339. 360. 392 . 354 . 406. 362 . 360. 352 . 3 64 . 331. 297. 381. 371. 57 407. 419. 354. 390. 427. 390. 438. 380. 386. 377. 398. 352. 315. 413. 391. 64 431. 452. 70a PRECOHABITATION b 448 . 472 . 480. 517. 375. 422. 457. 419. 467. 398. 406. 395 . 426. 383 . 339. 441. 417. 389. 436. 469. 441. 483 . 421. 418 . 407. 473 . 495 . 474 . 520. 450 . 439. 400. 451. 402. 417. 494 . 433 . 354 . 469. 432 . 376. 485. 458 . DAY ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED IN GRAMS ( G ) . Because body w eight values were recorded a t w eekly in te rv a ls , based on each r a t 's day postw eaning, was the l a s t day on which the youngest r a ts (in t h is group) had a body w eight v a lu e recorded. P r e c o h a b i t a t i o n bo dy w e ig h ts were re c o rd e d on th e d a y c o h a b i t a t i o n was begun f o r th e F I g e n e r a tio n r a t s w e re 92 t o 106 d a y s o f a g e . day 70 po stw ean in g ra ts ; a t th a t tim e 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) TA B LE D15 (PAGE 10) : BODY W EIGHTS - IN D IV ID U A L DATA - F I GENERATIO N MALE RATS ARGUS 418-020 Page 387 RAT # 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 DOSAGE GROUP I l l DAY 1 8 15 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. 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. 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. 3 MG/KG/DAY 43 50 384. 418 . 355. 389. 390. 429. 57 455. 428. 456. 328. 385. 332. 359. 280. 298. 325. 294. 342. 385. 324. 371. 356. 343 . 419. 377 . 392 . 319. 338. 368. 313 . 370. 414 . 360. 392 . 395. 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. 446. ' 438 . 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 ALL a. b. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS ( G ) . Because body w eight values were recorded a t weekly in te rv a ls , based on each r a t 's day postw eaning, was th e l a s t day on w hich th e yo u n g e st r a t s (in t h is group) had a body w e ig h t v a lu e re c o rd e d . P r e c o h a b ita tio n bo dy w e ig h ts were re c o rd e d on the day c o h a b ita tio n was begun f o r th e F I g e n e ra tio n r a t s w e re 92 t o 106 d a y s o f a g e . day 70 p o stw ea n in g r a ts ; a t th a t tim e 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) T A B LE D15 (PAGE 11) : BODY WEIGHTS - IN D IV ID U A L DATA - F I G ENERATIO N MALE RATS ARGUS 418-020 Page 388 RAT # DOSAGE GROUP I I I 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 D A Y 7 8 85 92 99a FOUND 462. 505. DEAD ON 471. 508. DAY 5 POSTWEANING 491. 497. 535. 504. 106 513 . 498. 399. 408. 414 . 425 . 450. FOUND 476. 465. 480. DEAD ON 492. 476 . DAY 505. 517. 2 POSTWEANING 512. 517. 490. 507. 507. 440. 430. 512 . 445 . 431. 530. 465. 451. 542 . 482 . 456. 405. FOUND 476 . 423 . 412 . DEAD ON 485. 422. DAY 428 . 436. 9 POSTWEANING 510. 526. 443 . 460. 372 . 483 . 445 . 377 . 477. 457. 383 . 512 . 474 . 394 . 520. 487 . 437. 536. 538. 524 . 561. 489. 472 . 443 . 545 . 475. 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-6889.6) TA B LE D15 (PAGE 1 2 ) : BODY WEIGHTS - IN D IV ID U A L DATA - F I GENERATIO N MALE RATS ARGUS 418-020 Page 389 RAT # DOSAGE GROUP I l l 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. 456. 477. 459. 478 . 377. 472 . 432 . 453 . 442 . 480. 475. 524 . 455. 478. 486. 486. 388. 481. 436. 465 . 450 . 518 . 490. 536. 482 . 491. 507. 516. 405. 496. 451. 480. 463 . 541. 512. 551. 496. 502. 526. 529. 417. 512 . 472 . 491. 480. 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) TA B LE D15 (PAGE 13) : BODY W EIGHTS - IN D IV ID U A L DATA - F I GENERATIO N MALE RATS ARGUS 418-020 Page 390 RAT # 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 DOSAGE GROUP IV DAY 1 8 15 22 2 9 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. 77. 58. 60. 54. 54. 80 . 82. 78. 88. 77. 79. 90. 84. 83. 78. 83 . 100. 70. 71. 95. 76. 70. 76. 70. 66. 66. 82. 83 . FOUND 121. 123 . 102. 101. 90. 92 . 131. 142 . 130. 149. 124. 120. 135 . 132 . 125 . 120. 125. 151. 109. 117 . 127. 126 . 116. 116. 112. 109. 102. 137. 135. DEAD ON 183 . 231. 189. 243 . 158. 161. 214 . 221. 134. 181. 143 . 199. 190. 247. 204. 202. 244 . 266. 218. 288. 182. 236. 183 . 201. 238. 254 . 198. 262. 183 . 233 . 179. 233 . 178 . 230. 218. 282 . 161. 207. 144 . 134 . 183 . 235. 187. 242. 178. 238. 186. 240 . 176 . 227 . 168. 215 . 158. 207. 198. 252 . 198. 246. DAY 4 POSTWEANING 36 283 . 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. 10 MG/KG/DAY 43 50 5 7 64 7 0 a P R E C O H A B I T A T I O N b 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 . M ORIBU N D S A C R I F I C E D ON D A Y 40 PO S TW EA N IN G 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED IN GRAMS ( G ) . Because body weight values were recorded at weekly in te rv a ls , based on was the la s t day on w hich the youngest r a ts (in t h is group) had a body P re c o h a b ita tio n body w eights were rec orde d on the day c o h a b ita tio n was r a t s w e re 92 t o 106 d a y s o f a g e . each r a t 's day postweaning, weight value recorded. begun fo r the F I generation day 70 postw ean in g r a ts ; a t th a t tim e 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) TA B LE D15 (PAGE 1 4 ) : BODY WEIGHTS - IN D IV ID U A L DATA - F I GEN ERATIO N MALE RATS ARGUS 418-020 Page 391 RAT # 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 DOSAGE GROUP IV DAY 1 8 15 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. 6 1 . 102. 89. 149. 90. 143 . 83 . 13 6. 82. 135. 7 6 . 122. 77 . 128 . 63. 108. 62. 104 . 84 . 135. 83 . 126. 88. 1 3 4 . 85. 132 . 52. 80. 54 . 92. 82. 132. 80. 130. 7 0 . 111. 68. 110. 65. 108 . 77. 127. 84 . 128. 89. 140. 93 . 149. 78. 125. 77. 129. 66. 1 0 4 . 75. 126. 83 . 132 . 85. 136. 22 161. 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. 29 204 . 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. 36 254. 330. 193 . 306. 315. 291. 296. 269. 238. 273 . 302 . 221. 251. 305. 253 . 259. 319. 301. 253 . 293 . 10 M G / K G / D A Y 43 50 287, 373 , 320. 416. 351, 334 , 336. 274 , 303 , 333 , 274 , 291, 345, 390. 370. 372 . 297. 334. 362 . 301. 310. 369. 276, 306. 290, 354 , 298. 400. 343 273 383 . 288. 328 362. 57 336. 440. 413. 404. 401. 309. 363. 384. 332. 342. 387. 324. 312. 421. 403. 305. 394. 64 358. 473 . 439. 439. 428 . 326. 335. 404 . 364. 370. 406. 346. 329. 462 . 432. 326. 424 . 70a PRECOHABITATION b 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED I N GRAMS ( G ) . Because body w eight va lue s were recorded a t w eekly in te r v a ls , based on each r a t 's day postw eaning, was th e l a s t d a y on w hich th e youngest r a t s (in t h i s group) had a body w eight v a lu e re c o rd e d . P r e c o h a b ita tio n bo d y w e ig h ts were re c o rd e d on th e day c o h a b ita tio n was begun f o r th e F I g e n e ra tio n r a t s w e re 92 t o 10 6 d a y s o f a g e . day 70 p o stw ea n in g r a ts ; a t th a t tim e 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) T A B LE D15 (PAGE 15) : BODY W EIGHTS - IN D IV ID U A L DATA - F I 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 S A C R IF IC E D ON DA Y 40 POSTW EANING 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) TA B LE D15 (PAGE 16) : BODY WEIGHTS - IN D IV ID U A L DATA - F I GENERATIO N MALE RATS ARGUS 418-020 Page 393 RAT # DOSAGE GROUP IV 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 DAY 78 388. 491. 471. 471. 458. 357. 382. 427. 414 . 393 . 443 . 386. 338. 503 . 452 . 350. 454 . 85 396. 497. 470 . 468. 452 . 346. 372. 446. 424. 396. 455. 392 . 348. 509. 455. 341. 458. 92 412 510 480 484 472 373 403 457 450 414 471 392 352 526 454 357 468 99a 428. 538. 492 . 500. 480. 382. 404. 480 . 466. 429. 484 . 402. 360. 545. 464 . 367. 489. 106 447. 542. 501. 507. 498 . 400. 413. 492 . 486. 424 . 489. 407. 365. 544 . 465. 386. 492. DAY ALL a. = DAY POSTWEANING W E IG H T S W E R E R E C O R D E D I N GRAMS (G) F ir s t weekly value recorded a fte r cohabitation. 113 455. 561. 512. 522. 503 . 402. 414. 502. 490. 429. 500. 411. 366. 556. 480. 381. 4 93 . 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) TA B LE D15 (PAGE 1 7 ) : BODY WEIGHTS - IN D IV ID U A L DATA - F I GENERATIO N 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 D O S A G E G R O U P 'V DAY 1 8 15 22 2 9 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. 61. 51. 68. 70. 65. 54 . 48. 46. 64 . 77. 71. 70. 58. 85. 86. 71. 61. 47. FOUND 68. 71. FOUND FOUND 66. 71. 73 . 83 . 86. 99. 100. 102. 91. 113 . 119. 100. 85. 80. 82 . 101. 126. 118. 107. 92. 133 . 132. 112. 97. 69. DEAD ON 103 . 109. DEAD ON DEAD ON 99. 107. 113 . 120. 128. 142. 157. 216. 158. 147. 216. 202 . 176. 237. 180. 244 . 156. 216. 136. 190. 129. 179. 132. 177. 148. 183 . 172. 213. 170 . 209. 160 . 204 . 145. 194 . 187. 241. 186. 240. 168. 231. 146. 182 . 118. 171. DAY 4 POSTWEANING 151. 199. 162. 208. DAY 2 POSTWEANING DAY 2 POSTWEANING 150. 198. 157. 213 . 165. 219. 181. 235. 197. 255. 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 M G /K G /D A Y 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 . 331. 306. 356. 57 397. 374. 407. 339. 305. 330. 304. 288. 381. 381. 312. 322 . 321. 391. 64 432. 402 . 421. 365. 317. 346. 323 . 311. 401. 406. 337. 349. 340. 417. 70a PRECOHABITATION b 448. 465. 422 . 428. 382 . 324 . 348 . 446 . 457. 399. 336. 360. 340 . 328. 410 . 416 . 353 . 359. 359. 350. 441. 420. 371. 377 . 352 . 369. 418. 442 . DAY ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED I N GRAMS ( G ) . Because body weight va lu e s were recorded a t w eekly in te rv a ls , based on each r a t 's day postw eaning, was the l a s t day on w hich th e youngest r a ts (in t h is group) had a body w eight va lu e recorde d. P r e c o h a b i ta ti o n bo dy w e ig h ts were re c o rd e d on th e day c o h a b i t a t i o n was begun f o r th e F I g e n e r a tio n r a t s w e r e 92 t o 106 d a y s o f a g e . day 70 postw ean in g r a ts ; a t th a t tim e 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) TAB LE D15 (PAGE 18) : BODY W EIGHTS - IN D IV ID U A L DATA - F I G ENERATIO N MALE RATS ARGUS 418-020 Page 395 RAT # 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 DOSAGE GROUP V DAY 1 8 15 22 2 9 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. 100. 66. 63 . 77. 69. 72. FOUND 40. 52. FOUND 70. 79. 81. 71. 70. 55. 56. 52 . 77. 80. 76. 87. 84. 81. 79. 76. 67. 65. 75. 76. 152. 102. 100. 127 . 117. 111. DEAD ON 67. 83 . DEAD ON 113 . 122 . 124 . 108. 111. 85. 88. 85. 119 . 125. 124 . 134 . 114 . 112 . 123 . 119. 114 . 106. 122. 120. 205 256. 1 5 5 201. 147 199. 184 242. 162 145. 169 199. D A Y 4 'P O S T W E A N I N G 108 144 . 130 187. D A Y 3 !P O S T W E A N I N G 167 214. 175 223 . 1 7 1 232 . 1 6 4 210. 170 188. 138 187. 137 181. 130 182. 180 234. 185 239. 178 224. 185 232. 167 224. 172 229. 182 237. 180 218 . 1 6 7 220. 158 203 . 182 239. 1 7 7 210. 36 298. 238. 239. 285. 116. 244 . 172 . 234 . 261. 260. 276. 256. 238. 226. 278 . 284 . 259. 270 . 261. 242 . 267. 30 M G /K G /D A Y 43 50 5 7 64 7 0 a P R E C O H A B I T A T I O N b 330. 362. 388. 410 436. 469. 265. 323 . MORIBUND 282 . 299. 348. 376. S A C R IFIC E D ON DAY 320 334 . 412 440. 3 9 :P O S T W E A N I N G 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED IN GRAMS ( G ) . Because body w eight values were recorded a t weekly in te rv a ls , based on each r a t 's day postweaning, was th e l a s t day on w hich the youngest r a t s (in t h is group) had a body w e ig h t v a lu e recorde d. P r e c o h a b ita tio n body w e ig h ts were re c o rd e d on th e day c o h a b ita tio n was begun f o r th e F I g e n e ra tio n r a t s w e re 92 t o 106 d a y s o f a g e . day 70 postw ea n in g ra ts ; a t th a t tim e 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) TA B LE D15 (PAGE 19) : BODY W EIGHTS - IN D IV ID U A L DATA - F I G EN ER ATIO N MALE RATS ARGUS 418-020 Page 396 RAT # DOSAGE GROUP V DAY 78 85 92 99a 106 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 456. 457. 461. 477. 432 . 435 . 394 . 332. 355. 436. 449. 398. 338. 353 . 466. 472 . 413 . 356. 364. 469. 477. 418. 358. 372 . 354 . 352 . 365. 382 . 343. 429. 346. 433 . 361. 443 . 366. 448. 416. 378. 415. 427. 365. FO U N D 370. 378. DEAD ON 357. DAY 384. 397. 4 P O S TW EA N IN G 378. 367. FO U N D D EA D O N D A Y 2 P O S TW EA N IN G FO U N D D EA D O N D A Y 2 P O S TW EA N IN G 366. 367. 380. 390. 437. 445. 467. 477. 476. 486. 480. 427 . 368. 383 . 396. 380. 462 . 444 . 411. 384. 403. 495. DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. First weekly value recorded after cohabitation. 113 441. 492. 490. 439. 377. 378. 403 . 401. 476. 446. 422 . 376. 423. 498. 30 M G/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) T A B LE D15 (PAG E 20) : BODY W EIGHTS - IN D IV ID U A L D A TA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 397 RAT # 1D O S A G E G R O U P 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 . 4 5 7. 465. 465. 478. 350. 450. M ORIBUND 3 4 1. 356. 448. 469. SA C R IFIC ED ON DAY 359. 372. 475. 486. 39 PO STW EANING FOUND D EAD ON D AY 4 POSTW EANING 323 . 326. 334 . 345. 369. FOUND 407. 334 . DEAD ON 412. 350. DAY 3 POSTW EANING 423 . 437. 355 . 363 . 450. 362 . 384. 396. 406. 423 . 434 . 378. 3 4 1. 385. 3 9 1. 350. 373 . 355. 388. 388. 359. 388. 360. 3 9 1. 393 . 372 . 405. 3 71. 412 . 403 . 386. 413 . 382. 422 . 415 . 396. 405 . 3 9 1. 338 . 3 9 1. 408. 394. 344 . 386. 417 . 402 . 352 . 394. 433 . 414 . 378. 401. 435. 284 . 372 . 4 19 . DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. First weekly value recorded after cohabitation. 113 4 9 1. 378. 490 . 30 M G/KG/DAY 120 510. 3 94 . 5 0 7. 382 . 466. 383 . 435. 420. 397. 428. 427 . 397. 440. FOUND D EA D ON D A Y 10 7 POSTW EANING 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) T A B LE D 16 (PAG E 1) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 398 RAT # DOSAGE GROUP I 0 M G/KG/DAY 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 10 17 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 DAY 1 - 8 8 -1 5 1 5 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 5 7 5 7 - 64 64 - 7 0 a 9 9 b - 10 6 1 0 6 - 1 1 3 6 0 . 1 1 6 . 163 . 72 . 124. 165. 88. 1 4 4 . 1 9 1 . 7 6 . 13 5 . 164 . 81. 140. 178. 74 . 130. 16 1. 78. 117. 151. 8 7. 130. 165. 82 . 143 . 19 1. 69. 114 . 145. 78 . 129. 156. 73 . 156. 165. 68. 1 3 7 . 1 5 0 . 96. 143 . 171. 9 7. 16 9 . 194 . 86. 1 4 7 . 158. 7 0 . 142 . 162 . 50. 10 7. 131. 85. 143 . 15 5 . 80. 135 . 151. 76. 132 . 149. 82 . 15 1. 16 7. 68 . 1 1 6 . 147. 76 . 12 9 . 14 9 . 69. 1 1 8 . 143 . 66. 1 2 5 . 1 4 0 . 1117 8 . . 123 . 66. 1 0 8 . 1 3 9 . M ORIBUND S A C R IFIC E D ON 71. 134 . 168. 188. 202. 19 9 . 195. 215. 18 1. 205. 231. 200. 212. 173 . 177. 172 . 180. 183 . 193 . 19 7. 2 19 . 165. 178 . 172 . 189. 16 9 . 183 . 171. 193 . 203 . 211. 209. 234 . 176 . 195. 18 1. 19 2 . 144 . 260. 166. 16 9 . 178 . 19 1. 205. 174 . 193 . FOUND DEAD ON DAY 179 . 195. 16 6 . 18 1. 137. 156. 158. 176 . D AY 4 POSTW EANING 19 6 . 205. 19 7. 233 . 222. 195. 183 . 207 . 204 . 188. 203 . 201. 206. 199. 182 . 208. 186. 218 . 189. 186. 193 . 204. 205. 203 . 25 POSTW EANING 186. 182 . 177. 168. 194 . 223 . 210. 194 . 209. 202 . 223 . 19 9 . 193 . 224 . 205 . 200. 173 . 194 . 229. 203 . 197. 211. 209. 225 . 197. c 225. 212. 200. 165. 159. 173 . 175 . 170 . 19 2 . 173 . 19 1. 164 . 16 7. 186. 185. 173 . 143 . 15 9 . 218. 206. 19 7. 206. 211. 218 . 19 5 . 18 6 . 223 . 208. 205. 173 . 178 . 213 . 19 1. 188. 2 19 . C c 202 . c 220 . c 214 . 147 . DAY A LL a. b. c. = D AY POSTW EANING W EIGHTS W ERE REC O RD ED IN GRAMS ( G ) . Because fe e d co nsu m ption was rec o rd e d a t w e e kly in te r v a ls , based th e l a s t i n t e r v a l i n w h ich a fe e d consum ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d the c a lc u la tio n o f th is v a lu e . on each fo r the r a t 's da y p o stw e a n in g , days 6 4 -70 youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D16 (PAGE 2 ) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 399 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 - 8 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. 8 -1 5 115 . 109. 106. 110. d 122. 100. 112. 112. 121. 103 . 118 . 12 8 . 143 . 124 . 136. 135. 124 . 119 . 117. 128 . 143 . 115 . 12 9 . 136. 14 1. 12 6 . 133 . 118 . 111. 15 - 22 165. 158. 147. 142 . 140. 163 . 136. 154 . 15 7. 147. 13 1. 136. 170 . 16 2 . 151. 158. 16 1. 159. 145. 138. 166. 177. 149. 153 . 172 . 170 . 16 1. 168. 163 . 163 . 22 - 29 196. 19 1. 180. 174. 171. 190. 155. 180. 18 1. 165. 147. 15 7. 186. 173 . 177. 175 . 175 . 182 . 172 . 174 . 19 9 . 189. 19 3 . 206. 201. 19 1. 72 . 192. 19 1. 183 . 29 - 36 200. 19 9 . 189. 187 . 19 1. 188. 162 . 2 0 7. 188. 179 . 183 . 190. 212. 212 . 19 9 . 237. 210. 215 . 216 . 214 . 208. 18 7. 36 - 43 2 0 7. 43 - 50 203. 50 - 57 213. 5 7 - 64 C 64 - 70 a 9 9 b -10 6 10 6 - 1 1 3 174 . 204 . 212 . 194 . 18 1. 185. 160. 194. 18 2 . 188. 173 . 156. 133 . 193 . 162 . 200 . 16 6 . FOUND 183 . 18 1. DEAD ON 19 2 . 19 9 . DAY 42 POSTW EANING 177. 179 . 198. 185. 218. 224. 249. 267 . 198. 211. 221. 221. 228. 244. 227. 228. 243. 214. 240. 246. 206. 254 . 210. 200 . 201. 263. c 232. 196. 200. 240. c 242. 204. 204. C c 264. 190. 196. 144. 14 9 . 196 . 15 6 . 19 1. 185. 163 . 215. 185. 176 . 246. 209. 237 . 192 . 209. 237. 2 0 7. 2 0 1. c 206. 219 . 241. 193 . 18 1. 201. 153 . 18 7. 19 0 . 232 . 18 7. 220. 2 16 . 198 . 259. 218. 188 . 206. 2 0 7. 180 . 19 0 . 180. 19 5 . 213 . 189. 224 . 212 . 194 . 246. 217. 192 . 207 . 213 . DAY A LL a. b. c. d. = D AY POSTW EANING W EIGHTS W ERE RECORDED IN GRAMS ( G ) . Because fe e d consum ption was re c o rd e d a t w e e kly in te r v a ls , based th e la s t in te r v a l in w h ich a fe e d consum ption v a lu e was re c o rd e d F i r s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d ed th e c a lc u la tio n o f th is v a lu e . S o ile d fe e d pre clu ded th e c a lc u la tio n o f th is v a lu e . on each fo r the r a t 's day po stw e a n in g , days 6 4 -70 youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 16 (PAG E 3) : F E E D CO NSUM PTION V A LU E S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 400 RAT # DOSAGE GROUP I I 1 MG/KG/DAY 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 10 71 1072 1073 1074 1075 1076 10 77 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 DAY 1 - 8 8 -1 5 15 - 22 22 - 29 29 - 36 67. 77. 69. FOUND 66. 64 . 54. 69. 62. 79. 72. 65. 86. 72. 72. 80. 68. 84. 70. 84 . 74 . 74 . 61. 72. 69. 72 . 87. 90. 92. 78 . 120. 125. 123 . DEAD ON 106. 106. 99. 119 . 108. 121. 117. 13 0 . 14 6 . 123 . 145. 132 . 13 2 . 15 1. 114 . 128. 124 . 135. 121. 119 . 110. 117. 122. 121. 136. 124. 15 9 . 168. 15 1. 16 9 . 12 8 . 16 4 . D AY 6 POSTW EANING 134 . 160. 13 9 . 155. 145 . 174 . 155. 176 . 138. 16 2 . 159. 176 . 14 1. 16 1. 159. 18 1. 177. 189. 16 9 . 179 . 19 1. 200. 16 5 . 185. 160. 173 . 182 . 19 2 . 146 . 164 . 150. 171. 154 . 168. 144 . 16 7. 152. 173 . 140. 158. 140. 156. 135. 14 7. 172. 19 1. 16 7. 173 . 158. 175 . 136. 154 . 178 . 185. 18 7. 180. 16 9 . 190. 196. 19 2 . 203 . 179 . 201. 201. 2 0 7. 213 . 18 7. 19 1. 208. 172 . 184 . 18 1. 177 . 192 . 176 . 178 . 158. 203 . 188. 19 1. 159. 36 - 43 175 . 207 . 171. 200. 200. 190. 19 9 . 19 1. 231. 192 . 193 . 195 . 211. 213 . 198. 19 1. 43 - 50 50 - 5 7 5 7 - 64 64 - 7 0 a 9 9 b - 1 0 6 1 0 6 - 1 1 3 170 . 180 . 169. 140. 16 5 . 16 8 . 180. 183 . 180. 152. 19 1. 18 7. 168. 177. 209. 174. 18 1. 182. 18 6 . 204. 174. 188. 16 7. 185. 204 . 176 . 189. 142 . 139. 158. C 162 . 176 . 186. 195. 184. 177 . 182 . 165. 189. 18 1. 171. 19 0 . 208. 195. 180. 175 . 195. 243 . 211. 184 . 188. 204 . 239. 215 . 183 . 183 . 16 9 . 2 0 7. 177. 159. 15 7. 222 . 241. 204 . 193 . 184 . 16 1. c c 130. FOUND D EA D ON D AY 45 POSTW EANING 190. c C 174 . 179 . 19 1. 179. 145. 13 1. 204 . C 189. 240 . 200 . 182 . 183 . 171. 256. 174 . DAY A LL a. b. c. = D AY POSTW EANING W EIGHTS W ERE RECORDED IN GRAMS ( G ) . Because fe e d consum ption was re c o rd e d a t w e ekly in te r v a ls , based th e la s t in te r v a l in w hich a fe e d co nsum ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d th e c a lc u la tio n o f th is v a lu e . on each r a t 's da y p o stw e a n in g , days 6 4 -70 fo r the youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 16 (PAGE 4 ) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 401 RAT # DOSAGE GROUP I I 1 M G/KG/DAY 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 110 3 110 4 1.105 110 6 110 7 110 8 110 9 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 DAY 1 - 8 8 -1 5 15 - 22 22 - 29 29 - 36 70 . 75 . 65. 74 . 80. 66. 66. 70. 84 . 96. 90. 65. 74 . FOUND 65. 59. 75. 75. 67. 72. 59. 77 . 82 . 80. 62 . 68. 72 . 71. 60. 66. 115 . 120. 108. 115 . 125. 118 . 12 8 . 12 9 . 15 1. 134. 16 2 . 12 9 . 132 . DEAD ON 115 . 100. 111. 115 . 118 . 109. 109. 120. 120. 128 . 108. 101. 112. 117. 112. 117. 145. 171. 150. 170 . 14 9 . 18 1. 15 7. 180. 16 7. 203 . 147. 16 7. 143 . 16 7. 153 . 183 . 170 . 218 . 160. 180. 154. 170 . 170 . 200. 168 . 189. DAY 2 POSTW EANING 14 1. 120. 174 . 13 7. 135. 159. 14 9 . 172 . 13 9. 168. 124. 164 . 148 . 164 . 154. 186. 165. 196. 16 1. 183 . 136. 162 . 13 6 . 148 . 13 7. 146. 14 9. 16 7. 15 7. 175 . 15 7. 185. 189. 189. 193 . 19 9 . 228 . 184. 18 7. 195. 175 . 203 . 183 . 19 7. 205 . 188. 15 1. 16 7. 19 7. 176 . 173 . 173 . 206. 200. 178 . 193 . 202 . 36 - 43 195. 215. 19 9 . 198. 202 . 201. 16 2 . 178 . 18 2 . C 19 7. 193 . 183 . 19 9 . 43 - 50 198. 214 . 222 . 200. 184. 19 9 . 172 . 188. 180. 206. 188. 203 . 188. 198 . 50 - 57 200. 223 . 238. 210. 19 7. 207 . 186. 184 . 19 2 . 208. 201. 205. 198. c 57 - 64 195. 222. 236. 198. 200. 204 . 188. 204 . 179 . 223 . 207. 205 . 19 9 . 203 . 64 - 70 a 9 9 b -10 6 106 -1 1 3 15 9 . 185. 194 . 193 . 2 0 7. 18 7. 156. 221. 218. 193 . 18 1. C 238. 19 1. 18 7. 175 . 198. 194 . 165. 183 . 194 . 214 . 19 0 . 210. 147. 184 . 177. 171. 154. 165. 16 5 . 206. 209. 212. 182 . 202 . 16 7. 207 . 198 . 209. 19 7. 194 . DAY A LL a. b. c. = D A Y POSTW EANING W EIGHTS W ERE RECORDED IN GRAMS ( G ) . Because fe e d consu m ption was re c o rd e d a t w e e kly in t e r v a ls , based th e la s t in te r v a l in w h ich a fe e d consum ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d th e c a lc u la tio n o f th is v a lu e . on each r a t 's day p o stw e a n in g , days 6 4 -70 fo r the youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 16 (PAGE 5 ) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 402 RAT # 1121 1122 1123 1124 112 5 1126 112 7 112 8 1129 1130 113 1 1132 1133 1134 1135 1136 113 7 1138 1139 1140 114 1 1142 1143 1144 1145 1146 1147 1148 1149 1150 DOSAGE! GROUP I I I DAY 1 - 8 8 -1 5 15 - 22 22 - 2 9 29 - 36 3 MG/KG/DAY 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70 a 9 9 b -10 6 10 6 -1 1 3 FOUND 89. 90 . 68. 58. 68. 56. 64. 51. FOUND 59. 8 1. 86. 83 . 82 . 42 . 73 . 92 . 82 . 63 . 72 . 50. 69. 56. 62. 68. 89. 91. 87. 8 1. DEAD ON 13 1. 13 7 . 114 . 114 . 104. 101. 117. 112. DEAD ON 122. 12 8 . 138. 14 9 . 143 . 99. 123 . 147. 12 9 . FOUND 119 . 102 . 138. 109. 160. 177. 159. 149 . 135. 12 6 . D A Y 5 POSTW EANING 16 9 . 61. 198. 171. 18 4 . 203 . 153 . 175 . 189. 14 6 . 173 . 18 1. 13 7. 16 6 . 175 . 13 1. 154. 175 . 165. 18 7. c 157 . 185. 199. D A Y 2 POSTW EANING 145. 170 . 178 . 164 . 179 . 16 1. 154 . 176 . 16 7. 198. 178 . 210. 180. 205. 2 17. 153 . 165. 179 . 164 . 18 1. 185. 175 . 19 1. 208. 170 . 208. 195. D EA D ON D AY 9 POSTW EANING 14 6 . 165. 176 . 13 1. c 170. 143 . 170 . 190. 13 9. 15 7. 180. 137. 15 7. 171. 147. 175 . 194 . 180. 173 . 195. 144 . 160. 173 . 16 1. 169. 195. 155. 18 2 . 198. 200. 213 . 195. 198. 211. 189. 222 . 2 0 7. 190. 203 . 198. 18 1. 165. 214. 213 . 19 2 . 19 9 . 188. 202 . 2 19 . 183 . 213 . 189. 190. 19 2 . 189. 178 . 172 . 212 . C 189. 2 16 . 192 . 212. 233 . 19 6 . 218. 189. 203 . 19 7. 194 . 176 . 172 . 211. 207 . 18 1. 211. 190 . 207. 226. 196. 212 . 189. 201. 199 . 190 . 177. 164 . 209 . 210. 15 7. 178 . 160 . 185. 183 . 164 . c 16 9 . 16 4 . 165. 162 . 156. 144 . 185. 164 . 176 . 121. 193 . 229. 215 . 200 . 19 9 . 210 . 192 . c 19 9 . 182. 167 . 203 . 19 1. 183 . 13 6 . 184 . 231. 229. 202. 19 7. 210. 113 . 183 . 204 . 19 1. 164 . 162 . 190 . DAY A LL a. b. c. = D A Y POSTW EANING W EIGHTS W ERE REC ORDED IN GRAMS ( G ) . Because fe e d consum ption was re c o rd e d a t w e ekly in te r v a ls , based th e la s t in te r v a l in w h ich a fe e d consu m ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d th e c a lc u la tio n o f th is v a lu e . on each r a t 's day po stw e a n in g , days 6 4 -70 fo r the youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D16 (PAG E 6 ) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 403 RAT # 115 1 1152 1153 1154 1155 1156 115 7 115 8 1159 116 0 116 1 1162 116 3 116 4 116 5 1166 116 7 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 118 0 DOSAGE GROUP I I I 1D A Y -8 8 -1 5 15 - 22 101. 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 . 8 1. 87. 78. 8 1. 15 1. 162. 149. 146. 147. 124. 119 . 123 . 146. 142. 129. 111. 112 . 144 . 13 8 . 69. 90. 99. 99. 113 . 105. 133 . 133 . 142 . 136. 113 . 139. 13 1. 122. 117. 18 1. 176 . 176 . 179 . 18 1. 162 . 150. 160. 185. 176 . 164 . 12 9 . 132 . 18 1. 177. 101. 121. 135. 125. 13 7. 129. 159. 152. 182. 175 . 13 7. 166. 170 . 168. 155. 22 - 29 210. 19 7. 185. 205. 203 . 195. 178 . 182 . 208. 193 . 188. 170 . 165. 195. 214 . 128. 148 . 15 9 . 142 . 154 . 147. 205. 180. 213 . 206. 14 9. 18 1. 183 . 190. 184 . 29 - 36 225. 213 . 202 . 2 19 . 224 . 218. 195. 204. 233 . 220. 19 9 . 190. 179 . 2 16 . 230. 14 9 . 16 7. 18 7. 16 6 . 195. 230. 16 5 . 204 . 218. 3 MG/KG/DAY 36 - 43 43 - 50 228. 227. 217. 217. c 213 . 212 . 222. 179 . 209. 173 . 185 . 203 . 164 . 189. 227. 182. 206. 212 . 202. 262. 183 . 209. 186. 218. 2 16 . 16 7. 200. 228 . 198. 206. 229. 50 - 57 235. 236. 225. 256. 269. 186. 220. 217. 218 . C 209. 176 . 203 . 208. 206. 5 7 - 64 223 . C 224. 254 . 235. 180. 212 . 225. 2 16 . C 211. 123 . 202. 203 . 194. 64 - 70 a 9 9 b -10 6 106 -1 1 3 19 4 . 19 9 . 211. 193 . 182 . 205. 209. c 210 . 198. 202 . 151. 177. 176 . 177. 139. 16 7. 15 1. 16 7. 180. 16 8 . 2 0 7. 2 16 . 19 0 . 19 4 . 224 . 218. 168. 193 . 19 9 . 15 7. 186. 206. 228 . 210. 200. 204 . 220 . 201. 168 . 18 6 . 155 . 145. 213 . 200. DAY A LL a. b. c. = D A Y POSTW EANING W EIGHTS W ERE REC O RDED IN GRAMS ( G ) . Because fe e d consu m ption was re c o rd e d a t w e e kly in t e r v a ls , based th e la s t i n t e r v a l in w hich a fe e d consu m ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d the c a lc u la tio n o f th is v a lu e . on each r a t 's day p o stw e a n in g , days 6 4-70 fo r the youngest ra ts in th is group . p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D16 (PAGE 7) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 404 RAT # DOSAGE GROUP IV 10 M G/KG/DAY DAY 1 - 8 8 -1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 5 7 - 64 64 - 7 0 a 9 9 b -1 0 6 10 6 - 1 1 3 118 1 118 2 118 3 118 4 118 5 118 6 118 7 118 8 118 9 1190 119 1 1192 1193 1194 119 5 1196 119 7 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 76. 75. 58. 63 . 56. 64. 78. 84 . 80. 88. 84 . 87. 95. 85. 85. 8 1. 59. 9 1. 72. 75 . 86. 83 . 75. 84 , 80. 79. 73 . 85. 84 . FOUND 13 7. 119 . 101. 103 . 110. 10 7. 136. 134 . 16 0 . 194 . 138. 135. 14 0 . 138. 143 . 12 9 . 117. 152 . 142 . 143 . 140. 12 6 . 155. 123 . 127. 123 . 112 . 137. 122. DEAD ON 15 6 . 190. 163 . 19 9 . 134. 159. 147. 174 . 127. 174 . 13 5 . 16 9 . 16 0 . 178 . 174 . 164 . 184 . 201. 180. 238. 15 7. 176 . 155. 173 . 16 6 . 199. 164 . 190. 155. 195. 13 7. 165. 13 1. 155. 16 9 . 192. 142 . 177. 170 . d 162 . 178 . 148 . 174. 168. 205 . 16 1. 208. 15 7. 203 . 14 6 . 168. 132 . 16 1. 156. 183 . 154 . 184. D A Y 4 POSTW EANING 205. 211. 176 . 189. 206. 179 . 19 7. 200. 241. 265. 189. 203 . 223 . 219. 218. 18 4 . 183 . 223 . 198. 18 1. 208. 199. 216. 225 . 239. 194. 179 . 206. 211. 212. 195. 16 2 . 201. 231. 19 9 . 218. 213 . 198. 16 9 . 178 . 18 7. 243 . 195. 213 . 19 6 . 206. 18 1. 182. c 230. 200. 221. 206. 213 . 176 . 182 . 199. 218. 193 . 220. 19 2 . 172. 15 9 . 154 . 155. 193 . 16 7. 194 . 163 . 195. 19 6 . 190 . 208. 239. 198 . 205. 19 9 . 238. 241. 260 . 2 5 7. 213 . M ORIBUND S A C R IFIC E D ON D AY 40 PO STW EANING 233 . 19 7. 211. 179 . 198 . 190. 219 . 178. 213 . 14 1. 178 . 183 . 240 . 18 9 . 206. 18 7. 212 . 189 . 212. 182 . 215 . 157 . 184 . 185 . 209. 194 . 204 . 188 . 2 0 7. 239. 19 1. 226. 200. 236. 18 7. 229 . 180 . 211. DAY A LL a. b. c. d. = D AY POSTW EANING W EIGHTS W ERE REC O RD ED IN GRAMS ( G ) . Because fe e d consum ption was re c o rd e d a t w e ekly in te r v a ls , based th e l a s t i n t e r v a l in w h ic h a fe e d c o n su m p tio n v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d feed pre clu d e d th e c a lc u la tio n o f th is va lu e . Wet fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . on each r a t 's day po stw e a n in g , days 6 4-70 fo r the youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 16 (P A G E 8) : F E E D CO NSUM PTION V A LU E S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 405 RAT # DOSAGE GROUP IV 10 M G/KG/DAY 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 12 3 7 1238 1239 1240 DAY 1 - 8 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. 8 -1 5 106. 145 . 13 2 . 125. 121. 116 . 125. 105. 80. 121. 112. 123 . 117. 76 . 83 . 122. 113 . 110. 109. 112 . 121. 114 . 122 . 13 0 . 10 7. 10 7. 104 . 120. 119 . 118 . 15 - 22 130. 185 . 165. 16 1. 188. 114 . 165. 132. 125. 145. 129. 149. 156. 112. 119 . 159. 142 . 13 6. 147 . 145. 16 1. 135. 166. 16 6 . 145 . 148 . 140. 16 9 . 152. 15 1. 22 - 29 154. 212 . 198. 193 . 204 . 155. 18 1. 16 2 . 152. 165. 155. 183 . 179 . 150 . 174 . 176 . 16 1. 16 1. 177 . 171. 193 . 16 1. 19 1. 193 . 177. 165. 173 . 202 . 179 . 194 . 29 - 36 16 7. 220. 99. 201. 211. 170 . 194 . 179 . 177 . 16 4 . 193 . 16 9 . 190. 19 7. 198. 166. 211. 178 . 281. 217. 36 - 43 174 . 224 . 206. 184 . 19 7. 18 6 . 16 6 . 19 1. 174. 19 2 . 209. C 16 1. 208. 183 . 177. 204 . 43 - 50 183 . 230. 200. 194 . 2 17. 184 . 183 . 18 6 . 178 . 202 . 212. 184 . 153 . 222. 19 9 . 188. 227. 50 - 5 7 18 9 . 229. 203 . 212 . 232 . 190 . 189. 188. 177 . 2 0 7. 212 . 184 . 14 6 . 228 . 197 . 192 . 228 . 5 7 - 64 183 . 221. 190. 216 . 226. 176 . 165. 185. 183 . 220. 210. 165. 145. 232. 204 . 203 . 226. 64 - 70 a 9 9 b -10 6 10 6 - 1 1 3 159. 188. 19 7. 209. 200. 220 . 16 4 . 18 1. 19 1. 15 7. 109. 14 1. 14 9 . 173 . 180. 178 . 203 . 203 . 184 . 19 2 . 188. 187 . 18 9 . 206. 18 1. c 193 . 18 1. 206. 19 9 . 177 . 18 7. 19 9 . 143 . 154 . 152 . 124 . 202 . 15 1. 221. 145 . 214 . 168. 165. 186 . 260. 19 1. c 158. 193 . 190 . DAY A LL a. b. c. = D AY PO STW EANING W E IG H T S W ERE R EC O R D E D I N GRAMS (G) . Because fe e d consum ption was recorde d a t w e ekly in te r v a ls , based th e la s t i n t e r v a l i n w h ich a fe e d consum ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d th e c a lc u la tio n o f th is v a lu e . on each r a t 's d a y p o stw e a n in g , days 6 4 -70 fo r the youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 1 6 (P A G E 9) : F E E D C O N S U M P T IO N V A L U E S - I N D I V I D U A L D A T A - F I G E N E R A T IO N M A L E R A T S 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 12 6 7 1268 1269 1270 DAY 1 - 8 8 -1 5 15 - 22 22 - 29 29 - 36 52. 60. 47. 70. 75 . 68. 55. 74 . 49. 6 1. 8 1. 73 . 69. 59. 83. 83 . 70. 58. 50. FOUND 66. 74. FOUND FOUND 69. 75. 72 . 69. 81. 9 1. 99. 10 7. 94 . 123 . 127. 108. 92 . 92 . 93 . 100. 13 2 . 12 9 . 114 . 10 6 . 12 6 . 123 . 125. 120. 88. DEAD ON 133 . 146 . DEAD ON DEAD ON 12 6 . 123 . 14 9 . 19 7. 138. 135. 137. 16 6 . 143 . 180. 147. 180. 177. 168. 2 17. 211. 144 . 171. 118 . 150. 117. 142. 113 . 14 9. 136. 152. 143 . 16 7. 147. 16 1. 139. 170 . 133 . 174. 148. 174. 142 . 165. 137. 162. 128. 14 0 . 118 . 15 1. D AY 4 POSTW EANING 129 . 155. 134 . 169. D AY 2 POSTW EANING D AY 2 POSTW EANING 139. 171. 13 5 . 15 7. 143 . 174 . 172. 18 7. 205. 222. 242. 172 . 185. 18 7. 176 . 237. 248. 188. 168. 168. 176 . 158. 184. 188. 184 . 18 2 . 19 4 . 178 . 185. 148. 16 7. 16 1. c 188. 176 . 200. 215. 229. 194 . 36 - 43 210. 250. 259. 182 . 174 . 190. 19 6 . 195. 19 7. 19 1. 178 . 165. 180. 2 6 1. 43 - 50 193 . 232. c 172 . 159. 16 7. 185. 174 . 199. 203 . 176 . 172 . 170 . 230. 50 - 5 7 188. c 246. 184 . 16 9 . 176 . 200. 175 . 19 6 . 218. 170 . 180. 170 . 239. 5 7 - 64 210. 215. 239. 177 . 158 . 159. 189. 185. 18 7. 216. 16 6 . 18 1. 16 7. 231. 64 - 70 a 9 9 b -10 6 106 -1 1 3 165 . 178 . 142 . 193 . 179 . 159. 135. 118 . c 230. 173 . 156. 152 . 217. 236. 174 . 164 . 147. 168. 16 1. 15 9 . 180. 140. 144 . 203 . 234. 18 1. 19 7. 171. 179 . 185 . 19 1. 19 9 . 198. 176 . 162 . 144 . 182 . 190 . 222 . 192. 226. DAY ALL a. b. c. = D A Y POSTW EANING W EIGH TS W ERE REC ORDED IN GRAMS ( G ) . Because fe e d consu m ption was re c o rd e d a t w e e kly in t e r v a ls , based th e la s t in te r v a l in w h ich a fe e d consum ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d feed pre clu d ed th e c a lc u la tio n o f th is v a lu e . on each r a t 's day p o stw e a n in g , days 6 4 -70 fo r the youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D16 (PAGE 10) : F E E D CONSUM PTION V A LU ES - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 407 RAT # DOSAGE GROUP V 30 M G /KG /D AY 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 12 9 7 1298 1299 1300 DAY 1 - 8 8 -1 5 15 - 22 2 2 - 2 9 29 - 36 92. 63 . 67. 79. 70. 49. FOUND 29. 44. FOUND 70 . 67. 65. 59. 59. 55. 56. 55. 68. 73 . 60. 74 . 70 . 57. 67. 59. 55. 55. 63 . 63. 136. 95. 101. 116 . 113 . 10 7. DEAD ON 68. 8 1. DEAD ON 113 . 110. 111. 102. 111. 88. 82 . 9 1. 112. 113 . 117. 13 6 . 10 7. 82 . 119 . 109. 108. 100. 109. 102 . 9 9 . 202. 128. 15 7. 12 8 . 16 8 . 165. 200. 164 . 235. 14 6 . 145. D AY 4 POSTW EANING 105. 128. 119 . 159. D AY 3 POSTW EANING 134 . 165. 136. 163 . 13 1. 180. 155. 182. 159. 205. 118 . 121. 148. 16 1. 117. 147. 14 6 . 18 7. 150. 195. 144 . 167 . 168. 194 . 128. 177. 14 1. 188. 154 . 185. 14 1. 151. 134. 15 7. 132 . 159. 144 . 171. 14 8 . 164. 206. 163 . 186. 213 . 173 . 16 9 . 134. 177. 189. 173 . 188. 198. 185. 18 2 . 203 . 218. 169. 205. 16 7. 175 . 203. 36 - 43 221. 43 - 50 227. 50 - 57 231. 5 7 - 64 215. 64 - 70 a 9 9 b -10 6 10 6 - 1 1 3 190. 203 . 221. 179 . 210. 16 6 . 192 . 168 . 19 9 . 167. 214 . 142 . 178 . M O RIBUND S A C R IF IC E D ON D A Y 39 PO STW EANING 16 9 . 178 . 162 . 18 1. 14 1. 18 1. 183 . 18 7. 15 7. 19 7. 182 . 180. 16 1. 2 16 . 171. 186. 165. 201. 174 . 173. 142 . 16 4 . 14 9 . 153 . 180. 204. 163 . 203 . 177. 206. 183 . 194 . 184. 19 0 . 205. 209. 16 6 . 211. 179 . 177. 210. C 183 . 204 . 200. 211. 213 . 182 . 189. 221. c 189. 2 16 . 212 . 168. 19 7. 185. 185 . 222 . 226. 178. 215. 207. 173 . 194. 182. 16 7. 230. 228 . 168 . 172. 173 . 125. 162 . 142 . 13 7. 165. 218 . 189. 212 . 202 . 16 7. 194 . 124 . 174 . 213 . 2 16 . 19 1. 19 6 . 19 9 . 160 . 170 . d e 218 . DAY A LL a. b. c. d. e. = D A Y POSTW EANING W EIGHTS W ERE RECORDED IN GRAMS ( G ) . Because fe e d consum ption was re c o rd e d a t w e ekly in te r v a ls , based th e la s t in te r v a l in w h ich a fe e d consum ption v a lu e was re c o rd e d F ir s t va lu e recorded a fte r c o h a b ita tio n . S p ille d fe e d p re clu d e d th e c a lc u la tio n o f th is v a lu e . R a t 1296 was fou nd dead on d a y 10 7 po stw e a n in g . Wet fe e d p re clu d e d th e c a lc u la tio n o f th is v a lu e . on each fo r the r a t 's da y po stw e a n in g , days 6 4 -70 youngest ra ts in th is group. p o stw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 17 (PAGE 1) : S EXU A L M ATURATIO N - IN D IV ID U A L D A TA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 408 DOSAGE GROUP - MG/KG/DAY I II III IV V 0 1 3 10 3 0 RAT # P R EP U TIA L S EP A R A T IO N (DAY) 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 10 17 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 52 49 49 49 48 49 47 46 47 45 51 48 46 47 49 48 b 46 52c 52 49 52 d 52 53 49 48 a 50 PR EPU TIA L R AT # S EP A R A T IO N (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 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 PR EPU TIA L R A T # S E P A R A T IO N (DAY) 1121 1122 1123 112 4 112 5 1126 112 7 112 8 112 9 1130 113 1 1132 1133 1134 1135 1136 113 7 1138 113 9 1140 1141 1142 1143 1144 1145 1146 114 7 1148 1149 115 0 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 P R EP U TIA L R AT # S EP A R A T IO N (DAY) 118 1 118 2 118 3 118 4 118 5 118 6 118 7 118 8 118 9 119 0 119 1 1192 1193 1194 119 5 1196 119 7 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 P R EP U TIA L RAT # S EP A R A T IO N (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 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 a. b. c. d. = DAY POSTPARTUM R a t was fo u n d dead o r m oribund s a c r ific e d b e fo re th e s t a r t o f s e xu a l m a tu ra tio n S e xu a l m a tu ra tio n te s tin g was d is c o n tin u e d b e fo re r a t became s e x u a lly m ature . R a t d id n o t have p re p u tia l s e p a ra tio n re c o rd e d on one day and was se p a ra te d th e averages and s ta tis tic a l a n a lys e s. R a t was fo u n d de ad o r m oribu nd s a c r ific e d . e va lu a tio n . fo llo w in g day; va lu e exc lud ed fro m g ro u p PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 1 7 (P A G E 2 ) : S E X U A L M A T U R A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 409 DOSAGE GROUP - M G/KG/DAY I II III IV V 0 1 3 10 3 0 P R EP U T IA L R A T # S E P A R A T IO N (D A Y) 103 1 1032 1033 1034 10 3 5 1036 10 3 7 10 3 8 1039 1040 10 4 1 10 4 2 1043 10 4 4 10 4 5 10 4 6 10 4 7 1048 10 4 9 10 5 0 10 5 1 1052 1053 1054 10 5 5 1056 10 5 7 10 5 8 1059 10 6 0 48 50 48 51 48 48 51 49 49 C 49 47 44 47 50 47 49 50 50 47 47 C 49 48 48 44 48 49 d d RAT # P R E P U T IA L S E P A R A T IO N (D AY) 10 9 1 10 9 2 10 9 3 10 9 4 10 9 5 10 9 6 10 9 7 10 9 8 10 9 9 1100 1101 1102 110 3 110 4 110 5 110 6 110 7 110 8 110 9 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 P R E P U T IA L R A T # S E P A R A T IO N (D AY) 115 1 115 2 115 3 115 4 115 5 115 6 115 7 115 8 115 9 116 0 116 1 116 2 116 3 116 4 116 5 116 6 116 7 116 8 116 9 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 118 0 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 P R E P U T IA L R A T # S E P A R A T IO N (D A Y) 1211 1212 12 13 12 14 12 15 12 16 12 17 12 18 1219 1220 1221 1222 1223 12 2 4 1225 1226 12 2 7 1228 1229 12 3 0 123 1 12 3 2 1233 12 3 4 1235 12 3 6 12 3 7 12 3 8 12 3 9 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 50 47 47 P R EP U T IA L R A T # S EP A R A T IO N (D AY) 12 71 1272 1273 12 74 1275 12 76 12 77 12 78 12 79 1280 128 1 12 8 2 12 8 3 12 8 4 1285 12 8 6 12 8 7 1288 12 8 9 12 9 0 129 1 12 9 2 12 9 3 12 9 4 12 9 5 12 9 6 12 9 7 12 9 8 12 9 9 13 0 0 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 a. b. c. d. = D AY POSTPARTUM R a t was fo u n d d e a d o r m o rib u n d s a c r ific e d . R a t w as fo u n d d e a d o r m o rib u n d s a c r ific e d b e fo re th e s t a r t o f s e x u a l m a tu ra tio n S e xu a l m a tu ra tio n te s tin g was d is c o n tin u e d b e fo re r a t becam e s e x u a lly m a tu re . S e xu a l m a tu ra tio n was n o t o b s e rv e d on r a ts 1059 and 10 6 0 . e v a lu a tio n . PR O TO C O L 4 18 -0 2 0 : O R A L (G A V A G E ) T W O -G E N E R A T IO N (O N E L I T T E R P E R G E N E R A T IO N ) R E P R O D U C T IO N S T U D Y O F AM M O N IU M P E R F L U O R O O C T A N O A T E (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 .6 ) T A B LE D 18 (P A G E 1 ) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 410 DOSAGE GROUP I RAT # 1002 10 0 3 10 0 5 10 0 7 1011 1012 10 13 10 14 10 17 1021 1023 10 2 6 1028 10 3 1 1034 10 3 5 1040 10 41 1043 10 4 5 10 4 7 10 4 8 10 5 0 10 5 1 1052 1054 10 5 5 10 5 8 10 5 9 10 6 0 DAYS IN C O H A B IT A T IO N 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 = M ATED ( ) = FE M A LE R A T NUM BER C = C O N FIR M ED P = PREGNANT NP = NOT PREGNANT 0 M G/KG/DAY M A TIN G S TA TU S M M M M M D ID M M M M M M M M M M M M M M M M M M M M M M M M NOT M ATE M A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P (13 4 1) P (13 0 2 ) P (13 3 5 ) P (13 18 ) P (13 0 8 ) -(13 5 8 ) P (13 3 4 ) P (13 0 4 ) P (13 46 ) P (13 5 9 ) P (13 5 0 ) P (13 5 5 ) P (13 3 6 ) P (13 4 2 ) P (13 28 ) P (13 4 4 ) N P (13 16 ) P (13 3 0 ) P (13 5 3 ) P (13 4 8 ) P (13 40 ) P (13 3 8 ) P (13 3 1) P (13 45 ) P (13 0 6 ) P (13 13 ) P (13 12 ) P (13 2 1) P (13 10 ) P (13 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) T A B LE D 18 (P A G E 2 ) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 411 DOSAGE GROUP I I RAT # 10 6 1 10 6 3 10 6 6 10 6 7 10 6 9 10 71 10 73 10 77 10 78 10 8 1 10 8 2 10 8 3 1086 10 8 8 10 9 0 109 1 10 9 4 10 9 6 10 9 8 1100 110 3 110 6 110 7 11101112 1114 1116 1118 1120 DAYS IN C O H A B IT A T IO N 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 M G/KG/DAY M A TIN G S TA T U S 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 A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P (14 15 ) P (14 10 ) P (13 6 4 ) P (13 6 2 ) P (13 8 7) P (13 92) P (13 6 3 ) N P (13 78 ) P (13 71) P (13 6 8 ) P (14 18 ) P (13 6 7) P (140 9 ) P (13 8 9 ) P (14 0 4 ) P (14 13 ) P (13 75 ) P (13 9 7) P (14 0 7) P (13 76 ) P (13 8 3 ) P (13 9 9 ) P (14 0 1) P (13 8 2) P (13 79 ) P (13 8 4 ) P (14 16 ) P (13 9 3 ) P (13 8 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) T A B L E D 18 (P A G E 3) : M A TIN G A N D F E R T IL IT Y - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 412 DOSAGE GROUP I I I RAT # 1122 112 3 112 7 112 9 113 1 113 2 113 4 113 5 113 6 113 9 114 1 114 2 114 5 114 7 114 9 115 1 115 3 115 4 115 8 115 9 116 2 116 4 116 7 116 8 1171 1173 1175 1176 1177 118 0 DAYS IN C O H A B IT A T IO N 1 2 4 3 2 4 4 2 2 2 3 4 1 4 1 3 1 4 1 2 4 2 1 3 2 3 2 4 1 1 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP = NOT PREGNANT 3 M G/KG/DAY M A TIN G S TA TU S 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 A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P (145 6 ) P (1443 ) P (14 76 ) P (14 6 1) P (14 74 ) P (14 72 ) P (145 5 ) P (1448 ) P (143 0 ) P (14 2 4 ) P (14 5 0 ) N P (1446 ) P (148 0 ) P (14 3 7) P (14 2 6 ) P (143 9 ) P (14 3 1) P (14 77) P (14 69) P (14 5 2 ) P (143 6 ) P (145 9 ) N P (145 8 ) P (1428 ) P (146 5 ) P (143 3 ) P (14 6 3 ) P (146 8 ) P (14 2 1) P (14 4 2 ) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 18 (P A G E 4) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - F I G E N E R A T IO N M ALE R A TS ARGUS 418-020 Page 413 DOSAGE GROUP IV RAT # DAYS IN C O H A B IT A T IO N 118 2 118 4 118 6 118 8 118 9 119 2 119 4 119 5 119 8 12 0 3 12 0 4 12 0 7 12 0 9 1211 1212 12 15 12 16 12 17 12 19 1221 1222 1224 1225 1226 12 2 9 12 3 2 1233 12 3 6 12 3 7 1240 3 4 4 2 4 7 1 1 2 2 3 1 1 3 4 4 3 4 4 4 1 5 1 1 1 2 1 3 4 1 M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP = NOT PREGNANT 10 M G/KG/DAY M A TIN G S TA TU S 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 A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P (15 28 ) P (15 23 ) P (15 16 ) P (15 13 ) P (15 2 7) N P (15 11) P (15 19 ) P (15 0 2 ) P (14 9 6 ) P (14 9 1) P (15 3 3 ) N P (14 8 3 ) P (14 8 8 ) P (15 0 0 ) P (15 2 1) P (15 3 1) P (15 0 5 ) P (15 0 8 ) P (14 97) P (14 94) P (148 6 ) P (15 3 9 ) P (15 3 4) P (15 17) P (15 24) P (15 14 ) P (148 2 ) P (15 3 7) P (15 0 7) P (14 9 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) T A B LE D 18 (P A G E 5) : M A TIN G AN D F E R T IL IT Y - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 414 DOSAGE GROUP V RAT # DAYS IN C O H A B IT A T IO N 12 4 1 12 4 4 1245 1247 1248 12 4 9 12 5 2 12 5 4 12 5 5 12 5 7 12 5 9 126 1 12 6 6 12 6 9 12 71 1273 12 74 12 78 128 1 12 8 2 12 8 4 12 8 7 1288 12 8 9 12 9 0 129 1 12 9 4 12 9 6 12 9 8 13 0 0 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 M G /K G /D A Y M A TIN G S TA TU S 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 A TIN G D A T E 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 FEM A LE PREGNANCY STATUS P (15 8 8 ) P (15 6 5 ) P (15 5 7) P (15 6 0 ) P (15 6 6 ) P (15 5 5 ) P (15 4 6 ) P (15 4 8 ) P (15 73 ) P (15 8 6 ) P (15 4 1) P (15 9 8 ) P (15 6 8 ) P (15 5 8 ) P (16 0 0 ) P (15 8 9 ) P (15 71) N P (15 78 ) P (15 4 5 ) P (15 5 2 ) P (15 9 1) P (15 44) P (15 8 4 ) P (15 8 3 ) P (15 9 3 ) P (15 5 0 ) P (15 76 ) P (15 79 ) P (15 8 7) P (15 6 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) T A B LE D 19 (P A G E 1) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS ARGUS 418-020 Page 415 DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF D O S A G ES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S a 1001 1002 10 0 3 1004 10 0 5 1006 10 0 7 10 0 8 1009 1010 1011 1012 10 13 10 14 10 15 10 16 10 17 6553 6554 6555 1021 1022 1023 DP 39 DP 119 DP 119 DP 39 DP 118 DP 38 DP 118 DP 38 DP 38 DP 38 DP 118 DP 117 DP 1 17 DP 117 DP 37 DP 37 DP 118 DP 35 DP 35 DP 35 DP 118 DP 37 DP 118 38 118 118 38 117 37 117 37 37 37 117 116 116 116 36 36 117 34 34 34 117 36 117 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES TIS S U ES T IS S U ES TIS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NO RM AL. NO RM AL. NORM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. 10 2 4 DP 25 25 FO U N D D EA D O N D A Y 25 P O S TW EA N IN G (D EA T H O C C U R R ED 56 M IN U T ES A FT ER DOSAGE A D M IN IS T R A T IO N ). LUN G S: A L L LO B ES , M O TTLED , DARK R ED . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 10 2 5 10 2 6 DP 37 DP 118 36 117 A L L T IS S U ES A P P EA R ED N O RM AL. A L L T IS S U ES A P P EA R ED N O RM AL. 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) T A B LE D 19 (P A G E 2 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 416 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF DOSAGES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S a I 0 C O N I. 10 2 7 10 2 8 DP 37 DP 117 36 116 A L L T IS S U ES A P P EA R ED NO RM AL. A L L T IS S U ES A P P EA R ED NO RM AL. 10 2 9 DP 4 4 M O R IB U N D S A C R IF IC E D O N D A Y 4 P O S T W EA N IN G . A L L T IS S U ES A P P EA R ED NO RM AL. 10 3 0 103 1 1032 10 3 3 1034 10 3 5 1036 10 3 7 10 3 8 DP 36 DP 117 DP 36 DP 36 DP 117 DP 119 DP 36 DP 36 D P 35 35 116 35 35 116 118 35 35 34 A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 10 3 9 DP 42 42 FO U N D D EA D O N D A Y 42 P O S TW EA N IN G A F T E R DOSAGE A D M IN IS T R A T IO N ). A L L T IS S U ES A PPEA R ED NO RM AL. (D EA T H O C C U R R ED 33 M IN U T ES 10 4 0 10 41 10 4 2 1043 10 4 4 1045 10 4 6 10 4 7 1048 10 4 9 10 5 0 10 5 1 DP 118 DP 118 DP 35 DP 118 DP 35 DP 118 D P 35 DP 118 DP 118 D P 35 DP 118 DP 119 117 117 34 117 34 117 34 117 117 34 117 118 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE D 19 (P A G E 3) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y DOSAGES A D M IN IS T ER ED O B S ER V A TIO N S a I 0 CONT. 10 5 2 1053 1054 1055 1056 10 5 7 1058 1059 10 6 0 DP 119 DP 34 DP 118 DP 118 DP 34 DP 31 DP 115 DP 109 DP 109 118 33 117 117 33 30 114 108 10 8 A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL D P = D A Y P O S T W EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) f o r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . ARGUS 418-020 Page 417 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 19 (P A G E 4) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a ARGUS 418-020 Page 418 10 6 1 10 6 2 1063 10 6 4 DP 119 DP 39 DP 119 DP 6 118 38 118 5 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. FO U N D D EA D O N D A Y 6 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) A L L T IS S U ES A PP EA R ED NO RM AL. 10 6 5 DP 39 38 A L L T IS S U ES A PP EA R ED NO RM AL. 10 6 6 DP 119 118 P R O S T A T E : S M A LL ( 0 .2 7 1 6 G ) . A L L O TH ER T IS S U ES APPEAR ED NORM AL. 106 7 10 6 8 1069 10 70 10 71 10 72 10 73 10 74 10 75 10 76 10 77 10 78 10 79 10 8 0 10 8 1 DP 119 DP 39 DP 119 D P 38 DP 118 D P 38 DP 118 DP 38 D P 38 D P 38 DP 118 DP 119 DP 38 D P 38 DP 119 118 38 118 37 117 37 117 37 37 37 117 118 37 37 118 A LL A LL b A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 10 8 2 DP 119 118 T E S T E S : L E F T , F L A C C ID , S M A LL (1 .0 5 9 0 G ) . E P I D I D Y M I D E S : L E F T , S M A L L (0 .3 3 9 3 G ) . A L L O TH ER T IS S U ES APPEAR ED NORM AL. 10 8 3 1084 10 8 5 1086 DP 119 DP 38 D P 38 DP 119 118 37 37 118 A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S TW EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s b . N e c ro p s y o b s e rv a tio n s w ere n o t re c o rd e d . ta b le (T a b le D 14 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 19 (P A G E 5) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 419 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a II 1 CONT. 10 8 7 DP 45 44 FOUND D EA D ON D A Y 45 A D M IN IS T R A T IO N ). A L L T IS S U ES A P P EA R ED P O S TW EA N IN G NORM AL. (D EA TH O C C U RRED P R IO R TO D O SAG E 10 8 8 1089 10 9 0 10 9 1 10 9 2 10 9 3 10 9 4 10 9 5 10 9 6 10 9 7 10 9 8 10 9 9 1100 1101 1102 110 3 110 4 DP 119 DP 38 DP 119 D P 120 DP 37 DP 37 D P 120 DP 37 D P 120 DP 37 D P 120 DP 37 D P 120 DP 37 DP 36 DP 119 DP 2 118 37 118 119 36 36 119 36 119 36 119 36 119 36 35 118 1 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. FO U N D D EA D O N D A Y 2 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L TIS S U ES A P P EA R ED NO RM AL. 110 5 110 6 110 7 110 8 110 9 1110 D P 36 DP 119 D P 120 DP 36 DP 36 D P 120 35 118 119 35 35 119 A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE D 19 (P A G E 6) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF D O S A G ES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S 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 D P 35 DP 119 D P 35 DP 119 35 118 34 118 34 118 34 118 34 118 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL D P = D A Y P O S T W EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B LE D 19 (P A G E 7 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN E R A T IO N M ALE R ATS ARGUS 418-020 Page 421 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y DOSAGES A D M IN IS T ER ED O B S ER V A TIO N S a III 3 1121 1122 112 3 DP 5 DP 119 DP 118 4 118 117 FO U N D D EA D O N D A Y 5 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A PPEA R ED NORM AL. A L L T IS S U ES APPEA R ED NORM AL. A L L T IS S U ES A PPEA R ED NORM AL. 112 4 D P 38 37 L I V E R : L E F T L A T E R A L L O B E , N U M ER O U S T A N A R E A S , ( P I N P O I N T T O 0 .3 CM) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 112 5 112 6 D P 38 D P 38 37 37 L I V E R : L E F T L A T E R A L L O B E , F O U R T A N A R E A S ( P I N P O I N T T O 0 . 1 <C M ) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 0.2L I V E R : L E F T L A T E R A L L O B E , N U M E R O U S T A N A R E A S , ( P I N P O I N T T O CM) . A L L O TH ER T IS S U ES A P PEA R ED NORM AL. 112 7 DP 118 117 A L L T IS S U ES APPEAR ED NORM AL. 112 8 D P 38 37 L I V E R : L E F T L A T E R A L L O B E , T A N A R E A ( 0 .4 CM X 0 .2 CM) . A L L O TH ER T IS S U ES A P PEA R ED NORM AL. 112 9 113 0 DP 118 DP 2 117 1 A L L T IS S U ES A P P EA R ED NO RM AL. FO U N D D EA D O N D A Y 2 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES APPEAR ED NORM AL. 113 1 113 2 113 3 113 4 113 5 113 6 113 7 113 8 113 9 DP 118 DP 118 D P 38 DP 118 DP 119 DP 119 D P 38 D P 38 DP 119 117 117 37 117 118 118 37 37 118 A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S T W EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 19 (P A G E 8) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 422 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF D O S A G ES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S a III 3 CONT. 114 0 DP 9 8 FO U N D D EA D O N D A Y 9 P O S T W EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ). A L L T IS S U ES A P P EA R ED N O RM AL. 114 1 114 2 114 3 114 4 114 5 114 6 114 7 114 8 114 9 115 0 115 1 115 2 115 3 115 4 115 5 DP 119 DP 118 DP 37 DP 37 DP 118 DP 37 DP 118 DP 37 DP 118 DP 37 D P 120 DP 37 D P 120 D P 120 DP 37 118 117 36 36 117 36 117 36 117 36 119 36 119 119 36 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES T IS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NO RM AL. NO RM AL. T E S T E S : L E F T , LA R G E ( 3 .0 1 7 1 G ) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. A L L TIS S U ES A P P EA R ED N O RM AL. A L L TIS S U ES A P P EA R ED N O RM AL. 115 6 DP 36 35 L I V E R : L E F T L A T E R A L L O B E , S I X T A N A R E A S (P IN P O IN T T O 0 .3 C M ). A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 115 7 115 8 115 9 116 0 116 1 116 2 116 3 116 4 DP 36 DP 119 DP 119 DP 36 DP 36 DP 119 DP 36 DP 119 35 118 118 35 35 118 35 118 A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES TIS S U ES T IS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. NORM AL. 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) T A B L E D 19 (P A G E 9) : N EC R O P S Y O B S ER V A T IO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y DOSAGES A D M IN IS T ER ED O B S ER V A TIO N S a III 3 CONT. 116 5 DP 36 35 L I V E R : L E F T L A T E R A L L O B E , N U M ER O US T A N A R E A S , ( P IN P O IN T T O 0 .2 CM) A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 116 6 116 7 116 8 116 9 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 118 0 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 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S TW EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B LE D 19 (P A G E 10 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 424 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A T IO N S a IV 10 1 1 8 1 DP 38 37 A L L T IS S U ES A P P EA R ED NORM AL. 118 2 DP 118 117 A L L T IS S U ES A P P EA R ED NORM AL. 118 3 DP 38 37 A L L T IS S U ES A P P EA R ED NORM AL. 118 4 DP 118 117 A L L T IS S U ES A P P EA R ED NORM AL. 118 5 DP 38 37 A L L T IS S U ES A P P EA R ED NORM AL. 118 6 DP 118 117 K ID N E Y S : R IG H T , P E L V IS , M ODERATE D IL A T IO N . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 118 7 118 8 118 9 D P 38 DP 118 DP 117 37 117 116 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 119 0 DP 37 36 L IV E R : L E F T L A T E R A L AN D M ED IA N L O B E S , (P IN P O IN T T O 0 .2 C M ). A L L O TH ER T IS S U ES A PPEA R ED NORM AL. NUM EROUS TAN AR EAS, 119 1 DP 37 36 L I V E R : L A T E R A L L O B E , N U M E R O U S T A N A R E A S , ( P I N P O I N T T O 0.1 C M ) . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 119 2 119 3 DP 117 DP 37 116 36 A L L T IS S U ES A P P EA R ED NORM AL. 0.2L I V E R : L E F T L A T E R A L L O B E , F O U R T A N A R E A S ( P I N P O I N T T O CM) . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 119 4 119 5 119 6 119 7 119 8 119 9 DP 117 DP 118 DP 37 DP 37 DP 118 DP 37 116 117 36 36 117 36 A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. PR OTOC OL 4 18 -0 2 0 : O R A L (G A V A G E ) T W O -G E N E R A T IO N (O N E L I T T E R P E R G E N E R A T IO N ) R E P R O D U C T IO N S T U D Y O F AM M O N IU M P E R F L U O R O O C T A N O A T E (A P F O ) I N R A T S (S P O N S O R ' S S T U D Y N U M B E R : T - 6 8 8 9 .6 ) T A B LE D 19 (P A G E 1 1 ) : N EC R O P S Y O B S ER V A TIO N S : - IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 425 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF D O S A G ES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S a IV 10 CONT. 1200 DP 40 39 1201 1202 1203 12 0 4 DP 37 DP 37 DP 118 DP 117 36 36 117 116 M O R IB U N D S A C R IF IC E D O N D A Y 40 P O S T W EA N IN G . I N T E S T I N E S : D IS T E N D E D W IT H G A S . T H Y M U S : S M A L L , (0 .0 2 G ) . STO M A C H : TW O R E G IO N S O F T H E C A R D IA C R E G IO N , N U M ER O U S U L C E R A T IO N S , (P IN P O IN T T O 0 .1 CM I N SECOND R E G IO N , F IV E U LC ER A T IO N S (P IN P O IN T ). A L L O TH ER T IS S U ES A PPEA R ED NORM AL. F IR S T R EG IO N , D IA M ET ER ), A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. 1205 DP 36 35 L I V E R : L E F T L A T E R A L L O B E , N U M ER O US T A N A R E A S , (P IN P O IN T T O 0 .5 C M ). A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 12 0 6 D P 36 35 L IV E R : L E F T L A T E R A L L O B E , NUM EROUS ( P IN P O IN T T O 0 .5 CM X 0 .1 C M ). A L L O TH ER T IS S U ES A PPEA R ED NORM AL. TAN AR EAS, 12 0 7 12 0 8 12 0 9 1210 1211 1212 12 13 12 14 12 15 12 16 12 17 DP 117 D P 36 DP 117 DP 4 DP 117 DP 117 DP 36 DP 36 DP 119 DP 119 DP 119 116 35 116 3 116 116 35 35 118 118 118 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. FO U N D D EA D O N D A Y 4 P O S TW EA N IN G (D EA T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED NO RM AL. A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE D 19 (P A G E 12 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 426 DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF D O S A G ES N EC R O P SY A D M IN IS T ER ED O B S ER V A TIO N S a IV 10 CONT. 12 18 DP 36 35 L IV E R : L E F T LA T ER A L LO B E, TAN AND BLACK A R EA C A U D A T E L O B E , T A N A R E A ( 0 .4 C M ). A L L O TH ER T IS S U ES A P P EA R ED NORM AL. (0 .2 CM X 0 .2 CM) ; 12 19 1220 1221 1222 DP 119 DP 35 DP 118 DP 118 118 34 117 117 A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NO RM AL. NORM AL. NORM AL. 1223 DP 35 34 L IV E R : L E F T L A T E R A L L O B E , NUM EROUS T A N A R E A S , ( P IN P O IN T T O 0 .2 CM I N D IA M E T E R ) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 2 4 DP 118 117 K ID N E Y S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 1225 12 2 6 1227 1228 DP 119 DP 119 DP 35 DP 35 118 118 34 34 A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. 12 2 9 DP 119 118 S P L E E N : T A N A R E A E X T E N D E D IN T O T H E P A R EN C H YM A ( 2 .0 CM X 1 .5 CM) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 1230 DP 35 34 A L L T IS S U ES A P P EA R ED N O RM AL. 123 1 DP 35 34 L I V E R : L E F T L A T E R A L L O B E , F IV E T A N A R E A S (P IN P O IN T T O 0 .5 C M ). A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 3 2 DP 119 118 K ID N E Y S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 3 3 DP 119 118 A L L T IS S U ES A P P EA R ED N O RM AL. 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) T A B LE D 19 (P A G E 1 3 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a IV 10 CONT. 12 3 4 D P 35 34 L IV E R : L E F T L A T E R A L L O B E , NUM EROUS TA N A R E A S , (P IN P O IN T TO 0 .7 C M ); M ED IA N L O B E , O N E T A N A R EA A L L O TH ER T IS S U ES A P P EA R ED NORM AL. ( 0 .2 C M ). 12 3 5 D P 35 34 L IV E R : L E F T LA T E R A L L O B E , 4 TO 5 TA N A R EA S , (P IN P O IN T TO 0 .1 C M ); M E D IA N L O B E , N U M ER O U S T A N A R E A S , (P IN P O IN T T O 0 .3 CM) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 3 6 12 3 7 1238 12 3 9 DP 119 DP 119 D P 35 D P 35 118 118 34 34 A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. 1240 DP 119 118 K ID N E Y S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER TIS S U ES A P P EA R ED NORM AL. D P = D A Y P O S T W EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te rn a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B LE D 19 (P A G E 14 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 428 DOSAGE GROUP D O SAG E (M G /K G /D AY) RAT NUM BER DAY OF D O S A G ES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S a V 30 12 4 1 DP 119 118 A L L T IS S U ES A P P EA R ED N O RM AL. 12 4 2 DP 39 38 A L L T IS S U ES A P P EA R ED NO RM AL. 1243 DP 39 38 A L L T IS S U ES A P P EA R ED N O RM AL. 12 4 4 DP 118 117 A L L T IS S U ES A P P EA R ED N O RM AL. 1245 DP 118 117 A L L T IS S U ES A P P EA R ED NO RM AL. 1246 D P 38 37 A L L T IS S U ES A P P EA R ED NO RM AL. 12 4 7 DP 118 117 A L L T IS S U ES A P P EA R ED NO RM AL. 1248 DP 118 117 A L L T IS S U ES A P P EA R ED NO RM AL. 1249 DP 118 117 A L L T IS S U ES A P P EA R ED NO RM AL. 1250 DP 38 37 A L L T IS S U ES A P P EA R ED NO RM AL. 12 5 1 D P 38 37 L IV E R : L E F T L A T E R A L AN D M ED IA N LO B E S , (P IN P O IN T T O 0 .3 CM I N D I A M E T E R ) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. NUM EROUS TAN AR EAS, 1252 1253 1254 12 5 5 DP 118 DP 38 DP 119 DP 118 117 37 118 117 A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. 1256 DP 37 36 L I V E R : L E F T L A T E R A L L O B E , T A N A R E A ( 0 .8 C M ). A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 5 7 1258 1259 DP 118 DP 37 DP 118 117 36 117 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 12 6 0 DP 4 3 FO U N D D EA D O N D A Y 4 P O S TW EA N IN G (D EA T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED N O RM AL. 126 1 DP 118 117 A L L T IS S U ES A P P EA R ED NO RM AL. 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) T A B L E D 19 (P A G E 15 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N M A LE R ATS ARGUS 418-020 Page 429 DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a V 30 CONT. 12 6 2 12 6 3 12 6 4 DP 37 36 L IV E R : L E F T L A T E R A L L O B E , S IX TA N A R EA S (P IN P O IN T TO 1 .0 M E D IA N L O B E , F I V E T A N A R E A S (P IN P O IN T T O 0 .3 C M ). A L L O TH ER T IS S U ES A PP EA R ED NORM AL. C M ); DP 2 1 FO U N D D E A D O N D A Y 2 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED NORM AL. DP 2 1 FO U N D D EA D O N D A Y 2 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED NORM AL. 12 6 5 12 6 6 12 6 7 DP 37 DP 118 DP 37 36 117 36 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 12 6 8 DP 37 36 L IV E R : M ED IA N L O B E , NUM EROUS T A N A R E A S , ( P IN P O IN T T O 0 .4 CM X 0 .2 C M ). A L L O TH ER T IS S U ES A P PEA R ED NORM AL. 12 6 9 12 70 12 71 1272 12 73 12 74 DP 118 DP 37 DP 120 DP 37 DP 120 DP 120 117 36 119 36 119 119 A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 12 75 DP 39 38 M O R IB U N D S A C R IF IC E D ON D A Y 39 P O S T W EA N IN G . L I V E R : M ED IA N L O B E , NUM EROUS T A N A R E A S , (P IN P O IN T T O 0 .1 CM) . S P L E E N : S M A LL ( 0 .0 4 G ) . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 12 76 DP 37 36 L I V E R : L A R G E ( 2 6 .6 4 G ) . A L L O TH ER T IS S U ES A P PEA R ED NORM AL. 12 77 DP 4 3 FO U N D D E A D O N D A Y 4 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED NORM AL. 12 78 DP 119 118 A L L T IS S U ES A P P EA R ED NORM AL. D P = D A Y P O S T W EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te rn a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 19 (P A G E 16 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 430 DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y D O S A G ES A D M IN IS T ER ED O B S ER V A TIO N S a V 30 CONT. 12 79 12 8 0 DP 36 35 L I V E R : L E F T L A T E R A L L O B E , N U M ER O US T A N A R E A S , ( P IN P O IN T T O 0 .3 CM) . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. DP 3 2 FO U N D D EA D O N D A Y 3 P O S TW EA N IN G (D EA T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED NORM AL. 128 1 12 8 2 DP 119 DP 119 118 118 A L L T IS S U ES A P P EA R ED NO RM AL. A L L T IS S U ES A P P EA R ED NO RM AL. 1283 D P 36 35 L IV E R : L E F T L A T E R A L AN D M ED IA N L O B E S , (P IN P O IN T T O 0 .3 CM X 0 .1 C M ). A L L O TH ER T IS S U ES A P P EA R ED NORM AL. NUM EROUS TAN AR EAS, 12 8 4 12 8 5 12 8 6 12 8 7 12 8 8 12 8 9 12 9 0 12 9 1 12 9 2 DP 118 D P 35 D P 35 DP 118 DP 119 DP 119 DP 119 DP 119 D P 35 117 34 34 117 118 118 118 118 34 A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 12 9 3 D P 35 34 L I V E R : L E F T L A T E R A L L O B E , N U M ER O U S T A N A R E A S , ( P IN P O IN T T O 0 .5 CM) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 9 4 DP 119 118 K ID N EY S : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 12 9 5 D P 35 34 LIV E R : L E F T LA T ER A L LO B E, (P IN P O IN T T O 0 .3 CM) . A L L O TH ER T IS S U ES A PPEA R ED FOUR TAN NORM AL. AND W H ITE A R EA S 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) T A B LE D 19 (P A G E 1 7 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF D O S A G ES N EC R O P S Y A D M IN IS T ER ED O B S ER V A TIO N S a V 30 12 9 6 DP 10 7 10 6 FO U N D D EA D O N D A Y 1 0 7 P O S TW EA N IN G (D E A T H O C C U R R ED O V E R N IG H T ) . A L L T IS S U ES A P P EA R ED N O RM AL. 129 7 12 9 8 12 9 9 13 0 0 D P 34 DP 118 D P 33 DP 117 33 117 32 116 A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S TW EA N IN G a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le D 14 ) fo r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B LE D20 (P A G E 1) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 432 DOSAGE GROUP I 0 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 1002 10 0 3 1005 1007 1011 1012 10 13 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 10 5 0 1051 1052 1054 10 5 5 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. E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW 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 T E S T IS LEFT ABS. R EL. W T. % TBW 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 L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW 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 .6 1 11 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 .0 0 7 7 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . WT . = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE D20 (PAG E 2) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE RATS ARGUS 418-020 Page 433 DOSAGE GROUP I 0 M G/KG/DAY RAT T ER M IN A L BO D Y NUM BER W EIG H T 1002 1003 10 0 5 1007 1011 1012 10 13 10 14 1017 1021 10 2 3 10 2 6 10 2 8 1031 10 3 4 1035 10 4 0 1041 1043 1045 1047 1048 10 5 0 10 5 1 1052 1054 10 5 5 10 5 8 1059 10 6 0 567. 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 . E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . V a lu e was m u ltip lie d b y 1000. T E S T IS R IG H T ABS. R EL. W T. % 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 PROSTATE ABS. W T. R EL. % TBW 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 P IT U IT A R Y ABS. W T. R EL. % TBW a 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 B R A IN ABS. W T. R EL. % TBW 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 LIV E R ABS. W T. 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 2 0 .17 16.10 17 .8 1 R EL. % TBW 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 A B S . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 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) T A B L E D 2 0 (P A G E 3 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 434 DOSAGE GROUP I 0 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 1002 10 0 3 10 0 5 10 0 7 1011 1012 10 13 10 14 1017 1021 1023 10 2 6 1028 103 1 10 3 4 1035 1040 1041 10 4 3 1045 10 4 7 1048 10 5 0 10 5 1 10 5 2 10 5 4 10 5 5 10 5 8 1059 10 6 0 567. 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. K ID N EY LEFT ABS. R EL. W T. % TBW 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 .3 1 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 .3 1 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 K ID N EY R IG H T ABS. R EL. W T. % TBW 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 A D R EN A L LEFT ABS. R EL. W T. % TBW a 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 A D R EN A L R IG H T ABS. R EL. W T. % TBW a 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. 0 1 1 b 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 . 3 6b 4.77 3.35 4.84 4.28 7.66 5.14 5.61 5.76 6.36 6.21 4.75 6.44 5.31 7.69 4.62 S P LEEN ABS. W T. R EL. % TBW 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 .1 7 0 .1 7 0 .1 7 0.19 0.16 0.14 0.17 0.17 0.14 0.16 0.15 0 .1 7 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 .1 7 0.14 0.15 0.22 0.15 THYM US ABS. W T. R EL. % TBW 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 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . a . V a lu e was m u ltip lie d b y 1000. A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (ORG AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 10 0 b . Dam aged d u rin g p ro c e s s in g (w e ig h t a f f e c t e d ) ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D20 (P A G E 4) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 435 DOSAGE GROUP I I 1 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 10 6 1 10 6 3 10 6 6 106 7 10 6 9 1071 10 73 1077 1078 1081 1082 10 8 3 1086 10 8 8 10 9 0 10 9 1 10 9 4 10 9 6 10 9 8 1100 110 3 110 6 110 7 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. EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % 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 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 T E S T IS LEFT ABS. R EL. W T. % 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 . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. 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 .8 7 1 7 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 0.29 0.36 S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW 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 S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW 1.0157 1 .1 16 7 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 .0 7 0 1 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 a. W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . WT . = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) R a t 10 8 2 h a d a s m a ll , l e f t e p id id y m is a n d cau da e p id id y m is , s m a ll , fla c c id l e f t t e s t i s , and a f l u i d f i l l e d l e f t t e s t is tu n ic a a lb u g in e a ; v a lu e s in c lu d e d in g ro u p a v e ra g e s an d s t a t is t ic a l a n a ly s e s . X 100. m in u s PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D20 (P A G E 5) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 436 DOSAGE GROUP I I 1 M G/KG/DAY RAT T ER M IN A L B O D Y NUM BER W EIG H T 1061 1063 10 6 6 106 7 1069 1071 10 73 1077 1078 1081 10 8 2 10 8 3 1086 10 8 8 10 9 0 1091 10 9 4 1096 10 9 8 1100 110 3 110 6 110 7 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 . EP ID ID Y M IS R IG H T ABS. R EL. W T. % TBW 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 T E S T IS R IG H T ABS. R EL. W T. % TBW 1.8528 1.8505 1.5745 1.5154 1.6782 1.5542 1.9825 1.8037 1.7230 1.7244 1 .7 2 6 1 1 .4 7 17 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 PROSTATE ABS. W T. R EL. % TBW 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 P IT U IT A R Y ABS. W T. R EL. % TBW a 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 .2 1 2.73 4.21 2.53 3.01 4.86 2.26 2.47 7.40 3.43 3.08 4.08 4 .7 1 4.24 5.33 B R A IN ABS. W T. R EL. % TBW 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2.25 2.35 2 .1 7 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 LIV E R ABS. W T. R EL. % TBW 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 .3 1 4.36 4.69 4.95 4.85 3.87 4.15 4.28 ALL a. b. c. W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e w as m u ltip lie d b y 1000 . R a t 1066 h a d a s m a ll p r o s ta te ; v a lu e s Dam aged d u rin g p ro c e s s in g (w e ig h t n o t A B S . W T. = ORGAN W EIG H T . in c lu d e d in g ro u p a ve ra g e s a ffe c te d ). and R E L . % TBW s ta tis tic a l = (ORG AN W E IG H T / T E R M IN A L a n a ly s e s . BODY W EIG H T) 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) T A B LE D20 (P A G E 6) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 437 DOSAGE GROUP I I 1 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 1061 10 6 3 10 6 6 106 7 10 6 9 1071 1073 1077 1078 1081 10 8 2 10 8 3 1086 10 8 8 10 9 0 1091 10 9 4 10 9 6 10 9 8 1100 110 3 110 6 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. K ID N EY LEFT ABS. R EL. 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 K ID N EY R IG H T ABS. R EL. 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 A D R EN A L LEFT ABS. R EL. W T. % 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 A D R EN A L R IG H T ABS. R EL. W T. % 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 S P LEEN ABS. W T. R EL. % 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 THYM US ABS. W T. 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 R EL. % TBW 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . V a lu e was m u ltip lie d b y 1000. A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (OR G AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 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) T A B LE D20 (P A G E 7) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 438 DOSAGE GROUP I I I 3 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 1122 1123 1127 112 9 113 1 113 2 113 4 1135 1136 113 9 114 1 114 2 114 5 1147 1149 115 1 115 3 115 4 115 8 1159 116 2 116 4 116 7 116 8 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. E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA EP ID ID Y M IS LEFT ABS. R EL. 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 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 T E S T IS LEFT ABS. R EL. W T. % TBW 1.6159 1.8182 1.6347 1.9335 1.7682 1.7645 1.8988 1 .7 2 3 7 1.9009 1.6472 1.5627 1.6597 1.8607 1.6976 2.0462 1.8091 3 .0 1 7 1 a 1 .7 0 0 7 1.7179 1.8480 1.7050 1.9198 1 .7 1 0 1 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 . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. 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 S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW 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 .7 2 1 1 2.3386 2.2078 1.9461 1.8889 2.1813 2.3263 2.0033 1.9163 2.0326 1.5592 1.8020 2.1183 1.7132 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 S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . R a t 1 1 5 3 h a d a l a r g e , l e f t t e s t i s a n d t e s t i s m in u s t u n ic a a lb u g in e a ; v a lu e s in c lu d e d i n g ro u p a v e r a g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 2 0 (P A G E 8 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 439 DOSAGE GROUP I I I 3 M G/KG/DAY RAT T ER M IN A L BO DY NUM BER W EIG H T 1122 112 3 112 7 112 9 1131 113 2 113 4 113 5 1136 1139 114 1 114 2 114 5 114 7 114 9 115 1 115 3 115 4 115 8 1159 116 2 116 4 116 7 116 8 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. E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW 0.6838 0.6106 0.6629 0 .7 1 1 1 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 T E S T IS R IG H T ABS. R EL. W T. % TBW 1.6035 1.7572 1.6197 1.8049 1.7444 1.7356 1.9533 1.6461 1.8638 1 .7 1 3 7 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. W T. R EL. % 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 P IT U IT A R Y ABS. W T. R EL. % 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 B R A IN ABS. W T. R EL. % TBW 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2.17 2.16 2.29 2 .1 7 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 LIV E R ABS. W T. R EL. % TBW 28.00 27.20 28.00 37.2031.29 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 .1 7 4.82 5.70 5.91 5.84 5.53 5.56 5.13 5.22 5.17 7.18 4.84 ALL a. b. W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000. Dam aged d u rin g p ro c e s s in g (w e ig h t n o t A B S . W T. a ffe c te d ). = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE D20 (P A G E 9) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 440 DOSAGE GROUP I I I 3 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 1122 112 3 112 7 112 9 1131 113 2 1134 113 5 1136 1139 114 1 114 2 114 5 1147 114 9 1151 115 3 115 4 115 8 1159 116 2 116 4 116 7 116 8 1171 1173 1175 1176 1177 118 0 518. 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. K ID N EY LEFT ABS. R EL. W T. % 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 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was multiplied by 1000. K ID N EY R IG H T ABS. R EL. 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 .1 7 2.50 2.78 2.55 2 .7 1 2.57 2.92 2 .7 1 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 A D R EN A L LEFT ABS. R EL. W T. % 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 7.3 7 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 A D R EN A L R IG H T ABS. R EL. W T. % 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 S P LEEN ABS. W T. 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 .7 7 0.91 0.93 1.01 0.86 1.08 0.78 0.80 1.17 0.94 0 .7 7 0.73 0.94 0.76 0.89 1.05 R EL. % TBW 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 THYM US ABS. W T. R EL. % 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 A B S . W T. O RG AN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 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) T A B LE D20 (P A G E 10 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE RATS ARGUS 418-020 Page 441 DOSAGE GROUP IV 10 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW T E S T IS LEFT ABS. R EL. W T. % TBW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % TBW 118 2 118 4 118 6 118 8 1189 119 2 119 4 119 5 1198 12 0 3 12 0 4 12 0 7 12 0 9 1211 1212 12 15 12 16 1217 1219 1221 1222 12 2 4 1225 12 2 6 1229 12 3 2 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 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 .3 1 1 7 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. O RG AN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE D20 (P A G E 1 1 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 442 DOSAGE GROUP IV 10 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW T E S T IS R IG H T ABS. R EL. W T. % TBW PROSTATE ABS. W T. R EL. % TBW P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW 1182 118 4 1186 1188 1189 119 2 119 4 1195 1198 1203 12 0 4 1207 12 0 9 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 12 2 6 1229 1232 12 3 3 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 .8 1 2.50 5.23 5.91 4.08 3 .19 3.98 2.56 2.65 2.54 4.08 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 25.00 30.64 20.80 27.64 32.61 30.76 29.51 26.56 35.89 26.54 3 1.8 1 2 4 .1 1 35.57 27.46 34.89 30.79 33.30 30.02 27.85 24.86 3 1.7 1 26.90 3 1.1 7 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . WT . = ORGAN W EIG H T . a . V a lu e was m u ltip lie d b y 1000. b . Dam aged d u r in g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE D20 (P A G E 12 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 443 DOSAGE GROUP IV 10 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T 118 2 118 4 1186 1188 118 9 119 2 119 4 119 5 1198 12 0 3 12 0 4 12 0 7 12 0 9 1211 1212 1215 12 16 12 17 12 19 1221 1222 12 2 4 1225 12 2 6 1229 12 3 2 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. 3 77 . 585. 491. 393 . 490. K ID N EY LEFT ABS. R EL. 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 .7 7 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 K ID N EY R IG H T ABS. R EL. W T. % TBW 2.06 2.30 1.81b 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 A D R EN A L LEFT ABS. R EL. W T. % 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 A D R EN A L R IG H T ABS. R EL. W T. % TBW a 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 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 S P LEEN ABS. W T. R EL. % TBW 0.67 0.72 0.69 0.78 0.85 0.92 0.81 0.76 0.81 0.81 0 .7 1 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 THYM US ABS. W T. R EL. % 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 a. b. c. d. e. W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 O 0 . V a lu e was m u ltip lie d b y 1000. R a t 118 6 h a d m o d e ra te d i l a t io n o f th e p e lv is o f th e r ig h t k id n e y ; v a lu e in c lu d e d in g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . R a t 12 2 4 h a d s lig h t d ila t io n o f th e p e lv is o f th e r ig h t k id n e y ; v a lu e in c lu d e d in g ro u p a ve ra g e s an d s t a t i s t i c a l a n a ly s e s . R a t 1229 h a d ta n a re a s on th e s p le e n th a t e xte n d e d in to th e p a re n ch ym a ; v a lu e in c lu d e d in g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s is . R a t 123 2 h a d s lig h t d ila t io n o f th e p e lv is o f th e r ig h t k id n e y ; v a lu e in c lu d e d in g ro u p a ve ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D20 (P A G E 1 3 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 444 DOSAGE GROUP V 30 M G /K G /D A Y RAT T ER M IN A L BODY NUM BER W EIG H T 1241 1244 1245 1247 1248 1249 1252 1254 12 5 5 1257 1259 126 1 12 6 6 12 6 9 1271 1273 1274 1278 1281 12 8 2 12 8 4 1287 1288 12 8 9 1290 1291 12 9 4 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 , EP ID ID Y M IS LEFT ABS. R EL. W T. % TBW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % TBW 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 T E S T IS LEFT ABS. R EL. W T. % TBW 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 L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % TBW 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 0.41 0.35 0.36 S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % TBW 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 .8 1 1 1 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 S EM IN A L V E S IC LE S W IT H O U T F L U ID ABS. R EL. W T. % TBW 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 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T,. = O R G A N W E I G H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 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) T A B LE D20 (P A G E 14 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 445 DOSAGE GROUP V 30 M G /K G /D AY RAT T ER M IN A L BO D Y NUM BER W EIG H T 12 4 1 12 4 4 1245 1247 1248 1249 12 5 2 12 5 4 1255 1257 1259 1261 12 6 6 12 6 9 1271 1273 1274 1278 1281 1282 12 8 4 1287 1288 1289 12 9 0 1291 12 9 4 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 . E P ID ID Y M IS R IG H T ABS. R EL. W T. % TBW 0.6533 0.6699 0.6880 0.6936 0 .7 1 7 7 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 .7 4 1 1 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 T E S T IS R IG H T ABS. R EL. W T. % 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 .7 3 1 1 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. W T. R EL. % 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 .1 15 6 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 P IT U IT A R Y ABS. W T. R EL. % 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. 0 2 1 b 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 B R A IN ABS. W T. 2.21 2.14 2.14 2.19 2.02 2.08 2.16 2.00 2.29 2.11 1.95 2 .1 7 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 R EL. % TBW 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 LIV E R ABS. W T. R EL. % 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 2 5 .7 1 33.07 34.68 26.73 33.81 2 7 .5 1 33.29 7.3 7 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 .3 7 6.82 6.35 6.32 7.46 7.76 6.70 7 .5 1 7.14 7.60 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . a . V a lu e was m u ltip lie d b y 10 0 0 . b . Dam aged d u rin g p ro c e s s in g (w e ig h t a f f e c t e d ) ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D20 (P A G E 15) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 446 DOSAGE GROUP V 30 M G /K G /D AY RAT T ER M IN A L BODY NUM BER W EIG H T K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW 1241 1244 1245 1247 1248 1249 1252 1254 12 5 5 1257 1259 1261 12 6 6 1269 1271 12 73 12 74 1278 1281 12 8 2 12 8 4 1287 1288 12 8 9 12 9 0 1291 12 9 4 12 9 8 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. 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 2.28 2.41 2.40 1 .6 7 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 1.8 1 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 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 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 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 .1 7 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 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 a. b. W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . V a lu e w as m u ltip lie d b y 1000. R a t 1294 had s lig h t d ila tio n o f th e A B S . W T. = ORGAN W EIG H T . p e lv is o f th e r ig h t k id n e y ; v a lu e R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 0 0 . in c lu d e d in g ro u p a ve ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 2 1 (P A G E 1 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 447 DOSAGE GROUP I 0 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 1002 1003 10 0 5 1007 1011 1012 10 13 10 14 1017 1021 1023 10 2 6 1028 1031 1034 10 3 5 1040 1041 1043 1045 1047 1048 10 5 0 1051 1052 1054 10 5 5 10 5 8 10 5 9 10 6 0 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 EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW 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 T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % BRW 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 .6 1 11 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 7 1 .6 7 65.86 69.94 72.77 74.31 70.20 7 2 .8 1 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 . 5 4 0 6 101.22 1.6431 71.44 1.8339 80.79 1.6675 74 .1 1 2.2373 88.78 1.5930 73 .4 1 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 8 4 . 2 6 1.76 12 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 4 3 .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) T A B LE D 2 1 (P A G E 2) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 448 DOSAGE GROUP I 0 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 1002 10 0 3 1005 1007 1011 1012 10 13 10 14 1017 1021 10 2 3 1026 1028 1031 10 3 4 10 3 5 1040 1041 1043 1045 1047 10 4 8 10 5 0 10 5 1 10 5 2 10 5 4 10 5 5 1058 1059 10 6 0 2.27 2.40 2.36 2.23 2.22 2.32 2.29 2 .5 1 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 EP ID ID Y M IS R IG H T ABS. R EL. W T. % BRW 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 33 . 4 1 30.11 28.86 30.23 30.78 29.31 29.77 32.56 29.63 32.35 29.30 29.26 3 1.8 7 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 T E S T IS R IG H T ABS. R EL. W T. % 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 7 1 .4 7 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 PROSTATE ABS. W T. R EL. % BRW 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 .1 2 17 1.1027 0.8592 1.0457 1.4155 1.0329 1 .0 3 1 1 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 5 0 .1 1 56.62 36.08 46.93 49.01 35.80 45.86 58.49 43.04 46.87 51.85 4 7 .3 7 47.07 46.60 57.39 30.72 34.44 P IT U IT A R Y ABS. W T. R EL. % BRW 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 LIV E R ABS. W T. R EL. % BRW 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 1 7 .8 1 933.92 1041.67 834.74 950.67 1114.86 1077.16 951.53 876.89 741.30 1104.84 1052.89 885.32 869.12 883.67 756.44 749.33 852.72 1058.67 887.50 803.51 1206.61 1135.83 967.73 957.63 985.42 815.04 878.60 1039.69 659.84 742.08 K ID N EY LEFT ABS. R EL. W T. % BRW 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 .3 1 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 .3 1 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 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) T A B LE D 2 1 (P A G E 3) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T I O S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 449 DOSAGE GROUP I 0 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 1002 10 0 3 10 0 5 1007 1011 1012 10 13 10 14 1017 1021 10 2 3 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 10 5 0 10 5 1 1052 1054 10 5 5 1058 1059 10 6 0 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 .1 7 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 K ID N EY R IG H T ABS. R EL. 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 A D R EN A L LEFT ABS. R EL. W T. % 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 A D R EN A L R IG H T ABS. R EL. W T. % 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. 0 1 1 a 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 0.49a 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 S P LEEN ABS. W T. R EL. % 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 THYM US ABS. W T. R EL. % BRW 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 1 9 .1 1 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 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . a . Dam aged d u rin g p ro c e s s in g (w e ig h t a ff e c t e d ) ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 2 1 (P A G E 4) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 450 DOSAGE GROUP I I 1 M G/KG/DAY RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U ID ABS. R EL. W T. % BRW 1061 10 6 3 1066 1067 1069 1071 10 73 1077 1078 1081 1082 10 8 3 1086 1088 10 9 0 1091 1094 10 9 6 10 9 8 1100 110 3 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 .1 7 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 0.7660 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 35.46 3 1.72 30.18 30.93 32.01 27.46 31.23 3 7 .8 1 33.77 30.13 15.64 27.98 26.66 3 1.1 4 30.29 25.04 28.19 27.98 29.67 27.23 28.46 28.15 30.70 26.69 26.44 26.50 28.41 27.39 30.90 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 16.45 14.60 13.15 14.58 14.84 13.79 11.98 19.30 17.68 15.80 6.73 15.04 11.92 15.12 13.75 12.29 14.26 13.31 16.24 14.20 14.34 12.95 14.29 13.31 13.04 12.43 12.37 12.48 14.09 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 82.70 82.44 84.71 78.56 86.40 67.96 87.97 86.65 79.46 75.26 48.80 64.11 78.38 71.44 72.86 69.76 73.25 68.50 81.88 72.18 74.12 73.16 74.73 71.05 68.58 77.84 66.19 71.24 82.43 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 .8 7 1 7 75.44 77.52 78.85 72.99 80.98 63.78 82.04 79.39 73.99 68.27 20.97 59.63 73.36 66.15 68.02 55.18 63.88 63.37 73.86 66.00 66.06 66.73 67.09 65.21 64.04 71.38 59.94 66.89 77.02 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 88.35 101.06 108.85 87.83 99.46 95.55 96.35 107.87 88.08 84.89 93.30 102.41 86.27 88.11 82.57 99.25 100.85 81.20 104.05 82.88 73.27 83.63 70.00 78.98 82.80 91.92 87.06 91.21 96.20 1.0157 1 .1 16 7 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 3 7 .7 7 38.26 46.56 48.00 43.16 42.46 44.04 A L L W E I G H T S W E R E :R E C O R D E D I N G R A M S ( G ) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (OR G AN W E IG H T / B R A IN W EIG H T) X 1 0 0 . 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) T A B L E D 2 1 (P A G E 5 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 451 DOSAGE GROUP I I 1 M G/KG/DAY RAT IM BER B R A IN W EIG H T E P ID ID Y M IS R IG H T ABS. R EL. W T. % BRW T E S T IS R IG H T ABS. R EL. W T. % BRW PROSTATE ABS. W T. R EL. BRW P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW 10 6 1 10 6 3 10 6 6 1067 1069 1071 10 73 1077 1078 10 8 1 1082 10 8 3 1086 10 8 8 10 9 0 1091 10 9 4 1096 10 9 8 1100 110 3 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 .1 7 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 0.7284 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 0.6993b 0.6575 0.6578 0.6330 0.6748 0.7494 0.6639 0.6786 0.6911 33.72 3 1.4 7 30.46 32.48 30.93 28.89 32.99 36.60 33.53 29.89 32.21 27.34 29.81 29.38 31.33 26.93 30.31 30.22 32.06 26.73 29.76 30.87 30.60 27.17 25.56 29.39 28.13 28.63 28.44 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 0.4761 0.8821 0.2716a 0.5982 0.8284 1.3268 1.3308 0.8947 1.3800 1.3717 1.2924 1.3446 . 9942 .5251 .2761 .1454 .0867 .0373 .1216 .1903 .8336 .2108 .9999 0.9081 4610 15 6 4 2054 0908 15 17 22.04 39.03 12.93 30.21 40.61 55.98 58.88 43.01 61.33 58.37 59.56 58.46 48.03 65.45 56.97 46.75 47.66 42.00 47.13 51.08 35.47 56.84 46.51 38.97 55.34 45.35 51.08 46.02 47.40 0,.011 0,.012 0,.011 0,.012 0,.011 0,.012 0,. 0 1 6 0,.011 0. 0 1 4 0. 0 1 4 0. 0 1 6 0,. 0 1 4 0,.012 0,. 0 1 4 0,. 0 1 7 0. 0 1 4 0,. 0 2 5 0.. 0 1 6 0.. 0 1 5 0. 0 2 4 0.. 0 1 3 0., 0 1 3 0.. 0 3 3 0.. 0 1 5 0.. 0 1 8 0.. 0 2 3 0.. 0 2 6 0.. 0 2 3 0 ., 0 2 8 0,. 5 1 0,.5 3 0,. 5 2 0,. 6 1 0. 5 4 0. 5 1 0. 7 1 0. 5 3 0,. 6 2 0. 6 0 0. 7 4 0,. 6 1 0.. 5 8 0.. 6 0 0., 7 6 0.. 5 7 1..10 0.. 6 5 0.. 6 3 1.. 0 3 0.. 5 5 0.. 6 1 1., 5 3 0., 6 4 0.,68 0. 9 0 1.,10 0.. 9 7 1 . 15 20. 7 7 26 .6 0 20. 8 0 20 . 9 7 21. 6 1 26 .3 5 27 .94 25 .28 30 .05 22 . 8 1 24..34 23 . 1 5 15..51 29,.13 21,. 4 8 27,.07 29,.60 32..95 30..3 7 22. 7 9 27..76 22 ..68 19..46 20.. 5 0 28..97 2 7 . .29 21.. 3 7 22 .. 5 1 22.. 4 9 9 6 1 .5 7 1 1 7 6 . 99 990 .48 1059 .09 10 5 9 .3 1 1111,.8 1 1236,.28 1 2 1 5 , .38 1335,.56 970,.64 1121,.66 1006..52 749..28 1 2 5 0 . .21 958..93 110 4 .90 1298..24 1 3 3 4 . .01 1276 ..05 978.. 1 1 1 1 8 1 ..28 1 0 6 4 .. 7 9 9 0 5 .,12 87 9.,83 10 9 7..35 1 0 7 0 . ,20 905.,51 949.,79 925.,51 2.0 6 2. 5 0 2. 0 3 1. 9 5 2.10 2.4 3 2. 4 3 2. 3 9 2. 6 7 2. 2 4 2. 1 6 2. 2 7 1,. 7 9 2,.22 2,. 2 7 2,.68 2,. 3 9 2. 3 9 2. 3 5 2. 5 9 2. 5 4 2. 1 9 2., 0 5 2..21 2.. 9 0 2., 8 0 2., 3 3 2., 7 4 2., 4 6 95 .3 7 110 . 6 2 96 . 6 7 98 . 4 8 102,.9 4 102,.5 3 1 0 7 , .52 1 1 4 ,. 9 0 118,.67 95,.32 99,.54 98.. 7 0 86. 4 7 95..28 101. 3 4 109..39 1 0 4 .. 8 2 96..76 98.. 74 I l l .. 1 6 1 0 8 . ,08 102., 8 2 95.,35 9 4 ., 8 5 1 0 9 . ,85 1 0 9 . 80 98. 73 115. 61 101. 2 3 A L L W EIG H T S W ERE R EC O R D E D I N GRAM S (G) A B S . W T. = O RGAN W EIG H T . 100. % T B W = ( O R G A N W E I G H T / B R A I N W E I G H T ) X . a . R a t 1066 h a d a s m a ll p r o s ta te ; v a lu e s in c lu d e d in g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . b . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e 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) T A B LE D 2 1 (PAG E 6) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G E N ER A T IO N M A LE RATS ARGUS 418-020 Page 452 DOSAGE GROUP I I 1 M G/KG/DAY RAT NUM BER B R A IN W EIG H T K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW 1061 10 6 3 10 6 6 10 6 7 10 6 9 1071 10 73 1077 1078 1081 1082 10 8 3 1086 1088 10 9 0 1091 10 9 4 1096 10 9 8 1100 110 3 110 6 110 7 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 .1 7 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 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 .0 1 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 1 1 1 .3 7 100.42 1 15 .1 9 104.12 ALL WEIGHTS WERE RECORDED IN GRAMS (G). 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 1.8 1 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 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 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 3 7 .1 7 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 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 1 7 .1 7 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 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) T A B L E D 2 1 (P A G E 7 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M A LE R A TS ARGUS 418-020 Page 453 DOSAGE GROUP I I I 3 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 1122 112 3 1127 112 9 1131 113 2 113 4 1135 1136 1139 114 1 114 2 114 5 1147 114 9 115 1 115 3 115 4 1158 115 9 116 2 116 4 1167 116 8 1171 1173 1175 1176 1177 118 0 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2.17 2.16 2.29 2 .1 7 2.16 2.04 2.33 2.36 2.41 2.35 2.23 2.28 2.24 2 .3 1 2.41 2.23 2 .5 1 2 .3 1 2.41 2.53 2.33 2.43 2.47 EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % 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 3 1 .1 7 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 1 5 .7 7 14.30 16.34 13.67 15.96 15.40 1 7 .5 1 13.19 14.25 1 3 .1 1 13.26 16.51 13.42 14.99 14.58 11.56 12.57 13.58 10.85 12.29 14.38 13.56 T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN EA ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U ID ABS. R EL. W T. % BRW 1.6159 67.33 1.8182 75.76 1.6347 74.3 0 1.9335 84.43 1.7682 79.29 1.7645 79.48 1.8988 79.12 1.723 7 79.43 1 . 9 0 0 9 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 . 0 1 7 1 a l 2 8 .3 9 1.700 7 76.26 1 .7 1 7 9 75.35 1.8480 82.50 1.7050 73.81 1.9198 79.66 1 .7 1 0 1 76.69 1.8227 72.62 1.5240 65.97 1.5 7 4 1 65.32 1.7498 69.16 1 .9 7 1 8 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 . 7 6 8 7 a l l 7 .82 1.4274 64.01 1.5439 6 7.71 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 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 .7 2 1 1 2.3386 2.2078 1.9461 1.8889 2.1813 2.3263 2.0033 1.9163 2.0326 1.5592 1.8020 2.1183 1.7132 1.4040 2.0790 2.1032 85.29 95.89 78.16 95.76 104.60 107.68 89.10 85.25 61.19 74.40 80.77 96.74 90.65 73.87 99.09 91.61 82.81 84.70 95.67 103.85 86.72 79.51 91.15 62.12 78.01 87.90 67.72 60.26 85.56 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 a. W EIG H T S W ER E R a t 115 3 had a n a ly s e s . R EC O R D ED a la rg e , I N GRAM S (G) . le ft te s tis and ABS. te s tis W T. = m in u s ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . tu n ic a a lb u g in e a ; v a lu e s in c lu d e d in g ro u p a ve ra g e s an d s t a t is t ic a l PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E D 2 1 (P A G E 8 ) : B R A I N W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 454 DOSAGE GROUP I I I 3 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 1122 112 3 112 7 112 9 1131 113 2 113 4 113 5 1136 113 9 114 1 114 2 1145 1147 1149 1151 115 3 115 4 1158 1159 116 2 116 4 1167 116 8 1171 1173 1175 1176 1177 1180 2.40 2.40 2.20 2.29 2.23 2.22 2.40 2 .1 7 2.16 2.29 2 .1 7 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 EP ID ID Y M IS R IG H T ABS. R EL. W T. % BRW 0.6838 0.6106 0.6629 0 .7 1 1 1 0.6877 0.6987 0.7236 0.6703 0.6601 0.6262 0.6701a 0.6442 0.6614 0.6789 0.7538 0.6490 0.7007 0.6741 0.6996 0.7245 0.6761a 0.7592 0.7044 0.6950 0.5841 0.6720 0.6517 0.6153 0.7824 0.7608 28.49 25.44 30.13 31.05 30.84 3 1.4 7 30.15 30.89 30.56 27.34 30.88 29.82 32.42 29.14 31.94 26.93 29.82 30.23 30.68 32.34 29.27 31.50 31.59 27.69 25.28 27.88 25.76 26.41 32.20 30.80 T E S T IS R IG H T ABS. R EL. W T. % BRW 1.6035 1.7572 1.6197 1.8049 1.7444 1.7356 1.9533 1.6461 1.8638 1 .7 1 3 7 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 PROSTATE ABS. W T. R EL. % BRW 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 P IT U IT A R Y ABS. W T. R EL. % BRW 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 LIV E R ABS. W T. R EL. % BRW 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 1166.67 1133.33 1272.73 1624.45 1403.14 1101.80 1302.08 1 2 1 7 .5 1 1137.96 1176.42 1124.88 1155.56 1184.80 114 7 .2 1 1204.66 1288.80 638.30 1409.86 1488.16 1262.95 1356.28 1281.74 1482.06 1258.96 1090.04 1128.22 1027.67 1096.14 1418.93 1 14 7 .7 7 K ID N EY LEFT ABS. R EL. W T. % BRW 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 12 1 .9 7 107.89 113.39 112.12 1 10 .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. 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) T A B LE D 2 1 (P A G E 9) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 455 DOSAGE GROUP I I I 3 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 1122 112 3 1127 112 9 113 1 113 2 113 4 113 5 1136 1139 1141 114 2 114 5 1147 1149 1151 115 3 115 4 1158 1159 116 2 116 4 1167 116 8 1171 1173 1175 1176 1177 118 0 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 .3 1 2.41 2.53 2.33 2.43 2.47 K ID N EY R IG H T ABS. R EL. 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 .1 7 2.50 2.78 2.55 2 .7 1 2.57 2.92 2 .7 1 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 1 11 .5 7 108.30 103.22 100.00 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 1 14 .8 1 101.62 ALL WEIGHTS WERE RECORDED IN GRAMS (G). A D R EN A L LEFT ABS. R EL. 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 A D R EN A L R IG H T ABS. R EL. 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 S P LEEN ABS. W T. 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 .7 7 0.91 0.93 1.01 0.86 1.08 0.78 0.80 1.17 0.94 0 .7 7 0.73 0.94 0.76 0.89 1.05 R EL. % BRW 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 THYM US ABS. W T. R EL. % 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 1 2 .7 1 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 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) T A B LE D 2 1 (PAG E 1 0 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 456 DOSAGE GROUP IV 10 M G/KG/DAY RAT NUM BER B R A IN W EIG H T E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA E P ID ID Y M IS LEFT ABS. R EL. W T. % BRW T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % BRW 118 2 118 4 118 6 118 8 1189 119 2 119 4 119 5 1198 1203 1204 12 0 7 1209 1211 1212 12 15 12 16 1217 1219 1221 1222 1224 1225 1226 1229 12 3 2 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 3 1.1 4 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 1 7 .5 1 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 7 8 .7 1 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 7 1 .5 1 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 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 97.87 121.89 75.24 83.15 87.18 101.97 102.60 84.14 95.66 92.23 92.88 91.76 94.05 98.72 105.84 74.43 87.56 76.06 98.41 71.00 1 0 3 .1 1 95.12 96.36 71.10 64.85 82.70 96.27 75.43 87.82 109.73 1.0993 1.3573 0.7547 1.0218 0.9952 1 .3 1 1 7 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 3 9 .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) T A B LE D 2 1 (P A G E 1 1 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 457 DOSAGE GROUP IV 10 M G/KG/DAY RAT NUM BER B R A IN W EIG H T 118 2 118 4 118 6 118 8 1189 119 2 119 4 119 5 1198 1203 12 0 4 1207 1209 1211 1212 12 15 12 16 1217 1219 1221 1222 12 2 4 1225 1226 1229 1232 1233 12 3 6 123 7 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 E P ID ID Y M IS R IG H T ABS. R EL. W T. % BRW 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 0.7102a 0.6257 0.6549 0.7082 0.7384 0.6937 0.6851 0.7064 0.6704 0.6843 0.6360 0.6242 0.7558 27.12 32.86 32.32 31.79 31.38 31.29 32.76 27.91 30.58 2 7 .3 7 3 2 .1 1 31.48 29.79 31.38 29.91 26.48 29.34 30.61 29.94 29.63 34.21 30.90 29.90 28.08 32.86 30.20 28.51 28.52 26.34 32.58 T E S T IS R IG H T ABS. R EL. W T. % BRW 1.6680 1.8710 1 .6 1 7 1 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. W T. R EL. % 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 3 9 .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 P IT U IT A R Y ABS. W T. R EL. % 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 LIV E R ABS. W T. R EL. % BRW 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 3 1 .7 1 26.90 3 1.1 7 32.01 22.60 26.98 38.30 25.35 28.38 28.51 1121.08 1332.17 962.96 1256.36 1358.75 1385.58 1329.28 1229.63 1520.76 1195.50 1383.04 1076.34 1602.25 1204.39 1429.92 1236.55 1447.83 1293.96 1332.54 1124.89 1531.88 1125.52 1343.53 1311.88 1051.16 1215.32 1595.83 1 13 6 .77 1197.47 1228.88 K ID N EY LEFT ABS. ] W T. % 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 .1 7 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 1 11 .3 0 105.80 100.45 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) T A B LE D 2 1 (P A G E 12 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M A LE R ATS ARGUS 418-020 Page 458 DOSAGE GROUP IV 10 M G /KG /D AY RAT NUM BER B R A IN W EIG H T 1182 1184 1186 1188 1189 119 2 1194 1195 1198 1203 12 0 4 1207 1209 1211 1212 1215 1216 12 17 1219 1221 1222 1224 1225 1226 1229 1232 1233 1236 12 3 7 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 K ID N EY R IG H T ABS. R EL. W T. % BRW 2.06 2.30 1.81a 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 2.50b 2.18 2.60 2.13 2 . 07d 2.85 2.44 2.02 2.67 92.38 100.00 83.80 100.45 110.42 104.05 122.52 105.09 110.59 99.55 108.26 97.77 105.40 92.54 104.10 102.81 87.83 . 92.24 114.35 94.57 1 1 4 .0 1 104.60 93.96 106.56 99.07 93.24 118.75 109.42 85.23 115.09 A D R EN A L LEFT ABS. R EL. W T. % 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 .3 1 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 .5 1 1.19 1 .7 7 1.17 1.50 1.26 1.10 1.68 A D R EN A L R IG H T ABS. R EL. W T. % 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 S PLEEN ABS. W T. R EL. % 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 3 1.1 5 33.73 34.35 3 0 .1 7 30.14 35.75 3 6 .71 34.31 32.76 37.70 90.70 36.94 43.33 39.46 27.43 30.17 THYM US ABS. W T. R EL. % BRW 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 1 3 .1 1 12.85 13.91 17.24 22.49 24.89 19.81 18.41 14.66 18.44 14.42 1 7 .5 7 22.92 16.14 11.39 10.34 ALL a. b. c. d. W EIG H TS W ERE Rat 1186 had R a t 1224 had R at 1229 had a n a ly s is . R a t 1232 had R EC O R D ED IN GRAMS ( G ) . A B S . W T,. = O R G A N W E I G H T . R E L . % TBW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . m o d e ra te d ila t io n o f th e p e lv is o f th e r ig h t k id n e y ; v a lu e in c lu d e d in g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . s lig h t d ila t io n o f th e p e lv is o f th e r ig h t k id n e y ; v a lu e in c lu d e d in g ro u p a ve ra g e s an d s t a t i s t i c a l a n a ly s e s . t a n a re a s on th e s p le e n th a t e x te n d e d in to th e p a re n ch ym a ; v a lu e in c lu d e d in g ro u p a v e ra g e s an d s t a t i s t i c a l s lig h t d ila t io n o f th e p e lv is o f th e r ig h t k id n e y ; v a lu e in c lu d e d in g ro u p a ve ra g e s an d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE D 2 1 (PAG E 1 3 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G E N ER A T IO N M A LE R ATS ARGUS 418-020 Page 459 DOSAGE GROUP V 30 M G /KG /D AY RAT NUM BER B R A IN W EIG H T 1241 1244 1245 1247 1248 1249 12 5 2 1254 1255 1257 1259 1261 12 6 6 1269 1271 1273 1274 1278 1281 12 8 2 1284 1287 1288 1289 1290 1291 1294 12 9 8 1300 2.21 2.14 2.14 2.19 2.02 2.08 2.16 2.00 2.29 2.11 1.95 2 .1 7 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 EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW CAUDA EP ID ID Y M IS LEFT ABS. R EL. W T. % BRW 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 T E S T IS LEFT ABS. R EL. W T. % BRW L . T E S T IS M IN U S T U N IC A A LB U G IN E A ABS. R EL. W T. % BRW S EM IN A L W IT H ABS. W T. V E S IC LE S FLU ID R EL. % BRW S EM IN A L V E S IC LE S W IT H O U T F L U I D ABS. R EL. W T. % BRW 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 8 1 .1 7 85.51 67.12 87.55 76.05 86.26 91.60 77.64 7 8 .7 1 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 7 7 .5 7 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 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 .8 1 11 1.9824 83.10 134.57 100.92 81.00 128.48 97.74 87.46 96.07 73.23 107.23 104.44 84.06 91.00 85.48 68.24 88.80 73.13 87.22 89.97 66.40 71.12 75.28 90.15 7 7 .8 7 73.20 80.63 59.00 87.92 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 4 3 .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 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) T A B LE D 2 1 (PA G E 14 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 460 DOSAGE GROUP V 30 M G /KG /D AY RAT NUM BER B R A IN W EIG H T 1241 12 4 4 1245 1247 1248 1249 1252 12 5 4 1255 1257 1259 1261 12 6 6 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 1290 129 1 12 9 4 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 EP ID ID Y M IS R IG H T ABS. R EL. W T. % BRW 0.6533 0.6699 0.6880 0.6936 0 .7 1 7 7 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 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 T E S T IS R IG H T ABS. R EL. W T. % 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 .7 3 1 1 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 7 1 .4 7 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. W T. R EL. % 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 3 7.9 1 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 P IT U IT A R Y ABS. W T. R EL. % 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. 0 2 1 a 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 LIV E R ABS. W T. R EL. % 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 2 5 .71 33.07 34.68 26.73 33.81 2 7 .5 1 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 1 15 8 .1 1 1413.25 1527.75 1137.45 1426.58 1335.44 1527.06 K ID N EY LEFT ABS. R EL. W T. % BRW 2.30 2.60 2.60 1.85 1.90 1.94 1.78 1 .9 1 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 ALL WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. 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) T A B LE D 2 1 (P A G E 1 5 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N M ALE RATS ARGUS 418-020 Page 461 DOSAGE GROUP V 30 M G /K G /D AY RAT NUM BER 1241 1244 1245 1247 1248 1249 12 5 2 12 5 4 1255 1257 1259 1261 12 6 6 1269 1271 1273 1274 1278 1281 1282 12 8 4 1287 1288 1289 1290 1291 12 9 4 1298 1300 B R A IN W EIG H T 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 K ID N EY R IG H T ABS. R EL. W T. % BRW 2.28 2.41 2.40 1 .6 7 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 1.8 1 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 A D R EN A L LEFT ABS. R EL. W T. % 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 .4 1 1.53 0.88 1.52 1.44 1.64 1 .5 1 0.96 1.26 0.81 1.14 0.98 1.64 1.07 1.19 A D R EN A L R IG H T ABS. R EL. W T. % 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 S P LEEN ABS. W T. R EL. % 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 39.72 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 THYM US ABS. W T. R EL. % 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 3 4 .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) T A B LE D22 (PAG E 1 ) : CAUDA EP ID ID Y M A L SPERM M O T IL IT Y , C O U NT, D E N S IT Y AND S PER M ATID COUNT - IN D IV ID U A L D ATA - F I G EN ER A T IO N M A LE RATS (See fo o tn o te s a t th e end o f t h is t a b l e . ) ARGUS 418-020 Page 462 DOSAGE GROUP I RAT NUM BER NUM BER 1002 1003 M O T ILE 205 220 1005 10 0 7 1011 1012 216 198 224 229 1013 10 14 10 17 1021 217 383 19 1 226 1023 320 1026 1028 253 160 10 3 1 204 1034 300 1035 1040 10 4 1 1043 373 197 183 424 1045 370 10 4 7 1048 3 14 256 1050 336 1051 244 1052 1054 1055 1058 295 218 179 202 1059 175 1060 19 1 M O T ILE 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 M G/KG/DAY S T A T IC COUNT (N O N M O TILE) 50 40 31 11 40 110 71 71 17 43 10 29 56 51 35 31 29 31 42 60 40 89 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 D EN S ITY 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 S PER M ATID 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 S PER M ATID D EN S ITY 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-6889.6) T A B LE D22 (PAG E 2 ) : CAUDA E P ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND S PER M A TID COUNT - IN D IV ID U A L DATA - F I G EN ER A T IO N M ALE RATS (S ee fo o t n o t e s a t th e e n d o f t h i s t a b l e ..) ARGUS 418-020 Page 463 DOSAGE GROUP I I RAT NUM BER NUM BER M O T ILE 1061 189 1063 165 1066 171 10 6 7 267 1069 193 1071 232 10 73 342 1077 327 10 78 203 1081 337 1082f 9 1083 213 1086 348 1088 1090 238 222 1091 255 1094 184 1096 203 1098 1100 214 312 1103 273 110 6 346 1107 1110 1112 282 381 318 1114 265 1116 624 1118 1120 189 167 1 M G/KG/DAY M O TILE S TA T IC COUNT PERCENT (N O N M O TILE) 76 61 7 7 48 75 57 78 77 67 94 7 8 66 80 83 76 104 87 30 94 20 3 1 20 88 28 90 40 94 16 83 44 89 3 1 88 25 9 1 21 9 1 21 87 47 81 62 88 4 7 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 D EN S ITY C 854.9 955.5 418.9 801.9 1041.6 867.2 555.7 648.6 1344.9 1465.1 19.8 1153.7 879.4 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 SPER M ATID 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 S PER M ATID D EN S ITY 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 98.4 107.2 112.7 111.9 103.5 111.8 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-6889.6) T A B LE D22 (PAG E 3 ): CAUDA EP ID ID Y M A L SPERM M O T IL IT Y , C O U NT, D E N S IT Y AND SPER M ATID COUNT - IN D IV ID U A L D ATA - F I G EN ER A T IO N M A LE RATS (S ee f o o t n o t e s a t th e e n d o f t h i s t a b l e ..) ARGUS 418-020 Page 464 DOSAGE GROUP I I I RAT NUM BER NUM BER 1122 M O T ILE 205 1123 198 1127 171 1129 186 1131 252 113 2 244 113 4 298 113 5 292 113 6 280 113 9 182 1141 391 1142 298 114 5 271 1147 183 1149 204 1151 271 115 3 236 1154 232 1158 395 115 9 231 1162 294 116 4 406 1167 337 1168 311 1171 434 1173 282 1175 243 1176 254 1177 178 1180 390 M O T ILE 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 M G/KG/DAY S T A T IC COUNT (N O N M O TILE) 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 34 108 TOTAL COUNT a 220 253 213 310 285 285 3 76 336 3 16 233 444 352 2 94 215 229 288 257 263 441 307 361 470 399 349 538 349 309 330 212 498 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 D EN S ITY 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 SPER M ATID 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 S PER M ATID 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 32.8 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B ER : T-- 6 8 8 9 . 6 ) T A B LE D22 (PAG E 4 ) : CAUDA EP ID ID Y M A L SPERM M O T IL IT Y , C O U NT, D E N S IT Y AND SPER M ATID COUNT - IN D IV ID U A L DATA - F I G EN ER A T IO N M ALE RATS (See fo o tn o te s a t th e end o f t h is ta b le .) ARGUS 418-020 Page 465 DOSAGE GROUP IV RAT NUM BER NUM BER M O T ILE 1182 288 118 4 175 1186 188 1188 206 1189 338 119 2 239 119 4 286 119 5 194 119 8 192 1203 1204 18 1 200 1207 1209 1211 1212 190 221 233 194 1215 189 1216 252 1217 294 1219 1221 1222 338 229 263 1224 407 1225 319 1226 299 1229 264 1232 341 1233 292 1236 16 2 1237 340 1240 454 M O T ILE 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 M G/KG/DAY S T A T IC COUNT (NONM O TIL E ) 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 2 17 222 237 403 331 320 214 212 218 293 262 260 300 216 217 266 354 425 277 371 472 423 389 335 3 71 325 223 384 559 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 D EN S ITY 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 SPER M ATID 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 S PER M ATID D EN S ITY 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) T A B LE D22 (PAG E 5 ) : CAUDA EP ID ID Y M A L SPERM M O T IL IT Y , CO UNT, D E N S IT Y AND S PER M ATID COUNT - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS (S e e fo o t n o t e s a t th e e n d o f t h i s t a b l e ..) ARGUS 418-020 Page 466 DOSAGE GROUP V RAT NUM BER NUM BER M O T ILE 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 12 9 8 184 1300 182 M O T ILE 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 M G/KG/DAY S T A T IC COUNT (N O N M O TILE) 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 D EN S ITY C 656.1 552.4 617.2 900.7 721.1 343.0 476.3 1325.6 1186.8 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 S PER M ATID 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 S PER M ATID D EN S ITY 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-6889.6) T A B LE D22 (PAG E 6 ) : CAUDA EP ID ID Y M A L SPERM M O T IL IT Y , C O U N T, D E N S IT Y AND SPER M ATID COUNT - IN D IV ID U A L D ATA - F I G EN ER A T IO N M ALE RATS F O O T N O T E S _____ _________ __ a . Sum o f n um ber m o tile a n d s t a t i c c o u n t. G ro u p s o f f i v e f i e l d s w e re e v a lu a te d u n t i l a sp erm c o u n t o f a t l e a s t 200 was a c h ie v e d o r 20 f i e l d s w e r e e v a l u a t e d . b . Sperm c o u n t u se d in th e c a lc u la tio n o f sperm d e n s ity . Te n f i e l d s w ere e v a lu a te d . c . Th e sperm d e n s it y was c a lc u la t e d b y d i v i d i n g th e sperm c o u n t b y th e vo lu m e in th e im age a re a ( 3 4 . 3 x 1 0 ' 6 m L ) , m u lt ip ly in g b y 2 ( d ilu t io n fa c to r ) and m u lt ip ly in g b y 10~ to o b ta in th e sperm c o n c e n tr a tio n . Th e c a lc u la te d sperm c o n c e n tr a tio n v a lu e (ro u n d e d t o 1 d e c im a l p la c e ) w as m u l t i p l i e d b y 50 (vo lu m e ) a n d d i v i d e d b y th e w e ig h t o f th e l e f t c a u d a e p id id y m is (s e e T a b le D 20 f o r th e w e ig h t o f th e l e f t cauda e p id id y m is ) to o b ta in th e sperm d e n s ity . Th e c a lc u la te d v a lu e w i l l v a r y b y a p p ro x im a te ly 0.8% fro m th e C o m p u te r A u to m a te d S p e rm A n a l y s i s b e c a u s e t h e d i g i t a l im a g e e v a lu a t e d i s s l i g h t l y s m a lle r (4 p i x e l s ) th a n th e a c t u a l f i e l d c a u s in g a s l i g h t u n d e re s tim a te o f th e a c tu a l vo lu m e and an o v e re s tim a te o f th e c o n c e n tr a tio n . d . S p e rm a tid c o u n t u se d in th e c a lc u la tio n o f s p e rm a tid d e n s ity . Ten f ie ld s w ere e v a lu a te d . e . Th e s p e rm a tid d e n s it y w as c a lc u la t e d b y d i v i d i n g th e s p e rm a tid c o u n t b y th e vo lu m e i n th e im a ge a re a ( 3 4 . 3 x 1 0 " 6 m L ) , m u ltip ly in g b y 2 ( d ilu t io n fa c to r ) and m u ltip ly in g b y 10 "6 to o b ta in th e s p e rm a tid c o n c e n tra tio n . The c a lc u la te d s p e rm a tid c o n c e n tr a tio n v a lu e (ro u n d e d t o 1 d e c im a l p la c e ) was m u lt ip lie d b y 50 (vo lu m e ) an d d iv id e d b y th e w e ig h t o f th e l e f t t e s t i s m in u s t u n ic a a lb u g in e a (se e T a b le D20 f o r th e w e ig h t o f th e l e f t t e s t i s m in u s t u n ic a a lb u g in e a ) t o o b ta in th e s p e rm a tid d e n s i t y . Th e c a lc u la t e d v a lu e w i l l v a r y b y a p p r o x im a te ly 0 . 8 % fro m th e C o m p u te r A u to m a te d Sperm A n a ly s is b e c a u s e th e d i g i t a l im age e v a lu a t e d i s s l i g h t l y s m a lle r (4 p i x e ls ) th a n th e a c t u a l f i e l d c a u s in g a s l i g h t u n d e r e s tim a te o f th e a c tu a l vo lu m e a n d an o v e re s tim a te o f th e c o n c e n tra tio n . f . R a t 1082 h ad le s s th a n 200 sperm p e r 20 f i e l d s ; v a lu e s e x c lu d e d fro m g ro u p a ve ra g e s and s t a t i s t i c a l a n a ly s e s . 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) T A B LE D23 (P A G E 1) : C AU DA E P ID ID Y M A L SPERM M ORPH O LO GY - IN D IV ID U A L D A T A - F I G EN ER A T IO N M ALE R A TS ARGUS 418-020 Page 468 DOSAGE GROUP I RAT NUM BER 1002 10 0 3 10 0 5 10 0 7 1011 1012 10 13 10 14 10 17 1021 1023 10 2 6 1028 1031 1034 10 3 5 1040 1041 10 4 3 1045 1047 1048 10 5 0 10 5 1 1052 10 5 4 10 5 5 10 5 8 1059 10 6 0 NORM AL 19 8 19 6 19 3 19 5 19 7 19 6 19 2 19 5 19 6 19 4 191 19 7 19 7 196 19 6 19 5 19 8 193 19 4 196 193 193 19 7 19 8 19 6 19 3 19 8 19 5 19 6 19 5 0 M G/KG/DAY DETAC H ED H EA D NO H EA D B R O K EN FLAG ELLU M NO HOOK C O ILED FLAG ELLU M B EN T FLAG ELLU M B EN T FLAG ELLU M T IP P ER C EN T ABNORM AL 110 3 10 610 23 0 210 220 620 4 10 112 3 12 5 22 111 201 211 3 01 3 11 101 5 20 4 20 202 4 21 430 210 200 121 5 20 100 23 0 13 0 23 0 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 01 00 00 00 0 0 1.0 0 0 2.0 0 0 3 .5 0 0 2 .5 0 0 1 .5 0 0 2.0 0 0 4 .0 0 0 2 .5 0 0 2.0 0 0 3 .0 0 0 4.5 0 0 1 .5 0 0 1 .5 0 0 2.0 0 0 2.0 0 0 2 .5 0 0 1.0 0 0 3.5 0 0 3 .0 0 0 2.0 0 0 3.5 0 0 3.5 00 1 . 5 0 0 1.0 0 0 2.0 0 0 3 .5 0 0 1.0 0 0 2 .5 0 0 2.0 00 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) T A B LE D23 (P A G E 2 ) : CAUDA EP ID ID Y M A L SPERM M ORPHOLOGY - IN D IV ID U A L D A TA - F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 469 DOSAGE GROUP I I 1 M G/KG/DAY RAT NUM BER 106 1 10 6 3 10 6 6 10 6 7 10 6 9 10 71 10 73 10 77 10 78 10 8 1 10 8 2 a 10 8 3 1086 10 8 8 10 9 0 109 1 10 9 4 10 9 6 10 9 8 1100 110 3 110 6 110 7 1110 1112 1114 1116 1118 1120 NORM AL 19 4 19 7 19 5 19 6 19 8 19 5 19 3 19 6 19 1 19 3 0 19 6 19 0 19 6 19 7 19 4 19 6 19 6 19 6 19 5 19 1 19 7 19 8 19 0 19 9 19 9 19 3 19 7 19 8 D ETA C H ED H EA D NO H EA D B R O K EN FLAG ELLU M NO HOOK C O ILED FLAG ELLU M B EN T FLAG ELLU M B EN T FLAG ELLU M T IP 24 0 210 3 20 3 10 200 4 10 610 3 10 530 5 20 001 3 00 64 0 3 10 210 330 4 00 3 10 3 10 5 00 63 0 120 200 7 30 100 100 4 21 210 020 00 00 00 00 00 00 00 00 10 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 00 00 00 00 00 00 00 00 00 00 00 00 00 a . R a t 1082 h ad le s s th a n 200 sperm p e r 20 f i e l d s ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t i c a l a n a ly s e s . P ER C EN T ABNORM AL 3 .0 1 .5 2 .5 2.0 1.0 2 .5 3 .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) T A B LE D23 (P A G E 3) : C AU D A E P ID ID Y M A L SPERM M ORPH OLOGY - IN D IV ID U A L D A T A - F I G E N E R A T IO N M ALE R ATS ARGUS 418-020 Page 470 DOSAGE GROUP I I I RAT NUM BER 1122 112 3 112 7 112 9 113 1 113 2 113 4 113 5 113 6 113 9 114 1 114 2 114 5 114 7 114 9 115 1 115 3 115 4 115 8 115 9 116 2 116 4 116 7 116 8 1171 1173 1175 1176 1177 118 0 NORM AL 19 3 19 1 19 3 19 7 19 6 19 6 19 5 19 7 19 5 19 5 19 4 19 6 19 4 19 7 19 5 19 9 19 0 19 8 19 3 19 5 19 6 19 5 19 6 19 6 19 5 19 5 19 3 19 4 19 2 19 6 DETAC H ED H EA D 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 M G/KG/DAY NO H EA D B R O K EN FLAG ELLU M 20 40 20 10 11 20 20 11 11 20 40 10 40 30 10 10 11 10 31 20 11 10 30 02 10 00 01 30 21 10 NO HOOK C O ILED FLAG ELLU M 00 00 00 00 00 00 00 00 00 00 00 10 00 00 00 00 00 00 00 00 00 00 00 00 00 01 00 00 01 01 B EN T FLAG ELLU M 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 B EN T FLAG ELLU M T IP 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 P ER C EN T ABNORM AL 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) T A B LE D23 (P A G E 4) : CAUDA E P ID ID Y M A L SPERM M ORPHOLOGY - IN D IV ID U A L D A T A - F I G EN ER A T IO N M ALE R ATS ARGUS 418-020 Page 471 DOSAGE GROUP IV RAT NUM BER 118 2 118 4 118 6 118 8 118 9 119 2 119 4 119 5 119 8 12 0 3 12 0 4 12 0 7 12 0 9 1211 1212 12 15 12 16 12 17 12 19 1221 1222 12 2 4 12 2 5 1226 12 2 9 12 3 2 12 3 3 12 3 6 123 7 1240 NORM AL 19 6 19 6 19 5 19 5 19 6 19 7 19 8 19 5 19 7 19 3 19 3 19 6 19 2 19 4 19 2 19 4 19 3 19 6 19 5 19 9 19 5 19 3 19 7 19 7 19 8 19 8 19 8 19 1 19 7 19 3 DETAC H ED H EA D 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 M G/KG/DAY NO H EA D B R O K EN FLAG ELLU M 12 11 01 12 20 00 00 20 10 30 10 00 00 30 10 20 11 10 10 00 01 30 10 10 00 10 .1 1 50 10 31 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 C O ILED FLAG ELLU M 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 B EN T FLAG ELLU M 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 B EN T FLAG ELLU M T IP 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 P ER C EN T ABNORM AL 2.0 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) T A B LE D23 (P A G E 5) : CAUDA E P ID ID Y M A L SPERM M ORPHOLOGY - IN D IV ID U A L D A TA - F I G EN ER A T IO N M ALE R ATS ARGUS 41S-020 Page 472 DOSAGE GROUP V RAT NUM BER 12 4 1 12 4 4 1245 12 4 7 1248 12 4 9 12 5 2 1254 12 5 5 12 5 7 1259 126 1 12 6 6 12 6 9 12 71 1273 1274 12 78 128 1 12 8 2 12 8 4 12 8 7 12 8 8 12 8 9 12 9 0 129 1 12 9 4 12 9 8 13 0 0 NORM AL 19 1 19 7 19 6 19 3 19 6 19 7 18 9 19 5 19 5 19 6 19 7 19 3 19 6 19 6 19 8 19 5 19 4 19 3 19 2 19 1 19 6 19 6 19 4 18 8 19 2 19 2 19 7 19 4 19 1 D ETA C H ED H EA D 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 M G /KG /D AY NO H EA D B R O K EN FLAG ELLU M 21 10 10 30 11 10 50 10 21 10 10 31 21 01 00 01 20 40 12 50 02 11 41 42 32 50 00 12 30 NO HOOK C O ILED FLAG ELLU M 00 00 00 01 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 B EN T FLAG ELLU M 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 B EN T FLAG ELLU M T IP 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 P ER C EN T ABNORM AL 4 .5 1 .5 2.0 3 .5 2.0 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 - Fl 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) T A B LE E l (P A G E 1 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 474 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 P R E C O H A B IT A T IO N (D A Y 1 O F S TU D Y T O T H E D A Y O F C O H A B IT A T IO N ) M AXIM U M P O S S IB L E IN C ID E N C E FOUND DEAD A B D O M IN A L D IS T E N T IO N U R IN E -S T A IN E D A B D O M IN A L FU R COLD TO TOUCH A N N U LA R C O N S T R IC T IO N O F T H E T A IL C H R O M O R H IN O R R H EA R ALES T I P O F T A I L M IS S IN G BACK OR H EA D : SCAB LO C A LIZE D A LO P E C IA : TO TAL LIM B S N EC K H EA D 3 2 8 3 / 60 0 64 7 / 8/ 2 0/ 0 0/ 0 4/ 2 0/ 0 0/ 0 1/ 1 21 9 / 4/ 1 0/ 0 11 5 / 3 3 0 6 / 60 2b , c 56/ 7 4 8 / 5c 1/ l b 21 6 / 14/ 4b, c 0/ 0 26 1 / b 0/ 0 22/ 1 22/ 1 0/ 0 0/ 0 3 3 10 / 60 Id 29/ 4 22/ 4 d 0/ 0 0/ 0 17/ 7d 0/ 0 0/ 0 0/ 0 24 2 / 24 2 / 0/ 0 0/ 0 3 2 8 1/ 60 le 39/ 5 14 / 4e 1/ l e 0/ 0 1/ 1 0/ 0 17 0 / 9/ 1 21 8 / 11 5 / 3/ 1 0/ 0 S T A T IS T IC A L A N A LY S ES O F C L IN IC A L O B S ER V A T IO N D A T A W ERE R ES T R IC T E D TO TH E NUM BER O F R ATS M A XIM U M P O S S IB L E IN C ID E N C E = (D A Y S x R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . R a ts ! 15 6 2 an d 1563 d id n o t h a v e c l i n i c a l o b s e rv a tio n s re c o rd e d on d a y 1 p o s tw e a n in g b . R a t 1365 was fo u n d d e ad on d a y 4 p o s tw e a n in g . c . R a t 13 73 was fo u n d d e ad on d a y 5 1 p o s tw e a n in g . d . R a t 1432 was fo u n d dead on d a y 7 p o s tw e a n in g . e . R a t 1484 was fo u n d dead on d a y 3 p o s tw e a n in g . 8f . R a t 1 5 4 9 w a s f o u n d d e a d o n d a y p o s tw e a n in g . 6g - R a t 1 5 5 9 w a s f o u n d d e a d o n d a y 2h . R a t 1 5 6 2 w a s f o u n d d e a d o n d a y p o s tw e a n in g . p o s tw e a n in g . 2i . R a t 1 5 6 3 w a s f o u n d d e a d o n d a y p o s tw e a n in g . j R a t 15 74 was fo u n d dead on d a y 3 p o s tw e a n in g . k . R a t 15 75 was fo u n d de ad on d a y 3 p o s tw e a n in g . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 .0 1 ) . W IT H O B S ER V A T IO N S . V 30 3 17 1 / 60a 6* * f - k 7 2 / 10 21/ 5 f , g , j 8/ 3 f , g , j 3/ 3 27 / f 2/ 2 11 8 / 6/ 1 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) T A B LE E l (P A G E 2 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 475 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 P R E C O H A B IT A T IO N (D A Y 1 O F S TU D Y TO T H E D A Y O F C O H A B IT A T IO N ) M A XIM U M P O S S IB L E IN C ID E N C E FOUND DEAD D EC R EA S ED M OTOR A C T IV IT Y EM A C IA T IO N T A IL BENT IN C IS O R S : TOTAL M IS A LIG N ED M IS S IN G /B R O K EN LA C R IM A T IO N R IG H T OR L E F T E Y E : SW O LLEN LA B O R ED B R EA T H IN G S O FT OR LIQ U ID FEC ES CHROM ODACRYORRHEA SW OLLEN EA R (S ) 3 2 8 3 / 60 0 0/ 0 4/ 1 0/ 0 30/ 3 11 7 / 21 3 / 1/ 1 0/ 0 0/ 0 0/ 0 5/ 2 12 4 / 3 3 0 6 / 60 2b , c 27 / b , c 16 / lc 0/ 0 2/ 1 0/ 0 2/ 1 4/ 1 4/ 1 0/ 0 1/ 1 1/ l c 11 6 / 3 3 10 / 60 Id 0/ 0 2/ 2d 0/ 0 57/ 3 21 5 / 43/ 3 0/ 0 0/ 0 0/ 0 3/ 2 11 9 / 3/ 1 3 2 8 1/ 60 le 1/ . l e 1/ 1 0/ 0 10/ 1 10/ 1 0/ 0 1/ 1 1/ 1 1/ l e 0/ 0 0/ 0 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L I N IC A L O B S E R V A T IO N D A T A W ERE R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H M A XIM U M P O S S IB L E I N C I D E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S E R V A T IO N S /N U M B E R O F R A T S W IT H O B S E R V A T IO N . a . R a ts 15 6 2 a n d 1563 d id n o t h a v e c l i n i c a l o b s e rv a tio n s re c o rd e d on d a y 1 p o s tw e a n in g . b . R a t 1365 w as fo u n d d e a d on d a y 4 p o s tw e a n in g . c . R a t 13 73 w as fo u n d d e a d o n d a y 5 1 p o s tw e a n in g . d . R a t 14 3 2 w as fo u n d d e a d on d a y 7 p o s tw e a n in g . e . R a t 14 8 4 w as fo u n d d e a d on d a y 3 p o s tw e a n in g . f . R a t 15 4 9 w as fo u n d d e a d on d a y 8 p o s tw e a n in g . g . R a t 15 5 9 w as fo u n d d e a d o n d a y 6 p o s tw e a n in g . h . R a t 15 6 2 w as fo u n d d e a d on d a y 2 p o s tw e a n in g . i . R a t 1563 w as fo u n d d e a d on d a y 2 p o s tw e a n in g . j . R a t 15 74 w as fo u n d d e a d on d a y 3 p o s tw e a n in g . k . R a t 15 75 w as fo u n d d e a d o n d a y 3 p o s tw e a n in g . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 .0 1 ) . O B S ER V A T IO N S . V 30 3 17 1/ 60a 6* * f - k 2/ I f 1/ lg 1/ 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-6889.6) T A B LE E l (P A G E 3 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N FE M A LE R ATS ARGUS 418-020 Page 476 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 P R E C O H A B IT A T IO N (D A Y 1 O F S TU D Y T O TH E D A Y O F C O H A B IT A T IO N ) M A XIM U M P O S S IB L E IN C ID E N C E FOUND DEAD D EH Y D R A T IO N H EA D : SW OLLEN S N O U T: SW OLLEN P T O S IS 3 2 8 3 / 60 0 5/ 1 0/ 0 0/ 0 20/ 2 3 3 0 6 / 60 2b / c 22 3 / c 1/ 1 1/ 1 0/ 0 3 3 10 / 60 id 0/ 0 0/ 0 0/ 0 0/ 0 3 2 8 1 / 60 le 0/ 0 0/ 0 0/ 0 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L IN IC A L O B S E R V A T IO N D A T A W ERE R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H M A XIM U M P O S S IB L E IN C ID E N C E = (D A Y S X R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S E R V A T IO N S / N U M B ER O F R A T S W IT H O B S E R V A T IO N . a . R a ts 15 6 2 a n d 1563 d id n o t h a v e c l i n i c a l o b s e rv a tio n s re c o rd e d o n d a y 1 p o s tw e a n in g . b . R a t 1365 was fo u n d dead on d a y 4 p o s tw e a n in g . c . R a t 13 73 was fo u n d dead on d a y 51 p o s tw e a n in g . d . R a t 143 2 was fo u n d de ad on d a y 7 p o s tw e a n in g . e . R a t 148 4 was fo u n d de ad on d a y 3 p o s tw e a n in g . 8f . R a t 1 5 4 9 w a s f o u n d d e a d o n d a y p o s tw e a n in g . 6g - R a t 1 5 5 9 w a s f o u n d d e a d o n d a y 2h . R a t 1 5 6 2 w a s f o u n d d e a d o n d a y p o s tw e a n in g . p o s tw e a n in g . 2i . R a t 1 5 6 3 w a s f o u n d d e a d o n d a y p o s tw e a n in g . j R a t 15 74 was fo u n d de ad on d a y 3 p o s tw e a n in g . k . R a t 15 75 was fo u n d dead on d a y 3 p o s tw e a n in g . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e (p < 0 .0 1 ) O B S ER V A T IO N S . V 30 3 17 1 / 60a G'* * 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) T A B LE E l (P A G E 4 ) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page A ll DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 PRESUM ED G ES T A T IO N : a M AXIM U M P O S S IB L E IN C ID E N C E M O R T A LIT Y L O C A L IZ E D A L O P E C IA : LIM B S R IG H T A X IL L A : M ASS T IP O F T A I L M IS S IN G CHROM ODACRYORRHEA SW OLLEN EA R (S ) P T O S IS IN C IS O R S : TO TAL M IS A LIG N ED M IS S IN G /B R O K EN 6 44/ 29 0 2/ 1 0/ 0 0/ 0 0/ 0 65/ 4 22/ 1 22 9 / 22 9 / 0/ 0 6 4 4 / 29 0 22/ 1 0/ 0 22/ 1 0/ 0 22 3 / * 0/ 0 0/ 0 0/ 0 0/ 0 669/ 30 0 7/ 1 0/ 0 0/ 0 22/ 1 0/ 0* * 0/ 0 22 8 / 0/ 0 22 8 / 6 70 / 30 0 0/ 0 0/ 0 11 7 / 0/ 0 0/ 0* * 0/ 0 3/ 1 3/ 1 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L IN IC A L O B S E R V A T IO N D A T A W ER E R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H O B S E R V A T IO N S . M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S x R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L NU M B ER O F O B S ER V A T IO N S /N U M B ER O F R A T S W IT H O B S E R V A T IO N , a . R e s t r ic t e d t o r a t s w ith a c o n firm e d m a tin g d a te . * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 .0 5 ) . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 .0 1 ) . V 30 663 / 30 0 16/ 4 8/ 1 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) T A B LE E l (P A G E 5) : C L IN IC A L O B S ER V A TIO N S - SUMMARY - F I G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 478 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 LA C T A T IO N : M A XIM U M P O S S IB L E IN C ID E N C E M O R T A LIT Y L O C A L IZ E D A L O P E C IA : LIM B S R IG H T A X IL L A : M ASS SW OLLEN EA R (S ) R ED P E R IV A G IN A L SUBSTANC E S O FT OR LIQ U ID FEC ES U R IN E -S T A IN E D A B D O M IN A L FU R IN C IS O R S : TO TAL M IS S IN G /B R O K EN M IS A LIG N ED CHROM ODACRYORRHEA T IP O F T A IL M IS S IN G P T O S IS 6 16 / 28 0 22/ 1 0/ 0 88/ 4 0/ 0 0/ 0 0/ 0 24 2 / 11 9 / 22 9 / 0/ 0 0/ 0 22/ 1 6 16 / 28 0 22/ 1 0/ 0 22/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 22/ 1 0/ 0 6 16 / 28 0 81/ 4 0/ 0 0/ 0 4/ 4 ** 5/ 3 0/ 0 24 4 / 24 4 / 0/ 0 22/ 1 0/ 0 0/ 0 6 16 / 28 0 23 3 / 0/ 0 0/ 0 0/ 0 6/ 2 3/ 2 0/ 0 0/ 0 0/ 0 0/ 0 22/ 1 0/ 0 S T A T IS T IC A L A N A L Y S E S O F C L I N IC A L O B S E R V A T IO N D A T A W ERE R E S T R IC T E D T O T H E N U M B ER O F R A T S W IT H O B S E R V A T IO N S . M AXIM U M P O S S IB L E IN C ID E N C E = (D A Y S x R A T S )/ N U M B E R O F R A T S E X A M IN E D P E R G R O U P . N / N = T O T A L N U M B ER O F O B S E R V A T IO N S / NU M B ER O F R A T S W IT H O B S E R V A T IO N . * * S ig n ific a n t ly d i f f e r e n t fro m th e G ro u p I v a lu e ( p ^ O . O l ) . V 30 638/ 29 0 72/ 4 11 9 / 11 8 / 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 PROTOCOL 418-020: O R A L ( G A V A G E ) 'T W O - G E N E R A T I O N ( O N E L I T T E R P E R G E N E R A T I O N ) R E P R O D U C T I O N S T U D Y O F A M M O N I U M P E R F L U O R O O C T A N O A T E (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 . 6 ) T A B L E E 2 ( P A G E 1 ) : B O D Y W E I G H T S - P R E C O H A B I T A T I O N - S U M M A R Y - F I G E N E R A T I O N F E M A L E R A T S DOSAGE GROUP D O S A G E (M G /K G /D A Y) I II III 0 13 IV 10 RATS TESTED N 60 60 60 60 IN C LU D ED IN A N A LY S ES N 60 60 60 60 B O D Y W EIG H T (G ) DAY 1 DAY 8 DAY 15 D A Y 22 D A Y 29 M E A N S .D . M EANS.D . M EANS.D . M E A N S .D . M E A N S .D . 41.4 6.8 7 1 .7 9.9 111.3 1 3 . 0 148.9 1 4 . 2 [ 59] a 177.0 16.2 [ 47] a 39.2 6.3 66.8 8 . 5 * [ 59] a 104.2 10 .6 ** [ 59] a 142.9 1 1 .1 * [ 59] a 170.2 12.0* [ 53] a 42.9 8.7 73.5 12.6 [ 59] a 112.7 1 3 . 7 [ 59] a 15 1.1 12.3 [ 59] a 180.6 14.2 [ 51] a 43.3 7.3 72.1 11.5 [ 59] a 108.6 13.8 [ 59] a 146.8 15 .1 [ 59] a 175.0 1 4 . 8 [ 48] a D A Y = D A Y P O S T W EA N IN G t ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n o r fo u n d d e a d . * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . V 30 60 58a 39.2 7.9 66.9 9.9* [ 54] a 102.8 13 .2 ** [ 54] a 139.4 1 3 .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) T A B L E E2 (P A G E 2) : B O D Y W EIG H T S - P R E C O H A B IT A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 480 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV V 10 3 0 RATS TES TED N 60 60 60 60 60 IN C LU D ED IN A N A LY S ES N 30a 30a 30a 30a 3 0a B O D Y W EIG H T (G ) D AY 36 M E A N S .D . 199.9 + 15 .7 193.5 1 9 . 7 203.8 15.3 198.5 18 .1 190.1 19 .1 DAY 43 M EANS.D . 219.8 18.4 212.5 24.6 225.6 13.2 219.3 18.4 209.7 18.4 D A Y 50 DAY 57 D A Y 64 DAY 70b P R EC O H A B IT A T IO N C M EANS. D . M EANS. D . M EANS. D . M EANS. D . M EANS.D . 237.1 + 19.2 248.6 1 7 .1 259.6 + 19.9 264.9 1 9 .7 276.7 + 22.9 228.3 29.6 244.2 20.7 255.6 + 20.7 [ 29] a 263.4 20.7 ( 29] a 278.1 23.6 [ 29] a 243.5 1 4 .7 254.6 14 .7 266.9 16 .7 274.2 16.4 287.4 18.1 236.0 18.0 247.0 19.0 259.4 21.9 2 6 6 . 2 + 21.0 2 7 7 . 0 22.1 224.4 19 .2* 202 3 6 . 1 .8* 2 4 8 . 7 22.1 2 5 4 . 5 21.8 263.7 23.0* DAY [] a. b. c. * = D A Y P O S T W EA N IN G = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n o r fo u n d d e a d . B e cau se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a se d on ea ch r a t ' s d a y p o s tw e a n in g , w as th e la s t d a y o n w h ic h th e y o u n g e s t r a t s ( in t h is g ro u p ) h a d a b o d y w e ig h t v a lu e re c o rd e d . P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was begu n fo r th e F I g e n e ra tio n r a ts w e re 92 t o 10 6 d a y s o f a g e . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . d a y 70 p o s tw e a n in g r a t s ; a t th a t tim e th e se PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 (P A G E 1 ) : B O D Y W EIG H T C H A N G ES - P R E C O H A B IT A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 01 3 RATS TES TED N 60 60 60 IN C LU D ED IN A N A LY S ES N 60 59a 59a B O D Y W EIG H T C H A N G E (G) 1D A Y S -8 8D A Y S - 15 D AYS 15 - 22 22D A Y S - 29 M EANS.D . M EAN+S.D . M EANS.D . M EAN+S.D . +30.3 4.6 +39.6 4.3 +37.6 5.2 [ 59] a +28.2 5.4 [ 47] a +27.4 3 .9 ** +37.4 3 .8* +38.7 4.4 +28.0 5.9 [ 53] a +30.4 5.6 +39.2 4.5 + 3 8 . 4 6.0 +28.7 6.7 [ 51] a . D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s f o r r a ts th a t w e re s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n o r fo u n d d e a d . * S i g n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . * * S i g n i f i c a n t l y d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . 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) T A B L E E3 (P A G E 2 ) : B O D Y W EIG H T C H AN G ES - P R E C O H A B IT A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 482 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 0 13 IV V 10 3 0 RATS TES TED N 60 60 60 60 60 IN C LU D ED IN A N A LYS ES N 30a 30a 30a 30a 30a B O D Y W EIG H T C H A N G E (G) D A YS 29 - 36 D A Y S 36 - 43 M EANS. D . M E A N S .D . + 2 5 . 1 6.1 +19.9 + 7.9 +23.3 9.8 +19.0 + 7.8 +25.0 8.9 +21.8 8.4 +23.9 4.2 +20 . 8 + 5 . 9 +22.8 5.5 +19.6 4 .7 D A Y S 43 - 50 D A Y S 50 - 5 7 D A Y S 57 - 64 D A Y S 64 - 70 b 1D A Y S - 70b DAYS 1 P R EC O H A B IT A T IO N C M EANS.D . M EANS.D . M EANS.D . M EANS.D . M EAN+S.D . M EANS.D . +17.3 7 .7 +11.5 7.6 + 1 1 .0 5 .9 +5.3 4 .7 +223.3 18.0 20+ 2 3 5 . 2 .9 +15.8 + 7.9 + 1 1.8 + 6.5 [ 29] a +11.4 + 7.4 [ 29] a +7.8 7.3 [ 29] a +224.3+ 19.0 [ 29] a + 2 3 9 . 0 2 2 . 6 [ 29] a +18.0 5.8 + 1 1 . 1 8.1 +12.3 +7.3 5.2 6.0 + 2 3 1 . 3 1 8 . 8 + 2 4 4 . 5 20.6 +16.6 4.5 + 1 1 . 1 6.0 +12.4 5.7 + 6 .8 + 4 .9 + 2 2 2 . 6 1 7 . 5 +233.4 1 9 .1 +14.7 3.6 + 1 1.7 5.3 +12.7 3.4 +5.8 5.0 + 2 1 5 .1 19.3 21+ 2 2 4 . 3 .0* D A Y (S ) = D A Y (S ) P O S TW EA N IN G [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s f o r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n o r fo u n d d e a d . b . B e cau se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a se d on ea ch r a t ' s d a y p o s tw e a n in g , w as th e la s t d a y o n w h ic h th e y o u n g e s t r a t s ( in t h is g ro u p ) h ad a b o d y w e ig h t v a lu e re c o rd e d . c . P r e c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was be gu n f o r th e F I g e n e ra tio n r a t s w e re 92 t o 10 6 d a y s o f a g e . * S i g n ific a n t ly d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . d a y 70 p o s tw e a n in g r a t s ; a t t h a t tim e th e se PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E 4 (P A G E 1 ) : M A T ER N A L B O D Y W EIG H T S - G E S T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TESTED N 30 29 P R EG N A N T N 28 28 M A T E R N A L B O D Y W EIG H T (G) 0D A Y M EAN+S.D . 274.8 20.9 275.4 23.6 DAY 7 D A Y 10 M E A N + S .D . M EANS.D . 304.0 23.0 316.8 23.9 303.4 25.5 317.0 26.8 DAY 14 M EANS.D . 333.9 24.5 333.2 28.4 DAY 18 D A Y 21 M EANS.D . M EANS.D . 380.2 29.6 4 17 .9 33.0 [ 27] a 380.8 31.6 418.0 32.9 [ 26] a DAY [] a. * = D A Y O F G ES T A T IO N = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s v a lu e s fo r dams th a t d e liv e r e d . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e (p<0.05). III 3 30 28 285.4 17.6 312.2 19.4 326.1 20.2 343.1 2 2 .2 394.8 2 7 .7 427.8 31.3 [ 20] a IV V 10 3 0 30 30 28 29 275.0 23.2 303.3 24.3 314.0 24.0 331.4 + 24.6 380.6 28.9 415.1 3 1.1 [ 25] a 262.1 23.2* 287.4 22.6* 299.6 23.2* 316.1 25.4* 366.6 28.9 399.2 34.8 [ 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) 1T A B L E E 5 ( P A G E ) : M A TER N A L B O D Y W EIG H T C H A N G ES - G E S T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D A Y) I 0 RATS TES TED N 30 P R EG N A N T N 28 M ATERNAL BODY W EIG H T C H A N G E (G) 0D A Y S -7 10D A Y S 7 - 10D A Y S - 14 M EANS.D . M EANS.D . M EANS.D . +29.1 5.8 + 1 2 .8 4 .2 + 1 7 .1 5.3 D AYS 14 - 18 21D A Y S 1 8 D A Y S 0 - 21 M EANS. D . M EANS.D . M EANS.D . +46.2 11.5 +37.6 9.2 [ 27] a + 1 4 2 . 8 1 9 . 6 [ 27] a D AYS = D AYS O F G ES T A T IO N [ ] = NUM BER O F V A LU ES AVER AG ED a . E x c lu d e s v a lu e s f o r dams th a t d e liv e re d . II III 13 29 30 28 28 IV V 10 3 0 30 30 28 29 +28.0 7.0 +13.6 6.7 + 1 6 . 2 6.1 + 4 7 . 6 10.2 +38.1 6.7 [ 26] a + 1 4 3 . 6 1 7 . 9 t 26] a +26.8 6.4 +13.9 4.4 +17.0 5.6 +51.7 10.3 + 3 2 . 5 6.2 [ 20] a + 1 4 1 . 5 1 8 . 2 t 20] a +28.4 7.2 +10.6 + 3.8 +17.5 5.2 + 4 9 . 2 11.6 +35.9 9.2 ( 25] a + 1 4 1 . 2 1 6 .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 + 1 3 8 .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) T A B L E E6 (P A G E 1 ) : M A T ER N A L B O D Y W EIG H T S - L A C T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A L E R A T S DOSAGE GROUP D O S AG E (M G /K G /D AY) I II 01 RATS TESTED N 30 29 P R EG N A N T N 28 28 D E LIV E R E D i A L IT T E R N 28 28 M A T ER N A L B O D Y W EIG H T (G) 1D A Y M EANS. D . DAY 5 8D A Y D A Y 11 M EANS. D . M EANS. D . M E A N S .D . 313.6 24.6 320.2 25.2 328.8 26.7 335.5 25.8 314.8 25.8 3 2 1 . 7 21.1 3 3 3 . 3 21.6 340.9 22.7 DAY 15 D A Y 22 M EANS. D . M E A N S .D . 336.9 23.4 322.9 23.4 338.1 21.9 321.7 24.2 D A Y = D AY O F LA C T A T IO N * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e * * S ig n ific a n t ly d iffe r e n t fro m th e G ro u p I v a lu e (p<0.05). (p < 0 .0 1). III 3 30 28 28 325.5 23.1 3 2 8 . 7 + 20.8 3 3 8 . 8 22.0 346.4 18 .1 3 4 3 . 3 + 20.1 329.2 21.5 IV V 10 3 0 30 30 28 29 28 29 313.2 23.4 3 1 7 . 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 2 3 .5 ** 321.8 2 4 .7* 323.6 26.6* 203 1 5 . 7 .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) T A B L E E 7 (P A G E 1) : M A T ER N A L B O D Y W EIG H T C H A N G ES - L A C T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D A Y) RATS TES TED N P R EG N A N T N D E LIV E R E D ' A L IT T E R N M ATERNAL BODY W E IG H T C H A N G E (G) 1D A Y S -5 8D A Y S 5 - D A Y S 8 - 11 11D A Y S - 15 1D A Y S - 15 22D A Y S 1 5 - D A Y S 1 - 22 M EANS. D . M EANS. D . M EANS.D . M EANS.D . M EANS.D . M EAN+S.D . M EANS.D . D AYS = D AYS O F LA C T A T IO N I 0 30 28 28 + 6 .6 9 .8 +8.5 9.2 + 6 .8 1 6 . 4 +1.4 + 19.0 +23.2 14.2 -14.0 15.3 +9.2 18.9 II III 13 29 30 28 28 28 28 IV V 10 3 0 30 30 28 29 28 29 +7.0 10.7 +11.6 +7.6 7.1 8.8 -2.8 13.4 +23.3 14.5 -16.4 13.1 +6.9 14.8 + 3 . 1 + 10.0 + 1 0 . 2 8.1 +7.5 13.9 -3.0 13.3 +17.8 16.5 -1 4 .1 16.0 +3.6 23.2 +4.7 8.9 +7.4 9.9 + 1 0 . 7 + 10.1 -1.6 + 14.6 +21.2 17.8 -9.3 15.4 +11.9 22.4 11+ 3 . 1 + , 10+ 4 . 7 , 11+ 1 1 . 9 , + 1 .9 + 16, +21.6 14, -8.0 17, + 13.6 19, 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) T A B L E E8 (P A G E 1 ) : A B S O LU T E F E E D C O N S U M PTIO N V A LU E S (G /D A Y ) - P R E C O H A B IT A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 487 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 RATS TES TED N 60 60 60 60 IN C LU D ED IN A N A LYS ES N 60 59a 59a 59a F E E D C O N S U M P TIO N (G /D A Y ) 1D A Y S -8 M EANS. D . 8D A Y S - 15 M EANS.D . 10.1 16.4 1 .5 2.0 9 .4 15.0 1 .2 ** 1 .5 ** 10.0 16.2 1.6 1.9 10.0 15.8 1.7 1.8 DAYS 15 - 22 22D A Y S - 29 D AYS 29 - 36 D A Y S 36 - 43 D A Y S 43 - 50 D A YS 50 - 57 D A YS 5 7 - 64 D AYS 64 - 70C 1D A Y S - 70c M EANS.D . M EANS.D . M E A N + S .D . M EANS. D . M EANS.D . M EANS.D . M EANS.D . M EAN+S.D . M EANS.D . 19.0 1.9 [ 58]a,b 19.4 2.4 [ 47] a 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 [ 30] a 18.8 2.0 19.6 2.5 [ 46]a,b 19.2 1.7 [ 29] a , b 20.2 2.4 [ 30] a 22.8 5.2 [ 26]a,b 20. 9 2.7 ( 27]a,b 20.6 2 . 8 [ 26]a,b 19.6 2.3 ( 29] a, b 18.4 1.6 [ 29] a , b D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n o r fo u n d d e a d . b . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d , as w e ll as th o s e a s s o c ia te d w ith s p illa g e , s o ile d o r w et fe e d . c . L a s t w e e k ly v a lu e re c o rd e d b e fo re c o h a b ita tio n . * * S ig n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . V 30 60 55a 9.0 1 .4 ** 14.7 1 .5 ** [ 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 [ 27] a ,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) T A B L E E9 (P A G E 1 ) : R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - P R E C O H A B IT A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 488 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 01 3 IV 10 RATS TES TED N 60 60 60 60 IN C LU D ED IN A N A LY S ES N 60 59a 59a 59a F E E D C O N S U M P TIO N (G /K G /D A Y ) 1D A Y S -8 M EANS.D . 8D A Y S - 15 M EANS.D . 180.7 22.3 180.6 16 .1 177.5 19.4 176.3 16.5 173 .7 18.8 174.6 15.6 174.2 17.6 176.9 17.3 D AYS 15 - 22 22D A Y S - 29 D A YS 29 - 36 D A YS 36 - 43 D A Y S 43 - 50 D A Y S 50 - 5 7 D A YS 5 7 - 64 D A Y S 64 - 70 C 1D A Y S - 70C M EANS.D . M EAN+S. D . M EANS.D . M EANS.D . M EANS.D . M EANS. D . M EANS.D . M EAN+S.D . M EANS.D . 146.5 13 .1 [ 58]a,b 119.5 11.6 [ 47] a 106.8 9.1 [ 30] a 96.0 8.4 [ 29] a , b 94.5 1 2 .1 [ 28]a,b 86.9 8.9 [ 28]a,b 81.4 8.8 [ 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 1 3 . 8 t 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 t 30] a 99.6 23.5 [ 26] a , b 86.6 1 4 . 3 [ 27] a ,b 80.6 11.6 t 26]a,b 74.5 7.4 [ 29] a , b 103.0 7.3 [ 29] a , b D A Y S = D A Y S P O S TW EA N IN G [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s fo r r a ts th a t w ere s a c r ific e d fo llo w in g s e x u a l m a tu ra tio n o r fo u n d d e a d . b . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d , as w e ll as th o s e a s s o c ia te d w ith s p illa g e , s o ile d o r w e t fe e d . c . L a s t w e e k ly v a lu e re c o rd e d b e fo re c o h a b ita tio n . V 30 60 55a 172.2 16.7 174.2 14.1 [ 54] a 149.3 16.4 [ 52]a,b 121.9 12.6 [ 44]a,b 106.0 12.2 [ 29]a,b 96.7 10.2 [ 29] a , b 103.4 + 31.6 [ 26]a,b 86.2 1 0 . 6 [ 27]a,b 79.2 13.2 [ 28]a,b 76.2 11.5 t 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) T A B L E E 1 0 (P A G E 1 ) : M A T ER N A L A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - G E S T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A T S DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 RATS TES TED N 29 29 30 30 P R EG N A N T N 28 28 28 28 M ATERNAL FEED C O N S U M P TIO N (G /D A Y ) DAYS 0 - 7 DAYS 7 - 1 0 DAYS 1 0 - 1 4 DAYS 14 - 18 DAYS 1 8 - 2 1 DAYS 0 - 2 1 M EAN+S.D . M EANS.D . M EAN+S.D . M EANS.D . M EANS.D . M EANS.D . 22.8 [ 27] a 24.2 [ 27] a 24.4 2 .5 3.8 3.0 24.1 23.0 3.0 2.8 23.7 2.7 22.7 [ 25] a 24.1 3.0 3.6 23.7 3.3 24.0 2 .7 23.1 [ 27] a 23.2 [ 27] a 2.8 2.5 22.2 [ 25] a 24.1 [ 27] a 24.2 2 .7 2.9 2.9 2 5 . 1 2.6 23.7 [ 25] a 23.7 [ 25] a 2 .7 2.4 22.3 ( 27] a 22.8 [ 27] a 23.4 2.3 2.5 2.1 23.9 2.4 22.5 [ 27] a 23.0 [ 27] a 2.6 1.9 D AYS = D AYS O F G ES T A T IO N [ ] = NUM BER O F V A LU ES A V ER A G ED a . E x c lu d e s v a lu e s th a t w ere n o t re c o rd e d * S ig n ific a n t ly d iff e r e n t fro m th e G ro u p as w e ll I v a lu e as th o s e a s s o c ia te d w ith (p<0.05). s p illa g e or wet fe e d . V 30 30 29 21.0 2.6 [ 27] a 22.0 2 . 7 * [ 28] a 22.8 2.6 2 4 . 2 2.6 23.2 [ 26] a 22.4 [ 26] a 2.3 2.2 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) T A B L E E l l (P A G E 1 ) : M A T ER N A L R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - G E S T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A T S DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV 10 RATS TES TED N 29 29 30 30 P R EG N A N T N 28 28 28 28 M ATERNAL FEED C O N S U M P TIO N (G /K G /D A Y) DAYS 0 - 7 DAYS 7 - 1 0 D AYS 10 - 14 DAYS 1 4 - 1 8 M EANS.D . M EAN+S. D . M EAN+S.D . M EANS.D . 79.3 7.3 [ 27] a 78.3 10.8 [ 27] a 74.8 6.9 67.4 6.3 78.3 [ 25] a 77.6 8.1 7.6 72.7 6.5 67.2 5.3 74.3 [ 25] a 75.4 [ 27] a 72.3 7.9 6.9 6.6 68. 2 5.4 76.9 [ 27] a 74.0 [ 27] a 72.7 7.9 7.8 6 .1 67.2 6.3 DAYS 1 8 - 2 1 DAYS 0 - 2 1 M EANS. D . M EANS.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 D AYS = D AYS O F G ES T A T IO N [ ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s th a t w ere n o t b . E x c lu d e s v a lu e s fo r dams th a t re c o rd e d as d e liv e re d . w e ll as th o se a s s o c ia te d w ith s p illa g e or wet fe e d . V 30 30 29 76.6 [ 27] a 74.4 [ 28] a 74.2 9.8 6.8 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) T A B L E E 1 2 (P A G E 1 ) : M A T ER N A L A B S O LU T E F E E D C O N S U M P TIO N V A LU E S (G /D A Y ) - L A C T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A T S DOSAGE GROUP D O S AG E (M G /K G /D AY) I II III 013 IV V 10 3 0 RATS TES TED N 28 28 28 28 29 P R EG N A N T N 28 28 28 28 29 D E LIV E R E D A L IT T E R N 28 28 28 28 29 M ATERNAL FEED C O N S U M P TIO N (G /D A Y ) DAYS 1 - 5 DAYS DAYS 5 -8 8-11 DAYS 1 1 - 15b DAYS 1 - 15b M EANS.D . M EANS.D . M EAN+S.D . M EANS.D . M EANS. D . 3 0 . 3 6.8 [ 27] a 48.1 8.3 54.0 8.5 59.0 t 27]a 48.0 + [ 27] a 8.5 6.1 30.6 48.5 55.4 57.5 47.4 + 5.9 7.0 7.2 9.5 5.3 28.6 [ 27] a 46.2 4.2 5.8 5 5 . 2 6.2 [ 27] a 57.3 7.2 46.5 4.4 28.9 [ 26] a 46.7 + 5.3 8.7 5 2 . 3 8.1 56.3 12.4 46.0 + 6.7 29.2 44.6 50.4 52.2 43.6 4.9 6.7 7.7 9.5 5.5** DAYS = DAYS O F LA C T A T IO N [ ] = NUM BER O F V A LU ES AV ER A G ED a . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e . b . B e cau se i t is pre su m e d th a t th e p u p s b e g in to consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w ere n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . 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) T A B L E E 1 3 (P A G E 1) : M A TER N A L R E L A T IV E F E E D C O N S U M P TIO N V A LU E S (G /K G /D A Y ) - LA C T A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 013 IV V 10 3 0 RATS TESTED N 28 28 28 28 29 P R EG N A N T N 28 28 28 28 29 D E LIV E R E D A L IT T E R N 28 28 28 28 29 M ATERNAL FEED C O N S U M P TIO N (G /K G /D A Y ) DAYS 1 - 5 DAYS 5 - 8 DAYS 8 - 1 1 DAYS 11 - 15b DAYS 1 - 15b M EANS.D . M EANS.D . M EANS. D . M EAN+S. D . M EANS.D . 95.7 18.4 [ 27] a 14 7 .7 18.5 16 2.7 23.8 17 4 .7 22.6 [ 27] a 146.1 15.4 [ 27] a 9 6 . 9 21.0 148.4 21.3 1 6 4 . 6 21.0 16 9 .1 25.3 14 4 .1 16.5 87.8 15.3 [ 27] a 138.5 15.9 161.5 21.1 [ 27] a 166.2 19.3 138.5 15.0 92.6 18 .7 [ 26] a 145.3 26.9 158.7 26.1 168.2 3 7 .1 1 4 1 . 9 21.8 96.5 16 .9 144.8 159.5 18.2 21.8 16 1.7 25.9 139.7 15.6 D AYS = DAYS O F LA C T A T IO N ( ] = NUM BER O F V A LU ES AV ER AG ED a . E x c lu d e s v a lu e s th a t w ere a s s o c ia te d w ith s p illa g e . b . B e cau se i t is presu m ed th a t th e p u p s b e g in to consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w ere n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . 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) T A B LE E 1 4 (P A G E 1 ) : S E X U A L M A T U R A T IO N - SUM M ARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) FEM ALE RATS N I 0 60 II III 13 60 60 IV 10 60 IN C LU D ED IN A N A LY S ES N 60 5 8 a ,b 5 8 a ,b 58a, b V A G IN A L P A TEN C Y c M E A N + S .D . 34.9 2 .1 35.5 2.3 34.1 2.6 34.8 2 .1 a . E x c lu d e s v a lu e s fo r r a ts th a t w ere fo u n d d e a d . b . E x c lu d e s v a lu e s f o r r a t s in w h ic h t e s t in g w as d is c o n tin u e d b e fo r e th e r a t becam e s e x u a lly m a tu re . c . A ve ra g e d a y p o s tp a rtu m th a t th e v a g in a was o b s e rv e d to be p a te n t. * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . V 30 60 54a 36.6 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) T A B L E E 1 5 (P A G E 1) : M A TIN G A N D F E R T IL IT Y , ES TR O U S C Y C LIN G A N D D A YS IN C O H A B IT A T IO N - SUMMARY - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 494 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 ES TR O U S C Y C LIN G O B S ER V A TIO N S P R EC O H A B IT A T IO N ES TR O U S C Y C LIN G RATS EVALU ATED N 30 2 9a ESTROUS STAGES/ 21 DAYS M EAN+S. D . 4 .7 + 0 . 9 5 .0 + 0 .9 R A T S W IT H 6 O R M O RE C O N S EC U TIV E D AYS O F D IES T R U S N 1 0 R A T S W IT H 6 O R M O RE C O N S EC U TIV E DAYS O F ESTRUS N 0 0 ESTROUS STAG E A T S A C R IFIC E RATS EVALU ATED N 30 29 D IES T R U S P R O ES TR U S ES TR U S M ETESTRUS N 18 N2 N6 N4 15 1 10 3 a . E x c lu d e s r a t 1 3 7 3 , w h ic h . w as fo u n d d e a d p r io r t o c o h a b it a t io n . * * S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e (p < 0 . 0 1 ) . Ill 3 IV 10 30 5 .0 + 0 .8 0 0 30 20 3 5 2 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) T A B L E E 1 5 (P A G E 2) : M A TIN G AN D F E R T I L I T Y , ES TR O U S C Y C LIN G A N D D A YS IN C O H A B IT A T IO N - SUMMARY - F I G E N E R A T IO N F E M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D A Y) R A TS IN C O H A B IT A T IO N D AYS IN C O H A B IT A T IO N b N M EAN+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 TH A T M ATED N (%) 29 ( 9 6 .7 ) 29(100.0) 30 (10 0 .0 ) F E R T IL IT Y IN D EX c N /N (% ) 2 8 / 29 ( 96.6) 2 8 / 29 ( 96.6) 2 8 / 30 ( 93.3) R A T S W IT H C O N FIR M ED M A TIN G D A T ES N 29 29 30 R A TS M A TIN G d DAYS 1 -7 N(%) 29(100.0) 29(100.0) 30(100.0) RATS PREGNANT/RATS IN C O H A B IT A T IO N N /N (% ) 2 8 / 30 ( 93.3) 2 8 / 29 ( 96.6) 2 8 / 30 ( 93.3) a . E x c lu d e s r a t 1 3 7 3 , w h ic h was fo u n d d e a d p r i o r t o c o h a b ita tio n . b . R e s t r ic t e d t o r a ts w ith a c o n firm e d m a tin g d a te an d r a ts th a t d id n o t m a te . c . Num ber o f p re g n a n c ie s /n u m b e r o f r a t s th a t m a te d . d . R e s t r ic t e d t o r a ts w ith a c o n firm e d m a tin g d a te . 30 ( 1 0 0 . 0 ) 2 8 / 30 ( 93.3) 30 30 ( 1 0 0 .0 ) 2 8 / 30 ( 93.3) 30(100.0) 2 9 / 30 ( 96.7) 30 30 ( 1 0 0 .0 ) 2 9 / 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) T A B LE E 16 (P A G E 1 ) : N EC R O P S Y O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N FEM A LE R ATS (S e e fo o tn o te s o n th e la s t pa ge o f t h is t a b le .) ARGUS 418-020 Page 496 DOSAGE GROUP D O S AG E (M G /K G /D AY) R A TS EX A M IN ED a FOUND DEAD IN C LU D ED IN A N A LY S ES APPEARED NORMAL L IV E R : L E F T L A T E R A L L O B E , FIR M M ASS CUT SU RFAC E R EV EA LED YELLO W AND DARK R ED AREAS CAUDATE LO B E ADHERED TO LE FT LA TER A L LOB E K ID N EY S : B ILA T ER A L, D ILA T IO N P E LV IS , S LIG H T R IG H T , P E L V IS , M ODERATE D ILA T IO N U R IN A R Y B LA D D ER : W ALLS T H IC K EN ED U RETER: B ILA T E R A L, M ODERATE D ILA T IO N ONE C A LC U LI LOC ATED A T TH E CAUDAL END N N N N N N N N N N N I 0 60 0 60 59 0 0 0 0 0 0 0 II 1 60 2b , c 59 1 5 7b 1 1 0 0 0 0 0 III 3 60 Id 60 59d 0 0 1 0 0 0 0 IV 10 60 le 60 60e 0 0 0 0 0 0 0 V 30 60 6f-k 60 59f-k 0 0 0 1 1 1 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) T A B LE E 16 (P A G E 2 ) : N EC R O P S Y O B S ER V A TIO N S - SUMMARY - F I G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page 497 DOSAGE GROUP D O S A G E (M G /K G /D AY) I I I I I I IV V 0 1 3 10 30 R A TS EX A M IN ED a N 60 60 60 60 60 FOUND DEAD N0 2b , c Id le 6 f - k IN C LU D ED IN A N A LYS ES N 60 59 1 60 60 60 STOM ACH: D IS T EN D ED N0 lc 0 00 IN T E S T IN E S : D IS T EN D ED N0 lc 0 00 LUN G S: DORSAL SU RFACE, LO B E, DEPRESSED R IG H T W H ITE A P IC A L A R EA N 0 lc 0 00 S PLEEN : SM ALL N1 0 0 0 0 a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le E26 ) f o r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . b . R a t 13 6 5 w as fo u n d d e a d on d a y 4 p o s tw e a n in g . c . R a t 1 3 7 3 w as fo u n d d e a d on d a y 51 p o s tw e a n in g . d . R a t 14 3 2 w as fo u n d d e a d on d a y 7 p o s tw e a n in g . e . R a t 14 8 4 w as fo u n d d e a d on d a y 3 p o s tw e a n in g . f . R a t 15 4 9 w as fo u n d d e a d on d a y 8 p o s tw e a n in g . g . R a t 15 5 9 w as fo u n d d e a d on d a y 6 p o s tw e a n in g . h . R a t 15 6 2 w as fo u n d d e a d on d a y 2 p o s tw e a n in g . i . R a t 156 3 w as fo u n d d e a d on d a y 2 p o s tw e a n in g . j . R a t 15 74 w as fo u n d d e a d on d a y 3 p o s tw e a n in g . k . R a t 1 5 7 5 w as fo u n d d e a d on d a y 3 p o s tw e a n in g . l . E x c lu d e s r a t 1 3 6 2 , w h ic h d id n o t h a ve n e c ro p s y o b s e rv a tio n s re c o rd e 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) T A B L E E 1 7 (P A G E 1 ) : T E R M IN A L B O D Y W EIG H TS A N D O R G A N W EIG H T S - SUM M ARY - F I G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 498 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 28 28 T E R M IN A L B O D Y W EIG H T M EAN+S.D . 322.9 23.4 3 21.7 + 24.2 P IT U IT A R Y M E A N + S .D . 0.017 0.004 0.016 0.003 B R A IN M EANS.D . 2.0 7 + 0.09 2.09 + 0.12 LIV E R M EANS.D . 16.57 + 1.58 15.96 + 1.76 K ID N EY L E F T M EANS.D . 1.36 + 0.13 1.39 + 0.14 K ID N E Y R IG H T M EAN+S.D . 1.38 + 0.12 1.4 1 + 0.14 ADRENAL LEFT M EANS.D . 0.043 + 0.008 0.044 + 0.007 A D R EN A L R IG H T M EANS.D . 0.040 + 0.007 0.041 + 0.007 S P LEEN M EAN+S.D . 0.60 + 0.07 0.61 + 0.12 THYM US M EAN+S.D . 0.20 + 0.06 0 .19 0.05 OVARY LEFT M EANS.D . 0.050 + 0.012 0.054 + 0.012 O V A R Y R IG H T M EAN+S.D . 0.054 + 0.012 0.053 0.012 U TER U S N O N -G R A V ID M EANS.D . 0.54 0.16 0.56 + 0.16 A LL a. * * W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . E x c lu d e s a v a lu e th a t a p p e a re d in c o r r e c tly re c o rd e d . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . III 3 28 329.2 + 21.5 0.015 0.003* 2.08 + 0.10 16.41 + 1.40 1 .4 1 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 3 15.7 + 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) T A B L E E 1 8 (P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T - SU M M ARY - F I G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 499 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 28 28 T E R M IN A L B O D Y W EIG H T M EANS. D . 322.9 23.4 321.7 24.2 P IT U IT A R Y a M EANS.D . 5.462 + 1.605 4.976 0.861 B R A IN M EAN+S.D . 0.644 + 0.058 0.653 + 0.054 LIV E R M EAN+S.D . 5.130 + 0.305 4.958 0.340 K ID N EY L E F T M EAN+S.D . 0 .4 2 1 0.038 0.432 + 0.040 K ID N E Y R IG H T M EAN+S.D . 0.427 0.030 0.438 + 0.037 ADRENAL LE FT a M EANS.D . 13.285 + 2 .1 4 7 13.551 + 1.994 A D R EN A L R IG H T a M E A N S .D . 1 2 . 3 0 1 + 1 . 9 7 9 12.743 + 2.192 S P LEEN M EANS.D . 0.184 0.021 0.189 + 0.041 THYM US M EANS.D . 0.062 0.020 0.058 + 0 .0 17 OVARY LE FT a M EANS.D . 15.652 + 3.706 16.844 3.672 O VAR Y R IG H T a M EANS.D . 16 .754 + 4.015 16.742 4.266 U TER U S N O N -G R A V ID M EANS.D . 0 .1 6 7 + 0.050 0 .176 0.058 A LL a. b. * W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . V a lu e was m u ltip lie d b y 1000. E x c lu d e s a v a lu e th a t ap p e a re d in c o r r e c tly re c o rd e d . S i g n ific a n t ly d i f f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . III 3 IV 10 V 30 28 28 29 329.2 21.5 325.1 23.5 315.7 20.9 4.648 + 0.860* 4.715 + 0.898* 4.749 + 1.028* 0.632 0.045 0.648 0.063 0.659 + 0.044 4.991 0.377 5.136 0.409 5.326 0.455 0.426 0.036 [ 27] b 0.432 0.034 0.426 0.038 0.435 + 0.046 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 .19 1 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 .1 7 1 + 0.058 R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 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) T A B L E E l 9 (P A G E 1 ) : R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - S U M M A R Y - F I G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 500 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II 01 RATS TES TED N 28 28 B R A IN W EIG H T P IT U IT A R Y M EAN+S.D . M EAN+S.D . 2.07 0.09 0.84 0.21 2.09 + 0.12 0.76 + 0.14 LIV E R M E A N S .D . 8 0 2 . 6 0 8 5 . 5 9 764.62 + 81.65 K ID N EY L E F T M E A N S .D . 65.77 6.04 66.51 6.49 K ID N E Y R IG H T M E A N S .D . 66.76 + 6.09 67.36 5.83 ADRENAL LEFT M EANS.D . 2.08 0.38 2.08 0.32 A D R EN A L R IG H T M EANS.D . 1.93 0.37 1.96 + 0.34 S P LEEN M E A N S .D . 28.89 3.82 29.10 5.58 THYM US M EANS.D . 9.65 2 .7 4 9.10 2.84 OVARY LEFT M EANS.D . 2.43 0.56 2.58 0.52 O VAR Y R IG H T M EANS.D . 2.60 0.59 2.56 0.58 U TER U S N O N -G R A V ID M EAN+S.D . 25.95 7.78 27.06 7.66 A LL a. * ** W E IG H T S W ER E R EC O R D E D I N GRAM S (G) . E x c lu d e s a v a lu e th a t ap p e a re d in c o r r e c tly re c o rd e d . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 5 ) . S ig n ific a n t ly d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . III 3 IV 10 V 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 .1 6 ** 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 6 7.5 7 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 4.3 1 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 R A T IO S (%) = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 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) T A B LE E2 0 (PA G E 1 ) : N A T U R A L D E L IV E R Y O B S ER V A TIO N S - SUMMARY - F I G EN E R A T IO N FEM A LE R ATS ARGUS 418-020 Page 501 DOSAGE GROUP D O S A G E (M G /K G /D AY) R ATS A S S IG N ED TO N A TU R A L D E LIV E R Y N I 0 28 II III 13 28 28 IV V 10 30 28 29 P R EG N A N T N 28 28 28 28 29 D E LIV E R E D A L IT T E R N (%) 28(100.0) 28(100.0) 28(100.0) 28(100.0) 29 (10 0.0) D U R A T IO N O F G E S T A T IO N a M EA N S . D . 22.8 0.4 22.6 0.6 22.7 + 0.5 22.8 0.6 22.7 0.5 IM P LA N T A T IO N S IT E S P ER D E LIV E R E D L IT T E R N M EANS.D . 414 14.8 3.0 443 15.8 2 .1 412 14.7 2.8 419 15.0 2.9 420 14.5 2.9 DAM S W IT H S T IL L B O R N PU PS N(%) 3 ( 10.7) 4 ( 14.3) 3 ( 10.7) 5 ( 18.5) 2( 7 .1 ) DAM S W IT H N O L IV E B O R N PU P S N ( % ) G ES T A T IO N IN D EX b % N /N 0 ( 0 .0) 100.0 2 8 / 28 0 ( 0 .0) 100.0 2 8 / 28 0 ( 0 .0) 100.0 2 8 / 28 0 ( 0 .0) 100.0 27/ 27 0 ( 0 .0) 100.0 2 8 / 28 DAM S W IT H A L L P U P S D Y IN G DAYS 1 -4 POSTPARTUM N (%) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) DAM S W IT H A L L P U P S D Y IN G DAYS 5 - 2 1 POSTPARTUM N (%) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) 0 ( 0 .0) a . C a lc u la te d a s th e tim e ( in d a y s ) e la p s e d b e tw e e n c o n firm e d m a tin g ( a r b i t r a r i l y d e fin e d as d a y 0) a n d th e tim e ( in d a y s ) th e f i r s t pup was d e liv e r e d . b . Num ber o f r a ts w ith liv e o ffs p rin g /n u m b e r o f p re g n a n t r a t s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E 2 1 (P A G E 1 ) : L IT T E R O B S ER V A TIO N S (N A T U R A LLY D E L IV E R E D PUPS) - SUMMARY - F2 G EN ER A T IO N PUPS ARGUS 418-020 Page 502 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 0 13 D E L IV E R E D L IT T E R S W IT H O N E O R M ORE LIV EB O R N PUPS N 28 28 28 PUPS D E LIV E R E D (TO T A L) N M EANS.D . 386 13.8 2.9 388 13.8 2.5 3 94 14.1 3.0 LIV EB O R N M EANS.D . N(%) 13.6 2.9 380 ( 98.4) 13.7 2.4 383( 98.7) 13.8 3.0 388 ( 98.5 ) S T ILLB O R N M EANS.D . N (%) UNKNOW N V IT A L STATUS N 0 .2 0 .5 5( 1.3) 1 0 .2 0 .5 5( 1.3) 0 0.2 0.6 6 ( 1.5) 0 PUPS FOU ND D EA D OR PRESUM ED C A N N IB A LIZE D DAY DAYS DAYS DAYS DAYS 1 2 -5 6- 8 9-15 16-22 V IA B IL IT Y IN D EX a n / n (%) N / N (%) n / n (%) N / N (%) n / n (%) % N/N 0/380 ( 2/380 ( 0/378 ( 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 LA C T A T IO N IN D E X b % N/N 98.7 373/378 98.9 374/378 98.7 373/378 D A Y (S ) = D A Y (S ) POSTPARTUM a . Num ber o f l i v e pups on d a y 5 p o stp a rtu m /n u m b e r o f liv e b o r n pups b . Num ber o f l i v e pups on d a y 22 p o stp a rtu m /n u m b e r o f liv e pups on * * S i g n i f i c a n t l y d if f e r e n t fro m th e G ro u p I v a lu e ( p < 0 . 0 1 ) . on day 1 p o s tp a rtu m . d a y 5 p o s tp a rtu m . 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 4/378 ( 3/374 ( 1/3 71 ( 1/370 ( 1/369 ( 1.0 )** 0.8) 0.3) 0.3) 0.3) 98.1 371/378 99.2 368/371 1/387 ( 3/386( 4/383( 0/379( 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) T A B LE E 2 1 (P A G E 2 ) : L IT T E R O B S ER V A TIO N S (N A T U R A LLY D E L IV E R E D PUPS) - SUMMARY - F2 G EN ER A T IO N PU PS ARGUS 418-020 Page 503 DOSAGE GROUP D O S AG E (M G /K G /D AY) I II III 013 D E L IV E R E D L IT T E R S W IT H O N E OR M ORE LIV EB O R N PUPS N 28 28 28 S U R V IV IN G P U P S / LIT T E R a DAY lb M EAN+S. D . 13.6 + 2.9 13.7 2.4 13.8 + 3.0 DAY 5 M EAN+S.D . 13.5 2.8 13.5 2.3 13.5 2.9 DAY 8 M EAN+S.D . 13.5 + 2.8 13.5 2.3 13.3 2.9 DAY 15 M EANS.D . 13.4 + 2.8 13.4 2.2 13.3 2.9 DAY 22 M EANS.D . 13.3 + 2 .7 13.4 2.2 13.3 + 2.9 PER C EN T M ALE PUPS PER NUM BER O F PUPS S EX ED DAY lb M EANS. D . 50.2 11.8 51.9 + 11.2 51.5 + 13 .1 DAY 5 M EANS.D . 49.9 12.0 52.2 + 11.5 51.7 13.7 DAY 8 M EANS.D . 49.9 12.0 52.1 11.5 52.1 + 13.7 DAY 15 M EANS.D . 49.8 + 11.8 52.4 11.6 52.1 13.7 DAY 22 M EANS.D . 50.0 + 1 1 . 7 52.5 + 11.8 52.1 + 13.7 DAY a. b. = DAY POSTPARTUM A ve rag e num ber o f liv e pups p e r In c lu d e s pups b o rn a liv e , fo u n d l i t t e r , in c lu d in g lit t e r s dead day 1 p o s tp a rtu m . w ith no s u rv iv in g pups. IV V 10 30 28 29 13.5 3 .1 13.2 + 3.0 13.2 2.9 13.2 2.9 1 3 . 1 2 .9 13.3 + 2.8 13.2 + 2.8 1 3 .1 + 2.8 1 3 .1 2.8 13.0 + 2 .7 55.6 15 .7 5 5 .6 1 5 . 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 4 7 .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) T A B L E E 2 1 (P A G E 3 ) : L IT T E R O B S ER V A TIO N S (N A T U R A LLY D E L IV E R E D PU PS) - SUM M ARY - F2 G EN ER A T IO N PU PS ARGUS 418-020 Page 504 DOSAGE GROUP D O S A G E (M G /K G /D AY) D E L IV E R E D L IT T E R S W IT H O N E OR M ORE LIV EB O R N PUPS N L I V E L IT T E R S I Z E A T W EIG H IN G DAY 1 M EANS. D . DAY 5 M EANS.D . DAY 8 M EANS.D . DAY 15 M EANS.D . DAY 22 M EANS.D . P U P W E IG H T / L IT T E R (GRAM S) DAY 1 M EANS.D . DAY 5 M EANS. D . DAY 8 M EANS.D . DAY 15 M EAN+S.D . DAY 22 M EANS. D . DAY = DAY POSTPARTUM 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 2.9 13.3 2.9 6 .4 0 .7 10.1 1.6 14.3 2.3 25.8 4.4 39.6 + 7 .1 IV V 10 3 0 28 29 13.4 3.0 13.2 3.0 13 .2 + 2 .9 13 .2 + 2 .9 1 3 .1 + 2 .9 13.3 2.8 13.2 + 2.8 1 3 .1 2.8 1 3 .1 + 2.8 13.0 2 .7 6 .4 0 .7 1 0 . 2 1 .5 14.3 2.3 24.8 3 .7 3 9 .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) T A B LE E2 2 (P A G E 1 ) : C L IN IC A L O B S ER V A TIO N S FROM B IR T H TO D A Y 22 POSTPARTUM - SUMMARY - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 505 M ATERNAL DOSAGE GROUP M A TER N A L D O S AG E (M G /K G /D AY) L IT T E R S E X A M IN E D (N) I I I I I I IV V 0 1 3 10 3 0 28 28 28 28 29 T R A N S IE N T C L IN IC A L O B S ER V A T IO N S : a COLD TO TOUCH T A I L : A B R A S IO N NO T A IL PRESENT T IP O F T A I L M IS S IN G T A IL : SCAB M OUTH : MASS B A C K : A B R A S IO N BACK: SCAB P A LE IN APPEARANCE B A S E O F T A I L : A B R A S IO N T IP O F T A IL BLACK EM A C IA T IO N DOM ED H EA D D EH Y D R A T IO N T A IL BENT 2/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 34/ 3 0/ 0 T O T A L FR E Q U E N C Y (D A YS X P U P S ) / L IT T E R S W IT H O B S E R V A T IO N S 5/ 1 1/ 1 1/ 1 3/ 0/ 0 0/ 0 0/ 0 10/ 0/ 0 0/ 0 0/ 0 22/ 0/ 0 0/ 0 0/ 0 12/ 0/ 0 0/ 0 0/ 0 9/ 0/ 0 0/ 0 0/ 0 8/ 0/ 0 0/ 0 0/ 0 7/ 0/ 0 0/ 0 0/ 0 4/ 0/ 0 0/ 0 0/ 0 3/ 0/ 0 0/ 0 0/ 0 3/ 0/ 0 0/ 0 0/ 0 2/ 0/ 0 0/ 0 1/ 1 1/ 0/ 0 0/ 0 0/ 0 1/ 1/ 1 0/ 0 2/ 2 0/ 0/ 0 0/ 0 22/ 1 0/ 3 2 1 1 1 1 1 1 1 1 1 1 1 0 0 N / N = T O T A L F R E Q U E N C Y (D A Y S x P U P S ) / L IT T E R S W IT H O B S E R V A T IO N S . a . T a b u la tio n r e s tr ic te d to a d ve rs e o b s e rv a tio n s ; a l l o th e r p u p s a p p e a re d n o rm a l. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E2 2 (P A G E 2) : C L IN IC A L O B S ER V A T IO N S FROM B IR T H TO D A Y 22 PO STPAR TU M - SUM M ARY - F2 G EN ER A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O S AG E (M G /K G /D AY) L IT T E R S E X A M IN E D (N) I I I I I I IV V 0 1 3 10 3 0 28 28 28 28 29 T R A N S IE N T C L IN IC A L O B S ER V A T IO N S : a R IG H T E Y E : N O T P R ES EN T T H R EA D -LIK E T A IL NO A N A L O P EN IN G P R ES EN T UNGROOM ED C O AT NO M ILK P R ES EN T IN STOM ACH 0/ 0 0/ 0 0/ 0 11 6 / 1/ 1 T O T A L FR E Q U E N C Y (D A Y S X P U P S )/ L IT T E R S W IT H O B S E R V A T IO N S 0/ 0 0 /0 3 /1 0/ 0 22/ 1 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 N / N = T O T A L F R E Q U E N C Y (D A Y S x P U P S ) / L IT T E R S W IT H O B S E R V A T IO N S . a . T a b u la tio n r e s tr ic te d to a d ve rs e o b s e rv a tio n s ; a l l o th e r pu ps a p p e a re d n o rm a l. 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) T A B LE E23 (P A G E 1) : N EC R O P S Y O B S ER V A TIO N S - SUMMARY - F2 G EN ER A T IO N PUPS ARGUS 418-020 Page 507 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) I I I I I I IV V 0 1 3 10 3 0 L IT T E R S EX A M IN ED N T O T A L P U P S S T I L L B O R N O R F O U N D :D E A D a S T ILLB O R N N FOUND DEAD N 28 3 1 2 28 28 28 29 6 10 10 6 3 4 62 63 4 4 NO M ILK IN STOM ACH b N(%) 1( 50.0) 3(100.0) 5 ( 83.3) 3 ( 75.0) 3 ( 75.0) PUPS S A C R IF IC E D AN D N EC R O P S IED ON D AY 22 POSTPARTUM L IT T E R S EV A LU A TED PUPS EV A LU A TED N 28 N 168 28 16 8 28 16 7 28 16 4 29 170 APPEARED NORM AL L IT T E R IN C ID EN C E PUP IN C ID EN C E 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 (10 0.0) 170(100.0) K ID N E Y S : P E L V IS S LIG H T M ODERATE D ILA T IO N L IT T E R IN C ID EN C E PUP IN C ID EN C E OR N(%) N(%) 1( 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 ) B R A IN : T H IR D AND LA T E R A L V E N T R IC LE S , M ARKED D IL A T IO N L IT T E R IN C ID EN C E PUP IN C ID EN C E N (%) N (%) 0( 0 .0 ) 0( 0 .0 ) 0( 0 .0 ) 0( 0 .0 ) 0( 0.0 ) 0( 0.0 ) M 3.6) 0M . 6 ) 0( 0 . 0 ) 0( 0 .0 ) a . R e s t r ic t e d t o p u p s in w h ic h c o m p le te n e c ro p s ie s w e re p e rfo rm e d . C o m p le te n e c ro p s ie s w e re n o t p e rfo rm e d o n p u p s i n w h ic h a u to ly s is o r c a n n ib a liz a tio n p re c lu d e d e v a lu a tio n . b . A n a ly s is r e s tr ic te d to pups fo u n d de ad an d n e c ro p s ie 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) T A B L E E2 4 (P A G E 1 ) : P U P O R G A N W EIG H T S - SUM M ARY - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 508 M ATERNAL DOSAGE GROUP M A T ER N A L D O SAG E (M G /K G /D AY) I II III IV 01 3 10 V 30 L IT T E R S EX A M IN ED N 28 28 28 28 29 T E R M IN A L B O D Y W EIG H T W EIG H T /LIT T ER M ALE PUPS FEM A LE PUPS M EAN+S. D . M EAN+S. D . M EAN+S.D . 39.10 + 7.23 40.01 + 7.43 38.38 + 7.3 7 [ 27] a 39.02 + 5.9 1 39.73 + 6.39 38.30 + 5.98 39.70 + 7.5 1 [ 27] a 39.95 + 8.48 [ 27] a 39.46 + 7.19 [ 27] a 40.06 + 6.88 4 1.15 + 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 B R A IN W EIG H T /LIT T ER M EAN+S. D . 1 . 4 9 + 0.10 1 .4 7 + 0.08 1.48 + 0.11 1.48 + 0.07 1.44 + 0.08 M ALE PUPS FEM A LE PUPS M EAN+S. D . M EAN+S. D . 1.50 + 0.15 1 . 4 8 + 0.11 1.50 + 0.09 1.44 + 0.09 1.50 + 0.12 1.45 + 0 .11 1.50 + 0.07 1.46 + 0.10 [ 27] b 1.46 + 0.08 1.42 + 0.10 S P LEEN W EIG H T /LIT T ER M EAN+S. D . 0.15 + 0.04 0.14 + 0.04 0.14 + 0.04 0.15 + 0.04 0.14 + 0.05 M ALE PUPS M EAN+S.D . 0.14 + 0.04 0.14 + 0.04 0 . 1 4 + 0.05 0.15 + 0.04 0.14 + 0.06 FEM A LE PUPS M EAN+S.D . 0.15 + 0.05 0.15 + 0.04 0.14 + 0.04 0.14 + 0.04 [ 27] b 0.13 + 0.05 THYM US W EIG H T /LIT T ER M E A N + S .D . 0.18 + 0.06 0.17 + 0.04 0.16 + 0.05 0 .1 7 + 0.04 0.16 + 0.05 M ALE PUPS M EAN+S.D . 0 .19 + 0.06 0.16 + 0.05 0.16 + 0.06 0 .1 7 + 0.05 0.16 + 0.06 FEM A LE PUPS M E A N + S .D . 0.18 + 0.06 0 .17 + 0.04 0 .1 7 + 0.06 0 .1 7 + 0.04 [ 27] b 0.16 + 0.05 A LL [] a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . = NUM BER O F V A LU ES A V ER A G ED E x c lu d e s v a lu e s f o r p u p s in w h ic h th e te r m in a l b o d y w e ig h t c o u ld in c o rre c tly re c o rd e d . E x c lu d e s v a lu e s f o r l i t t e r ( s ) t h a t h a d n o fe m a le p u p s e xa m in e d . n o t be d e te rm in e d b e ca u se p u p id e n tific a tio n ap peared PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E 2 4 (P A G E 2) : P U P O R G A N W EIG H TS - SUM M ARY - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 509 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) I II III IV V 0 1 3 10 3 0 L IT T E R S EX A M IN ED N 28 28 28 28 29 IN C LU D ED IN A N A LY S ES N 28 28 27a 28 283. R A T IO S (% ) O F B R A IN T O T E R M IN A L B O D Y W E IG H T W E IG H T / LIT T ER M EAN+S.D . 3.92 + 0.65 3.83 + 0.44 3.83 + 0.54 3.80 + 0.55 3.98 + 0.56 M ALE PUPS M E A N + S .D . 3.86 + 0.69 3.83 + 0.46 3.89 + 0.70 3.73 + 0.50 3.98 + 0.57 FEM A LE PUPS M EAN+S. D . 3.97 + 0.72 [ 27] a 3.82 + 0.48 3 .7 7 + 0.50 3.92 + 0.68 [ 27] b 3.99 + 0.59 R A T IO S (% ) O F S P L E E N T O T E R M IN A L B O D Y W E IG H T W E IG H T / LIT T ER M ALE PUPS FEM A LE PUPS M EAN+S. D . M EAN+S.D . M EAN+S.D . 0.38 + 0.07 0.36 + 0.08 0.39 + 0.09 [ 27] a 0.36 + 0.06 0.34 + 0.08 0.39 + 0.07 0.35 + 0.06 0.34 + 0.08 0.36 + 0.06 0.36 + 0.06 0.36 + 0.07 0.36 + 0.07 [ 27] b 0.37 + 0.37 + 0.37 + 0.09 0.10 0.10 R A T IO S (% ) O F T H Y M U S T O T E R M IN A L B O D Y W E IG H T W E IG H T / LIT T ER M ALE PUPS FEM A LE PUPS M EAN+S.D . M EAN+S.D . M EAN+S.D . 0.47 + 0.11 0.46 + 0 .11 0.47 + 0.11 [ 27] a 0.42 + 0.07 0 . 4 1 + 0.10 0.43 + 0.06 0.40 + 0.08 0.40 + 0.09 0 .4 1 + 0.09 0.44 + 0.08 0.42 + 0.10 0.45 + 0.09 [ 27] b 0.42 + 0.42 + 0.43 + 0.09 0.10 0.10 A L L W E IG H T S W ER E R E C O R D E D I N G R AM S (G) . R A T IO S (% ) = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 0 0 . [ ] = NUM BER O F V A LU ES A V ER AG ED a . E x c lu d e s v a lu e s f o r p u p s in w h ic h th e te r m in a l b o d y w e ig h t c o u ld n o t be d e te rm in e d b e c a u se pu p id e n t i f i c a t i o n a p p e a re d in c o rre c tly re c o rd e d . b . E x c lu d e s v a lu e s f o r l i t t e r ( s ) th a t h a d n o fe m a le p u p s e xa m in e 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) T A B L E E 2 4 (P A G E 3 ) : P U P O R G A N W EIG H TS - SUM M ARY - F2 G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) I II III 013 IV V 10 3 0 L IT T E R S EX A M IN ED N 28 28 28 28 29 R A T IO S (% ) O F S P L E E N T O B R A IN W E IG H T W E IG H T / LIT T ER M E A N + S .D . 9.93 + 2.44 9.70 + 2.39 9.44 + 2.38 9.81 + 2.51 9.46 + 3.18 M ALE PUPS M EAN+S.D . 9.66 + 2.62 9.04 + 2.70 9.06 + 2.72 9.97 + 2.67 9.46 + 3.42 FEM A LE PUPS M EAN+S.D . 10.19 + 2.95 10.36 + 2.54 9.82 + 2.38 9.55 + 2.78 [ 27] b 9.44 + 3.31 R A T IO S (% ) O F T H Y M U S T O B R A IN W E IG H T W E IG H T /LIT T ER M EAN+S. D . 12.34 + 3.30 11.2 7 + 2.52 10.94 + 3.02 11.75 + 2.76 10.97 + 3.41 M ALE PUPS M EAN+S.D . 12.41 + 3.62 10.98 + 3.22 10.53 + 3.32 1 1 .5 1 + 3.22 11.05 + 3.95 FEM A LE PUPS M EAN+S.D . 12.28 + 3.64 11.5 7 + 2.40 11.34 + 3.21 11.9 6 + 3.05 [ 27] b 10.90 + 3.38 A LL [] a. b. W EIG H T S W ER E R EC O R D ED I N GRAM S (G) = NUM BER O F V A LU ES AV ER A G ED E x c lu d e s v a lu e s f o r p u p s in w h ic h th e te r m in a l b o d y w e ig h t c o u ld in c o rre c tly re c o rd e d . E x c lu d e s v a lu e s f o r l i t t e r ( s ) th a t h a d n o fe m a le p u p s e xa m in e d . not R A T IO S (% ) = be d e te rm in e d (O R G AN W E IG H T / B R A IN W EIG H T) X 1 0 0 . because pup id e n tific a tio n ap peared 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) T A B LE E2 5 (P A G E 1) : A N O G E N IT A L D IS T A N C E - SUMMARY - F2 G EN ER A T IO N PUPS ARGUS 41S-020 Page 511 DOSAGE GROUP D O S A G E (M G /K G /D AY) I II III 01 3 IV 10 L IT T E R S W IT H O N E OR MORE L IV E PUPS N 28 28 28 28 DAY 1 POSTPARTUM : A N O G E N I T A L D I S T A N C E (MM) D IS T A N C E/ L IT T E R M EANS.D . 1 . 8 3 0.20 1.86 0 . 1 9 1.8 7 0.22 1.96 0.41 M ALE PUPS FEM A LE PUPS D AY 22 PO STPARTU M : M EANS.D . M EANS.D . 2.59 + 0 .17 1 .0 7 0.06 2.58 0 .17 1 . 0 8 0.10 2.60 0.20 1.10 0 . 0 8 2.64 0.26 1.08 0.08 [ 27] a A N O G E N I T A L D I S T A N C E (MM) D IS T A N C E/ L IT T E R M EANS. D . M ALE PUPS M EANS.D . FEM A LE PUPS M EANS.D . 11.06 + 0.92 1 3 . 9 0 1.10 8.24 + 0.78 11.26 1.04 1 3 . 9 5 1.10 8.28 0.60 11.01 1 . 2 6 [ 27] b 13.58 1.26 ( 27] b 8.33 0.86 [ 27] b 11.31 1.70 13.70 1.44 8.10 0.74 ( 27] a [] a. b. =. N U M B E R O F V A L U E S A V E R A G E D L i t t e r 15 24 h ad no fe m a le p u p s . E x c lu d e s l i t t e r 1 4 7 4 , w h ic h d id n o t have a n o g e n ita l d is ta n c e s re c o rd e d on day 22 p o s tp a rtu m . V 30 29 1.83 0.24 2.63 0 .17 1.12 0.10 10.55 1.46 13.31 1.34 8.02 0 . 8 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) T A B LE E2 6 (P A G E 1) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 512 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 130 1 13 0 2 13 0 3 . 1304 13 0 5 13 0 6 1307 1308 13 0 9 1310 1311 13 12 13 13 13 14 13 15 1316 1317 13 18 19779 19780 1321 13 2 2 1323 1324 1325 13 2 6 1327 DP ( 62 - 65) DG ( 19 - 20) 1D L ( - 22) DG ( 16 - 22) 1D L ( - 22) DP ( 6 1- 68) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 24 - 25) 2 4 - 28) 25 - 28) 26 - 28) 27 ) 2 7- 28) 28 ) 4 1 - 55) 27 ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS A LIG N ED IN C IS O R S : M IS A LIG N ED a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA D EH Y D R A T IO N a EM A C IA T IO N a U R IN E -S T A IN E D A B D O M IN A L FU R LA C R IM A T IO N P T O S IS CHROM ODACRYORRHEA a LO C A LIZED A LO P E C IA : H EAD H E A D : S C A B ( 0 . 5 CM I N D IA M E T E R ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S D P = D A Y P O S TW EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D A Y O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E2 6 (P A G E 2) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 513 DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 13 2 8 1329 1330 1331 1332 1333 13 3 4 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 DP ( 3- 7) D P ( 8- 12) 21D G ( 1 4 - ) D L ( 1- 22) DP ( 3 - 4) 10D P ( 7 - ) DP ( 50- 54) D G ( 1- 21) D L ( 1- 22) D P ( 6- 12) 6D P ( - 16) 6D P ( - 15) D G ( 8- 21) D L ( 1- 22) DP ( 5 7- 81) D G ( 0- 21) D L ( 1- 22) DP ( 6 4- 83) D G ( 0- 21) 1 6D L ( - ) 22D L ( 4 - ) D L ( 22 ) 6D P ( - 15) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N SW OLLEN EA R (S ) SW OLLEN EA R (S ) a C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N IN C IS O R S M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S SW OLLEN EA R (S ) SW OLLEN EA R (S ) a A B D O M IN A L D IS T E N T IO N A B D O M IN A L D IS T E N T IO N A B D O M IN A L D IS T E N T IO N SW OLLEN EA R (S ) SW OLLEN EA R (S ) a SW OLLEN EA R (S ) SW OLLEN EA R (S ) SW OLLEN EA R (S ) a NO A D V ER S E FIN D IN G S IN C IS O R S M IS A LIG N ED IN C IS O R S M IS A LIG N ED IN C IS O R S M IS A LIG N ED IN C IS O R S M IS S IN G /B R O K EN a IN C IS O R S M IS A LIG N ED a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S 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) T A B LE E2 6 (P A G E 3 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FE M A LE R A TS DOSAGE GROUP I 0 M G/KG/DAY RAT # D ES C R IP T IO N 1349 1350 1351 1352 1353 13 5 4 1355 13 5 6 1357 1358 1359 13 6 0 D P ( 62D G ( 0D L ( 1- 81) 21) 22) D P ( 1 - 4) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S P T O S IS P T O S IS P T O S IS NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S CHROM ODACRYORRHEA NO A D V ER S E FIN D IN G S D P = D A Y P O S T W EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N ARGUS 41S-020 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) T A B LE E2 6 (P A G E 4 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 515 DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 1361 13 6 2 1363 1364 1365 13 6 6 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 DP ( DP ( DP ( DP ( DP ( DP ( DP ( 63- 64) 3 - 5) 1 - 3) 3) 3) 3) 4) DP ( DP ( DP ( DP { DP ( 9- 14) 17 ) 17 ) 1 7 - 20) 1 7 - 20) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 2) 28 - 35) 29 - 50) 3 2- 50) 35 ) 3 5 - 50) 4 5 - 50) 51 ) 26- 31) 2 6- 35) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN C H R O M O R H IN O R R H EA T IP O F T A I L M IS S IN G a D EC R EA S ED M OTOR A C T IV IT Y C H R O M O R H IN O R R H EA a COLD TO TOUCH FOUND DEAD NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N H EA D : SW OLLEN S N O U T: SW OLLEN LA C R IM A T IO N R IG H T E Y E : SW O LLEN NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES C H R O M O R H IN O R R H EA D EH Y D R A T IO N a U R IN E -S T A IN E D A B D O M IN A L FU R CHROM ODACRYORRHEA EM A C IA T IO N a D EC R EA S ED M OTOR A C T IV IT Y FOUND DEAD A N N U LA R C O N S T R IC T IO N O F T H E A N N U LA R C O N S T R IC T IO N O F T H E NO A D V ER S E FIN D IN G S T A IL T A IL D P = D A Y P O S TW EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E2 6 (P A G E 5 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N FE M A LE R ATS ARGUS 418-020 Page 516 DOSAGE GROUP I I 1 M G/KG/DAY RAT # 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 . 1387 1388 1389 1390 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 2D P ( ) 2D P ( - 3) D P ( 2- 10) DP ( 9- 19) D G ( 6- 21) D L ( 1- 22) 12D P ( 9 - ) DP ( 6 7 - 83) 0 6D G ( - ) 8D P ( - 14) 1D P ( - 9) D ES C R IP T IO N D EH Y D R A T IO N C H R O M O R H IN O R R H EA U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SW OLLEN EA R (S ) SW OLLEN E A R (S ) a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SW OLLEN EA R (S ) SW OLLEN EA R (S ) A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S 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) T A B LE E2 6 (P A G E 6 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 517 DOSAGE GROUP I I 1 M G/KG/DAY RAT # D ES C R IP T IO N 14 0 4 1405 14 0 6 14 0 7 1408 14 0 9 14 10 14 11 14 12 14 13 14 13 14 14 14 15 14 16 14 17 14 18 14 19 1420 DP ( DP ( 63 - ) 7 - 13) DP ( 2 4 - 83) D G ( 0- 21) D L ( 1- 22) 6D P ( - 15) DP ( 59 - 83) D G ( 0- 21) D L ( 1- 22) DP ( DP ( 1- 7 ) 6- 1 6 ) NO AD V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S T IP O F T A I L M IS S IN G T IP O F T A I L M IS S IN G T IP O F T A IL M IS S IN G a NO AD V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a L O C A L IZ E D A L O P E C IA : LIM B S NO AD V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S D P = D A Y P O S T W EA N IN G DG = D A Y O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E2 6 (P A G E 7 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 518 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # 14 2 1 14 2 2 1423 14 2 4 1425 14 2 6 14 2 7 1428 14 2 9 1430 143 1 14 3 2 1433 1434 1435 1436 14 3 7 1438 1439 1440 14 4 1 14 4 2 1443 14 4 4 1445 2D L ( ) DP ( DP ( DP ( DL ( 23- 26 13 3) 5) ) ) DP ( 5 9 - 66) DP ( 4- 11) D P ( 4 - 6) D P ( 4 - 6) 6D P ( ) DP ( 7) DP ( DL ( 23 ) 1) DP ( 2 - 4) D L ( 5- 21) DP ( 6 2- 79) DG ( 15 - 21) 1D L ( - 22) DP ( DP ( DP ( 3) 3 - 10) 9- 13) 1D P ( ) D ES C R IP T IO N R ED P E R IV A G IN A L SUBSTANCE NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SO FT OR LIQ U ID FEC ES U R IN E -S T A IN E D A B D O M IN A L FU R S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN U R IN E -S T A IN E D A B D O M IN A L FU R C H R O M O R H IN O R R H EA a U R IN E -S T A IN E D A B D O M IN A L FU R EM A C IA T IO N a FOUND DEAD C H R O M O R H IN O R R H EA R ED P E R IV A G IN A L SUBSTANCE C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S EM A C IA T IO N U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S 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) T A B LE E2 6 (P A G E 8) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FE M A LE R ATS ARGUS 418-020 Page 519 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # D ES C R IP T IO N 1446 14 4 7 1448 14 4 9 14 5 0 145 1 14 5 2 14 5 3 14 5 4 1455 1456 14 5 7 1458 14 5 9 14 6 0 146 1 14 6 2 14 6 3 14 6 4 14 6 5 DL ( DL ( DL ( 2) 17 ) 19 - 20) DP ( 37 ) DP ( DP ( DP ( DP ( DP ( DP ( DG ( DG ( DL ( DL ( DL ( 4 1 - 64) 5 1- 53) 5 1- 82) 54 ) 5 4 - 55) 65- 82) 0- 2 1 ) 0- 2 1 ) 1- 2 2 ) 1- 2 2 ) 1- 2 2 ) D L ( 3 - 22) DP ( 1 - 3) 6D P ( - 18) DP ( 14 - 15) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R ED P E R IV A G IN A L SUBSTANC E S O FT OR LIQ U ID FEC ES S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S C H R O M O R H IN O R R H EA IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS A LIG N ED CHROM ODACRYORRHEA CHROM ODACRYORRHEA CHROM ODACRYORRHEA IN C IS O R S : M IS S IN G /B R O K EN CHROM ODACRYORRHEA a IN C IS O R S : M IS S IN G /B R O K EN a L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA A B D O M IN A L D IS T E N T IO N C H R O M O R H IN O R R H EA 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) T A B LE E2 6 (P A G E 9) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G E N E R A T IO N FEM A LE R ATS DOSAGE GROUP I I I 3 M G/KG/DAY RAT # 14 6 6 14 6 7 14 6 8 14 6 9 14 70 14 71 14 72 14 73 14 74 1475 14 76 14 77 1478 14 79 14 8 0 DP ( DP ( 6- 1 2 ) 7 - 10) D L ( 22 ) 2D L ( ) DP ( 6 0- 63) DP ( 64- 77) DG ( 16 - 21) 1D L ( - 22) D P ( 5 7 - 59) D ES C R IP T IO N A B D O M IN A L D IS T E N T IO N A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S S O FT OR LIQ U ID FEC ES NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R ED P E R IV A G IN A L SUBSTANCE NO A D V ER S E FIN D IN G S IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS A LIG N ED IN C IS O R S : M IS S IN G /B R O K EN IN C IS O R S : M IS S IN G /B R O K EN NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S SW OLLEN EA R (S ) a D P = D A Y P O S T W EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D AY O F LA C T A T IO N 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) T A B LE E2 6 (P A G E 1 0 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N FE M A LE R A TS ARGUS 418-020 Page 521 DOSAGE GROUP IV 10 M G /KG /D AY RAT # D ES C R IP T IO N 148 1 14 8 2 . 1483 14 8 4 1485 14 8 6 14 8 7 14 8 8 14 8 9 14 9 0 14 9 1 14 9 2 14 9 3 14 94 14 9 5 14 9 6 14 9 7 14 9 8 14 9 9 1500 DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 2- 8 ) 3) 9- 18) 1- 2 ) 2) 2) 2) 3) D P ( 5 - 8) DP ( 9 - 20) 8D P ( - 10) DP ( 15 - 17) DP ( DP ( DG ( DL ( DL ( DL ( 8- 9 ) 13 - 83) 0- 2 1 ) 18 ) 18 - 22) 1- 2 2 ) DP ( DP ( 30 ) 30 ) 6D P ( ) 6D P ( ) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R EM A C IA T IO N A B D O M IN A L D IS T E N T IO N U R IN E -S T A IN E D A B D O M IN A L FU R D EC R EA S ED M OTOR A C T IV IT Y COLD TO TOUCH LA B O R ED B R EA T H IN G FOUND D EAD NO A D V ER S E FIN D IN G S U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N LO C A LIZED A LO P E C IA : NECK NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N T IP O F T A IL M IS S IN G T IP O F T A IL M IS S IN G U R IN E -S T A IN E D A B D O M IN A L FU R SO FT OR LIQ U ID FEC ES T IP O F T A IL M IS S IN G NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S LA C R IM A T IO N L E F T E Y E : SW OLLEN NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S C H R O M O R H IN O R R H EA U R IN E -S T A IN E D A B D O M IN A L FU R NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S D P = D A Y P O S T W EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E2 6 (P A G E 1 1 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FEM A LE R ATS ARGUS 418-020 Page 522 DOSAGE GROUP IV 10 M G / K G / D A Y RAT # D ES C R IP T IO N 15 0 1 15 0 2 1503 1504 15 0 5 1506 15 0 7 15 0 8 1509 15 10 15 11 15 12 15 13 15 14 15 15 15 16 15 17 15 18 15 19 15 2 0 15 21 1522 1523 1524 1525 15 2 6 15 2 7 1528 DP ( 7DP ( 65DL ( 5- 18 ) 79 ) 22) DP ( 59 - 67) 8D L ( - 22) DL ( 14 ) D L ( 15 - 16) NO AD V ER SE FIN D IN G S NO AD V ER SE FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO AD V ER SE FIN D IN G S NO AD V ER SE FIN D IN G S NO AD V ER SE FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S B A C K : S C A B (D ID N O T E X C E E D 0 .5 CM X 0 .3 CM) NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S a NO AD V ER SE FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER S E FIN D IN G S NO AD V ER SE FIN D IN G S NO AD V ER SE FIN D IN G S NO AD V ER SE FIN D IN G S S O FT OR LIQ U ID FEC ES U R IN E -S T A IN E D A B D O M IN A L FU R NO AD V ER SE FIN D IN G S 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) T A B LE E 2 6 (P A G E 1 2 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS DOSAGE GROUP IV 10 M G / K G / D A Y RAT # D ES C R IP T IO N 15 2 9 15 3 0 153 1 15 3 2 15 3 3 1534 15 3 5 1536 15 3 7 15 3 8 1539 1540 DP ( 7 1 - 83) 0 2D G ( - ) NO ADVERSE NO ADVERSE IN C IS O R S : IN C IS O R S : NO ADVERSE NO ADVERSE NO AD VER SE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO AD VER SE NO AD VER SE FIN D IN G S FIN D IN G S M IS A LIG N ED M IS A LIG N ED FIN D IN G S FIN D IN G S FIN D IN G S FIN D IN G S FIN D IN G S FIN D IN G S FIN D IN G S FIN D IN G S FIN D IN G S D P D A Y P O S T W EA N IN G DG = D A Y O F P R ES U M ED G E S T A T IO N D L D A Y O F L A C T A T IO N ARGUS 418-020 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) T A B LE E2 6 (P A G E 1 3 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 524 DOSAGE GROUP V 30 M G /KG /D AY RAT # D ES C R IP T IO N 15 41 15 4 2 . 1543 1544 15 4 5 15 4 6 15 4 7 15 4 8 1549 15 5 0 15 5 1 15 5 2 1553 15 5 4 1555 1556 15 5 7 1558 1559 . 1560 15 6 1 15 6 2 15 6 3 15 6 4 DP ( 10 - 19) 10D P ( - 11) DP ( DP ( DP ( DL ( 6 1- 66) 6 2- 66) 56 ) 2) DP ( DL ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 9- 13) 5- 22) 2 - 3) 2 - 7) 3 - 7) 5 - 7) 8) 9- 13) 40 ) 9- 14) 13 ) 1 4 - 3 1) DG ( 1 7 - 21) 1D L ( - 22) DP ( DP ( DP ( DP ( DP ( 8- 1 3 ) 3 - 5) 5) 5) 6) 2D P ( ) 2D P ( ) A B D O M IN A L D IS T E N T IO N A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S B A C K : S C A B ( 0 .5 CM X 0 .2 CM) L O C A L IZ E D A L O P E C IA : LIM B S C H R O M O R H IN O R R H EA R ED P ER IV A G IN A L SUBSTANCE NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N SW OLLEN EA R (S ) a D EC R EA S ED M OTOR A C T IV IT Y C H R O M O R H IN O R R H EA a COLD TO TOUCH U R IN E -S T A IN E D A B D O M IN A L FU R FOUND DEAD A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S T R IC T IO N S O F T H E T A IL A B D O M IN A L D IS T E N T IO N T A IL BENT T IP O F T A I L M IS S IN G a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N U R IN E -S T A IN E D A B D O M IN A L FU R COLD TO TOUCH EM A C IA T IO N a FOUND DEAD NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S FOUND DEAD b FOUND DEAD b NO A D V ER S E FIN D IN G S D P = D A Y P O S T W EA N IN G DG = D A Y O F PRESUM ED G ES T A T IO N D L = D A Y O F LA C T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . b . C l in ic a l o b s e rv a tio n s w e re n o t re c o rd e d o n d a y 1 p o s tw e a n in 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) T A B LE E2 6 (P A G E 1 4 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FEM A LE R ATS ARGUS 418-020 Page 525 DOSAGE GROUP V 30 M G /K G /D A Y RAT # D ES C R IP T IO N 15 6 5 15 6 6 156 7 15 6 8 15 6 9 15 70 15 71 15 72 15 73 15 74 15 75 15 76 15 77 15 78 15 79 15 8 0 15 8 1 15 8 2 15 8 3 15 8 4 15 8 5 1586 15 8 7 15 8 8 1589 15 9 0 15 9 1 DP ( DG ( DL ( DG ( DL ( 39 ) 14 - 21) 1- 2 2 ) 21 ) 1- 2 2 ) DP ( DP ( DP ( DP ( DP ( DP ( DP ( DP ( 8- 1 9 ) 2 - 3) 2 - 3) 3) 3) 3 - 8) 9- 13) 38 ) DG ( 14 - 21) D L ( 1 - 19) DP ( 24 ) 20D G ( - 21) 1D L ( - 6) A N N U LA R C O N S T R IC T IO N S O F T H E T A IL L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S a NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S A B D O M IN A L D IS T E N T IO N COLD TO TOUCH U R IN E -S T A IN E D A B D O M IN A L FU R FOUND DEAD FOUND DEAD U R IN E -S T A IN E D A B D O M IN A L FU R A B D O M IN A L D IS T E N T IO N A N N U LA R C O N S TR IC TIO N S O F T H E T A IL NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R IG H T A X I L L A : M ASS ( 0 .5 CM X 0 .5 CM X 0 .5 CM) R IG H T A X I L L A : M AS S ( D ID N O T E X C E E D 0 .5 CM X 0 .5 CM X 0 .5 CM) NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R ALES NO A D V ER S E FIN D IN G S L O C A L IZ E D A L O P E C IA : LIM B S L O C A L IZ E D A L O P E C IA : LIM B S D P = D A Y P O S T W EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N a . O b s e rv a tio n c o n firm e d a t n e c ro p s y . D L = D A Y O F LA C T A T IO N PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E2 6 (P A G E 1 5 ) : C L IN IC A L O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FE M A LE R A TS DOSAGE GROUP V 30 M G /K G /D AY RAT # D ES C R IP T IO N 15 9 2 1593 15 9 4 15 9 5 15 9 6 15 9 7 15 9 8 1599 16 0 0 D P ( 6- 12) D P ( 7 - 15) DP( 8) D P ( 5 - 16) U R IN E -S T A IN E D A B D O M IN A L A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S R ALES A B D O M IN A L D IS T E N T IO N NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S NO A D V ER S E FIN D IN G S FU R D P = D A Y P O S TW EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N ARGUS 418-020 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) T A B L E E 2 7 (P A G E 1) : B O D Y W EIG H TS - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R A T S ARGUS 418-020 Page 527 RAT # DOSAGE GROUP I 0 M G/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 5 7 6 4 7 0 a P R E C O H A B I T A T I O N b 1301 13 0 2 1303 13 0 4 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 39. 4 1. 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 . 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. 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. 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 . 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 . 180. 194 . 208. 201. 220. 230. 194 . 228. 228. 196. 191. 199. 184. 196. 208 . 219 . 215. 239. 248 . 211. 248. 271. 242 . 203 . 225 . 200. 206. 217 . 236. 234 . 249. 263 . 222 . 254 . 271. 274 . 224 . 239. 222. 219. 233. 252. 241. 267. 274. 242. 276. 284. 262. 235. 254. 230. 220. 246. 260. 253 . 285. 295. 254 . 279. 298. 274 . 245 . 268 . 239. 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 A LL a. b. = D A Y P O S TW EA N IN G W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . B e c a u s e b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a s e d o n e a c h r a t ' s d a y p o s tw e a n in g , was th e la s t d a y o n w h ic h th e y o u n g e s t r a ts (in t h is g ro u p ) h a d a b o d y w e ig h t v a lu e re c o rd e d . P re c o h a b ita tio n b o d y w e ig h ts w ere re c o rd e d on th e d a y c o h a b ita tio n was begun fo r th e F I g e n e ra tio n r a t s w e re 92 t o 10 6 d a y s o f a g e . d a y 70 p o s tw e a n in g r a t s ; a t t h a t tim e th e s e PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E 2 7 (P A G E 2 ) : B O D Y W EIG H TS - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 528 RAT # 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 DOSAGE GROUP I DAY 1 8 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. 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. 0 M G/KG/DAY 29 183 . 173 . 155. 146. 171. 167. 36 201. 167. 194 . 187. 181. 168. 174 . 170. 204. 200. 198. 200. 196. 186. 174 . 215. 213 . 197. 168. 191. 190. 222 . 163 . 180. 180. 209. 154 . 159. 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 . 70 a P R EC O H A B IT A T IO N 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 A LL a. b. = D A Y P O S TW EA N IN G W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . B e ca u se b o d y w e ig h t v a lu e s w e re re c o rd e d a t w e e k ly in t e r v a ls , b a se d on e a ch r a t ' s d a y p o s tw e a n in g , w as th e l a s t d a y on w h ic h th e y o u n g e s t r a t s ( in t h is g ro u p ) h a d a b o d y w e ig h t v a lu e re c o rd e d . P r e c o h a b ita tio n b o d y w e ig h ts w e re re c o rd e d on th e d a y c o h a b ita tio n was be g u n f o r th e F I g e n e ra tio n r a ts w e re 92 to 106 d a ys o f a g e . d a y 70 p o s tw e a n in g r a t s ; a t t h a t tim e th e s e PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E 2 7 (P A G E 3) : B O D Y W E IG H T S - P R E C O H A B IT A T IO N - I N D I V I D U A L D A T A - F I G E N E R A T I O N F E M A L E R A TS ARGUS 418-020 Page 529 RAT # 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 DOSAGE GROUP I I 1 MG/KG/DAY DAY 1 8 15 22 2 9 36 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. 66. 64 . 66. 59. FOUND 61. 48. 64 . 70. 66. 65. 80. 73 . 70 . 66. 62 . 43 . 79. 78. 65. 62 . 58. 49. 68. 76. 65. 69. 70. 73 . 73 . 100. 92 . 103 . 95. DEAD ON 98. 76. 102. 106. 108. 105. 120. 112 . 107. 104 . 96. 84. 121. 118. 98. 96. 96. 85. 110. 111. 98. 111. 107. 113 . 113 . 139. 169. 124 . 152 . 148. 176. 143 . 170 . DAY 4 POSTWEANING 131. 112 . 163 . 140 . 138 . 162 . 137. 162 . 151. 186. 146. 181. 156. 181. 151. 151. 147. 177. 143 . 170 . 127. 161. 134. 172. 158. 188. 162. 187 . 135 . 156. 136 . 159. 133 . 160. 124 . 153 . 140. 156. 150. 179. 132 . 160. 158. 184 . 149. 183 . 154 . 181. 148. 170. 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 . 57 212. 246. 241. 197. 230. 64 226. 261. 257 . 202 . 243 . 70a PRECOHABITATION b 236. 264 . 262 . 220 . 247. 245 . 282 . 272 . 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED I N GRAMS ( G ) . Because body w eight va lue s were recorded a t weekly in te rv a ls , based on was th e l a s t day on w h ich th e youngest r a t s (in t h is group) had a body P r e c o h a b ita tio n b o dy w e ig h ts were re c o rd e d on th e day c o h a b ita tio n was r a t s w e r e 92 t o 10 6 d a y s o f a g e . each r a t 's day postw eaning, weight value recorded. begun fo r the F I generation day 70 po stw ean in g ra ts ; a t th a t tim e 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) T A B LE E 2 7 (PAGE 4) : BODY W EIGHTS - PR EC O H AB ITATIO N - IN D IV ID U A L D ATA - F I GEN ER ATIO N FEM ALE RATS ARGUS 418-020 Page 530 RAT # DOSAGE GROUP I I 1 MG/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 5 7 6 4 7 0 a P R E C O H A B I T A T I O N b 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. 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. 64. 103 . 142 . 174 . 1227 3 . . 158. 187. 213 . 235. 246. 269. 258. 289. 316. 1016 5 . . 13 9. 171. 191. 214 . 230. 234. 260. 267. 279. 68. 109. 153 . 186. 58. 95. 13 1. 166. 74 . 108. 153 . 182 . 72 . 116. 159. 189. 206. 233 . 253 . 257 . 261. 284 . 301. 8853 . . 132 . 162 . 1218 5 . . 157. 181. 205. 231. 244 . 251. 260. 275 . 288. 82 . 117 . 150. 63 . 98. 132. 68. 1 0 4 . 1 3 8 . 177. 158. 164 . 177. 194. 208. 222 . 230. 235. 250. 62. 95. 135. 153 . 2125 7 . 94 . 134. 165. 188. . 230. 242 . 258. 263 . 285. 50. 84. 126. 166. 72. 105. 136. 164. 2107 5 . 1 1 6 . 1 5 5 . 1 8 3 . . 229. 242 . 259. 263 . 274 . 277. 1016 5 . . 1 3 6 . 1 6 2 . 66 212. 104 . 142. 174 . 204 . . 252. 263 . 258. 269. 280. 112 2217 2 . . 157. 189. . 239. 266. 275 . 285. 294 . 315. 74. 114. 154. 84 . 128 . 163 . 68. 106. 148 . 177 . 195. 216 . 237. 245. 252 . 264 . 273 . 63 . 98. 135. 2225 8 . 89. 129. 157 . 180 . 208 . . 232 . 249 . 250. 264 . 74 . 114 . 150. 181. 203 . 225 . 239. 240 . 248 . 256. 265 . 1127 2 . . 1 5 1 . 65. 99. 138. 163 . 186. 206. 219. 230. 245. 246. 262 . 69. 108. 149. 64. 104. 145. DAY ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED IN GRAMS ( G ) . Because body w eight values were recorded at weekly in te rv a ls , based on each r a t 's day postw eaning, was th e l a s t day on w hich th e youngest r a ts (in t h is group) had a body w e ight v a lu e recorde d. P r e c o h a b ita tio n body w e ights were re c o rd e d on the day c o h a b ita tio n was begun f o r the F I g e n e ra tio n r a t s w e re 92 t o 10 6 d a y s o f a g e . day 70 p o stw e a n in g r a t s ; a t th a t tim e 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) T A B LE E2 7 (PAGE 5 ): BODY WEIGHTS - PREC O HAB ITATIO N - IN D IV ID U A L DATA - F I G EN ER A T IO N FEM ALE RATS ARGUS 418-020 Page 531 RAT # 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 DOSAGE GROUP I I I DAY 1 8 15 3 MG/KG/DAY 22 2 9 36 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. 62. 62. 64. 72. 61. 60. 74 . 78. 76. 65. 52. FOUND 71. 52. 85. 81. 76. 75. 76. 76. 51. 61. 62. 65. 72. 70. 74 . 80. 93 . 90. 97. 100. 106. 111. 104 . 97. 121. 119. 112. 110. 86. DEAD ON 112. 102. 128. 124 . 114. 113 . 120. 122 . 90. 94 . 94. 107 . 108. 103 . 109. 117. 135. 131. 138. 170. 143 . 167. 143 . 180. 150. 177. 145. 177. 136. 157. 163 . 191. 158. 191. 150. 177. 160. 199. 138. 176. DAY 7 POSTWEANING 148. 182. 147. 183 . 169. 199. 162. 189. 145. 168. 136. 144 . 160. 184 . 162 . 189. 140 . 172 . 143 . 169. 136. 166. 150. 179. 150. 166. 137. 173 . 145. 191. 158. 180. 156. 182 . 159. 180. 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED IN GRAMS ( G ) . Because body w eight va lue s were recorded a t w eekly in te rv a ls , based on was the l a s t day on which the youngest r a ts (in t h is group) had a body P r e c o h a b ita tio n bo dy w e ig h ts were re c o rd e d on th e day c o h a b ita tio n was r a t s w e r e 92 t o 106 d a y s o f a g e . each r a t 's day postweaning, weight value recorded. begun fo r the F I generation day 70 postw ean in g r a ts ; a t th a t tim e 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) T A B L E . E 2 7 ( P A G E 6) : B O D Y W E I G H T S - P R E C O H A B I T A T I O N - I N D I V I D U A L D A T A - F I G E N E R A T I O N F E M A L E R A T S ARGUS 418-020 Page 532 RAT # DOSAGE GROUP I I I 3 MG/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 5 7 6 4 7 0 a P R E C O H A B I T A T I O N 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED I N GRAMS ( G ) . Because body w eight va lu e s were recorded a t w eekly in te rv a ls , based on each r a t 's day postweaning, was th e l a s t day on w hich th e youngest r a ts (in t h i s group) had a bo dy w e ig h t v a lu e recorde d. P r e c o h a b ita tio n bo dy w e ig h ts were rec orde d on th e day c o h a b ita tio n was begun f o r th e F I g e n e ra tio n r a t s w e r e 92 t o 10 6 d a y s o f a g e . day 70 postw ean in g r a t s ; a t th a t tim e 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) TA B LE E2 7 (PAGE 7) : BODY WEIGHTS - PRECO HAB ITATIO N - IN D IV ID U A L DATA - F I GENERATIO N FEM ALE RATS ARGUS 418-020 Page 533 RAT # DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 8 221 5 2 9 3 6 4 3 5 0 5 7 6 4 7 0 a P R E C O H A B I T A T I O N b 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1 4 94 1495 1496 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. 75. 48. FOUND 53 . 36. 78. 78. 70. 64. 73 . 67. 82 . 89. 78. 78. 98. 55. 71. 66. 68. 71. 72 . 67. 66. 63 . 69. 89. 81. 72 . 116. 112. 82. DEAD ON 93 . 63 . 115. 119. 105. 104 . 102. 104 . 127 . 101. 110. 116. 140. 93 . 107 . 100 . 102 . 110. 104 . 103 . 99. 97. 103 . 130. 112. 117. 155. 184 . 149. 172 . 124. 153 . DAY 3 POSTWEANING 134. 170. 99. 136. 146. 168. 153. 185. 142 . 178. 150. 186. 140. 169. 138. 168. 171. 196. 161. 191. 144. 164 . 154 . 176 . 182. 213 . 141. 182 . 140. 169. 139. 167. 147. 181. 156. 186. 143 . 173 . 142. 174 . 135. 161. 132 . 162 . 145. 171. 173 . 202 . 147. 167. 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 ALL a. b. = DAY POSTWEANING W E IG H T S W ERE R EC O R D ED I N GRAMS (G) . Because body weight values were recorded a t w eekly in te rv a ls , based on each r a t 's day postweaning, was the l a s t day on which the youngest r a ts (in t h is group) had a body w eight v a lu e recorded. P r e c o h a b ita tio n body w e ig h ts were re c o rd e d on th e day c o h a b it a t io n was begun f o r th e F I g e n e ra tio n r a t s w e re 92 t o 106 d a y s o f a g e . day 70 po stw ea n in g ra ts ; a t th a t tim e 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) T A B L E E 2 7 (P A G E 8) : B O D Y W E IG H T S - P R E C O H A B IT A T I ON - I N D I V I D U A L D A T A - F I G E N E R A T I O N F E M A L E R A T S ARGUS 418-020 Page 534 RAT # 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 DOSAGE GROUP IV DAY 1 8 15 38 . 46. 43 . 53 . 47. 45 . 45. 36. 34 . 52. 50. 49. 45 . 36. 35. 52 . 48 . 40. 34 . 50. 47 . 55. 56. 44 . 38. 42 . 37. 36. 47. 44 . 64. 103 . 75. 113 . 7 5 . 111. 90 . 131. 73 . 108. 8 4 . 121. 7 9 . 120. 64 . 105. 58. 95. 81. 119. 74 . 107. 8 5 . 122. 7 2 . 102. 63 . 91. 60. 91. 88. 1 2 3 . 79. 119. 70 . 103 . 50. 85. 83 . 123 . 76 . 117 . 86. 1 3 2 . 92 . 136. 78. 118. 72 . 114 . 67. 105. 5 8 . 94 . 60. 98. 7 3 . 112. 7 1 . 102. 22 139. 157. 150. 172 . 143 . 152 . 155. 149. 134 . 159. 140. 157. 136. 133 . 130. 164. 157. 125. 114 . 163 . 160 . 170. 175. 154 . 154. 133 . 127. 135. 153 . 138. 10 MG/KG/DAY 29 36 169. 182 . 175 . 196. 167. 181. 183 . 182 . 162 . 197. 201. 223 . 202 . 208. 190. 159. 180. 159. 161. 175. 186. 184 . 142 . 201. 162 . 180. 199. 178 . 208. 226. 206. 158. 182 . 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 ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED I N GRAMS ( G ) . Because body w eight va lu e s were recorded a t weekly in te rv a ls , based on each r a t 's day postw eaning, was th e l a s t d a y on w h ic h th e yo u n g e st r a t s (in t h i s group) had a body w e ig h t v a lu e re c o rd e d . P r e c o h a b ita tio n b o d y w e ig h ts were re c o rd e d on th e day c o h a b it a t io n was begun f o r th e F I g e n e r a tio n r a t s w e r e 92 t o 10 6 d a y s o f a g e . day 70 postw eaning r a ts ; a t th a t tim e 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) TA B LE E2 7 (PAGE 9 ): BODY WEIGHTS - PRECOHABITATION - IN D IV ID U A L DATA - F I G ENERATIO N FEM ALE RATS ARGUS 418-020 Page 535 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 DOSAGE GROUP V DAY 1 8 15 30 M G /K G /D A Y 22 2 9 36 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. 53 . 62. 56. 58. 62. 65. 58. 58. FOUND 54. 68. 70. 59. 70. 64 . 72 . 77. 57. FOUND 74 . 71. FOUND FOUND 63 . 67. 73 . 75. 106. 89. 70. 84. 97. 86. 93 . 104. 101. 91. 88. DEAD ON 80. 108. 116. 85. 108. 94 . 106. 113 . 91. DEAD ON 110. 109. DEAD ON DEAD ON 97. 100. 107. 116. 152. 123 . 108. 115. 144 . 139. 171. 114 . 136. 143 . 179. 140. 169. 142 . 171. 135. 165. 124 . 152. DAY 8 POSTWEANING 108. 132 . 150. 178. 142. 167. 119. 144 . 147. 172. 133 . 164. 139. 166. 153 . 186. 131. 163 . DAY 6 POSTWEANING 145. 171. 143 . 179. DAY 2 POSTWEANING DAY 2 POSTWEANING 129. 156. 135. 167 . 141. 176. 151. 183 . 182. 210. 151. 168. 146. 178 . 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 ALL a. b. c. = DAY POSTWEANING W EIGHTS WERE RECORDED IN GRAMS ( G ) . Because body w eight values were recorded at weekly in te rv a ls , based on each r a t 's day postw eaning, was th e l a s t day on which the youngest r a ts (in t h is group) had a body w e igh t va lu e recorde d. P re c o h a b ita tio n body w eights were recorded on the day c o h a b ita tio n was begun fo r the F I g e n e ra tio n r a t s w e r e 92 t o 10 6 d a y s o f a g e . Value not recorded. day 70 p o stw ea n in g r a ts ; a t th a t tim e 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) T A B LE E27 (PAGE 1 0 ) : BODY WEIGHTS - PRECOHABITATION - IN D IV ID U A L DATA - F I G EN ERATIO N FEM ALE RATS ARGUS 418-020 Page 536 RAT # 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 DOSAGE GROUP V DAY 1 8 15 30 M G /K G /D A Y 22 2 9 36 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 . 60. 68. 71. FOUND FOUND 43 . 54 . 61. 77. 73 . 76. 57. 64. 58. 57. 62 . 64 . 73 . 76. 73 . 72 . 67. 78. 73 . 74 . 71. 59. 65 . 69. 69. 89. 106. 110. DEAD ON DEAD ON 68. 85 . 98. 120. 104 . 112. 91. 97. 94 . 98. 96. 97. 112. 117. 107. 109. 103 . 120. 106. 115. 111. 94. 106. 110. 110. 123 . 153 . 150. 188. 156. 190. DAY 3 POSTWEANING DAY 3 POSTWEANING 108. 140. 126 . 154 . 135. 161. 156. 186. 145. 180 . 149. 177. 125. 140. 164 . 128. 148. 134. 131. 152 . 134 . 157 . 14 9. 169. 156. 176. 136. 143 . 169. 140. 152. 195 . 139. 148 . 147. 133 . 141. 172 . 154 . 149. 180. 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. 227. 222. 210. 220. 244 . 253. 233. 244. 240. 255. 64 229. 280. 228. 235. 285. 242 . 235. 217. 228. 259. 267. 246. 259. 252 . 273 . 70a PRECOHABITATION b 241. 247. 286. 302 . 241. 246. 285. 250. 251. 303 . 240. 245 . 227 . 231. 255. 274 . 246. 265 . 245. 251. 231. 236. 275 . 291. 262 . 275 . 257. 278 . 266. 290. DAY ALL a. b. = DAY POSTWEANING W EIGHTS WERE RECORDED I N GRAMS ( G ) . Because body weight va lue s were recorded a t w eekly in te rv a ls , based on was the l a s t day on w hich th e youngest r a t s (in t h i s group) had a body P re c o h a b ita tio n body w e ig h ts were re c o rd e d on th e day c o h a b ita tio n was r a t s w e re 92 t o 106 d a y s o f a g e . each r a t 's day postweaning, weight value recorded. begun fo r the F I generation d a y 70 p o s tw e a n in g r a ts ; a t th a t tim e 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) T A B LE E28 (PAGE 1) : M ATERNAL BODY WEIGHTS - PRESUMED G ES TA T IO N - IN D IV ID U A L DATA - F I GENERATION FEM ALE RATS ARGUS 418-020 Page 537 RAT # DOSAGE GROUP I 0 MG/KG/DAY PREGNANCY STATUS DAY 0 107 1 4 1 8 2 1 2 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 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 236. 266. 273 . 269. 303 . 305 . 264 . 299. 322 . 292 . 264 . 284 . 253 . 277. 239. 271. 264 . 297 . 282 . 286. 281. 267 . 293 . 250. 271. 292 . 255. 295. MATING 245. 262. 269. 294. 311. 306. 314 . 291. 298. 332. 342 . 327. 338. 288. 299. 304. 315. 366. 379. 325. 340. 296. 312 . 313 . 322. 274 . 285. 307. 319. 258. 271. 309. 327. 296. 321. 324. 336. 312. 324 . 314 . 328. 314. 334 . 298. 313 . 311. 326. 278 . 291. 306. 314 . 321. 329. 293 . 302 . 324. 342 . NOT CONFIRMED 273 . 284 . 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. 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 . 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 . 311. 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) T A B L E E28 (PAG E 2) : M ATER N AL BODY W EIG H TS - PRESUM ED G E S T A T IO N - I N D IV I D U A L D A T A - F I G E N E R A T IO N F E M A LE RATS ARGUS 418-020 Page 538 RAT # DOSAGE GROUP I I 1 MG/KG/DAY PREGNANCY STATUS DAY 0 7 10 1 4 1 8 21 1362 1363 13 64 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 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 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. 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. 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 . 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. 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. 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. 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) T A B L E E28 (P A G E 3) : M A T E R N A L B O D Y W E IG H TS - PRESUM ED G E S T A T I O N - I N D I V I D U A L D A T A - F I G E N E R A T I O N F E M A L E R A TS ARGUS 418-020 Page 539 RAT # DOSAGE GROUP I I I 3 MG/KG/DAY PREGNANCY STATUS DAY 0 7 10 1 4 1 8 21 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. 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. 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. 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. 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. 417 . 465. 444 . 494 . 472 . 452. 450. 379. 427 . 297. 445. 406. 385. 325. 448 . 417. 425 . 438. 400. 390. 3 94. 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) T A B LE E28 (PAGE 4 ) : MATERNAL BODY WEIGHTS - PRESUMED G ESTATIO N - IN D IV ID U A L DATA - F I GENERATIO N FEM ALE RATS ARGUS 418-020 Page 540 RAT # DOSAGE GROUP IV 10 MG/KG/DAY PREGNANCY STATUS DAY 0 7 10 1 4 1 8 21 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. 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 . 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. 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. 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. 449. 293 . 389. 468 . 437. 390. 431. 424 . 426. 400. 430. 399. 437. 339. 407. 437. 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) T A B L E E2 8 (P A G E 5 ) : M A T ER N A L B O D Y W EIG H TS - P R ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A L E R A T S ARGUS 418-020 Page 541 RAT # DOSAGE GROUP V 30 M G /K G /D A Y P R EG N A N C Y STATUS DAY 0 107 1 4 1 8 2 1 2 5 15 41 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 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 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 N P = N O T PR EG N AN T (V A LU ES D AY = D AY O F PRESUM ED G ES T A T IO N A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . EXCLUD ED FROM A V ER A G ES ) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E2 9 (P A G E 1) : M A T ER N A L B O D Y W EIG H T S - LA C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 542 RAT # DOSAGE GROUP I 0 M G/KG/DAY DAY 1 5 8 11 1 5 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 . 304. 324 . 324. 338. 302. 318. 342 . 346. 334. 329. 292. 308. NOT PREGNANT 370. 385. 326. 338. 308. 305. 326. 329. 265. 285 . 322. 323 . 276. 272 . 327. 331. 311. 341. 350. 357. 321. 317. 328. 331. 312. 326. 314. 310. 323 . 338. 301. 293 . 307. 305. 329. 330. 296. 292. 334 . 332 . NOT PREGNANT; 271. 279. 299. 331. 346. 329. 345. 339. 316. 396. 352. 315. 349. 258. 330. 287. 333. 349. 359. 325. 329. 325. 328. 351. 303 . 321. 344 . 299. 349. M A TIN G N O T 298. 303 . 343 . 363 . 352 . 361. 333 . 289. 398. 357. 318. 363 . 297. 336. 285. 327. 364. 330. 357. 323 . 321. 342 . 331. 308. 348. 348. 328. 352. C O N FIR M ED 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) T A B L E E 2 9 (P A G E 2) : M A T ER N A L B O D Y W EIG H T S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 543 RAT # DOSAGE GROUP I I 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 M G/KG/DAY 1 5 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) T A B L E E2 9 (P A G E 3) : M A T ER N A L B O D Y W EIG H T S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 544 RAT # DOSAGE GROUP I I I 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 M G/KG/DAY 1 5 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) T A B L E E 2 9 (P A G E 4) : M A T ER N A L B O D Y W EIG H TS - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS 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. 2 94 . 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 M G/KG/DAY 1 5 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 OP AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E2 9 (P A G E 5) : M A T ER N A L B O D Y W EIG H T S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A L E R A T S 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 M G /KG /D AY 1 5 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 3 64 346. 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) T A B L E E3 0 (P A G E 1) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 547 RAT # DOSAGE GROUP I 0 M G/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 -15 110. 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 . 15 - 22 128. 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. 22 - 29 129 . 119. 127. 145. 197. 133 . 136. 13 7 . 159. 154 . 120. 147 . 126. 183 . 174 . 136. 143. 153 . 126. 124. 121. 112. 136. 134 . 155. 132. 116. 146. 29 - 36 118 . 132. 131. 131. 163 . 180. 127 . 145. 157. 146. 146. 148. 122. 36 - 43 119. 132. 131. 130. 167. 167 . 125. 149. 189. 180. 145 . 148. 121. 43 - 50 109. 127. 138. 193 . 161. 180 . 126 . 151. 157. 210. 174 . 156. 130. 50 - 57 117. 138. 134 . 130. 193 . 168 . 129 . 148. b 158 . 164 . 159. 118. 5 7 - 64 115. 131. 128. 134 . 162. 181. 127 . 141. 169. 159. 165 . 167. 120. 64 - 7 0 a 102. 107. 112 . 109. 125 . 141. 112 . 116. 128. 123 . 106 . 142 . 108. DAY A LL a. b. c. = D A Y P O S TW EA N IN G W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly in t e r v a ls , b a s e d th e l a s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e was re c o rd e d S o ile d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . W et fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a ys 6 4 - 7 0 you n gest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 2) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 548 RAT # DOSAGE GROUP I 0 M G/KG/DAY STATUS DAY 1 - 8 8 -15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 5 7 - 64 64 - 7 0 a 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 . 111. 114 . 140. 145 . 127. 119. 116. 133 . 133 . 131. 13 9. 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. 13 6. 186. 129. 157. 14 9. 13 7 . 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 A LL a. b. c. = D A Y P O S TW EA N IN G W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . B e cau se fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly in t e r v a ls , b a se d th e la s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . S o ile d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on ea ch r a t ' s d a y p o s tw e a n in g , d a ys 6 4 -7 0 fo r th e you n gest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 3) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 549 RAT # DOSAGE GROUP I I 1 M G/KG/DAY STATUS DAY 1 - 8 8 -15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 5 7 - 64 64 - 7 0 a 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 63 . 49. 61. 57. FO U N D 63 . 52 . 69. 76. 63 . 65. 73 . 68. 75. 62. 66. 44 . 75. 69. 56. 62 . 66. 49. 54 . 80. 54 . 70. 74 . 71. 75. 98. 88. 99. 91. DEAD ON 79. 85. 115. 122 . 98. 113 . 122 . 110. 113 . 103 . 95. 92. 122. 116. 104 . 101. 109. 94. 89. 122. 101. 114. 108. 106. 116. 117. 114 . 109. 118. 136. 127. 133 . 184 . D A Y 4 P O S TW EA N IN G 129. 109. 116. 116. 142. 131. 141. 136. 129. 152 . 130. 138. 132. 131. 139. 196. 141. 141. 130 . 140 . 105. 127 . 131. 151. 141. 140. 146. 136. 136. 13 9. 124 . 117 . 126. 141. 126. 147. 118 . 130. 137. 133 . 119. 118. 136. 134 . 131. 130. C 127. C 130. 119. 133 . 194 . 109. 140. b 145. 221. 134. 127 . 136. 141. 121. 134 . 131. 111. 161. 150. 114. 13 9. 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. FO U N D D EA D ON D A Y 5 1 P O S T W EA N IN G 130. 152. 133 . 151. 113 . 126. 134. 156. 141. 157. 125. 129. 134 . 129 . 133 . 119. 128 . 129 . 131. 12 9 . 115. 100 . 108. 101. 153 . 156. 157. 165. 126. 126. DAY A LL a. b. c. = D A Y P O S TW EA N IN G W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly i n t e r v a ls , b a se d th e l a s t in t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . W et fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a y s 6 4 - 7 0 youngest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 4 ) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 550 RAT # DOSAGE GROUP I I 1 M G/KG/DAY STATUS 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 DAY 1 - 8 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 . 8 -15 101. 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. 15 - 22 129. 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. 22 - 29 132 . 126. 127. 135. 130. 127. 151. 130. 126. 123 . 137. 135. 121. 134. 142 . 123 . 116. 113 . 125. 134 . 147. 126. 135. 112 . b 29 - 36 148. 129. 150. 136. 123 . 147. 154 . 133 . 140. 130. 133 . 133 . 117. 36 - 43 b 127. 161. 138. 129. 146 . 157. 122 . 138. 129. 140 . 143 . 120. 43 - 50 159. 122. 152 . 142. 154. 157. 173 . 136. 144 . 136. 150. 137. 252 . 50 - 57 165. 108. 139. 134 . 124 . 151. 154 . 151. 143 . 144 . 149. 146. 204 . 5 7 - 64 176. 129. 135. 126. 116. 166. 141. 109. 127. 138. 146. 128. b 64 - 7 0 a 145 . 106. 125. 107. 108. 123 . 129 . b 116. 116. 105. 107. 96. DAY A LL a. b. = D A Y P O S T W EA N IN G W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . B e ca u se fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly i n t e r v a ls , b a se d th e l a s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e was re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . on e a ch r a t ' s d a y p o s tw e a n in g , d a ys 6 4 -7 0 fo r th e yo u n g e st ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 5) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T I ON - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 551 RAT # D O S A G E G R O U P :I l l 3 M G/KG/DAY STATUS 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 - 8 8 -15 15 - 22 22 - 29 29 - 36 61. 67. 67. 75. 66. 51. 68. 73 . 70. 71. 51. FOUND 73 . 61. 84 . 73 . 60. 69. 69. 74 . 45. 67. 61. 49. 70. 69. 64. 72 . 77. 79. 99. 105. 109. 114 . 116. 82. 120. 113 . 111. 131. 103 . DEAD ON 115 . 108. 124. 129. 115. 117. 115. 127. 95. 99. 94. 93 . 128. 112. 105. 106. 125. 124. 124 . 125. 121. 121. 130. 140. 131. 13 9. 149. 110. 173 . 108. 144. 153 . 142. 180. 141. 161. 164 . 185. 129. 147. D A Y 7 P O S TW EA N IN G 129. 138. 134 . 145. 149. 170. 142 . 144. 124 . 121. 130. 110. 151. 149. 146. 157. 126. 138. 130. 134. 118 . 123 . 133 . 13 0. 173 . 120. 172 . 121. 125. c 134. 135. C 161. c 124 . 123 . 120. 124 . 141. 175. 140. 140 . 140. 128. 13 7 . 135. 126. 132 . 142. b 13 9. 36 - 43 121. 127. 138 . 151. 174. 145. 13 7 . 130. 123 . 215. 162. 129 . 130. 145 . 140. 43 - 50 124. 124 . 150. 149. 164 . 150. 145. 150 . 163 . 153 . 158 . 140 . 235 . 177. 135. 50 - 57 126 . 127. 149. 153 . 162. 151. 149. 143 . 148 . 153 . 136. 137. b 128. 124. 5 7 - 64 127 . 124 . 158. 154 . 172 . 141. 155. 143 . 132 . 177. 138. 192 . 124 . 130. 125. 64 - 70 a 106. 104 . 123 . 124 . 135. 123 . 117. 130 . 108. 134 . 13 0 . 114 . 114 . 117. 103 . DAY A LL a. b. c. = D A Y P O S TW EA N IN G W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . B e c a u s e fe e d c o n s u m p tio n w as re c o rd e d a t w e e k ly i n t e r v a ls , b a se d th e la s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . W et fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on ea ch r a t ' s d a y p o s tw e a n in g , d a y s 6 4 -7 0 fo r th e yo u n g e st ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 6) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 552 RAT # DOSAGE GROUP I I I 3 M G/KG/DAY STATUS DAY 1 - 8 8 -15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 5 7 - 64 64 - 7 0 a 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 . 122 . 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. 13 9. 136. 145. 115. 136. 119. 126. 150. 160. 141. 163 . b 117. 132 . 163 . 147. 138. 157. 125. 134 . 130. 127. 153 . 180. 158. 182 . 196 . 123 . 127. 166. 147. 156 . 191. 152. 14 9. b 13 6. 162 . 196. 134 . b b 110. 123 . 151. 147. 147 . b 148 . 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 A LL a. b. = D A Y P O S TW EA N IN G W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . B e cau se fe e d c o n s u m p tio n w as re c o rd e d a t w e e k ly in t e r v a ls , b a s e d th e la s t in t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e was re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a y s 6 4 -7 0 youngest ra ts in th is gro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 7) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 553 RAT # DOSAGE GROUP IV 10 M G/KG/DAY STATUS DAY 1 - 8 8 -15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 5 7 - 64 64 - 7 0 a 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 71. 83 . 45. FO U N D 56. 35. 79. 73 . 67. 64. 73 . 69. 84 . 88. 89. 82 . 89. 36. 65. 65. 70. 67. 69. 76. 65. 67. 66. 85. 80. 75. 117. 117. 92. DEAD ON 110. 74 . 127. 132. 105. 116. 101. 107. 123 . 109. 124 . 116. 128. 103 . 104. 91. 115. 116. 104 . 101. 110. 108. 93. 127. 103 . 135. 129. 144 . 144 . 140. 133 . 135. D A Y 3 P O S TW EA N IN G 145. 107. 170 . 122. 138. 137. 140. 145. 139. 145. 147. 133 . 169. 120. 129. 131. 150. 140 . 140. 138. 128. 125. 133. 12 9 . 145. 146. 136. 150. 127. 133 . 179. c 141. 138 . 144. 113 . 166. 122. 124 . 134. 136. 111. 133 . 124 . 123 . 130. 13 9. 152. 118. 115. 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 . 13 9. 126. 146. 130 . 125 . 128 . 163 . 292 . 189. 128 . 131. 165 . 187. 206. 139. 132 . 141. 132. 126. 13 0. 163 . 174. 150. 130. 123 . 14 9. 138. 149 . 140. 123 . 138. 125. 146. 129. 168. 118. 146 . 13 9. 124 . 138. 128 . 173 . 135. 121. 136. 118. 104 . 108 . 143 . b 122 . 116. 116. 120. 109. 163 . 123 . 104 . 109. DAY A LL a. b. c. = D A Y P O S T W EA N IN G W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly in t e r v a ls , b a s e d th e l a s t i n t e r v a l i n w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . V a lu e w as n o t re c o rd e d . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a y s 6 4 -7 0 youngest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 8 ) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 554 RAT # DOSAGE GROUP IV 10 M G/KG/DAY STATUS DAY 1 - 8 8 -15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 5 7 5 7 - 64 64 - 7 0 a 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. 105. 119. 127. 137. 142. 143 . 140 . 136. 141. 85. 124 . 134. 136. 71. 107. 129. 139. 137. 138. 173 . 161. 177. 115. 83 . 117. 128. 133 . 137. 140 . 190. 166. 145 . 114 . 69. 106. 116 . 115 . 1109 1 . . 1 2 4 . 1 2 6 . 1207 9 . . 1 3 3 . 1 3 6 . 68. 1 1 8 . 138. 147. 1016 0 . . 1 2 4 . 1 3 5 . 137. 127. 125. 143 . 136. 129. 157. 142 . 125. 146. 145 . 130. 150 . 142 . 116. 128. 119 . 102 . 70. 125. 127. 121 1217 1 . 9 5 . 1 1 9 . . . 1 2 4 . b 138. b 116. 82 . 129. 127. 1006 4 . . 109. 108 . 115. 124 . b b b 108. 62. 76. 114 . 118. 130. 13 7 . b b 187. 109. 59. 96. 114 . 78. 116. 137. 92. 124. 142. 144 . 138. 148. b b 68. 122. 1 1 8 . 211b 114 . 116. 151. . b 121. b 92 . 52 . 96. 109. 75. 113 . 134 . 71. 113 . 140. 140 . 145. 143 . 150. 144. 137. 115. 75 . 127. 142 . 1218 1 . 132. 144 . 129. 151. 135. 152. 153 . 151. . 1017 1 . 118. 131. 123 . 133 . 128. 143 . 142 . 148 . . 68. 1 1 3 . 1 2 9 . 1206 7 . 1 1 9 . . 1025 8 . . 123 . 130. 132. 134 . 199. 143 . 176. 119. 1106 2 . . 1 3 2 . 1116 9 . . 133 . 209. 141. 165. 167. 166. 164 . 127. 1027 0 . . 1 1 9 . DAY A LL a. b. = D A Y P O S TW EA N IN G W EIG H TS W ER E R EC O R D ED IN GRAM S ( G ) . B e cau se fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly in t e r v a ls , b a se d th e la s t i n t e r v a l i n w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a ys 6 4 -7 0 youngest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 9) : F E E D C O N S U M P TIO N V A LU ES - P R E C O H A B IT A T I ON - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 555 RAT # DOSAGE: GROUP V 30 M G /KG /D AY 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 49. 57. 56. 58. 66. 65. 65. 62 . 15. 57. 62 . 65. 58. 66. 64. 70. 79. 63 . FO U N D 67. 72 . FOUND FOUND 65. 64. 70. 70. 83 . 79. 62 . 85. 101. 89. 102 . 111. 133 . 108. 142. 120. 135. 110. 157. 114 . 152 . 113 . 130. 157. 192 . 95. 1 19 . 1 19 . 123 . 96. 124. 138. 95. 1 1 7 . 128. 115 . FO U N D D EA D ON D A Y 8 P O S TW EA N IN G 92 . 107. 115. 104. 103 . 107. 91. 128. 120. 110. 137. 123 . 122. 119. 104 . 128 . 136. 95 . 124. 138. 118. 9 6 . 110. 112. 107. 124 . 124. 138. 106. 137. 143 . 136. D E A D O N D A Y 6 P O S TW EA N IN G 118. 141. b 137. 116. 135. 144 . D E A D ON D A Y 2 P O S TW EA N IN G D E A D O N D A Y 2 P O S TW EA N IN G 100. C 125. 133 . 95. C 123 . 115. 113 . 123 . 131. b 119. 138. 140. 133 . 118 . 138. 122 . 134 . 116. 138. 93 . 130. 126. 105. 157. 169. 130. 130. 126. 113 . 131. 137. 146. 155. 13 0. 113 . 139. 143 . 43 - 50 108. 158. 167. 142 . 133 . 121. 116. 143 . 149. 248. 291. 170 . 113 . 137. 145. 50 - 57 113 . 168. 181. 141. 133 . 123 . 126. 113 . 133 . b 149. 136. 104. 140. 132. 5 7 - 64 116. 165. 193 . 137. 139. 127. 125. 120. 130. 141. 140 . 129. 107. 132 . 129. 64 - 7 0 a 100. 136. 128 . 116. 111. 108 . 99. 106. 118 . 124 . b 114 . 95. 110. 109. DAY A LL a. b. c. = D A Y P O S TW EA N IN G W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly in t e r v a ls , b a s e d th e l a s t in t e r v a l i n w h ic h a fe e d c o n s u m p tio n v a lu e was re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . W et fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a y s 6 4 - 7 0 you n gest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 0 (P A G E 10 ) : F E E D C O N S U M P TIO N V A LU E S - P R E C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 556 RAT # DOSAGE: GROUP V 30 M G /K G /D A Y STATUS 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 - 8 8 -15 15 - 22 22 - 29 29 - 36 60. 54 . 66. FO U N D FO U N D 49. 53 . 56. 66. 63 . 71. 52 . 62 . 60. 62 . 61. 61. 62. 72 . 68. 69. 67. 76. 63 . 70. 59. 62. 72 . 63 . 68. 88. 99. 116. DEAD ON DEAD ON 82 . 94 . 104 . 107. 99. 106. 90. 106. 94 . 106. 93 . 106. 103 . 127 . 109. 108. 105. 103 . 103 . 111. 105. 89. 109. 108. 104. 110. 113 . 140 . 146. 143 . 143 . D A Y 3 P O S T W EA N IN G D A Y 3 P O S T W EA N IN G 114 . 116. 122. 123 . 120. 143 . 124 . 114 . 130. 121. 130. 128 . 118. 120. 115. 118. 126 . 131. 113 . 129 . 114 . 135. 114 . 113 . 174. 144 . 141. 175. 164 . 120. 122. 138 . 112 . 120. 126. 134. 130. 135 . 128. 119. 133 . 129. 146. 130. 13 9. 127. 137. 129. 117. 133 . 118. 136. 144 . 140. 139. 125. 36 - 43 132 . b 141. 125 . 134 . 136. 135 . 121. 134 . 128 . 133 . 142 . 132 . 147. 129. 43 - 50 129. 153 . 144 . 148. 137. b 144 . 235. b b b 204 . 135. 149 . 132. 50 - 57 122. 155. 137. 107. 139. 159. 132 . 140. 153 . 13 7 . b b 165. 156. 145. 5 7 - 64 51. 158. 129. 117. 128 . b 130. 140. 148 . 125 . b 156. 151. 146. 145 . 64 - 70 a 175. 134. 111. 94 . b 97. 99. 103 . 113 . 98. b 107 . 114 . 130 . 126. DAY A LL a. b. = D A Y P O S TW EA N IN G W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . B e c a u s e fe e d c o n s u m p tio n was re c o rd e d a t w e e k ly i n t e r v a ls , b a s e d th e l a s t i n t e r v a l in w h ic h a fe e d c o n s u m p tio n v a lu e w as re c o rd e d S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . on each fo r th e r a t ' s d a y p o s tw e a n in g , d a ys 6 4 -7 0 youngest ra ts in th is g ro u p . p o s tw e a n in g was PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E 3 1 (P A G E 1) : M A T ER N A L F E E D C O N S U M P TIO N V A LU ES - PR ESU M ED G E S T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 557 RAT # DOSAGE GROUP I 0 M G/KG/DAY PREGNANCY STATUS DAYS 0 -7 7 -10 10 - 14 14 - 18 18 - 21 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 1359 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 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. 76. 7 7 . 7 1 . 91. 95. 7 1 . 96. 91. 68. 9 5 . 99. 7 8 . 112. 112. 77. 114. 105. 68. 9 2 . 90. 64. 83 . 63. a 126. 119. 93 . 112. 112. 1107 9 . 1 1 6 . . 74 . 95. 89. 32 . 82. 76. 75. 97. 92. 68. 9 2 . 9 4 . 1118 5 . . 1 1 7 . 87. 114 . 107. 68. 9 4 . 100. 886 5 . . 8 2 . 77 . 89. 98. 72 . 94. 91. 88. 1 0 6 . 95. 1107 3 . 99. . 68. 88. 8 7 . 68. 9 0 . 92 . 68. 86. 9 2 . 68. 86. 7 9 . 1008 7 . . 1 0 7 . 68. 86. 8 0 . 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 N P = N O T P R EG N A N T (V A LU ES EX C LU D E D FROM A V ER A G ES ) 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) T A B L E E 3 1 (P A G E 2) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - PR ESU M ED G E S T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A L E R A T S ARGUS 418-021 Page 558 RAT # DOSAGE GROUP I I 1 M G/KG/DAY P R EG N A N C Y STATUS DAYS 0 -7 7 -10 10 - 14 14 - 18 18 - 21 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 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 123 . a a 139. 183 . 170. 135. 182. 149. 191. 13 6. a 144 . 148. 177. 194 . 191. 163 . 157. 130. 170 . 175. 154. 143 . 158. 159. 142 . 179. 133 . 62. 7 7 . 68. 9 0 . 79. 90. 67. 89. 99. 887 0 . . 8 7 . 78 . 105. 112 . 1209 5 . 1 1 7 . . 59. 87. 84. 1108 1 . . 1 0 6 . 55. 81. 79. 87. 108. 105. 865 8 . . 9 0 . 62. 84 . 90. 886 7 . . 9 2 . 886 2 . 8 0 . . 83 . 117. 110. 86. 1 0 8 . 109. 94. 118 . 108. 887 1 . . 9 3 . 10283 . 9 9 . . 5 8 . 83 . 93 . 1017 3 . 93 . . 85. 124. 106. 65. 91. 97. 887 1 . . 8 7 . 69. 85. 90. 73 . 89. 80. 886 7 . 8 7 . . 1007 4 . 93 . . 59. 80. 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 N P = N O T P R EG N AN T (V A LU ES EX C LU D ED FROM A V ER A G ES ) D A YS = D A YS O F PRESUM ED G ES T A T IO N A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . a . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . b . V a lu e was n o t re c o rd e 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) T A B L E E 3 1 (P A G E 3) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - P R ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 559 RAT # DOSAGE GROUP I I I 3 M G/KG/DAY P R EG N A N C Y STATUS DAYS 0 -7 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 463 1465 1468 1469 1472 1474 1476 1477 1480 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 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 -1 0 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. 10 - 14 84. 82. 104. 105. 110. 101. 106. 111. 88. 123 . 108. 96. 85. 74 . 80. 100. 113 . 104. 89. 93 . 92. 100. 102. 101. 87. 86. 86. 104 . 87. 87. 14 - 18 86. 90. 115. 105. 126. 111. 107. 93 . 90. 114. 112. 99. 73 . 96. 89. 102. 107 . 109. 83 . 99. 92 . 112 . 106. 100. 86. 88. 98. 95. 94 . 94. 18 - 21 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 N P = N O T P R EG N A N T (V A LU ES EX C LU D ED FROM A V ER A G ES ) D AYS = DAYS O F PRESUM ED G ES T A T IO N A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . b . V a lu e was n o t re c o rd e 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) T A B L E E 3 1 (P A G E 4) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - PR ES U M ED G E S T A T IO N - IN D IV ID U A L D A TA - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 560 RAT # DOSAGE GROUP IV 10 M G/KG/DAY PREGNANCY STATUS DAYS 0 -7 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 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 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. 13 9. 175. 165. 7 -1 0 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 - 14 101. 73 . 95. 102 . 109. 98. 95. 84 . 94 . 96. 107. 93 . 82 . 102. 88. 91. 86. 97. 91. 82. 71. 91. 100. 98. 88. 94. 104 . 82. 90. 99. 14 - 18 101. 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. 100. 113. 18 - 21 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 N P = N O T P R EG N A N T (V A LU E S EX C LU D ED FROM A V ER A G ES ) D AYS = D AYS O F PRESUM ED G ES T A T IO N A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . a . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . b . V a lu e was n o t re c o rd e 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) T A B L E E 3 1 (P A G E 5) : M A TER N A L F E E D C O N S U M P TIO N V A LU E S - P R ES U M ED G E S T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 561 RAT # DOSAGE GROUP V 30 M G /KG /D AY P R EG N A N C Y STATUS DAYS 0 -7 7 -10 10 - 14 14 - 18 18 - 21 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 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 119. 171. 183 . 14 9. a 147. 143 . 130. 135. 168. 170. 150. 121. 131. 115. 134. 157. 156. 104. 128. C 168. 136. 143 . 136. 166. 158 . 144 . 160. 162. 63 . 79. 87. 1128 7 . . 1 0 4 . 1117 9 . . 1 1 9 . 70. 92. 91. 57. 87. 106. a 9 4 . 102. 57. 84. 79. 59. 78. 80. 6 2 . 83 . 9 2 . 76. 96. 103 . 6 7 . 102. 111. 60. 95. 94 . 57. 74. 81. 866 2 . 8 3 . . 58. 92. 96. 59. 84. 96. 75. 95 . 106. 65. 97. 104 . 37. 57. 57. 6 5 . 7 2 . 93 . 866 2 . . 9 9 . 865 6 . 8 1 . . 60. 82 . 8 1 . 67. 93 . 104 . 57. 73 . 89. 106. 92 . 111. 72 . 98. 109. 69. 97. 98. 76. 94 . 89. 74. 106. 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 N P = N O T PR EG N AN T (V A LU ES EX C LU D ED FROM A V ER A G ES ) D AYS = D AYS O F PR ESUM ED G ES T A T IO N A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . Wet fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . b . V a lu e was n o t re c o rd e d . c . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 2 (P A G E 1) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 562 RAT # DAY DOSAGE GROUP I 1 -5 5- 8 8 -1 1 1 1 - 15a 0 M G/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 118. 118 . 125. 148. 14 9. 153 . 185. 167. b 84 . 120 . 170 . 101. 134 . NOT PREGNANT 154 . 184 . 129. 180. 104 . 157. 115. 141. 90. 1 1 7 . 108. 127. 83 . 107. 113 . 138. 161. 168. 195. 190. 125. 110 . 132. 132. 113 . 150. 124 . 155 . 131. 159. 109. 128, 103 . 156, 103 . 151, 115 . 98, 113 . 166. N O T P R E G N A N T ;; 96. 114 , 145. 180 . 176. 193 . 200 . 119. 138. 170. 120. 170 . 180 . 163 . 140 . 126. 151. 192. 150. 165. 117. 133 . 174 . 184 . 144 . 205 . 183 . 159. 180. M A TIN G N O T 177. 185 . 199. 239. 255. 234 . 158 . 186. 270. 250. 272 . 277 . 232 . 198 . b 225. 200. 254 . 306. 211. 214 . 244 . 271. 227. 244 . 245. 273 . 246 . C O N FIR M ED 256. D A Y = D A Y O F LA C T A T IO N A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . B e cau se i t is p re su m e d t h a t th e p u p s b e g in t o consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w ere n o t ta b u la te d on d a y s 15 to 22 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 2 (P A G E 2) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 563 RAT # DOSAGE GROUP I I 1 M G/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. 122 . 97. 148. 127. 145. 13 7 . 152. 174 . 194. 142 . 171. 116. 122. 13 9. 138. NOT PREGNANT 99. 134. 125. 141. 151. 112 . 166. 148. 160. 123 . 125. 146. 161. 159. 94 . 129. 97. 142. 109, 102. 163 . 121. 139. 146. 129. 113 . 161. 113 . 121. 163. 111. 177. 93 1 5 4 . 91, 102, 141. 156. 118, 160. 118 . 177. 167. 171. 210. 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. D A Y = D A Y O F LA C T A T IO N A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . B e c a u s e i t is pre su m e d th a t th e p u p s b e g in to consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w e re n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 2 (P A G E 3) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - LA C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 o00 Page 564 RAT # 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 DAY DOSAGE GROUP I I I 1 -5 5 -8 8-11 122 . 152. 109. 143 . 93 . 1 3 2 . 113 . 154. 108 . 127. 133 . 154. 133 . 163 . 109. 117. 128. 152. 109. 118. 148. 121. 123 . 155. NOT PREGNANT 107. 150. 99. 124. 110. 107. 114. 139. 121. NOT PREGNANT 123 . 177. 103 . 110. 126. 135 . 118. 161. 136. 114. b 130. 126. 136. 99. 128. 82. 149. 140. 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. 1 1 - 15a 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. 3 M G/KG/DAY D A Y = DAY O F LA C T A T IO N A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . a . B e cau se i t is p re su m e d th a t th e p u p s b e g in t o consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w ere n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f t h is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 2 (P A G E 4) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A T S ARGUS 418-020 Page 565 RAT # 14 8 2 14 8 3 14 8 6 1488 14 9 0 149 1 14 9 4 14 9 6 14 9 7 15 0 0 15 0 2 15 0 5 15 0 7 15 0 8 15 11 15 13 15 14 15 16 15 17 15 19 15 21 15 2 3 1524 15 2 7 1528 153 1 15 3 3 15 3 4 15 3 7 1539 DAY DOSAGE GROUP IV 1- 5 5 -8 100. 121. NOT PREGNANT 134 . 102 . 15 8 . 15 8 . b 152 . 15 7. 16 6 . 12 7. 133 . 99. 90. 123 . 152 . 117. 133 . b 14 9 . 118 . 130 . 92 . 16 9 . 9 6 . 122 . NOT PREGNANT 114 . 15 3 . 117. 15 5 . 15 2. 8 7. 138 . 120. 115 . 15 6 . 103 . 140 . 126 . 145 . 7 9 . 64 . 123 . 110. 154 . 86. 145 . 15 5 . 116 . 15 8 . 82. 13 0 . 118 . 15 7. 15 4. 178 . 8-11 16 0 . 178 . 178 . 176 . 18 8 . 154 . 16 6 . 16 8 . 178 . 15 6 . 113 . 140 . 135 . 16 8 . 19 0 . 16 7. 172 . 18 2 . 15 9 . 15 2 . 79 . 14 1. 153 . 133 . 15 5 . 13 7. 178 . 138 . 11 - 15a 18 5 . 253 . 205. 19 8 . 273 . 309. 225. 238. 252. 228. 249. 293 . 143 . 16 8 . 15 1. 23 1. 248 . 278 . 2 17. 257 . 112 . 153 . 23 7. 2 74 . 26 1. 193 . 18 9 . 289. 10 M G/KG/DAY D A Y = D AY O F LA C T A T IO N A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . a . B e c a u s e i t is p re su m e d th a t th e p u p s b e g in to consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w ere n o t ta b u la te d on d a ys 15 to 22 o f la c ta tio n . b . S p ille d fe e d p re c lu d e d th e c a lc u la tio n o f th is v a lu e . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E3 2 (P A G E 5) : M A T ER N A L F E E D C O N S U M P TIO N V A LU E S - L A C T A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 566 RAT # 15 41 15 4 4 1545 15 4 6 1548 15 5 0 1552 15 5 5 15 5 7 15 5 8 15 6 0 15 6 4 15 6 5 1566 15 6 8 15 71 15 73 15 76 15 78 15 79 15 8 3 1584 15 8 6 15 8 7 15 8 8 1589 15 9 1 15 9 3 15 9 8 16 0 0 DOSAGE GROUP V DAY 1 - 5 5 -8 122 . 13 0 . 130 . 14 7. 14 0 . 12 8 . 179 . 122 . 75 . 113 . 14 1. 120. 111. 112. 154 . 13 7. 119 . 13 1. 13 1. 18 1. 135 . 15 1. 123 . 110. 101. 121. 118 . 123 . 111. 119 . 84. 120. 123 . 148 . 92 . 1 1 6 . NOT PREGNANT 10 8 . 142 . 127 . 68. 144 . 8 7. 123 . 129 . 113 . 126 . 118 . 13 7. 9 1. 13 7. 14 0 . 12 9 . 145 . 120. 143 . 128 . 133 . 16 0 . 8-11 1 1 - 15a 152 . 171. 18 6 . 112 . 152 . 15 1. 15 8 . 146 . 16 2. 18 4. 15 5 . 152 . 116 . 115 . 16 2. 16 8 . 177. 145 . 216 . 289. 25 7. 205. 246. 203 . 18 1. 179 . 20 7. 218 . 2 4 1. 263 . 18 9 . 224 . 216 . 174 . 223 . 19 7. 155 . 169 . 9 1. 164 . 128 . 132 . 143 . 182 . 13 1. 153 . 170 . 194 . 16 7. 13 4 . 173 . 173 . 273 . 237 . 19 2. 129 . 225. 234. 30 M G/KG/DAY D A Y = D A Y O F LA C T A T IO N A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . a . B e c a u s e i t is p re su m e d th a t th e p u p s b e g in t o consum e m a te rn a l fe e d a f t e r d a y 15 o f la c t a t io n , m a te rn a l fe e d c o n s u m p tio n v a lu e s w ere n o t ta b u la te d on da ys 15 to 22 o f la c ta tio n . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E3 3 (P A G E 1) : S E X U A L M A T U R A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R A TS ARGUS 418-020 Page 567 DOSAGE GROUP - M G/KG/DAY I II III 0 13 RAT # V A G IN A L P A T EN C Y (D A Y) RAT # V A G IN A L P A T EN C Y (D AY) RAT # V A G IN A L P A T EN C Y (D AY) RAT # 13 0 1 13 0 2 13 0 3 13 0 4 13 0 5 13 0 6 130 7 13 0 8 13 0 9 13 10 13 11 13 12 13 13 13 14 13 15 13 16 13 17 13 18 19 779 19 78 0 13 2 1 13 2 2 1323 13 2 4 13 2 5 13 2 6 13 2 7 13 2 8 13 2 9 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 13 6 1 13 6 2 1363 13 6 4 13 6 5 13 6 6 136 7 13 6 8 13 6 9 13 70 13 71 13 72 13 73 13 74 13 75 13 76 13 77 13 78 13 79 1380 13 8 1 13 8 2 1383 13 8 4 13 8 5 13 8 6 13 8 7 13 8 8 13 8 9 13 9 0 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 14 2 1 14 2 2 1423 1424 1425 1426 14 2 7 1428 1429 14 3 0 14 3 1 1432 1433 1434 1435 1436 14 3 7 1438 1439 1440 14 4 1 14 4 2 1443 14 4 4 1445 1446 14 4 7 1448 1449 14 5 0 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 14 8 1 14 8 2 1483 14 8 4 14 8 5 14 8 6 14 8 7 14 8 8 14 8 9 14 9 0 149 1 14 9 2 14 9 3 14 9 4 14 9 5 14 9 6 14 9 7 14 9 8 14 9 9 15 0 0 15 0 1 1502 1503 15 0 4 15 0 5 15 0 6 15 0 7 15 0 8 1509 15 10 DAY a. b. c. = DAY POSTPARTUM R a t was fo u n d dead b e fo re S e xu a l m a tu ra tio n te s tin g R a t was fo u n d d e a d . th e was s ta r t o f s e xu a l m a tu ra tio n e v a lu a tio n . d is c o n tin u e d b e fo re r a t becam e s e x u a lly m a tu re . IV 10 V A G IN A L P A T EN C Y (D A Y) 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 # 15 41 15 4 2 1543 1544 15 4 5 1546 15 4 7 1548 1549 1550 15 5 1 15 5 2 1553 15 5 4 1555 15 5 6 15 5 7 1558 15 5 9 15 6 0 15 6 1 15 6 2 15 6 3 15 6 4 15 6 5 15 6 6 156 7 15 6 8 15 6 9 15 70 V 30 V A G IN A L P A T EN C Y (D A Y) 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) T A B L E E3 3 (P A G E 2 ) : S E X U A L M A T U R A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R A TS ARGUS 418-020 Page 568 DOSAGE GROUP - M G/KG/DAY I II III 0 13 RAT # V A G IN A L P A T EN C Y (D AY) RAT # V A G IN A L P A T EN C Y (D AY) RAT # V A G IN A L P A T EN C Y (D A Y) RAT # 133 1 13 3 2 1333 13 3 4 13 3 5 13 3 6 133 7 13 3 8 13 3 9 1340 13 41 1342 1343 1344 1345 1346 13 4 7 13 4 8 1349 13 5 0 135 1 13 5 2 1353 13 5 4 13 5 5 13 5 6 135 7 13 5 8 13 5 9 13 6 0 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 13 9 1 13 9 2 1393 13 9 4 13 9 5 13 9 6 13 9 7 13 9 8 13 9 9 14 0 0 140 1 14 0 2 14 0 3 1404 1405 14 0 6 14 0 7 1408 14 0 9 14 10 14 11 14 12 14 13 14 14 14 15 14 16 14 17 14 18 14 19 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 14 5 1 1452 14 5 3 1454 1455 1456 14 5 7 1458 1459 14 6 0 14 6 1 14 6 2 14 6 3 14 6 4 14 6 5 14 6 6 14 6 7 14 6 8 14 6 9 1470 14 71 1472 14 73 1474 1475 1476 14 77 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 15 11 15 12 15 13 15 14 15 15 15 16 15 17 15 18 15 19 1520 15 2 1 1522 15 2 3 1524 1525 1526 15 2 7 1528 1529 15 3 0 153 1 15 3 2 1533 15 3 4 15 3 5 1536 15 3 7 15 3 8 1539 1540 DAY a. b. = DAY POSTPARTUM R a t was fo u n d de ad b e fo re S e xu a l m a tu ra tio n te s tin g th e was s t a r t o f s e xu a l m a tu ra tio n e v a lu a tio n . d is c o n tin u e d b e fo re r a t becam e s e x u a lly m a tu re . IV 10 V A G IN A L P A T EN C Y (D AY) 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 RAT # 15 71 15 72 15 73 15 74 15 75 15 76 15 77 15 78 15 79 15 8 0 15 8 1 1582 15 8 3 1584 15 8 5 1586 15 8 7 15 8 8 1589 15 9 0 159 1 15 9 2 15 9 3 15 9 4 15 9 5 15 9 6 15 9 7 15 9 8 15 9 9 16 0 0 V 30 V A G IN A L P A T EN C Y (D A Y) 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 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E3 4 (P A G E 1) : M A TIN G AN D F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D AYS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R ATS ARGUS 418-020 Page 569 DOSAGE GROUP I 0 M G/KG/DAY RAT # 13 0 2 13 0 4 13 0 6 13 0 8 13 10 13 12 13 13 13 16 13 18 13 2 1 13 2 5 13 2 8 13 3 0 133 1 13 3 4 13 3 5 13 3 6 1338 13 4 0 13 4 1 1342 1344 13 4 5 1346 1348 1350 13 5 3 1355 1358 13 5 9 ESTROUS STAGES/ 21 D A Y S 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 C O H A B IT A T IO N 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 M A TIN G 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 D ID M NOT M ATE M A TIN G 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 = M ATED C = C O N FIR M ED NC = N O T C O N FIR M ED P = PREGNANT PRO = PROESTRUS E = ESTRUS M ET = M ETESTRUS D = D IES TR U S a . S ix o r m ore c o n s e c u tiv e d a ys o f d ie s tr u s w e re o b s e rv e d . NP = NOT PREGNANT P R EG N A N C Y 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 A T S A C R IFIC E M ET E D D E M ET D D D E D E D D D D M ET D D E E D D D M ET 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) T A B LE E3 4 (P A G E 2) : M A TIN G AN D F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 570 DOSAGE GROUP I I 1 M G/KG/DAY RAT # 13 6 2 13 6 3 13 6 4 136 7 13 6 8 13 71 13 73 13 75 13 76 13 78 13 79 13 8 1 13 8 2 13 8 3 13 8 4 13 8 7 13 8 9 13 9 2 13 9 3 139 7 13 9 9 140 1 1404 14 0 7 14 0 9 14 10 14 13 14 15 14 16 14 18 ESTROUS STAGES/ 21 DAYS DAYS IN C O H A B IT A T IO N 64 53 53 64 53 54 FO U N D D E A D O N D A Y 5 1 P O S TW EA N IN G 62 54 63 64 64 53 42 52 53 32 64 52 62 53 52 54 53 36 33 64 41 51 52 M A TIN G 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 ATED C = C O N FIR M ED NC = N O T C O N FIR M ED PRO = PROESTRUS E = ESTRUS M ET = M ETESTRUS P = PREGNANT D = D IES TR U S M A TIN G 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 NP = NOT PREGNANT P R EG N A N C Y 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 A T S A C R IFIC E E E M ET E D D D D E M ET D D D E E D D E M ET 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) T A B L E E3 4 (P A G E 3) : M A TIN G AN D F E R T I L I T Y , ES T R O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE R ATS ARGUS 418-020 Page 571 DOSAGE GROUP I I I 3 M G/KG/DAY RAT # 14 2 1 14 2 4 14 2 6 1428 1430 14 3 1 1433 1436 14 3 7 1439 14 4 2 1443 14 4 6 1448 1450 14 5 2 1455 14 5 6 14 5 8 14 5 9 146 1 14 6 3 14 6 5 14 6 8 14 6 9 14 72 14 74 14 76 14 77 14 8 0 ESTROUS STAGES/ 21 DAYS 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 DAYS IN C O H A B IT A T IO N 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 A TIN G 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 A TIN G 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 M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP = NOT PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS P R EG N A N C Y 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 A T S A C R IFIC E D D D M ET E D PRO D D M ET 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) T A B LE E3 4 (P A G E 4) : M A TIN G AN D F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D AYS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G EN ER A T IO N FE M A LE R ATS ARGUS 418-020 Page 572 DOSAGE GROUP IV 10 M G/KG/DAY RAT # 14 8 2 1483 14 8 6 14 8 8 14 9 0 149 1 14 9 4 14 9 6 14 9 7 15 0 0 15 0 2 15 0 5 15 0 7 15 0 8 15 11 15 13 15 14 15 16 15 17 15 19 15 2 1 1523 1524 15 2 7 15 2 8 153 1 15 3 3 15 3 4 15 3 7 15 3 9 ESTROUS STAG ES/ 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 C O H A B IT A T IO N 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 M A TIN G 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 = M ATED C = C O N FIR M ED NC = N O T C O N FIR M ED P = P R EG N A N T PRO = PROESTRUS E = ESTRUS M ET = M ETESTR U S D = D IES TR U S a . S ix o r m ore c o n s e c u tiv e d a y s o f d ie s tr u s w ere o b s e rv e d . M A TIN G 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 P R EG N A N C Y 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 A T S A C R IFIC E D E E D D E D PRO E D PRO D D D D D D D E D D M ET E D D D D D D D P R O TO C O L 4 18 -0 2 0 : O R A L (G A V A G E) T W O -G E N E R A T IO N (O N E L I T T E R P E R G E N E R A T IO N ) R E P R O D U C T IO N S T U D Y O F AM M O N IU M P E R F L U O R O O C T A N O A T E (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 .6 ) T A B L E E3 4 (P A G E 5) : M A TIN G AND F E R T IL IT Y , ES TR O U S C Y C LIN G AN D D A YS IN C O H A B IT A T IO N - IN D IV ID U A L D A T A - F I G E N E R A T IO N F E M A LE RATS ARGUS 418-020 Page 573 DOSAGE GROUP V 30 M G /K G /D A Y RAT # 15 4 1 15 4 4 1545 15 4 6 15 4 8 15 5 0 1552 15 5 5 15 5 7 15 5 8 15 6 0 15 6 4 15 6 5 15 6 6 15 6 8 15 71 15 73 15 76 15 78 15 79 15 8 3 1584 15 8 6 15 8 7 15 8 8 15 8 9 15 9 1 15 9 3 15 9 8 16 0 0 ESTROUS STAGES/ 21 D A Y S 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 C O H A B IT A T IO N 2 5 3 4 3 1 3 4 2 1 1 3 2 4 3 3 2 1 3 2 1 1 4 1 3 3 2 1 4 4 M = M ATED C = C O N FIR M ED NC = N O T C O N FIR M ED PRO = PROESTRUS E = ESTRUS M ET = M ETESTRU S M A TIN G 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 = D IES TR U S M A TIN G 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 A T S A C R IFIC E D M ET 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) T A B L E E3 5 (P A G E 1 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a ARGUS 418-020 Page 574 13 0 1 13 0 2 1303 13 0 4 13 0 5 13 0 6 130 7 13 0 8 13 0 9 13 10 13 11 13 12 13 13 13 14 13 15 13 16 13 17 13 18 19 779 DP 32 D L 22 DP 32 D L 22 D P 32 D L 22 DP 31 D L 22 DP 31 D L 22 DP 31 D L 22 D L 22 DP 30 DP 30 DG 25 DP 30 D L 22 DP 28 P - P - P - P - P - P P - NP - P - 31 130 31 128 31 129 30 126 30 12 7 30 126 126 29 29 10 7 29 126 27 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. 19 78 0 DP 28 - 27 S P LEEN : SM ALL (0.099 G ) . A L L O TH ER T IS S U ES A P P EA R ED NORM AL. 13 2 1 13 2 2 1323 13 2 4 13 2 5 1326 13 2 7 13 2 8 1329 1330 D L 22 D P 30 D P 30 D P 30 D L 22 D P 30 DP 30 D L 22 DP 29 D L 22 P - P - P - P 126 29 29 29 124 29 29 128 28 125 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. D P = D A Y P O S TW EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N a . R e fe r to th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le E26 ) fo r e x te rn a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E35 (P A G E 2) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FEM A LE R ATS ARGUS 418-020 Page 575 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a I 0 CONT. 13 3 1 13 3 2 1333 13 3 4 1335 13 3 6 133 7 13 3 8 13 3 9 1340 13 41 13 4 2 1343 13 4 4 1345 1346 13 4 7 1348 1349 13 5 0 13 5 1 13 5 2 13 5 3 13 5 4 13 5 5 13 5 6 135 7 13 5 8 13 5 9 13 6 0 D L 22 DP 29 D P 29 D L 22 D L 22 D L 22 DP 28 D L 22 DP 28 D L 22 D L 22 D L 22 DP 28 D L 22 D L 22 D L 22 DP 28 D L 22 DP 28 D L 22 DP 28 DP 27 D L 22 DP 27 D L 22 DP 27 DP 24 DP 114 D L 22 DP 18 P - P P P P - P P P P P P P - P - P - P - - NP P - 126 28 28 124 126 125 27 123 27 12 7 123 123 27 126 123 123 27 122 27 123 27 26 126 26 123 26 23 113 116 17 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED APPEARED APPEARED APPEARED APPEARED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED APPEARED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE E3 5 (P A G E 3) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FE M A LE R A TS ARGUS 418-020 Page 576 DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a II 1 1361 D P 32 - 3 1 A L L T IS S U ES A P PEA R ED N O RM AL. 13 6 2 D L 22 P 130 N EC R O P S Y O B S ER V A TIO N S W ERE N O T R EC O R D ED . 1363 13 6 4 D L 22 D L 22 P P 129 A L L TIS S U ES A P P EA R ED N O RM AL. 129 A L L T IS S U ES A PP EA R ED N O RM AL. 1365 DP 4 - 3 FO U N D D EA D O N D A Y 4 P O S TW EA N IN G (D EA TH OCCURRED O V E R N IG H T ). A L L T IS S U ES A P PEA R ED NO RM AL. 13 6 6 13 6 7 1368 13 6 9 13 70 13 71 13 72 DP 32 D L 22 D L 22 DP 32 DP 31 D L 22 DP 31 - P P P - 31 130 129 31 30 128 30 A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 13 73 DP 51 - 50 FO U N D D EA D O N D A Y 5 1 P O S T W EA N IN G . STOM ACH : D IS T E N D E D . IN T ES T IN ES : D IS T EN D ED . LU N G S : D O R S AL S U R FA C E, R IG H T A P IC A L L O B E , D EP R ES S ED W H IT E A R E A ( 0 . 3 CM I N D I A M E T E R ) . A L L O TH ER T IS S U ES A PPEA R ED NORM AL. 13 74 13 75 13 76 13 77 13 78 13 79 1380 13 8 1 13 8 2 1383 13 8 4 DP 31 D L 22 D L 22 DP 31 DG 25 D L 22 DP 31 D L 22 D L 22 D L 22 D L 22 - P P - NP P P P P P 30 12 7 128 30 110 129 30 12 9 128 126 12 7 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE E35 (P A G E 4) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 577 DOSAGE GROUP (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a II 1 CONT. 1385 13 8 6 13 8 7 13 8 8 13 8 9 13 9 0 139 1 13 9 2 1393 13 9 4 13 9 5 13 9 6 139 7 13 9 8 13 9 9 1400 140 1 14 0 2 14 0 3 14 0 4 14 0 5 14 0 6 14 0 7 1408 14 0 9 14 10 14 11 14 12 14 13 14 14 14 15 DP 31 DP 31 D L 22 DP 30 D L 22 DP 30 D P 30 D L 22 D L 22 D P 30 D P 30 D P 30 D L 22 D P 30 D L 22 D P 30 D L 22 D P 29 D P 29 D L 22 D P 29 D P 29 D L 22 D P 29 D L 22 D L 22 DP 28 DP 28 D L 22 DP 28 D L 22 - P - P - P P - P P - P - P - P - P P - P - P 30 30 12 7 29 126 29 29 126 125 29 29 29 126 29 12 7 29 12 4 28 28 12 7 28 28 125 28 129 126 27 27 126 27 122 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL TIS S U ES TIS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES TIS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NO RM AL. LIV E R : LE FT LA TER A L LO B E, F (2. () C M X 1 . 2 C M X 0 ,. 4 C M ) , CUT SURFACE R EV EA LED YELLO W CAUDATE LOB E ADHERED TO L E F T LA TER A L A L L O TH ER T IS S U ES A P P EA R ED N O RM AL. LO B E. 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 (A P F O ) I N R A T S (S P O N S O R 'S S T U D Y N U M B E R : T - 6 8 8 9 .6 ) T A B L E :E 3 5 ( P A G E 5 ) : N E C R O P S Y O B S E R V A T I O N S - I N D I V I D U A L D A T A - F I G E N E R A T I O N F E M A L E R A T S DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y PREGNANCY D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A T IO N S a II 1 CONT. 14 16 14 17 14 18 14 19 1420 D L 22 DP 28 D L 22 DP 28 DP 28 P P - 122 27 124 27 27 A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S TW EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le E26 ) f o r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B LE E35 (P A G E 6 ): N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page 579 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y PREGNANCY D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a III 14 2 1 D L 22 P 126 A L L T IS S U ES A P P EA R ED NO RM AL. 14 2 2 DP 32 - 3 1 A L L T IS S U ES A P P EA R ED NO RM AL. 1423 14 2 4 DP 31 D L 22 - P 30 125 A L L T IS S U ES A P P EA R ED N O RM AL. A L L T IS S U ES A P P EA R ED NO RM AL. 1425 1426 DP 31 D L 22 P 30 125 A L L T IS S U ES A P P EA R ED NO RM AL. A L L T IS S U ES A P P EA R ED NO RM AL. 14 2 7 DP 31 - 30 A L L T IS S U ES A P P EA R ED N O R M A L. 1428 D L 22 P 12 7 K ID N EY S : B ILA T E R A L , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED N ORM AL. 1429 14 3 0 14 3 1 1432 1433 1434 1435 1436 14 3 7 14 3 8 1439 1440 14 4 1 14 4 2 1443 14 4 4 1445 14 4 6 14 4 7 1448 14 4 9 DP 31 D L 22 D L 22 DP 7 - P P " D L 22 DP 31 DP 31 D L 22 D L 22 DP 31 D L 22 DP 31 DP 31 D L 22 D L 22 D P 30 D P 30 DG 25 D P 30 D L 22 D P 30 P - - P P - P - - P P - NP - P - 30 12 7 126 6 12 7 30 30 129 128 30 12 7 30 30 126 125 29 29 110 29 125 29 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NO RM AL. NO RM AL. FO U N D D EA D O N D A Y 7 P O S T W EA N IN G (D EA TH OCCURRED O V E R N IG H T ). A L L T IS S U ES A PPEA R ED NO RM AL. A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NO RM AL. NO RM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. 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) T A B LE E35 (P A G E 7) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 580 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A T IO N S a III 3 CONT. 14 5 0 14 5 1 1452 14 5 3 1454 14 5 5 1456 14 5 7 14 5 8 1459 14 6 0 146 1 14 6 2 1463 14 6 4 14 6 5 14 6 6 14 6 7 14 6 8 14 6 9 14 70 14 71 1472 1473 1474 14 75 14 76 14 77 14 78 14 79 1480 D L 22 DP 30 D L 22 DP 30 DP 30 D L 22 D L 22 DP 29 DG 25 D L 22 DP 29 D L 22 DP 29 D L 22 DP 29 D L 22 DP 28 DP 28 D L 22 D L 22 DP 28 DP 28 D L 22 DP 28 D L 22 DP 28 D L 22 D L 22 DP 27 DP 24 D L 22 P - P - - P P - NP P - P - P - P - - P P - P - P - P P - P 126 29 12 4 29 29 12 7 125 28 10 6 125 28 125 28 124 28 12 4 27 27 125 123 27 27 126 27 123 27 12 4 124 26 23 119 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED APPEARED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B LE E3 5 (P A G E 8) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G E N E R A T IO N FEM A LE R A TS DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF N EC R O P S Y P R EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a ARGUS 418-020 Page 581 14 8 1 14 8 2 1483 14 8 4 DP 31 D L 22 DG 25 DP 3 P NP - 30 125 108 2 A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. FO U N D D EA D O N D A Y 3 P O S T W EA N IN G (D EA TH OCCURRED O V E R N IG H T ). A L L T IS S U ES A P P EA R ED NO RM AL. 1485 14 8 6 14 8 7 1488 14 8 9 14 9 0 149 1 14 9 2 14 9 3 14 9 4 14 9 5 14 9 6 14 9 7 14 9 8 14 9 9 1500 15 0 1 1502 1503 1504 1505 15 0 6 15 0 7 1508 DP 31 D L 22 DP 31 D L 22 D P 30 D L 22 D L 22 DP 30 D P 30 D L 22 DP 30 D L 22 D L 22 D P 30 D P 30 D L 22 D P 30 D L 22 DP 29 DP 29 D L 22 DP 29 D L 22 D L 22 - P P - P P - - P - P P - - P - P - - P - P P 30 12 7 30 125 29 125 126 29 29 12 7 29 126 12 7 29 29 126 29 125 28 28 125 28 125 12 7 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 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) T A B L E E3 5 (PA G E 9) : N EC R O P S Y O B S ER V A T IO N S - IN D IV ID U A L D A TA - F I G E N E R A T IO N FE M A LE R ATS ARGUS 418-020 Page 582 DOSAGE GROUP D O S A G E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y PREGNANCY DOSAGES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a IV 10 CONT. 1509 15 10 15 11 15 12 15 13 15 14 15 15 15 16 15 17 15 18 15 19 1520 15 21 15 2 2 1523 15 2 4 1525 1526 15 2 7 15 2 8 1529 15 3 0 153 1 15 3 2 15 3 3 15 3 4 15 3 5 1536 15 3 7 15 3 8 1539 1540 DP 29 DP 29 DG 25 DP 29 D L 22 D L 22 DP 29 D L 22 D L 22 DP 29 D L 22 DP 28 D L 22 DP 28 D L 22 D L 22 DP 28 DP 28 D L 22 D L 22 DP 28 DP 28 D L 22 DP 28 D L 22 D L 22 DP 28 DP 28 D L 22 DP 28 D L 22 DP 28 NP P P P P P P P P P P P P P P P - 28 28 112 28 124 124 28 126 122 28 124 27 125 27 126 125 27 27 125 12 4 27 27 125 27 125 122 27 27 124 27 12 7 27 A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL NORM AL 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) T A B LE E35 (P A G E 10 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 583 DOSAGE GROUP D O S AG E (M G /K G /D A Y) RAT NUM BER DAY OF NECROPSY PREGNANCY DOSAGES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a V 30 15 41 D L 22 P 128 A L L T IS S U ES A P P EA R ED N O RM AL. 1542 DP 32 - 31 A L L T IS S U ES A PPEA R ED NORM AL. 15 4 3 DP 32 - 31 A L L T IS S U ES A PPEA R ED NORM AL. 1544 D L 22 P 129 A L L T IS S U ES A P P EA R ED NO RM AL. 1545 D L 22 P 12 7 A L L T IS S U ES A PPEA R ED NORM AL. 1546 D L 22 P 128 A L L T IS S U ES A P P EA R ED NO RM AL. 15 4 7 DP 31 - 30 A L L T IS S U E S A P P EA R ED N O R M A L. 15 4 8 D L 22 P 126 A L L T IS S U ES A P P EA R ED NO RM AL. 15 4 9 DP 8 - 7 FO U N D D EA D O N D A Y 8 P O S T W EA N IN G . A L L T IS S U ES A PPEA R ED NORM AL. 15 5 0 15 5 1 15 5 2 1553 1554 15 5 5 1556 15 5 7 15 5 8 D L 22 DP 31 D L 22 DP 31 DP 31 D L 22 D P 30 D L 22 D L 22 P P P P P 126 30 12 7 30 30 128 29 126 124 A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. . 15 5 9 DP 6 - 5 FO U N D D EA D O N D A Y 6 P O S T W EA N IN G . A L L T IS S U ES APPEAR ED NORM AL. 15 6 0 15 6 1 15 6 2 15 6 3 D L 22 D P 30 DP 2 DP 2 P " - 125 29 0 0 A L L T IS S U ES APPEAR ED NORM AL. A L L T IS S U ES APPEAR ED NORM AL. FO U N D D EA D O N D A Y 2 P O S TW EA N IN G (D EA TH OCCURRED O V E R N IG H T ). A L L T IS S U ES APPEAR ED NORM AL. FO U N D D EA D O N D A Y 2 P O S T W EA N IN G . A L L T IS S U ES A P P EA R ED NORM AL. 15 6 4 15 6 5 D L 22 D L 22 P P 12 7 A L L T IS S U ES A PPEA R ED NORM AL. 126 A L L T IS S U ES A P P EA R ED NO RM AL. 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) T A B LE E35 (P A G E 1 1 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 584 DOSAGE GROUP D O S A G E (M G /K G /D A Y) RAT NUM BER DAY OF N EC R O P S Y PR EG N A N C Y D O S A G ES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a V 30 CONT. 15 6 6 156 7 15 6 8 15 6 9 15 70 15 71 15 72 15 73 D L 22 D P 30 D L 22 D P 30 DP 30 D L 22 DP 30 D L 22 P P - P - P 128 29 12 7 29 29 125 29 125 A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES TIS S U ES T IS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NO RM AL. NORM AL. NORM AL. 15 74 15 75 15 76 15 77 15 78 15 79 15 8 0 15 8 1 15 8 2 15 8 3 15 8 4 15 8 5 1586 15 8 7 15 8 8 1589 15 9 0 15 9 1 15 9 2 DP 3 - DP 3 - D L 22 DP 29 DG 25 D L 22 DP 29 DP 29 DP 28 D L 22 D L 22 DP 28 D L 22 D L 22 D L 22 D L 22 DP 28 D L 22 DP 28 P NP P - - - P P - P P P P P - 3 2 124 28 108 12 4 28 28 27 123 122 27 126 123 125 123 27 124 27 FO U N D D EA D O N D A Y 3 P O S T W EA N IN G (D EA TH O CCURRED 6 7 M IN U T ES A F T E R A L L T IS S U ES A P P EA R ED N O RM AL. DOSAGE A D M IN IS T R A T IO N ). FO U N D D EA D O N D A Y 3 P O S TW EA N IN G (D EA TH OCCURRED O V E R N IG H T ). A L L T IS S U ES A PPEAR ED N O RM AL. A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES TIS S U ES T IS S U ES TIS S U ES T IS S U ES TIS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES TIS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NO RM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S T W EA N IN G DG = D A Y O F PRESUM ED G ES T A T IO N D L = D A Y O F LA C T A T IO N a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le E2 6 ) f o r e x te rn a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E35 (P A G E 1 2 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F I G EN ER A T IO N FE M A LE R A TS DOSAGE GROUP D O S AG E (M G /K G /D AY) RAT NUM BER DAY OF N EC R O P S Y PREGNANCY DOSAGES STATUS A D M IN IS T ER ED O B S ER V A TIO N S a V 30 CONT. 15 9 3 D L 22 P 123 K ID N E Y S : R IG H T , P E L V IS , M O D ERATE D IL A T IO N . U R IN A R Y B LA D D ER : W ALLS T H IC K E N E D . U R ET ER : B ILA T E R A L , M ODERATE D IL A T IO N ; O NE C A LC U LI L O C A T E D A T T H E C A U D A L E N D ( 1 .0 CM X 0 .5 C M ). A L L O TH ER T IS S U ES APPEAR ED NORM AL. 15 9 4 15 9 5 15 9 6 15 9 7 15 9 8 15 9 9 16 0 0 DP 28 DP 28 DP 28 DP 27 D L 22 DP 26 D L 22 - - P - P 27 27 27 26 125 25 123 A LL A LL A LL A LL A LL A LL A LL T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES T IS S U ES A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. D P = D A Y P O S TW EA N IN G DG = D AY O F PRESUM ED G ES T A T IO N D L = D AY O F LA C T A T IO N a . R e fe r t o th e in d iv id u a l c lin ic a l o b s e rv a tio n s ta b le (T a b le E26 ) f o r e x te r n a l o b s e rv a tio n s c o n firm e d a t n e c ro p s y . 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) T A B LE E36 (P A G E 1) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 586 DOSAGE GROUP I 0 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a B R A IN ABS. W T. R EL. % TBW 13 0 2 13 0 4 13 0 6 13 0 8 13 10 13 12 13 13 13 16 13 18 1321 13 2 5 1328 13 3 0 1331 13 3 4 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 13 5 3 1355 1358 1359 2 8 4 . 0.022 3 2 0 . 0.021 335. 0.017 357. 0.018 331. 0.014 3 3 6 . 0.022 2 9 8 . 0.020 NOT PREGNANT 369. 0.017 329. 0.014 323 . 0.009 328. 0.015 280. 0.018 300. 0.018 284. 324 . 0.016 0.012 331. 345. 0.016 0.022 338. 0.015 316. 0.029 294 . 333 . 0.023 0.020 364. 0.014 325. 0.018 339. 0.015 339. 0.016 293 . 0.024 313 . 0.007 N O T P R EG N A N T ; M A TIN G 313 . 0.017 7.75 6.56 5.07 5.04 4.23 6.55 6.71 2.10 2.10 2.05 2.01 1.99 2.15 2.14 4.61 2.06 4.26 2.79 2.05 2.00 4.57 6.43 6.00 2.09 2.00 2.33 5.63 1.96 3.70 1.93 4.83 6.38 2.06 2.10 4.44 2.07 9.18 2.06 7.82 6.01 1.93 2.26 3.85 2.03 5.54 2.03 4.42 2.05 4.72 8.19 2.03 2.22 2.24 2.04 N O T C O N FIR M ED 5 . 4 3 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 LIV E R ABS. W T. R EL. % 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 16.39 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 K ID N EY LEFT ABS. R EL. W T. % 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 .4 1 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 K ID N EY R IG H T ABS. R EL. 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 .4 7 1.17 1.26 1.22 1.40 1.46 1.53 1.65 1.18 1.25 1 .4 1 1.32 1.41 1.57 1.42 1 .3 1 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 .3 1 0.42 A D R EN A L LEFT ABS. R EL. W T. % TBW a 0.027 0.044 0.050 0.041 0.040 0.036 0.036 9.51 13.75 14.92 11.48 12.08 1 0 .7 1 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 . W T. O RGAN W EIG H T . R E L . % TBW = (ORG AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 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) T A B LE E3 6 (P A G E 2) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 587 DOSAGE GROUP I 0 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S PLEEN ABS. W T. R EL. % TBW 13 0 2 13 0 4 1306 1308 1310 13 12 13 13 1316 1318 1321 1325 13 2 8 13 3 0 1331 13 3 4 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 284. 320. 0.028 0.038 9.86 11.88 0.63 0.53 335 . 0.037 11.04 0.59 357. 331. 0.041 0.047 11.48 14.20 0.72 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. 339. 0.052 0.062 15.34 18.29 0.57 0.66 293 . 0.035 11.94 0.52 313. 0.031 9.90 0.43 N O T P R EG N A N T ; M A T IN G N O T C O N FIR M ED 313 . 0 . 0 3 4 10.86 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 THYM US ABS. W T. R EL. % TBW 0.13 0.26 0.21 0.11 0.18 0.26 0.30 0.04 0.08 0.06 0.03 0.05 0.08 0.10 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 0.06 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 0.25 0.08 OVARY LEFT ABS. R EL. W T. % TBW a 0.054 0.053 0.045 0.033 0.045 0.054 0.043 19.01 16.56 13.43 9.24 13.60 16.07 14.43 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 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 0.046 14.70 OVARY R IG H T ABS. R EL. W T. % TBW a 0.068 0.063 0.057 0.042 0.04 9 0.054 0.050 23.94 19.69 1 7 .0 1 11.76 14.80 16.07 16.78 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 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 1 5 .1 1 1 8 .7 7 18.29 17.70 25.60 15.97 0.053 16.93 U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW 0.48 0.80 0.65 0.34 0.70 0.45 0.58 0.17 0.25 0.19 0.10 0.21 0.13 0.19 0.49 0.38 0.78 0.87 0.33 0.66 0.40 0.48 0.39 0.30b 0.79 0.51 0.53 0.70 0.32b 0.42 0.60 0.43 0.52 0.42 0.13 0.12 0.24 0.26 0.12 0.22 0.14 0.15 0.12 0.09 0.23 0.16 0.18 0.21 0.09 0.13 0.18 0.13 0.18 0.13 0.74 0.24 A LL a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . V a lu e was m u ltip lie d b y 1000. Dam aged d u rin g p ro c e s s in g (w e ig h t n o t A B S . W T. affected). = ORGAN W EIG H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE E36 (P A G E 3) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page 588 DOSAGE GROUP I I RAT T ER M IN A L BO DY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a 13 6 2 1363 13 6 4 1367 13 6 8 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 13 9 2 1393 1397 1399 1401 1404 1407 14 0 9 14 10 14 13 14 15 14 16 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 3 5 5 . 0.021 282. 0.016 308. 0.017 350. 0.023 262 . 338. 0.014 0.012 344 . 347. 0.017 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. 339. 0.015 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 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . a . V a lu e w as m u ltip lie d b y 1000 . 1 M G/KG/DAY B R A IN ABS. W T. R EL. % 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 LIV E R ABS. W T. R EL. % 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 1 6 .1 7 18.85 16.60 1 7 .4 1 16.58 13.63 15.01 15.09 15.90 18.06 16.36 17.79 15.44 1 5 .7 1 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 K ID N EY LEFT ABS. R EL. W T. % 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 .5 1 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 K ID N EY R IG H T ABS. R EL. W T. % 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 .5 1 1.29 1 .5 1 1.15 1.43 1.29 1.59 1.29 1.57 1.38 1.19 1.22 1.36 1.28 1 .5 1 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 A D R EN A L LEFT ABS. R EL. W T. % 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 1 5 .7 7 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 . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE E3 6 (PAG E 4) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 589 DOSAGE GROUP I I 1 M G/KG/DAY RAT T ER M IN A L BO DY IM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a S P LEEN ABS. W T. R EL. % TBW THYM US ABS. W T. R EL. % TBW OVARY LEFT ABS. R EL. W T. % TBW a OVARY R IG H T ABS. R EL. W T. % TBW a U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW 13 6 2 13 6 3 1 3 64 1367 1368 1371 1375 1376 1378 1379 1381 13 8 2 13 8 3 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 14 13 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 1 0 .1 7 16.88 15.34 13.53 11.04 0.73 0.50 0.47 0.50 0.53 0.56 0.64 0.58 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 0.25 0.16 0.14 0.17 0.17 0.16 0.21 0.16 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 0.20 0.17 0.07 0.11 0.20 0.21 0.19 0.24 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 0.07 0.06 0.02 0.04 0.06 0.06 0.06 0.07 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 0.062 0.055 0.055 0.054 0.054 0.087 0.050 0.046 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 21.60 17.86 17.03 18.18 17.42 24.72 16.72 12.78 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 0.064 0.076 0.061 0.058 0.054 0.032 0.040 0.056 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 22.30 24.68 18.88 19.53 17.42 9.09 13.38 15.56 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 0.80 0.68 0.46 0.62 0.50 0.55 0.67 0.38 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 0.28 0.22 0.14 0.21 0.16 0.16 0.22 0.10 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 1W E I G H T S W E R E R E C O R D E D I N G R A M S ( G ) . A B S . W T. = ORGAN W EIG H T . a . V a lu e was m u ltip lie d b y 1000. b . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W E IG H T ) X 1 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) T A B L E E 3 6 (P A G E 5 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 590 DOSAGE GROUP I I I 3 M G/KG/DAY RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 14 6 3 1465 14 6 8 1469 1472 1474 1476 1477 14 8 0 326. 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. 332 . 0.016 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. 335 . 0.013 0.021 340. 0.018 2.76 4.23 5.15 4.79 5.52 4.19 4.46 5.28 4.82 4 .7 1 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 B R A IN ABS. W T. R EL. % 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 .1 7 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 LIV E R ABS. W T. R EL. % 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 K ID N EY LEFT ABS. R EL. 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 .5 1 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 .3 1 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 K ID N EY R IG H T ABS. R EL. 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 A D R EN A L LEFT ABS. R EL. W T. % TBW a 0.049 0.048 0.051 0.046 0.048 0.042 0.041 0.041 0.044 0.048 0.046 0.053 0.040 0.041 0.043 0.041 0.032 0.043 0.037 0.043 0.041 0.046 0.051 0.036 0.050 0.033 0.055 0.058 15.03 15.64 13.82 1 3 .7 7 15.58 11.73 13.06 12.02 14.15 13.30 13.37 1 5 .7 7 11.66 12.39 14.28 12.35 9.73 11.68 11.01 14.24 13.80 15.33 16.09 11.65 16.13 9.22 16.42 17.06 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S (G) . a . V a lu e was m u ltip lie d b y 1000. A B S . W T. = O RGAN W EIG H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T) X 1 0 0 . b . R a t 1428 had s lig h t d ila tio n o f th e p e lv is in b o th k id n e y s . c . V a lu e w as p re su m e d in c o r r e c t ly re c o rd e d ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s a n d s t a t i s t i c a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E3 6 (PA G E 6) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R A TS ARGUS 418-020 Page 591 DOSAGE GROUP I I I 3 M G/KG/DAY RAT T ER M IN A L BO D Y NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 14 6 5 14 6 8 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 S P LEEN ABS. W T. R EL. % 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 0.70 0.58 0.62 0.67 0.70 0.18 0.21 0.16 0.18 0.19 0.20 0.18 0.19 0.19 0.14 0.21 0.18 0.20 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 THYM US ABS. W T. R EL. % 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 0.20 0.21 0.23 0.35 0.29 0.12 0.18 0.18 0.22 0.18 0 .1 7 0.40 0.24 0.19 0.10 0.23 0.07 0.06 0.06 0.04 0.06 0.08 0.09 0.08 0.02 0.06 0.03 0.06 0.06 0.06 0.08 0.10 0.09 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. R EL. W 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 R IG H T ABS. R EL. W T. % 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 U TER U S N O N -G R A V ID ABS. R EL. W T. % 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 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . a . V a lu e was m u ltip lie d b y 1000 . b . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % TBW = (OR G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE E36 (P A G E 7) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G E N ER A T IO N FEM A LE RATS ARGUS 418-020 Page 592 DOSAGE GROUP IV RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a 1482 1483 1486 1488 1490 1491 1494 1496 1497 15 0 0 1502 1505 1507 1508 1511 1513 15 14 1516 1517 1519 1521 1523 15 2 4 1527 1528 1531 15 3 3 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 . 326. 0.011 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 M G/KG/DAY B R A IN ABS. W T. R EL. % TBW LIV E R ABS. W T. R EL. % TBW K ID N EY LEFT ABS. R EL. W T. % TBW K ID N EY R IG H T ABS. R EL. W T. % TBW A D R EN A L LEFT ABS. R EL. W T. % TBW a 2.23 0.71 15.34 4.90 1.26 0.40 1.25 0.40 0.045 14.38 1.90 2.06 2.12 2.05 2.12 1.76 2.23 1 .9 7 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 18.55 17.62 20.37 16.20 16.00 16.62 15.83 16.39 14.76 1 6 .7 7 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 1.37 1.33 1.65 1.24 1.52 1.33 1.50 1.48 1.18 1 .5 1 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 1.31 1.41 1.56 1.28 1.49 1.28 1.48 1.49 1.22 1.68 1 .5 1 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 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 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 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 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 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 1.8 1 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 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 1 5 .7 7 A B S . W T. O RGAN W EIG H T . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE E36 (P A G E 8) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 593 DOSAGE GROUP IV RAT T ER M IN A L BO D Y NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a 1482 1483 1486 1488 1490 1491 1494 1496 1497 15 0 0 1502 15 0 5 15 0 7 1508 1511 15 13 15 14 15 16 15 17 1519 15 2 1 1523 1524 1527 1528 1531 1533 15 3 4 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 was multiplied by 1000. 10 M G/KG/DAY S P LEEN ABS. W T. R EL. % 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 0.51 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 0.18 0.17 0.18 0.18 0.13 0.18 0.19 0.16 0.15 0.22 0.16 0.19 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 THYM US ABS. W T. R EL. % TBW 0.29 0.11 0.33 0.26 0.10 0.12 0.15 0.26 0.24 0.13 0.23 0.21 0.13 0.10 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 0.09 0.03 0.09 0.07 0.03 0.03 0.05 0.07 0.08 0.04 0.07 0.06 0.04 0.04 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. R EL. W T. % 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 R IG H T ABS. R EL. W T. % TBW a 0.044 14.06 0.049 0.033 0.068 0.049 0.059 0.063 0.070 0.054 0.066 0.045 0.056 0.044 15.51 9.19 18.48 15.51 1 6 .7 1 19.75 19.72 17.88 20.50 14.15 16.42 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 U TER U S N O N -G R A V ID ABS. R EL. W T. % 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 A B S . W T. O RGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE E3 6 (P A G E 9) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 594 DOSAGE GROUP V 30 M G /K G /D AY RAT T ER M IN A L BODY NUM BER W EIG H T P IT U IT A R Y ABS. W T. R EL. % TBW a 1541 1544 1545 1546 1548 1550 15 5 2 1555 1557 1558 15 6 0 15 6 4 15 6 5 15 6 6 1568 1571 1573 1576 1578 1579 15 8 3 1584 1586 1587 1588 1589 1591 1593 15 9 8 1600 2 9 6 . 0.022 342. 298. 0.016 0.012 329. 0.019 306. 0.017 298. 0.016 319. 0.018 312. 0.009 319. 0.018 288. 0.011 325. 309. 0.015 0.012 275. 324. 0.013 0.010 339. 304. 0.018 0.010 336. 0.015 292. 0.015 NOT PREGNANT 346. 0.013 303 . 0.014 2 94 . 0.016 294 . 0.015 300. 0.014 322 . 0.016 354 . 0.015 318. 0.015 342 . 0.023 317. 354 . 0.015 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 B R A IN ABS. W T. 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 R EL. % TBW 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 LIV E R ABS. W T. R EL. % 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 K ID N EY LEFT ABS. R EL. W T. % TBW 1.11 1.57 1.40 1.32 1.49 1.29 1.43 1.21 1.30 1.50 1.37 1 .3 7 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 .3 7 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 K ID N EY R IG H T ABS. R EL. W T. % 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 A D R EN A L LEFT ABS. R EL. W T. % 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 1 3 .1 7 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 1 7 .0 1 13.67 14.60 12.99 14.78 13.45 14.20 16.67 ALL a. b. W EIG H T S W ERE R EC O R D ED I N GRAM S (G ) . V a lu e was m u ltip lie d b y 1000. R a t 1593 h a d m o d e ra te d ila t io n o f th e ABS. p e lv is W T. = O RGAN W EIG H T . in th e r ig h t k id n e y . R E L . % TBW = (O R G AN W E IG H T / T E R M IN A L B O D Y W EIG H T ) X 1 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) T A B LE E3 6 (P A G E 10 ) : T E R M IN A L B O D Y W E IG H T S A N D O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O T E R M IN A L B O D Y W E IG H T IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 595 DOSAGE GROUP V 30 M G /K G /D A Y RAT T ER M IN A L B O D Y NUM BER W EIG H T A D R EN A L R IG H T ABS. R EL. W T. % TBW a 1541 1544 1545 1546 1548 1550 15 5 2 15 5 5 1557 1558 15 6 0 15 6 4 1565 1566 1568 1571 1573 1576 1578 1579 15 8 3 1584 1586 1587 1588 1589 1591 1593 1598 1600 296. 342 . 298. 329. 306. 298. 319. 3 12 . 319. 288. 325. 309. 275. 324 . 339. 304 . 336. 292 . 0.. 0 4 3 0., 0 5 0 0., 0 5 4 0., 0 4 4 0., 0 4 9 0., 0 5 3 0., 0 3 9 0., 0 4 0 0., 0 3 4 0., 0 3 9 0.. 0 4 3 0., 0 4 8 0.. 0 4 4 0., 0 3 5 0., 0 3 4 0.. 0 4 4 0.. 0 3 0 0.. 0 3 9 NOT PREGNANT 346. 0.. 0 3 7 303 . 0.. 0 3 6 294 . 0.. 0 3 9 294. 0.. 0 4 0 300. 0.. 0 3 4 322 . 0., 0 4 6 354. 0., 0 4 2 318. 0., 0 4 3 342. 0., 0 4 1 317, 0.. 0 3 7 354. 0.. 0 4 4 1 4 ,. 5 3 1 4 . .62 18., 12 1 3 .. 3 7 1 6 . ,01 17.,78 12,.22 12,. 8 2 10,.66 1 3 ,. 5 4 1 3 ,. 2 3 1 5 , .53 1 6 , .00 10,. 8 0 10,. 0 3 1 4 ,. 4 7 8. 9 3 1 3 ,. 3 6 10,. 6 9 11,.88 13 . 26 1 3 ,. 6 0 11,. 3 3 1 4 , .28 11,.86 1 3 ,. 5 2 11,. 9 9 11, 6 7 12, 4 3 S P LEEN ABS. W T. 0,, 5 0 0., 7 6 0,, 6 4 0., 5 9 0., 8 0 0., 6 0 0., 5 7 0. 5 2 0,. 4 8 0,. 7 4 0,. 6 5 0.. 6 5 0,. 6 4 0,. 5 6 0,. 5 6 0,. 5 6 0., 4 7 0,, 6 2 0,, 6 9 0,. 4 8 0,. 5 1 0,. 5 0 0. 5 2 0,. 5 8 0,. 5 9 0.. 6 4 0,, 9 5 0., 5 1 0..66 R EL. % TBW 0,. 1 7 0,.22 0,.21 0.. 1 8 0,. 2 6 0,.20 0,. 1 8 0,. 1 7 0,. 1 5 0. 2 6 0,.20 0,.21 0,. 2 3 0,. 1 7 0,. 1 6 0. 1 8 0,. 1 4 0,.21 0..20 0. 1 6 0,. 1 7 0,. 1 7 0,. 1 7 0,. 1 8 0,. 1 7 0,.20 0,. 2 8 0, 1 6 0.. 1 9 THYM US ABS. W T. 0,.20 0. 4 4 0,. 2 3 0,. 2 5 0,.21 0,. 1 4 0,.11 0,.21 0,.12 0,. 2 4 0,. 2 9 0,. 2 4 0. 2 6 0. 1 9 0,. 1 9 0,. 1 2 0,.20 0. 1 7 0,. 1 3 0,. 1 6 0,. 3 3 0,.12 0,. 2 6 0,. 3 7 0. 1 6 0,.22 0.. 5 0 0..20 0., 1 6 R EL. % TBW 0,. 0 7 0,. 1 3 0. 0 8 0,. 0 8 0,. 0 7 0,. 0 5 0,. 0 3 0,. 0 7 0,. 0 4 0,. 0 8 0,. 0 9 0,. 0 8 0,. 0 9 0,. 0 6 0,. 0 6 0,. 0 4 0,. 0 6 0,. 0 6 0., 0 4 0,. 0 5 0,.11 0,. 0 4 0,. 0 9 0..11 0., 0 4 0., 0 7 0.. 1 5 0., 0 6 0.. 0 4 OVARY LEFT ABS. R EL. W T. % TBW a 0. 0 3 7 0. 0 9 8 0. 0 3 8 0. 0 5 8 0. 0 6 2 0. 0 5 0 0. 0 5 8 0. 0 4 0 0. 0 4 4 0. 0 5 8 0. 0 3 8 0. 0 5 1 0. 0 6 4 0. 0 4 5 0. 0 4 6 0. 0 3 2 0,. 0 4 3 0,. 0 4 3 12. 5 0 28 .65 12 . 7 5 1 7 .63 20 . 2 6 16,.78 18,.18 12 . 8 2 13 .79 20 . 1 4 11,. 6 9 16,.50 23 . 2 7 1 3 ,. 8 9 1 3 ,. 5 7 10,. 5 3 12,. 8 0 1 4 ,. 7 3 0,. 0 5 1 0. 0 6 8 0. 0 5 2 0,. 0 4 3 0,. 0 6 0 0,. 0 4 3 0,. 0 4 3 0,. 0 4 9 0,. 0 6 9 0,. 0 6 5 0,. 0 4 6 14 . 74 22 . 4 4 1 7 ,.69 1 4 ,. 6 2 20,.00 1 3 ,. 3 5 12,. 1 5 15,.41 20,. 1 8 20.. 5 0 12.. 9 9 OVARY R IG H T ABS. R EL. W T. % TBW a 0. 0 4 9 0. 0 8 9 0. 0 6 8 0,. 0 6 5 0,. 0 4 9 0,. 0 4 9 0,. 0 5 5 0. 0 3 1 0. 0 4 3 0. 0 5 8 0,. 0 6 8 0,. 0 6 8 0,. 0 5 4 0,. 0 4 3 0,. 0 5 2 0,. 0 3 5 0,. 0 4 2 0,. 0 5 4 16 .55 2 6 .02 22 . 8 2 19,.76 1 6 .01 16,.44 1 7 , .24 9 .94 13 .48 20 . 1 4 20,. 9 2 22 .01 19..64 13 .27 1 5 ,. 3 4 11,. 5 1 12,. 5 0 18,.49 0,. 0 4 1 0,. 0 4 0 0,. 0 6 6 0,. 0 3 5 0,. 0 5 5 0,. 0 4 5 0.. 0 4 5 0,, 0 4 1 0., 0 6 9 0., 0 5 1 0.. 0 4 5 11,. 8 5 1 3 ,.20 22 ,. 4 5 11. 9 0 1 8 . ,33 1 3 ,. 9 8 12., 7 1 12., 8 9 20 ., 1 8 1 6 . .09 12.. 7 1 U TER U S N O N -G R A V ID ABS. R EL. W T. % TBW 0. 5 6 0. 8 2 0. 3 9 0. 3 7 0. 8 2 0. 2 7 0. 9 4 0. 4 9 0. 3 6 0. 7 1 0. 8 2 0. 4 5 0. 6 7 0. 4 6 b 0,. 4 2 0,. 3 1 0,. 3 9 0,. 3 4 0. 1 9 0. 24 0,. 1 3 0,. 1 1 0,. 2 7 0,. 0 9 0,. 2 9 0,. 1 6 0,. 1 1 0,. 2 5 0,. 2 5 0,. 1 4 0,. 2 4 0,. 1 4 0,, 1 2 0,. 1 0 0.. 1 2 0., 1 2 0,.66 0,. 3 8 0,. 5 1 0,. 4 5 0. 5 9 0,. 8 3 0,. 4 5 0,, 5 6 0,, 6 1 0., 6 0 0., 4 4 0,, 1 9 0,. 1 2 0., 1 7 0., 1 5 0..20 0., 2 6 0. 1 3 0. 1 8 0. 1 8 0. 1 9 0. 12 ALL a. b. W E I G H T S W E R E R E C O R D E D I N G R A M S <( G ) . V a lu e was m u ltip lie d b y 1000. Dam aged d u rin g p ro c e s s in g (w e ig h t n o t A B S . W T. affected). == O R G A N W E I G H T . R E L . % T B W == ( O R G A N W E I G H T / T E R M I N A L B O D Y W E I G H T ) X 1 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) T A B L E E 3 7 (P A G E 1 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE RATS ARGUS 418-020 Page 596 DOSAGE GROUP I 0 M G/KG/DAY RAT NUM BER 1302 1304 1306 1308 13 10 13 12 13 13 1316 1318 1321 1325 1328 1330 1331 13 3 4 1335 1336 1338 1340 1341 13 4 2 1344 1345 1346 1348 1350 1353 1355 1358 1359 B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW 2.10 0.022 2.10 0.021 2.05 2.01 0.017 0.018 1.99 0.014 2 . 1 5 0.022 2 . 1 4 0.020 N O T :P R E G N A N T 2.06 0.017 2.05 2.00 0.014 0.009 2.09 2.00 0.015 0.018 2.33 0.018 1.96 1.93 0.016 0.012 2.06 2.10 0.016 0.022 2.07 0.015 2.06 0.029 1.93 2.26 0.023 0.020 2.03 0.014 2.03 0.018 2.05 0.015 2.03 2.22 0.016 0.024 2.04 0.007 N O T P R EG N A N T ; M A TIN G 2.10 0.017 1.05 1.00 0.83 0.90 0.70 1.02 0.93 14.52 17.50 17.30 18.06 18.04 14.95 15.73 0.82 0.68 17.38 18.67 0.45 17.15 0.72 17.40 0.90 12.61 0.77 14.43 0.82 15.10 0.62 15.81 0.78 17.19 1.05 18.61 0.72 16.97 1.41 16.15 1.19 0.88 14.09 17.38 0.69 17.73 0.89 17.30 0.73 18.89 0.79 18.24 1.08 15.33 0.34 16.39 N O T 1C O N F I R M E D 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 K ID N EY LEFT ABS. R EL. 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 .6 1 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 K ID N EY R IG H T ABS. R EL. W T. % 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 .4 1 1.32 1.41 1.57 1.42 1 .3 1 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 A D R EN A L LEFT ABS. R EL. 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 .6 7 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 .7 1 1 .8 1 0.031 1.48 A D R EN A L R IG H T ABS. R EL. W T. % BRW 0.028 0.038 0.037 0.041 0.047 0.035 0.030 1.33 1 .8 1 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. % 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) T A B LE E3 7 (P A G E 2) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 597 DOSAGE GROUP I 0 M G/KG/DAY RAT NUM BER 1302 1304 1306 1308 13 10 13 12 13 13 13 16 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW THYM US ABS. W T. R EL. % BRW 2.10 2.10 2.05 2.01 1.99 0.63 0.53 0.59 0.72 0.66 30.00 25.24 28.78 35.82 33.16 0.13 0.26 0.21 0.11 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 2.00 0.71 0.57 34.63 28.50 0.16 0.23 2.09 2.00 2.33 1.96 1.93 2.06 2.10 0.61 0.56 0.56 0.52 0.56 0.47 0.65 29.19 28.00 24.03 26.53 29.02 22.82 30.95 0.15 0.16 0.20 0.22 0.20 0.10 0.19 2.07 0.76 36.71 0.30 2.06 1.93 2.26 0.55 0.60 0.64 26.70 31.09 28.32 0.31 0.20 0.20 2.03 2.03 0.65 0.52 32.02 25.62 0.13 0.20 2.05 2.03 2.22 2.04 0.57 0.66 0.52 0.43 27.80 32.51 23.42 21.08 0.18 0.15 0.26 0.12 N O T P R E G N A N T ; M A TIN G N O T C O N FIR M ED 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 OVARY LEFT ABS. R EL. W T. % BRW 0.054 0.053 0.045 0.033 0.045 0.054 0.043 2.57 2.52 2.20 1.64 2.26 2.51 2.01 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 2.67 2.20 1.85 2.10 2.00 2.14 1.48 2.02 2.28 2.10 3.38 2 .7 7 3.00 3.01 2.41 4.19 3.07 2.56 2.75 2.20 0.046 2.19 OVARY R IG H T ABS. R EL. W T. % BRW 0.068 0.063 0.057 0.042 0.049 0.054 0.050 3.24 3.00 2.78 2.09 2.46 2.51 2.34 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 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 0.053 2.52 U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW 0.48 0.80 0.65 0.34 0.70 0.45 0.58 22.86 38.10 3 1.7 1 16.92 35.18 20.93 27.10 0.49 0.38 0.78 0.87 0.33 0.66 0.40 0.48 0.39 0.30a 0.79 0.51 0.53 0.70 0.32a 0.42 0.60 0.43 0.52 0.42 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 0.74 35.24 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) T A B LE E 3 7 (P A G E 3) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 598 DOSAGE GROUP I I 1 M G/KG/DAY RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW 1362 1363 13 6 4 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 13 92 1 3 93 13 97 1399 1401 1404 1407 1409 1410 14 13 1415 1416 1418 2.09 0.015 2.13 2.10 0.017 0.019 1.98 0.016 1.95 0.014 2.34 2.00 0.013 0.017 2.05 0.014 NOT PREGNANT 2 . 3 2 0.021 2.13 0.016 2.06 0.017 1.97 0.023 1.94 2.06 0.014 0.012 2.04 2.23 2.02 2.10 0.017 0.021 0.013 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). LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW 14.91 15.01 17.48 13.92 15.62 19.98 1 4 .1 7 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 .3 1 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 .1 7 18.85 16.60 1 7 .4 1 16.58 13.63 15.01 15.09 15.90 18.06 16.36 17.79 15.44 1 5 .7 1 622.41 622.54 767.96 874.62 625.77 848.54 792.65 845.29 821.78 829.05 733.63 698.97 739.41 728.98 771.84 880.98 714.41 926.56 692.38 730.70 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 .5 1 1.29 1 .5 1 1.15 1.43 1.29 1.59 1.29 1.57 1.38 1.19 1.22 1.36 1.28 1 .5 1 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 .9 7 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) T A B LE E 3 7 (P A G E 4) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 599 DOSAGE GROUP I I 1 M G/KG/DAY RAT NUM BER 1362 1363 13 6 4 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 14 13 14 15 1416 1418 B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW 2.09 0.73 2.13 2.10 0.50 0.47 1.98 0.50 1.95 0.53 2.34 2.00 0.56 0.64 2.05 0.58 N O T :P R E G N A N T 2.32 0.60 2.13 0.50 2.06 0.83 1 .9 7 0.59 1.94 0.57 2.06 2.04 0.59 0.68 2.23 2.02 2.10 0.61 0.57 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 THYM US ABS. W T. 0.20 0.17 0.07 0.11 0.20 0.21 0.19 0.24 R EL. % BRW 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 1 0 .7 7 13.79 9.66 9 .7 1 9.76 7.42 16.67 6.28 6.51 OVARY LEFT ABS. R EL. W T. % 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 R IG H T ABS. R EL. W 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 U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW 0.80 0.68 0.46 0.62 0.50 0.55 0.67 0.38 38.28 31.92 21.90 3 1.3 1 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . a . Dam aged d u r in g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % TBW = (O R G AN W E IG H T / B R A IN W EIG H T ) X 1 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) T A B LE E 3 7 (P A G E 5) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 600 DOSAGE GROUP I I I 3 M G/KG/DAY RAT NUM BER B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW LIV E R ABS. W T. R EL. % BRW K ID N EY LEFT ABS. R EL. W T. % BRW K ID N EY R IG H T ABS. R EL. W T. % BRW A D R EN A L LEFT ABS. R EL. W T. % BRW A D R EN A L R IG H T ABS. R EL. W T. % BRW 1421 14 2 4 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 2.12 0.013 0.019 2.18 0.016 1.85 2.02 0.017 0.015 1.95 2.20 0.014 0.018 2.18 2.01 0.015 0.017 2.05 0.016 2.07 0.018 NOT PREGNANT 2.23 0.015 2.13 0.015 1.96 2.27 0.016 0.012 2.13 0.017 NOT PREGNANT 2.04 2.00 0.018 0.017 2.07 0.016 1.99 2.02 0.006 0.015 2 .1 7 0.016 2.08 2.10 0.013 0.014 1.96 2.25 0.013 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 16.89 16.43 18.04 16.19 15.49 19.48 16.49 15.80 17.76 16.30 15.42 14.80 17.20 18.62 1 5 .7 7 18.40 16.01 17.41 13.89 14.98 15.23 14.72 15.62 15.33 14.41 17.55 17.98 17.23 861.73 801.46 850.94 742.66 837.30 964.36 845.64 718.18 814.68 810.94 752.20 714.98 771.30 874.18 804.59 810.57 751.64 853.43 694.50 723.67 765.33 728.71 719.82 737.02 686.19 895.41 799.11 808.92 1.44 1.42 1.37 1.50a 15.30b 1.49 1.36 1.28 1.41 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 1.45 1.29 1.34 1 .5 1 1.54 65.02 60.56 68.37 66.52 72.30 1.45 1.29 1.34 1.38 1.45 1.24 1.62 1 .3 1 1.50 1.48 1.43 71.08 64.50 64.73 69.35 71.78 57.14 77.88 62.38 76.53 65.78 67.14 1.40 1.36 1.40 1.54a 1.63 1.63 1.42 1.30 1.47 1.43 1.38 1.33 1.50 1.36 1.38 1.44 1.55 1.48 1.32 1.32 1.25 1.45 1.26 1.32 1.37 1.48 1.50 1.44 71.43 66.34 66.04 70.64 88.11 80.69 72.82 59.09 67.43 71.14 67.32 64.25 67.26 63.85 70.41 63.44 72.77 72.55 66.00 63.77 62.81 71.78 58.06 63.46 65.24 75.51 66.67 67.60 0.049 0.048 0.051 0.046 0.048 0.042 0.041 0.041 0.044 0.048 0.046 0.053 0.040 0.041 0.043 0.041 0.032 0.043 0.037 0.043 0.041 0.046 0.051 0.036 0.050 0.033 0.055 0.058 2.50 2.34 2.40 2.11 2.59 2.08 2.10 1.86 2.02 2.39 2.24 2.56 1.79 1.92 2.19 1 .8 1 1.50 2.11 1.85 2.08 2.06 2.28 2.35 1.73 2.38 1.68 2.44 2.72 0.043 0.046 0.046 0.047 0.042 0.043 0.050 0.039 0.039 0.044 0.042 0.052 0.037 0.039 0.037 0.028 0.042 0.036 0.033 0.041 0.036 0.033 0.039 0.043 0.042 0.038 0.053 0.048 2.19 2.24 2.17 2.16 2.27 2.13 2.56 1.77 1.79 2.19 2.05 2.51 1.66 1.83 1.89 1.23 1.97 1.76 1.65 1.98 1 .8 1 1.63 1.80 2.07 2.00 1.94 2.36 2.25 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . A B S . W T. = ORGAN W EIG H T . R E L . % TBW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 0 0 . a . R a t 1428 had s lig h t d ila tio n o f th e p e lv is in b o th k id n e y s . b . V a lu e a p p e a re d in c o r r e c tly re c o rd e d ; v a lu e s e x c lu d e d fro m g ro u p a v e ra g e s an d s t a t i s t ic a l a n a ly s e s . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E 3 7 (P A G E 6) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 601 DOSAGE GROUP I I I 3 M G/KG/DAY RAT NUM BER 14 2 1 14 2 4 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 14 4 6 1448 1450 1452 1455 1456 1458 1459 1461 1463 14 6 5 1468 1469 1472 14 74 1476 1477 1480 B R A IN W EIG H T S PLEEN ABS. W T. R EL. % BRW 1.96 0.58 2.05 2.12 0.64 0.61 2.18 0.62 1.85 2.02 0.58 0.71 1.95 2.20 0.55 0.64 2.18 2.01 0.58 0.52 2.05 0.73 2 .0 7 0.60 N O T :P R E G N A N T 2.23 0.70 2.13 0.58 1.96 0.62 2 .2 7 0.67 2.13 0.70 N O T :P R E G N A N T 2.04 2.00 0.57 0.55 2 .0 7 0.57 1.99 2.02 0.51 0.55 2 .1 7 0.56 2.08 2.10 0.61 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 THYM US ABS. W T. R EL. % 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 0.20 0.21 0.23 0.35 0.29 0.12 0.18 0.18 0.22 0.18 0.17 0.40 0.24 0.19 0.10 0.23 11.73 9.76 9.90 6.42 10.81 14.36 14.36 11.82 3.21 11.44 5.36 10.63 8.97 9.86 11.73 15.42 13.62 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. R EL. W T. % 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 0.042 0.033 0.047 0.069 0.052 0.038 0.038 0.046 0.056 0.071 0.054 0.064 0.043 0.050 0.040 0.051 1.73 2.78 2.22 2.71 3.03 3 .71 2.82 3.09 1.70 2.09 3.02 2 .1 7 1.88 1.55 2.40 3.04 2.44 1.86 1.90 2.22 2.81 3.51 2.49 3.08 2.05 2.55 1.78 2.39 OVARY R IG H T ABS. R EL. W T. % 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 0.045 0.044 0.043 0.062 0.068 0.045 0.035 0.046 0.056 0.057 0.056 0.062 0.037 0.059 0.039 0.051 1.78 1.51 2.50 2.52 3.46 2.77 2.20 1.54 2.02 2.79 2.78 1.98 2.02 2.06 2.19 2.73 3.19 2.20 1.75 2.22 2.81 2.82 2.58 2.98 1.76 3.01 1.73 2.39 U TER U S N O N -G R A V ID ABS. R EL. 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 2 3 .1 1 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) T A B L E E 3 7 (P A G E 7 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 602 DOSAGE GROUP IV 10 M G /KG /D AY RAT NUM BER 1482 1483 1486 1488 1490 1491 14 9 4 14 9 6 1497 1500 1502 1505 15 0 7 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 15 3 3 1534 1537 1539 B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW 2.23 0.015 N O T :P R E G N A N T 1.90 0.017 2.06 2.12 0.013 0.015 2.05 2.12 0.014 0.016 1.76 0.015 2.23 0.016 1.97 0.018 2.05 0.014 2.05 2.21 2.20 0.015 0.015 0.013 N O T :P R E G N A N T 2.24 0.017 2.19 0.016 2.15 0.014 2.03 0.013 2.08 0.017 2.18 2.02 1.98 0.016 0.011 0.010 2.14 2.11 0.023 0.015 2.15 2.11 2.20 0.014 0.017 0.015 1.93 2.22 0.015 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 LIV E R ABS. W T. R EL. % BRW 15.34 687.89 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 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 K ID N EY LEFT ABS. R EL. W T. % BRW 1.26 56.50 1.37 1.33 1.65 1.24 1.52 1.33 1.50 1.48 1.18 1 .5 1 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 1.28 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 K ID N EY R IG H T ABS. R EL. W T. % BRW 1.25 56.05 1 .3 1 1.41 1.56 1.28 1.49 1.28 1.48 1.49 1.22 1.68 1 .5 1 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 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 1.8 1 58.04 63.01 59.07 55.66 75.00 65.14 68.32 6 1 .1 1 66.36 72.51 73.49 76.30 62.27 64.77 81.53 A D R EN A L LEFT ABS. R EL. W T. % BRW 0.045 2.02 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 .3 1 1.86 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 1.92 2.42 1 .6 7 2.12 2.26 2.11 2.03 1.52 2.38 2.08 2.51 2.51 1.86 2.38 2.52 A D R EN A L R IG H T ABS. R EL. W T. % BRW 0.035 1.57 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 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 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) T A B L E E 3 7 (P A G E 8 ) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 603 DOSAGE GROUP IV RAT NUM BER B R A IN W EIG H T S PLEEN ABS. W T. R EL. % BRW 1482 1483 1486 1488 14 9 0 1491 14 9 4 14 9 6 1497 1500 1502 15 0 5 1507 1508 1511 15 13 1514 15 16 1517 1519 1521 15 2 3 1524 1527 15 2 8 1531 15 3 3 1534 1537 1539 2.23 0.53 N O T :P R E G N A N T 1.90 0.58 2.06 2.12 0.61 0.66 2.05 2.12 0.56 0.46 1.76 2.23 0.57 0.68 1 .9 7 0.48 2.05 0.48 2.05 2.21 2.20 0.70 0.54 0.64 N O T :P R E G N A N T 2.24 0.51 2.19 0.67 2.15 0.55 2.03 0.58 2.08 0.52 2.18 2.02 0.60 0.54 1.98 0.74 2.14 2.11 0.82 0.67 2.15 2.11 2.20 0.67 0.66 0.50 1.93 2.22 0.51 0.57 2 3 .7 7 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 M G/KG/DAY THYM US ABS. W T. R EL. % BRW 0.29 0.11 0.33 0.26 0.10 0.12 0.15 0.26 0.24 0.13 0.23 0.21 0.13 0.10 0.16 0.18 0.10 0 .1 7 0.08 0.35 0.38 0.23 0.26 0.30 0.20 0.17 0.15 0.29 13.00 5.79 16.02 12.26 4.88 5.66 8.52 11.66 12.18 6.34 11.22 9.50 5.91 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 OVARY LEFT ABS. R EL. W T. % BRW 0.046 2.06 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 .5 1 1.84 2.56 2.91 2.34 3.07 2.34 1.8 1 2.18 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 OVARY R IG H T ABS. R EL. W T. % BRW 0.044 1.97 0.04 9 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 0.048 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 U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW 0.68 3 0 . 4 9 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 0.62 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) T A B LE E3 7 (P A G E 9) : B R A IN W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (% ) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 604 DOSAGE GROUP V 30 M G /KG /D AY RAT NUM BER 1541 1544 1545 1546 1548 1550 15 5 2 1555 1557 1558 15 6 0 15 6 4 15 6 5 1566 1568 1571 1573 1576 1578 1579 15 8 3 1584 1586 1587 15 8 8 1589 159 1 15 9 3 1598 16 0 0 B R A IN W EIG H T P IT U IT A R Y ABS. W T. R EL. % BRW 2.00 0.022 2.12 0.016 2 . 1 3 0.012 2.04 2.02 0.019 0.017 2.05 0.016 2.19 0.018 2.03 2.20 2.01 2.21 2.00 0.009 0.018 0.011 0.015 0.012 2.03 2.13 2.21 1 .9 1 0.013 0.010 0.018 0.010 2.03 0.015 1.78 0.015 NOT PREGNANT 1.99 2.11 0.013 0.014 2.13 0.016 2.15 2.02 2.10 2.02 2.11 0.015 0.014 0.016 0.015 0.015 2.04 0.023 2.18 2.18 0.015 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 LIV E R ABS. W T. R EL. % 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 K ID N EY LEFT ABS. R EL. W 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 K ID N EY R IG H T ABS. R EL. 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 A D R EN A L LEFT ABS. R EL. 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 0.044 0.044 0.024 0.050 0.041 0.047 0.046 0.047 0.046 0.045 0.059 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 1.8 1 2.25 1.62 2.42 2.21 2.08 1.13 2.32 2.03 2.24 2.28 2.23 2.25 2.06 2.71 A D R EN A L R IG H T ABS. R EL. 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 0.037 0.036 0.039 0.040 0.034 0.046 0.042 0.043 0.041 0.037 0.044 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 .1 7 1.64 1.54 2.30 1.48 2.19 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. R E L . % TBW = (O R G A N W E IG H T / B R A IN W E IG H T ) X 1 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) T A B LE E 3 7 (P A G E 1 0 ) : B R A I N W E IG H T S , O R G A N W E IG H T S A N D R A T IO S (%) O F O R G A N W E IG H T T O B R A IN W E IG H T - I N D I V I D U A L D A T A F I G EN ER A T IO N FEM A LE R ATS ARGUS 418-020 Page 605 DOSAGE GROUP V 30 M G /KG /D AY RAT NUM BER 1541 1544 1545 1546 1548 15 5 0 1552 1555 1557 1558 15 6 0 15 6 4 15 6 5 15 6 6 15 6 8 1571 1573 1576 1578 1579 15 8 3 15 8 4 1586 15 8 7 15 8 8 1589 1591 15 9 3 15 9 8 16 0 0 B R A IN W EIG H T S P LEEN ABS. W T. R EL. % BRW 2.00 2.12 0.50 0.76 2.13 0.64 2.04 2.02 0.59 0.80 2.05 0.60 2.19 0.57 2.03 2.20 2.01 2.21 2.00 0.52 0.48 0.74 0.65 0.65 2.03 0.64 2.13 2.21 0.56 0.56 1.91 0.56 2.03 0.47 1.78 0.62 N O T :P R E G N A N T 1.99 2.11 0.69 0.48 2.13 0.51 2.15 2.02 2.10 2.02 2.11 0.50 0.52 0.58 0.59 0.64 2.04 0.95 2.18 2.18 0.51 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 THYM US ABS. W T. 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 R EL. % BRW 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 0.13 0.16 0.33 0.12 0.26 0.37 0.16 0.22 0.50 0.20 0.16 6.53 7.58 15.49 5.58 12.87 17.62 7.92 10.43 24.51 9.17 7.34 OVARY LEFT ABS. R EL. W T. % BRW 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 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 0.051 0.068 0.052 0.043 0.060 0.043 0.043 0.049 0.069 0.065 0.046 2.56 3.22 2.44 2.00 2.97 2.05 2.13 2.32 3.38 2.98 2.11 OVARY R IG H T ABS. R EL. W T. % BRW 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 2.45 4.20 3.19 3.19 2.42 2.39 2.51 1.53 1.95 2.88 3.08 3.40 2.66 2.02 2.35 1.83 2.07 3.03 0.041 0.040 0.066 0.035 0.055 0.045 0.045 0.041 0.069 0.051 0.045 2.06 1.90 3.10 1.63 2.72 2.14 2.23 1.94 3.38 2.34 2.06 U TER U S N O N -G R A V ID ABS. R EL. W T. % BRW 0.56 0.82 0.39 0.37 0.82 0.27 0.94 0.49 0.36 0 .7 1 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 1 8 .3 1 18.14 40.59 1 3 .1 7 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . A B S . W T. = ORGAN W EIG H T . a . Dam aged d u rin g p ro c e s s in g (w e ig h t n o t a f f e c t e d ) . R E L . % TBW = (O R G A N W E IG H T / B R A IN W EIG H T ) X 1 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) T A B LE E3 8 (P A G E 1) : N A T U R A L D E L IV E R Y , IM P LA N T A T IO N S IT E S , AND PUP V IA B IL IT Y AND S EX - IN D IV ID U A L D A TA - F I G EN ER A T IO N FE M A LE R A T S /F2 G EN ER A T IO N L IT T E R S ARGUS 418-020 Page 606 DOSAGE GROUP I 0 M G/KG/DAY RAT/ L IT T E R NUM BER D U R A T IO N O F G ES T A T IO N (D A YS ) N L IT T E R D E LIV E R E D LIV E S T IL L - TO TAL BORN BORN BORN NNN 1302 13 0 4 1306 1308 13 10 13 12 13 13 13 16 13 18 1321 1325 1328 1330 1331 13 3 4 1335 1336 1338 1340 1341 1342 13 4 4 1345 1346 1348 13 5 0 1353 1355 1358 1359 22 11 0 11 23 12 0 12 22 01 6 1 6 22 01 6 1 6 02 3 1 4 1 4 02 3 4 4 02 3 1 3 1 3 NOT 23 23 23 22 23 23 23 23 23 23 22 23 23 23 23 23 23 23 22 23 P R EG N A N T 15 17 11 13 16 16 9 12 15 17 14 12 16 15 14 10 14 17 13 15 0 15 0 17 0 11 0 13 0 16 0 16 09 0 12 0 15 0 17 0 14 0 12 0 16 0 15 2 16 0 10 2 16 0 17 0 14 (1] 0 15 N O T P R E G N A N T ; M A T IN G N O T C O N FIR M ED 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 NUM BER O F L IV E C O M P LETIO N O F D A Y 58 MF MF PUPS A T POSTPARTUM 15 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 11 86 78 56 76 79 11 4 63 66 78 88 86 48 97 78 49 64 86 13 4 67 4 11 58 58 58 58 M = M ALE F = FEM ALE [ ] = N U M B ER O F P U P S I N W H IC H C A N N IB A L IZ A T IO N A N D /O R A U T O L Y S IS P R E C LU D E D T H E D E T E R M IN A T IO N O F V I A B I L I T Y . TO TAL IM P LA N T A T IO N S 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) T A B LE E3 8 (PAG E 2) : N A TU R A L D E L IV E R Y , IM P LA N T A T IO N S IT E S , AND PUP V IA B IL IT Y AND S EX - IN D IV ID U A L D A T A - F I G EN ER A T IO N FEM A LE R A T S /F2 G EN ER A T IO N L IT T E R S ARGUS 418-020 Page 607 DOSAGE GROUP I I RAT/ L IT T E R NUM BER D U R A T IO N O F G ES T A T IO N (D A YS ) N 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 13 8 4 1387 1389 1392 13 9 3 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 = M ALE F = FEM ALE L IT T E R D E LIV E R E D L IV E S T IL L- TO TAL BORN BORN BORN NNN 7 07 11 7 1 8 01 5 1 5 01 3 1 3 01 5 1 5 01 7 1 7 01 4 1 4 21 5 1 7 12 0 12 12 0 12 01 3 1 3 11 0 11 01 3 1 3 11 6 1 7 01 6 1 6 01 7 1 7 11 1 12 12 0 12 10 0 10 12 0 12 01 5 1 5 01 5 1 5 12 0 12 01 7 1 7 01 3 1 3 01 3 1 3 01 4 1 4 01 6 1 6 1 M G/KG/DAY 1 MF NUM BER O F L IV E 1C O M P L E T I O N O F D A Y 58 MF MF PUPS AT POSTPARTUM 15 MF 22 MF 43 7 10 78 85 87 11 6 95 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 43 79 78 85 87 11 6 95 10 5 66 66 58 65 57 97 88 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 68 43 79 78 85 87 11 6 95 10 5 66 66 58 65 57 97 78 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 68 43 79 78 85 87 11 5 95 10 5 66 66 58 65 57 97 78 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 67 43 79 78 85 87 11 5 94 10 5 66 66 58 65 57 97 78 98 56 75 46 57 10 5 78 75 13 3 76 76 3 11 67 TO TAL IM P LA N T A T IO N S 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) T A B LE E38 (P A G E 3) : N A TU R A L D E L IV E R Y , IM P LA N T A T IO N S IT E S , AND PUP V IA B IL IT Y AN D S EX - IN D IV ID U A L D A TA - F I G EN ER A T IO N FEM A LE R A T S /F2 G EN ER A T IO N L IT T E R S ARGUS 418-020 Page 608 DOSAGE GROUP I I I 3 M G/KG/DAY RAT/ LIT T E R NUM BER D U R A T IO N O F G ES T A T IO N (D AYS) N 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 14 6 5 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 L IT T E R D E LIV E R E D L IV E S T IL L- TO TAL BORN BORN BORN NN N 1 7 (2) 17 13 15 17 16(1) 18 12 16 10( 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 21 4 1 6 01 4 1 4 01 4 1 4 01 5 1 5 606 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 NUM BER O F L IV E C O M P LETIO N O F D A Y 58 MF MF PUPS A T POSTPARTUM 15 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 85 47 76 6 10 5 11 93 55 10 4 79 88 3 10 M = M ALE F = FEM ALE ( ) = NUM BER O F PU PS D Y IN G P R IO R TO W EIG H IN G O N D A Y 1 PO STPAR TU M . TO TAL IM P LA N T A T IO N S 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) T A B LE E3 8 (PA G E 4) : N A TU R A L D E L IV E R Y , IM P LA N T A T IO N S IT E S , AND PUP V IA B IL IT Y AND S EX - IN D IV ID U A L D A T A - F I G EN ER A T IO N FE M A LE R A T S /F2 G EN ER A T IO N L IT T E R S ARGUS 418-020 Page 609 DOSAGE GROUP IV 10 M G / K G / D A Y RAT/ LIT T E R NUM BER D U R A T IO N O F G ES T A T IO N (D AYS) N 1482 1483 1486 1488 1490 1491 1 4 94 1496 1497 15 0 0 15 0 2 1505 15 0 7 1508 1511 1513 1514 1516 1517 1519 1521 15 2 3 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 L IT T E R D ELIV ER ED L IV E S T IL L- TO TAL BORN BORN BORN NNN 15(1) 1 16 15 15 10 14 14(1) 13 11 14 13 16 16 13 0 0 0 0 0 0 0 1 0 0 0 0 15 15 10 15 [1] 14 13 11 15 13 16 16 13 13 17 13 15 16 12 12( 1 ) 2 17 10 13 19(1) 12 14 14 1 0 0 0 0 0 0 0 0 0 2 0 0 1 0 14 17 13 15 16 12 12 2 17 10 15 19 12 15 14 1 MF 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 NUM BER O F L IV E 1C O M P L E T I O N O F D A Y 58 MF MF PUPS AT POSTPARTUM 15 MF 68 68 68 96 87 73 4 10 85 76 47 95 48 79 97 48 96 87 73 4 10 85 76 47 95 48 79 97 48 96 87 73 4 10 85 76 47 95 48 79 97 48 22 MF 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 94 98 94 87 88 75 74 210 6 64 85 6 11 66 10 4 95 94 97 94 87 88 75 74 210 6 64 85 6 11 66 10 4 95 94 97 94 87 87 75 74 210 6 64 85 6 11 66 10 4 95 M = M ALE F = FEM ALE ( ) = NUM BER O F PU PS D Y IN G P R IO R T O W EIG H IN G O N D A Y 1 P O S TP A R TU M . [ ] = N U M B ER O F P U P S I N W H IC H C A N N IB A L IZ A T IO N A N D /O R A U T O L Y S IS P R E C LU D E D T H E D E T E R M IN A T IO N O F V I A B I L I T Y . TO TAL IM P LA N T A T IO N S 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) T A B LE E3 8 (P A G E 5) : N A TU R A L D E L IV E R Y , IM P LA N T A T IO N S IT E S , AND PUP V IA B IL IT Y AND S EX - IN D IV ID U A L D A TA - F I G E N ER A T IO N FEM A LE R A T S /F2 G E N ER A T IO N L IT T E R S ARGUS 418-020 Page 610 DOSAGE GROUP V 30 M G /KG /D AY RAT/ L IT T E R NUM BER D U R A T IO N O F G ES T A T IO N (D A YS ) N 1541 1544 1545 1546 1548 15 5 0 1552 15 5 5 1557 1558 1560 15 6 4 15 6 5 1566 1568 1571 1573 1576 1578 1579 15 8 3 1584 1586 1587 1588 1589 1591 1593 1598 16 0 0 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 L IT T E R D ELIV E R E D LIV E S T IL L- TO TA L BORN BORN BORN NN N 01 4 1 4 11 3 1 4 01 9 1 9 01 5 1 5 11 3 1 4 12 0 12 01 4 1 4 01 5 1 5 01 3 1 3 01 6 1 6 01 5 1 5 01 3 1 3 12 0 12 01 5 1 5 01 3 1 3 01 3 1 3 01 5 1 5 01 3 1 3 15 12 4 13 11 13 14 14 6 17 15(1) 0 0 0 0 0 0 0 0 0 0 0 15 12 4 13 11 13 14 14 6 17 15 1 MF 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 NUM BER O F L IV E C O M P LETIO N OF' D A Y 58 MF MF PUPS A T POSTPARTUM 15 MF 22 MF 4 10 66 99 87 49 57 77 78 58 10 6 78 67 66 2 13 76 67 78 85 4 10 66 99 87 49 57 77 77 58 10 6 68 67 66 2 13 76 67 78 65 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 87 47 31 76 56 49 68 10 4 24 7 10 10 4 87 47 31 76 56 49 68 10 4 24 7 10 10 4 87 47 31 76 56 49 68 10 4 24 7 10 10 4 M = M ALE F = FEM ALE ( ) = NU M B ER O F PU PS D Y IN G P R IO R TO W EIG H IN G O N D A Y 1 PO S TPA R TU M . TOTAL IM P LA N T A T IO N S N 15 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-6889.6) T A B LE E3 9 (P A G E 1 ) : P U P B O D Y W EIG H T L IT T E R A V ER A G ES FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 611 M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY RAT/ L IT T E R NUM BER 13 0 2 1304 1306 1308 1310 1312 1313 13 16 1318 1321 1325 1328 1330 1331 13 3 4 1335 13 3 6 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 1359 DAY 1 MF T DAY 5 MF T 6 .9 6 .3 6.6 1 1 . 7 1 0 . 4 11.0 6 . 5 6.1 6 . 3 11.6 1 0 . 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 1 0 . 7 10.2 1 0 . 5 8.0 8.28 . 4 1 3 . 8 1 4 . 2 1 4 . 0 6 . 7 6.2 6 . 4 10.8 1 0 . 5 10.6 NOT PREGNANT 7 . 3 7 .0 7 .2 6 . 4 6.2 6 . 3 6.8 6.6 6 . 7 6.2 6.0 6.1 6.6 6 . 3 6 . 5 6.1 6.0 6.1 7 .2 6 .5 7 .0 6.6 6.0 6 . 3 12.3 8.8 10.7 9.8 8.8 8.8 11.1 9.8 12.2 8.6 10.6 9.5 8.3 8.2 10.4 9.4 12.2 8.7 10.7 9.6 8.5 8.6 10.9 9.6 7 .1 6 .9 7 .0 1 0 . 4 1 0 . 4 1 0 . 4 6 . 4 6 . 3 6 . 3 1 0 . 4 10.0 10.2 6 . 4 5 . 9 6.2 1 0 . 9 10.2 10.6 7.2 6 .7 6.9 11.3 10 .7 10.9 6 . 3 5 . 8 6.1 1 0 . 3 9 . 5 10.0 6.6 6.87 . 0 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 1 0 . 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 1 0 . 5 1 0 . 7 6.8 6 . 5 6.6 9.9 9.8 9.8 N O T P R E G N A N T ; M A T IN G N O T C O N FIR M ED 6 . 3 6 .0 6 .1 9 .3 9 .2 9 .3 DAY 8 MF T 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 1 5 .1 14.5 15.7 14.8 14.3 15.8 14.0 14.2 1 5 .1 16.5 13.2 11.9 12.7 14.0 1 2 . 3 12.0 12.1 D AY 15 MF T 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 D AY 22 MF T 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 3 7 .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 4 1 .1 28.4 4 1 .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-6889.6) T A B L E E3 9 (P A G E 2) : PU P B O D Y W EIG H T L IT T E R A V ER A G ES FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 612 M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY R A T/ LIT T E R NUM BER 13 6 2 1 3 63 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 13 8 4 1387 1389 1392 1393 1397 1399 1401 14 0 4 1407 1409 1410 1413 1415 14 16 1418 DAY 1 MF T 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 6.0 5 . 3 6.7 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 MF T 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 MF T 17.6 12.8 13.5 16.0 15.8 12.0 14.6 12.9 17.1 12.4 12.8 15.5 1 5 .1 12.1 12.8 13.0 17.4 12.6 1 3 .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 12.9 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 1 3 .1 12.5 D A Y 15 MF T 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 2 1 .7 3 1.1 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 3 1.7 26.4 26.9 24.5 22.9 21.6 27.4 23.8 25.9 22.1 21.9 21.8 D A Y 22 MF T 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 3 1 .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 4 7 .1 41.5 36.4 34.7 28.6 43.0 4 7 .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) T A B L E E3 9 ( PA GE 3) : PU P BO D Y W E IG H T L I T T E R A V E R A G E S FROM B I R T H T O D A Y 22 POST PA RTU M - I N D I V I D U A L D A T A - F2 G E N E R A T I O N PUPS ARGUS 418-020 Page 613 MATERNAL DOSAGE GROUP I I I 3 MG/KG/DAY RAT/ LITTER NUMBER DAY 1 MF T DAY 5 MF T DAY 8 MF T DAY 15 MF T D A Y 22 MF T 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 5.5 6.7 6.9 6.7 6.3 6.1 6.4 6.0 6.8 8.3 6.3 NOT 6.8 6.3 6.6 5.2 5.3 6.2 6.2 6.1 6.5 5.9 5.8 5.9 6.5 6.5 6.5 6.3 6.4 6.0 6.2 6.0 6.7 7.9 8.1 6.2 6.2 PREGNANT 6.3 6.5 6.1 5.6 6.0 7.1 NOT 6.3 6.8 6.5 6.9 5.9 6.4 8.3 6.5 6.0 5.5 7.7 6.0 6.0 5.0 5.3 5.6 5.8 6.8 7.0 PREGNANT 5.9 6.2 6.7 6.7 6.0 6.7 6.3 6.8 5.5 5.6 6.5 6.4 7.9 8.1 6.4 6.5 5.7 5.8 5.5 5.5 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 10.9 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 1 5 .1 12.3 14.7 13.6 15.3 13.4 17.4 20.6 14.5 13.2 11.4 13.4 1 4 .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 2 7 .1 22.8 3 1 .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 3 7.1 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 3 1.1 43.2 37.8 37.2 3 8 .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 46.1 44.4 49.9 3 7.7 40.8 31.6 35.1 46.5 39.8 35.4 34.7 4 4 .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) T A B L E E3 9 ( PAG E 4) : PU P B O D Y W E I G H T L I T T E R A V E R A G E S FROM B I R T H T O D A Y 22 PO ST PA R TU M - I N D I V I D U A L D A T A - F 2 G E N E R A T I O N PUPS ARGUS 418-020 Page 614 MATERNAL DOSAGE GROUP I V 10 MG/KG/DAY RAT/ LITTER NUMBER DAY 1 MF T DAY 5 MF T DAY 8 MF T DAY 15 MF T D A Y 22 MF T 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 523 1524 1527 1528 1531 1533 1534 1537 1539 7.1 NOT 7.1 6.5 7.9 6.0 6.7 6.3 7.0 6.8 6.9 PREGNANT 6.8 7.0 6.0 6.3 7.1 7.7 5.7 5.8 6.0 6.4 6.3 6.3 6.9 6.9 6.1 6.4 6.3 5.5 6.5 NOT 6.8 6.3 6.2 5.8 6.2 6.0 6.1 6.2 5.4 5.4 5.7 6.0 PREGNANT 6.7 6.8 6.1 6.2 6.8 5.8 6.3 7.1 6.1 8.6 6.3 7.1 6.7 5.6 7.3 6.4 6.4 6.8 5.6 5.7 6.9 5.8 -- 5.9 6.5 5.8 5.3 6.9 5.8 6.4 6.8 5.7 6.0 7.0 6.0 8.6 6.2 6.8 6.3 5.4 7.1 6.2 6.4 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 1 3 .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 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 1 7 .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 1 2 .7 12.6 15.0 12.8 13.5 13.6 16.3 23.6 21.4 22.4 25.7 26.9 31.0 27.3 24.7 22.1 30.2 24.6 3 1 .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 2 7 .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 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 3 7.7 48.3 40.7 45.9 29.3 31.4 39.9 33.6 37.9 51.4 32.4 42.1 3 7 .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 34.4 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) T A B L E E 3 9 ( P A G E 5) : P U P B O D Y W E I G H T L I T T E R A V E R A G E S F RO M B I R T H T O D A Y 22 P O S T P A R T U M - I N D I V I D U A L D A T A - F 2 G E N E R A T I O N P U P S ARGUS 418-020 Page 615 MATERNAL DOSAGE GROUP V 30 MG/KG/DAY RAT/ LITTER NUMBER DAY 1 MF T DAY 5 MF T DAY 8 MF T DAY 15 MF T D A Y 22 MF T 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 6.4 6.3 5.6 5.3 5.6 6.4 6.1 5.4 5.2 5.7 6.4 6.2 5.5 5.2 6.6 6.3 6.3 6.8 6.5 5.8 6.2 6.2 6.2 6.8 5.6 6.5 5.8 NOT 6.4 5.4 6.8 5.7 5.8 6.4 5.7 6.1 7.0 5.9 6.3 6.0 6.2 6.0 6.2 5.4 5.8 6.5 6.6 6.5 6.5 5.5 5.7 5.8 6.0 5.8 6.0 5.9 5.9 6.5 6.7 5.2 5.3 6.0 6.3 5.8 5.8 PREGNANT 6.0 5.2 6.5 5.4 5.6 6.2 5.3 6.8 5.6 5.6 6.0 5.4 5.9 7.1 5.8 5.7 6.2 5.5 6.0 7.1 5.8 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 1 0 .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 1 2 .9 8.8 9.6 10.3 9.8 12.0 9.2 9.5 9.4 8.1 9.8 1 2 .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 10.5 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 1 3 .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 1 4 .1 10.7 14.0 15.5 18.6 1 3 .1 13.9 1 3 .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 1 8 .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 3 8 .1 33.5 45.4 29.2 36.8 32.9 33.3 45.0 33.0 3 1 .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 = 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) T A B L E E40 (PAGE 1) : PUP BODY W EIG H TS FROM B I R T H TO DAY 22 POSTPARTUM - I N D I V I D U A L D A T A - F2 G E N E R A T I O N PUPS ARGUS 418-020 Page 616 PUP # 1 2 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 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 .3 6 ., 4 5..9 6 ,. 5 8 .. 1 6 .. 8 NOT 7,.5 6 .. 2 6 .3 6 .1 6 ,. 7 6 ,. 8 7 ,. 2 6 ,. 9 6 .. 8 6 ,. 6 6 ,. 7 7 ,. 1 6 .6 7 , .1 7 , .6 6 .4 5 ,. 9 6 .1 6 .0 6 ,. 6 NOT 6 .4 6.9 6 .9 7. 2 6 .5 5. 8 6 .5 7 , .2 6 .8 6 .4 5. 7 6 .2 6 .4 6 .4 6 .6 5. 6 6 .5 6 . 9. 6 ,. 3 7 . .1 6 .3 7. 3 6 .2 6 .7 6 .2 6.7 8 .6 8 .4 7. 5 6 .4 6 ,. 8 6 .8 6 .8 6 .7 PREGNANT 7. 8 7,.7 7. 4 6 .9 7. 2 6 .. 7 6 .4 6 ,. 6 7 ,. 1 6 .7 6.7 6 .2 7 .5 6 .0 6 .0 6 .2 6 ,. 6 6 .2 6 .1 5. 6 6 .8 6 ,. 5 6 .8 6 .3 6.9 5.,4 6 .. 1 6 .0 5 .7 6 .1 7. 3 7 ,. 3 7. 1 7 .3 7. 1 6 ..1 7. 4 6 .9 7 ,. 4 6 .6 6.5 6 .6 7 .1 6 .2 7. 0 6 ., 4 6 .3 5. 8 6 .4 6.7 6 .. 0 6 .3 5. 8 6 .6 7 .0 7 .,1 7 ,. 5 7 .3 6 .7 6 .8 6 ., 4 7 .4 6 ,. 2 6 ,. 9 6 .1 6 .8 6 .1 6 .7 6 .2 7. 1 6 ., 5 7 ,. 3 7. 6 7 .5 MS 6 ., 3 6 .,8 6 ..0 6 .2 5,. 7 6 ,. 7 6 .2 5. 9 6 .1 6 .2 6 .5 5 .3 6 .0 6 .8 5. 4 6 ., 5 7 ,. 4 6 .7 5 .5 5. 5 6 ., 7 7 , .0 6 .9 6 .7 6 .5 PREGNANT; MATING NOT CONFIRMED 6 ., 7 5,. 7 6 .2 6 .5 6 .3 6 .9 6 .4 6 .3 6 .5 6 .7 6 .6 6 .7 6 .4 6 .6 6 .5 6 .3 6 .7 6 .9 5. 9 7. 6 6 .2 6 .5 6 .6 6 .7 7. 3 6 .7 5.6 MS 5. 9 6 .1 6 .4 6 .1 6 .3 5, .8 6 ,. 0 6 ,. 1 6 ,. 3 6 ,. 3 7 , .6 6 ,. 4 6 ,. 9 6 .. 1 6 ,. 3 5..9 6 .5 5,.9 7 , .1 6 ,. 6 6 ,. 5 6 ,. 0 6 .. 1 6 ,. 3 6 ,. 8 6 ,. 1 6 ,.2 7 ,. 0 6 .. 1 6 .3 5..9 6 ,. 7 5, .8 5, .8 6 ,. 1 6 ,. 8 5,.9 6 ,. 8 6 .3 6 ,. 0 5 , .8 6 .. 2 6 .7 6 ,. 2 6 .. 2 7 . .2 6 .5 6 ,. 5 7 , .0 6 .3 6 ,. 6 6 .3 5.7 6 .7 6 ,. 9 6 ..2 6 .5 6 .. 1 6 ,. 0 6 ,. 5 6 ,. 1 5 ,. 8 6 ,. 5 6 ., 1 5. .8 6 .. 2 7..3 6 .1 6 ,. 2 6 ,. 0 6 .. 0 6 .7 6 ,. 3 5..3 6 .. 6 5, . 7 6 .7 7 . .2 5 ,. 8 5. .8 6 .5 6 .4 6 .3 6 ..0 6 .2 5 .6 5 .6 6 .. 1 6 .2 5,.9 7 , .2 6 -. 1 6 ,. 5 5 ,. 8 6 ,. 0 6 ,. 1 6 ,. 1 6 .5 6 ,. 6 6 .0 7 .. 0 5 ,. 7 6 ,. 4 7 ,. 0 6 ,. 8 4 ,. 8 6 ,. 0 6 .3 6 .. 2 6 ,. 4 5,.4 6 ,. 3 6 ,. 4 6 ,. 1 7..3 6 ,. 5 6 ,. 0 6 .5 6 ,. 2 6 .. 0 6 .5 5..9 5 ..8 6 .9 5,. 7 7 . .2 6 ..2 6 .7 6 ..0 5.. 7 6 .,8 5.. 7 5 .8 5 .9 5 .9 6 .4 6 .9 6 .1 6 .1 6 .4 5 .. 6 7 , .2 6 ,. 8 5,.5 5 ,. 6 7 . .1 6 ,. 1 4 .9 6 ,. 8 6 .. 1 6 .4 6 .. 1 5. 9 5. 7 5. 5 7 .4 6 .0 6 .7 6 .4 7. 2 6 .5 6 .3 5. 9 6 .8 5. 8 5.5 6 .8 FU 6 .4 FS 6 .2 6 .6 7 , .2 6 .5 6 ,. 5 6 ,. 2 6 .. 8 6 .3 6 .. 2 5, .6 6 .7 6 .4 5..5 6 .. 7 6 .3 5. 8 5 .7 6 .3 5.8 5. 7 5. 8 FS FS 4 .9 A L L W E IG H T S WERE R E C O R D E D I N GRAMS (G) . MEAN L IT T E R WEIGHTS INCLUDE ONLY WEIGHTS OF L IV E PUPS. FIRST LETTER -- M-MALE, F-FEM ALE, U-SEX UNDETERMINABLE SECOND L ETTER -- S -STILLBOR N, U-UNCERTAIN, D -D IED , M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND L E T T E R " IN D IC A TES TH E 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) T A B L E E 4 0 (PA GE 2) : PUP BO DY WEIGHTS FROM B I R T H T O D A Y 22 POSTPARTUM - I N D I V I D U A L D A T A - F2 G E N E R A T I O N PUPS ARGUS 418-020 LO Page 617 PUP # RAT/ LITTER # 12 3 45 MATERNAL DOSAGE GROUP I I 6 7 8 <3 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0 1 MG/KG/DAY POSTPARTUM DAY 1 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1387 1389 13 92 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 6 .8 5 .7 5 .5 6 .6 6 .6 6 .3 6 .4 6 .4 NOT 6 .4 7 .6 6 .1 5 .4 7 .3 6 .3 5 .5 7 .0 7 .8 7 .1 6 .9 5 .7 6 .5 6 .2 5 .7 6 .5 6 .5 6 .2 6 .6 6 .4 6 .7 6 .3 6 .. 3 5. 6 7. 4 5. 7 5. .1 7 , .0 6 .7 7. 2 6 ,. 5 6 .9 7 , .2 6 .6 6 .. 2 PREGNANT 6 .2 6 .. 6 7. 9 7 . .0 6 .0 6 .. 0 6 .3 6 .9 7 , .0 7 . .1 6 .0 6 .. 2 5. 6 7. 3 7 .5 6 .5 6 ,. 5 7..3 7. 2 7 . ,1 6 .9 6 .. 2 6 .2 6 .4 6 .2 6 ,. 1 6 .1 5,.9 6 .0 5 .9 6 .4 6 .4 6 .7 6 .. 6 6 ,. 7 6 .. 1 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 4.5 FS A L L W E I G H T S WERE R E C O R D E D I N GRAMS (G) . MEAN L IT T E R WEIGHTS INCLUDE ONLY WEIGHTS OF LIV E PUPS. FIRST LETTER -- M-MALE, F-FEM ALE, U-SEX UNDETERMINABLE SECOND L E T T E R - - S -S T IL L B O R N , U-UNCERTAIN, D - D I E D , M-MISSING (PRESUMED CANNIB ALIZED ) 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) T A B L E E 4 0 ( PAG E 3) : PU P B O D Y W E IG H T S FROM B I R T H T O D A Y 22 PO ST PA R TU M - I N D I V I D U A L D A T A - F2 G E N E R A T I O N PUPS ARGUS 418-020 Page 618 PUP # RAT/ LITTER # 12 34 5 MATERNAL DOSAGE GROUP I I I 6 7 8 9 10 11 12 13 14 15 16 1 7 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 5.9 6.8 7.0 6.2 6.4 6.2 5.8 6.4 6.7 8.7 6.4 NOT 6.6 5.8 5.8 6.2 7.2 NOT 6.3 5.8 6.5 6.3 7.2 6.6 6.6 5.4 6.7 7.2 6.7 5.6 6.1 6.5 5.9 6.9 6.1 6.6 5.5 7.1 8.2 8.0 6.4 6.3 PREGNANT 7.4 6.8 6.6 5.7 5.4 5.7 5.7 5.9 6.9 7 .1 PREGNANT 6.8 7.0 6.4 6.6 5.9 6.3 8.7 6.7 6.0 5.9 8.0 6.0 6.5 6.5 7.3 5.9 6.5 8.8 6.3 5.7 5.8 7.6 6.0 7.2 6.0 6.9 6.1 6.8 8.5 6.0 5.6 5.0 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 5.4 7.1 7.0 6.6 6.3 5.9 6.8 6.4 6.6 8.3 6.4 7.3 6.2 5.8 5.9 6.9 6.2 7.2 6.9 6.7 6.0 5.9 7.8 7.0 6.0 6.1 7.7 6.8 5.1 6.7 6.9 7.0 6.4 5.4 6.9 6.0 6.5 8.0 6.5 6.1 6.4 5.5 6.1 6.6 6.4 6.0 6.5 7.1 4 .7 5.9 8.5 6.7 6.4 4.9 7.4 7.1 5.4 6.3 5.8 5.7 6.6 6.4 6.2 6.2 6.2 7.4 6.8 MS 5.6 5.3 6.0 6.5 5.3 6.2 5.6 6.1 6.5 6.2 6.0 6.7 6.4 5.1 MS 5.6 5.4 6.4 6.2 6.7 6.9 6.8 5.7 6.3 7.6 6.0 6.1 5.1 7.2 6.8 6.7 MS 6.4 5.3 7.0 7.6 6.5 MD 1 6.2 7.3 6.8 5.6 5.9 6.1 6.0 5.9 6.7 5.8 5.1 6.9 6.6 5.4 6.1 6.8 6.2 MD 1 6.7 5.8 6.1 FD 1 6.1 6.4 6.4 6.1 6.3 5.9 5.5 4.5 5.4 5.2 6.3 7.1 5.9 7.1 5.4 6.6 7.7 6.5 6.0 5.9 7.5 5.9 6.6 5.9 7.0 5.5 6.3 8.2 6.8 5.4 4.8 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 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 6.0 6.5 6.3 5 .8 6.8 6.3 6.1 5.9 7.6 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 6.2 5.8 5.5 6.4 6.9 5.8 5.8 5.6 6.0 6.7 6.5 5.9 FS 7.0 5.5 6.7 5.8 5.9 5.7 5.3 5.2 5.3 5.5 A L L WEIGHTS WERE RECORDED I N GRAMS ( G ) . MEAN L IT T E R WEIGHTS INCLUDE ONLY WEIGHTS OF L IV E PUPS. FIRST LETTER -- M-MALE, F-FEM ALE, U-SEX UNDETERMINABLE SECOND L E T T E R -- S-STILLBOR N, U-UNCERTAIN, D -D IED , M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER " INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 18 5.6 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) T A B L E E40 (PA GE 4) : PUP BO DY W EIGH TS FROM B I R T H TO DAY 22 POSTPARTUM - I N D I V I D U A L D A T A - F2 G E N E R A T I O N PUPS ARGUS 418-020 Page 619 PUP # RAT/ LITTER # 1 234 5 MATERNAL DOSAGE GROUP I V 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 10 MG/KG/DAY POSTPARTUM DAY 1 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 7.2 NOT 7.1 6.1 8.5 5.9 6.2 6.6 6.9 6.3 6.3 6.6 5.9 6.2 NOT 7.0 6.7 6.8 6.3 5.9 7.0 6.4 8.4 6.5 7.1 6.6 5.0 6.9 6.2 6.9 7.2 7 .1 PREGNANT 7.3 7 .7 7.2 6.3 7.5 8.1 6.1 5.9 6.6 6.9 5.7 6.7 7.2 6.9 6.0 6.5 6.6 6.7 6.1 6.2 5.6 5.3 7.0 6.4 PREGNANT 6.5 6 .7 6.5 6.5 7 .1 7.0 6.0 5.5 6.3 6 .7 7 .7 6.3 6.3 6.6 8.9 6.9 6.5 7.6 6.6 7.2 6.5 5.5 5.7 7.2 7.8 6.6 6.9 6.6 6.1 7.3 6.8 6.0 8.9 6.0 6.6 6.4 7.0 6.8 6.2 6.1 5.4 6.4 7.3 6.8 6.9 5.4 6.4 7.4 6.2 6.7 7.0 6.2 6.2 7.6 5.6 6.7 7.0 7.4 6.0 7.1 5.7 7.0 6.2 6.8 5.9 5.5 6.7 5.6 5.6 6.0 6.0 6.7 5.5 5.8 7.5 6.3 6.3 7.3 7.0 5.7 6.8 6.4 6.4 6.9 7.4 6.7 6.6 5.9 6.7 6.8 6.8 5.2 5.6 6.6 5.4 5.4 7.2 6.6 7 .1 6.0 6.4 7.0 6.6 6.3 7.0 6.3 5.5 7.4 6.7 6.4 6.3 5.9 6.9 6.5 6.5 8.5 4.8 6.6 5.9 6.6 5.9 6.0 6.0 5.4 5.9 7.2 7.2 7.5 6.2 6.9 6.0 7.3 6.3 5.8 6.3 5.7 5.6 6.5 6.1 6.2 5.9 MD 1 6.3 6.8 6.3 6.5 6.1 4.9 5.6 7.1 6.0 6.3 5.9 6.4 6.7 4.6 6.8 5.6 6.4 6.1 6.2 6.6 MD 1 6.9 6.2 7.4 5.8 6.5 7.2 4.6 6.8 6.3 6.7 5.4 7.3 6.3 6.4 6.3 6.6 6.9 5.3 7.2 6.6 6.7 4.4 6.5 MS 5.9 7.0 6.6 5.8 7.3 6.7 6.5 7.7 5.6 6.4 6.5 6.5 6.3 5.7 6.1 5.8 5.3 6.7 5.7 7.2 5.6 5.5 6.7 5.9 6.6 6.5 4.9 5.4 6.6 6.5 6.5 7.1 7.3 6.2 5.8 5.6 6.3 7.4 6.1 5.7 5.7 5.5 5.4 6.4 5.9 6.8 5.6 5.0 7.1 6.2 6.5 6.2 5.8 6.5 5.8 6.3 7.1 6.7 6.2 6.0 6.7 6.1 6.2 6.2 6.0 4.8 6.8 6.6 6.0 6.7 5.9 6.1 6.8 6.6 5.7 5.8 5.7 6.8 6.1 6.4 6.9 6.2 5.7 5.9 4.9 6.5 6.4 5.5 5.9 5.3 5.9 7.0 6.3 6.7 5.6 6.3 5.6 5.9 2.9 4.9 6.5 6.7 FD 1 7.1 6.1 6.7 5.6 4.9 6.2 UU 6.0 6.6 5.5 FS 5.7 5.4 MS 6.3 5 .7 5.5 5.4 5.3 5.6 6.4 6.0 6.3 FS 5.3 5.3 6.3 FS 6.5 FS 6.3 5.5 6.4 5.3 5.5 5.9 A L L W E I G H T S WERE R E C O R D E D I N GRAMS (G) . MEAN L IT T E R WEIGHTS INCLUDE ONLY WEIGHTS OF LIV E PUPS. FIRST LETTER -- M-MALE, F-FEM ALE, U-SEX UNDETERMINABLE SECOND L E T T E R -- S-STILLBORN, U-UNCERTAIN, D -D IE D , 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) T A B L E E 4 0 ( P A G E 5) : P U P B O D Y W E I G H T S FRO M B I R T H T O D A Y 22 P O S T P A R T U M - I N D I V I D U A L D A T A - F 2 G E N E R A T I O N P U P S ARGUS 418-020 Page 620 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 M G / K G / D A Y POSTPARTUM DAY 1 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 5.8 5.1 6.2 5.9 5.5 6.3 5.6 6.9 7.0 6.8 5.8 5.8 7.3 6.6 5.6 5.4 6.6 6.8 6.1 6.6 6.4 5.7 6.2 6.6 5.3 5.7 5.1 6.6 5.5 6.0 7.0 6.2 5.5 6.2 6.3 6.2 7.3 5.6 6.2 6.6 NOT 6.5 5.7 6.9 5.4 6.2 6.3 5.7 6.3 7.0 5.9 6.2 6.1 6.8 5 .7 6.3 6.2 5.6 4 .7 7.5 5.8 5.0 7.1 6.1 5.8 5.8 P R EG N A N T 6.6 6.3 5.2 5.7 6.9 6 .7 5.9 4.9 5.6 5.3 5.9 6 .7 5.7 5.5 6.4 6.0 7.0 7.6 5.6 6.3 7 .1 5.9 6.4 6.7 6.3 4.9 5.2 6.9 6.4 6.2 6.4 6.9 6.0 6.6 6.3 5.7 7.2 5.1 6.2 5.6 5.8 5.1 6.5 5.8 6.2 6.7 5.9 6.1 6.5 6.0 6.3 5.7 6.1 6.6 5.9 5.1 6.8 5.9 5.4 6.8 6.8 5.9 5.4 6.2 5.5 7.9 5.9 6.8 5.5 6.4 5.4 5.8 5.5 6.3 5.6 6.2 7.8 6.1 6.6 5.7 6.3 6.6 5.5 5.2 5.8 7.4 7.0 6.3 6.2 6.1 6.0 6.4 6.2 7.1 5.9 6.7 5.6 6.9 4.8 6.2 5.7 6.3 5.8 4.9 6.6 6.0 6.3 5.2 6.3 6.5 6.0 5.7 6.4 6.7 6.5 6.4 6.8 6.0 6.2 5.5 6.5 5.8 5.3 6.5 5.6 6.2 5.2 6.0 5.4 6.0 5.4 6.1 5.6 6.5 6.1 6.4 6.5 5.1 5.6 6.4 6.4 5.8 6.4 6.6 5.7 6.1 5.6 6.2 6.9 5.3 6.6 5.9 6.7 5.0 5.4 5.5 6.5 5.0 6.5 6.0 6.0 5.6 6.2 5.8 5.0 5.0 6.0 5.9 5.3 6.7 6.3 5.8 5.1 6.0 6.1 6.7 4.8 6.0 6.1 6.7 5.4 5.0 5.6 5.7 5.2 6.3 6.0 6.1 5.4 6.4 7.0 5.2 5.0 5.7 6.0 5.6 6.8 6.1 5.3 5.7 5.6 5.9 6.5 5.1 5.6 5.3 5.4 6.2 5.0 5.9 5.0 5.6 5.4 5.4 6.3 6.5 5.3 5.5 5.8 5.6 6.9 5.3 6.3 5.7 6.3 6.1 5.1 5.4 5.7 5.5 5.8 5.0 6.0 5.6 5.7 6.6 5.3 6.1 5.9 6.0 5.4 MD 1 5.8 6.5 6.0 5.4 5.4 5.9 6.2 5.4 6.4 6.8 5.7 5.8 6.0 5.6 6.2 5.1 5.8 5.9 5.8 5.2 5.2 5.8 6.0 6.0 6.2 6.0 5.7 6.6 4.6 5.3 5.0 6.0 5.8 6.6 6.4 5.2 5.9 5.3 5.9 5.3 5.7 5.8 5.4 5.7 5.5 5.1 6.7 5.6 5.5 5.3 FS 6.3 5.3 FS 5.9 4.9 6.4 5.7 6.2 6.3 6.0 6.0 4.7 5.4 5.6 6.1 5.7 5.3 6.5 5.3 6.1 6.1 6.1 5.5 5.8 6.6 6.6 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EA N L I T T E R W EIG H T S IN C L U D E O N L Y W EIG H TS F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPAR TU M T H E E V E N T O C C U R R ED . O F LIV E 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) T A B L E E4 0 (P A G E 6 ) : PU P B O D Y W EIG H T S FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 621 PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I 0 M G/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 12.2 9.5 8.4 10.6 14.2 11.2 NOT 12.0 8.3 9.9 9.9 8.6 10.3 10.3 10.0 10.5 10.1 10.8 12.3 10.6 10.7 10.3 11.1 8.8 8.7 10.4 10.6 NOT 9.1 12.9 11.5 11.0 1 1 .7 11.2 11.6 10.3 10.3 9.0 12.6 9.5 11.8 10.4 11.3 9.6 7.8 10.9 8.1 10.8 9.0 10.3 8.2 10.1 8.1 10.4 13.5 13.6 14.9 10.3 11.2 11.0 10.5 10.1 P R EG N A N T 11.0 11.9 12.5 13.3 13.5 9.0 8.5 9.5 9.2 7 .4 10.3 11.0 11.6 1 0 .7 11.5 9.4 10.3 9.9 8.9 9.8 9 .1 9.0 9.0 8.4 9 .1 9.5 11.4 9.2 11.2 8.4 11.2 8.6 11.3 7.4 11.4 9.7 10.0 9.8 9.3 10.1 10.7 10.4 10.8 10.0 10.2 11.2 10.2 9.2 10.3 11.2 11.1 10.4 11.2 11.4 10 .7 10.8 11.0 11.2 9.8 11.3 10.9 9.5 10.9 9.6 10.9 11.5 10.3 10.8 10.9 10.9 11.0 11.1 10.2 MD 4 MS 12.1 10.7 11.0 10.7 11.0 8 .7 9.3 8.6 9 .7 9 .1 9 .1 8.8 8.5 7.6 9.4 12.3 10.0 11.4 9.7 9.8 9.4 10.6 9.9 11.2 9.8 P R E G N A N T ; M A T IN G N O T C O N FIR M ED 9.5 10.0 9.5 8.6 9.6 11.4 10.7 9.7 8.3 11.0 11.1 11.4 9.6 10.2 10.3 8.1 8.8 10.0 9.5 10.6 10.3 10.5 10.8 11.0 10.0 8.8 10.3 MS 8.3 11.6 10.6 9.2 11.2 8.3 9.8 9.3 1 0 .9 10.9 11.5 11.0 8.3 11.2 10.6 10.6 9.9 8.1 9.5 10.5 10.6 9.9 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 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 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 9.4 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 1 0 .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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G ) . M EA N L I T T E R W EIG H TS IN C L U D E O N L Y W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ) NU M B ER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTU M T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E4 0 (P A G E 7 ) : P U P B O D Y W EIG H T S FROM B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 622 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY POSTPARTUM DAY 5 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 11.4 8.3 8.1 10.6 10.8 7.0 12.1 9.0 9.3 10.9 11.0 8.5 12.1 8.0 9.2 11.2 10.5 7.6 10.0 9.5 NOT 11.6 11.8 11.4 11.1 12.8 11.2 8.3 7.6 10.6 10.0 9 .1 9.3 P R EG N A N T 11.8 12.6 10.9 11.7 9.8 10.2 9.0 11.5 11.1 11.7 9.8 9.5 7.2 8.0 9.7 8.0 11.2 11.3 12.5 11.7 10.5 9.2 10.5 10.4 9.0 8.9 9.7 7.2 12.0 12.2 12.6 12.0 10.3 7.4 10.1 9.9 9.9 9.8 8.5 8.6 10.8 12.0 11.9 10.8 10.4 9.5 9.8 9.5 9.7 9.1 9.7 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 1 2 .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 8.8 FD 4 9.1 8.1 8.5 9 .7 10.6 8.2 7.4 10.3 7.7 7.7 FS 7.5 8.7 8.7 9 .7 9.4 FM 5 FD 3 FM 3 A L L W EIG H T S W ERE R EC O R D ED I N GRAM S (G) . M EA N L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D - D I E D , M -M IS S IN G (PRES U M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E4 0 (P A G E 8 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N P U P S ARGUS 418-020 Page 623 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 R A T/ L IT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY POSTPARTUM DAY 5 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 7.8 10.2 10.9 9.0 10.7 10.1 10.3 9.4 11.3 14.9 10.3 NOT 11.1 8.9 8.4 10.1 12.8 NOT 11.5 8.9 11.2 9.8 9.3 8.0 8.9 10.5 10.7 10 .7 10.8 9.3 9.4 11.5 10.5 9.7 10.1 10.6 10.9 9.8 9.6 11.1 1 1.5 14.2 13.2 10.4 10.3 PREGNANT 11.3 11.1 7.5 9.2 8.5 8.9 10.4 6.5 12.9 13.3 P R EG N A N T 11.1 9.7 10.3 9.8 10.3 1 0 .9 11.2 10.2 9.9 14.0 9.9 7.6 8.2 11.6 10.4 9.4 14.5 11.0 7.5 8.5 10.6 10.2 9.3 13.9 10.0 7.8 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 10.0 8.0 10.5 9.6 8.1 10.9 9.1 10.4 8.9 11.1 13.7 10.4 10.3 8.9 9.8 10.4 8.3 10.1 8.7 11.0 10.5 10.8 10.5 10.0 9.1 8.5 9.3 8.9 8.3 9.1 9.8 8.7 10.5 9.9 8.7 7.9 10.3 8.9 8.9 MD 1 8.3 9.8 9 .1 FD 1 10.5 10.7 8.8 8.6 9.9 12.4 MS 8.4 7.1 MD 5 MS 8.1 8.9 MM 3 9.1 9.2 7.1 6.6 9.6 8.1 8.1 9.3 11.7 10.0 10.1 11.8 9.9 11.0 12.6 10.2 7.7 10.0 12.6 10.5 10.5 10.7 10.9 8.9 9.1 12.6 9.8 8.2 7.4 10.9 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 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 10.3 8.8 9.5 7.6 9.5 9.9 9.4 10.4 6.5 9.5 9.1 8.1 8.7 12.0 9.5 8.4 10.6 10.4 8.1 9.8 9.7 9.5 10.0 8.4 7.9 9.1 9.1 10.1 9.8 10.6 8.7 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 FD 1 7.7 9.1 FM 2 9.2 9.4 8.8 7.5 8.5 11.0 10.1 6.9 7.9 6.9 9 .1 10.6 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H TS F IR S T L E T T E R - - M -M A LE, F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A LIZ E D ) NUM BER FO LLO W IN G "SEC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . OF L IV E PUPS. 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) T A B L E E4 0 (P A G E 9 ) : PU P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 624 PUP # 1 2 3 4 c r8 9 10 1 1 12 13 14 15 R AT/ LIT T E R # M A T E R N A L , D O S A G E iG R O U P I V 10 M G/KG/DAY POSTPARTUM DAY 5 1482 1483 1486 1488 1490 1491 1 4 94 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 1 1 .,0 1 0 . 7 1 1 . 9 1 1 ..0 14 . 8 15 . 3 15. 0 1 0 .4 9. 2 1 0 . 8 1 0 . 3 1 0 . 4 1 0 ., 9 9. 6 9 . 1 1 0 ., 3 1 0 . 8 1 1 . 9 1 1 ..2 9. 1 9 . 9 1 0 ., 3 1 1 . 4 1 1 . 8 1 1 ..0 9. 4 9. 0 9..4 7. 1 7. 4 8 ..8 11.6 8 . 9 1 2 ..2 NOT PREGNANT 10.3 9. 9 9..9 9. 5 9. 6 9..3 1 1 . 6 1 1 . 7 1 2 .. 9 10 . 2 9. 7 9, .0 9. 5 9 . 8 1 0 ,. 5 10.7 10.6 1 0 .. 2 1 0 . 9 1 1 .4 1 1 .3 14 . 8 15 . 2 9. 6 9. 6 8 ,. 4 1 1 . 5 1 0 . 4 1 0 ,. 5 1 0 . 9 1 1 . 1 1 0 ,. 8 8 .3 8 .5 9 .2 1 0 . 5 1 0 . 2 1 0 ,. 1 10.0 10.2 9 .7 1 1 . 3 1 0 . 9 11 .9 1 0 ., 7 1 0 ., 0 1 0 ., 6 1 3 ., 5 9.. 7 9 . ,8 8 .. 1 1 1 .. 6 8 .. 7 1 1 .. 3 1 0 .. 1 7..4 1 1 .. 6 1 0 .. 2 8 .. 8 1 1 .4 1 0 ,. 2 9 .8 1 0 ,. 8 1 0 ,. 6 9 .2 11 .9 10 .7 9 .6 9 .7 10 .3 10 .3 10.8 1 1 .. 1 1 0 ., 7 1 5 . .4 9..4 9 . ,6 9 . .6 1 0 .. 8 9. .2 1 0 ..2 8 .. 7 8 .. 5 7 . .8 1 0 .. 2 7..4 1 0 .9 1 0 ,. 1 9, . 9 1 0 ,. 4 7 , .6 9,.5 1 0 .8 1 1 .2 7,.9 1 0 ,. 5 1 0 ,. 0 10 .5 1 0 ., 9 1 0 .,8 1 0 ., 1 1 2 ..8 6 ., 9 9.,3 9 . .6 1 1 .. 6 7 . .5 1 1 ..2 8 .. 5 7. .3 1 0 .. 2 1 0 .4 1 0 .5 1 1 ., 4 1 0 ,. 2 9, . 4 1 1 ,. 0 1 1 ,. 1 8 .8 1 0 .8 1 1 .2 9 .7 9 .4 9 .6 10 .9 10 . 1 1 1 ., 1 1 1 .,8 1 1 ., 7 7.,7 1 0 .,2 8 ., 5 1 1 .. 6 7 . .8 1 0 ..8 9.,9 7 ., 5 1 0 ,. 8 9. .0 8 .. 9 1 0 ..2 8 .7 9. .6 1 1 ,. 1 1 1 ., 1 1 0 .. 1 9 .9 1 0 ,. 0 9, . 3 8 ,. 9 1 0 ,. 4 11 .4 9. 4 1 0 . 4 9.,4 9 . ,2 1 1 ., 5 1 0 ., 3 1 0 ., 7 9..9 1 2 ..0 9..3 1 1 ..1 8 ..0 7 . ,8 1 0 .. 6 11.1 10.5 13 . 9 10.2 MD 1 9. 4 10.4 9. 5 10.4 9. 5 7. 9 11.7 1 0 .. 7 1 0 ..2 1 2 .. 1 1 0 ,5 9, .8 1 1 ., 1 MD 1 10 .4 8 .4 10 .4 8 .9 8 .7 9. 6 10.7 1 0 ,.2 1 0 ,. 6 1 0 ,. 3 8 ,. 1 8 ,. 3 1 0 ,. 2 1 1 .2 8 .9 9. 6 MS 9. 0 7. 7 10.4 1 2 .3 1 0 ..0 9..5 8 .. 9 9. .8 1 4 . .0 9..4 9..9 1 0 .7 1 0 .7 8 .3 1 0 ..2 8 .9 7..3 1 0 .. 0 1 0 ..2 1 0 ..2 9..9 9..5 1 0 .. 1 1 0 ,. 3 8 .9 9..5 8 .4 7..9 9.. 7 9. .2 7 . .6 1 1 .. 1 9, .2 7 , .6 1 0 ,. 3 7..5 1 0 ,. 6 9. . 4 1 2 .. 0 1 0 ,. 0 9, . 9 1 0 ,. 7 1 1 ,. 6 8 ,. 9 10 . 9 1 0 ,. 6 9, .0 1 1 ,. 6 8 .8 10 .4 MM 5 1 1 .0 8 .6 1 0 ,. 3 8 ,. 8 1 1 .8 9..9 9..9 9. .6 8 ..8 9. .8 9. .1 9. .2 1 0 .. 1 8 .4 7 . .3 9. .1 1 0 .3 8 .. 0 1 0 .. 2 9,.9 8 ,. 1 1 0 ,. 1 1 0 .. 6 9.. 1 9 .7 4 ,. 0 1 0 ,. 6 9,. 1 1 0 ,. 9 1 1 ..0 9.,3 9 . ,6 1 0 .,0 9 . ,6 8 .. 9 8 ., 7 FD 2 8 .,6 8 .,0 FD 2 1 0 ., 7 9 . .1 1 1 ..2 9 . .8 9..4 8 .. 7 1 0 .. 1 9..5 7 . .5 1 1 .. 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 A L L W EIG H TS W ERE R EC O R D ED IN GRAM S ( G ) . M EA N L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y POSTPARTUM T H E E V E N T O C C U R R ED . O F L IV E PUPS. 16 FS 8.3 8.2 9.4 8.1 8.3 8.7 17 9, .2 8 ,. 4 8 ,. 7 18 19 20 7.8 FD 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 E40 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 625 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 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 10.1 10.6 10.4 9.5 9.9 8.6 9.0 9.7 9.9 9.8 10.0 9.6 9.7 12.2 10.8 8.6 11.3 11.5 12.3 11.2 11.1 10.4 11.1 10.8 10.7 FM 2 FS 10.4 9.9 10.7 9.1 9.6 10.1 8.5 9.0 8.2 9.0 7.7 9.3 6.7 8.8 9.8 8.5 9.4 9.1 FD 3 10.2 10.0 10.2 10.0 8.8 9.0 8.3 8.5 9.0 9.4 8.3 8.9 9.5 9.0 9.5 9.1 8.9 9.0 7.7 8.4 8.9 7.8 8.5 8.6 8.5 8.9 8.9 9.2 FS 11.8 9.8 10.4 10.3 10.2 9.6 10.2 10.2 9.8 9.5 8.3 9.6 9.8 9.3 8.3 9.3 8.4 8.5 9.3 8.6 8.9 7.8 9.3 8.3 8.4 8.6 8.6 10.3 8.8 7.9 9.5 9.2 9.0 7.8 7.5 8.1 8.0 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 10.9 11.1 11.2 11.3 10.8 10.1 10.7 9.8 9.8 9.6 9.5 9.3 9.3 10.4 10.5 10.6 9.6 10.4 9.8 10.2 7.7 7.6 6.9 8.1 6.7 8.6 6.3 5.9 7.1 7.9 6.2 7.8 7.2 7.2 7.1 10.2 9.8 9.2 10.0 11.1 10.7 9.3 9.5 9.6 10.1 8.9 9.1 8.3 11.1 11.6 11.2 11.1 10.6 10.7 10.2 9.9 9.6 8.8 10.5 10.3 9.2 9.5 7.4 9.1 8.5 7.0 8.2 8.6 9.0 8.5 7.8 9.2 8.4 8.5 8.4 11.3 7.4 11.8 10.6 11.7 9.0 10.8 10.5 10.6 10.4 9.5 10.7 10.0 8.1 7.3 7.9 8.2 8.3 7.9 6.7 7.8 7.5 7.4 7.6 7.3 7.3 11.9 10.0 10.6 8.9 10.4 9.9 10.6 9.4 9.5 9.9 9.0 9.6 8.8 9.9 10.2 6.8 7.1 6.8 7.6 7.7 7.6 7.5 7.1 7.6 7.7 7.2 7.0 7.4 NOT PREGNANT 10.2 11.2 11.2 11.0 9.8 9.5 10.9 9.6 9.3 10.7 10.2 11.1 10.2 8.7 10.4 9.6 10.2 9.8 10.7 MM 3 10.0 8.1 10.5 9.9 9.6 9.3 9.7 12.6 12.4 11.9 10.9 9.0 9.6 8.8 9.2 8.7 9.9 10.0 9.5 8.6 9.4 8.4 8.6 9.4 10.4 8.1 10.7 9.0 10.8 9.3 9.1 9.2 9.6 9.2 9.3 8.8 9.3 8.9 9.9 9.7 9.9 9.3 10.4 9.6 9.5 8.4 9.3 9.1 8.6 8.4 8.2 8.5 8.8 8.2 8.4 7.5 7.0 8.8 8.1 7.8 7.6 7.6 10.5 9.3 10.8 9.9 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 12.6 13.0 11.6 9.4 9.4 8.5 9.7 9.0 9.7 9.2 9.0 7.6 8.4 8.6 9.4 8.5 9.9 8.0 9.6 8.6 10.0 11.6 11.2 10.1 10.3 10.9 10.3 10.6 10.3 9.1 MD 1 10.0 9.9 8.5 10.1 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 10 11 12 13 14 15 16 17 18 19 20 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 12.1 12.2 12.2 11.0 13.2 11.3 12.7 14.5 17.2 17.0 15.6 16.0 15.5 15.9 20.4 22.0 22.5 21.0 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 12.8 11.2 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 12.1 11.2 10.0 12.3 11.5 12.1 11.8 12.1 13.7 12.7 11.1 12.8 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 12.8 16.5 16.2 18.2 16.6 16.1 16.9 15.8 12.0 13.5 13.3 13.9 12.8 14.3 MS 12.8 11.3 12.9 10.4 12.0 13.3 13.2 13.2 14.8 11.7 13.4 12.6 12.6 11.3 15.2 13.5 14.1 14.7 13.4 14.8 14.3 NOT PREGNANT; MATING NOT CONFIRMED 12.6 12.9 12.4 12.3 11.5 12.6 11.6 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-6889.6) TABLE E40 (PAGE 12) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 627 PUP *) 1 2 1 4 c 6 7 8 9 10 11 12 13 14 15 16 17 RAT/ LITTER # MATERNALi DOSAGE iGROUP 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 12 .3 12 .9 12 ..9 13 .3 13 .6 13 ..7 16. 6 16. 1 15.,6 14 .2 15. 5 17.,0 13 .9 13 .0 10.,1 14 .1 14 .4 15..1 13 . 6 13 . 9 1 2 .,3 NOT PREGNANT 1 7 . 2 1 6 . 1 1 6 ..3 1 6 . 3 1 7 . 0 1 7 ..1 1 5 . 4 1 5 . 5 1 5 ..5 1 6 . 7 1 6 . 0 13 ..8 1 8 . 3 1 7 . 5 1 7 ..3 13 . 9 1 5 . 0 1 5 ..2 1 1 . 5 8. 4 1 3 .. 1 12 . 4 1 1 . 4 1 1 .,7 1 7 . 7 1 7 . 3 1 7 ..9 1 6 . 8 1 8 . 8 1 7 ,.9 1 7 .7 17 .4 1 6 ..6 14 .6 1 6 . 1 1 6 ..3 13 .8 13 . 0 1 5 ,. 0 12 .6 1 5 . 0 14 ,.2 1 4 . 3 1 4 . 6 14 .1 1 4 . 0 13 .9 13 ,.7 1 2 . 6 13 .5 1 2 ,.6 1 2 . 5 1 4 . 0 13 ,.3 13 .5 1 2 . 1 13 ,.0 13 .,4 13 .6 15 .0 16..5 12,.9 14 ,.5 16..5 15,.9 13 ,.1 13 .0 13 .. 1 1 4 ,.6 1 5 .. 5 1 7 ,. 1 1 5 ,.7 1 8 ,.3 1 5 ,.7 1 2 ,.9 13 .0 1 6 ,. 2 1 8 ,.3 17 .4 16 .5 12 .2 12 .1 14 .6 14 .3 13 .1 13 .5 13 .3 15 .2 16..1 12..6 13 .6 16..8 16..2 11..1 15.. 1 1 2 ..1 1 5 ..6 1 7 ..4 1 4 ..8 1 6 ..4 1 6 ..1 1 4 ..9 1 2 ..9 1 1 ..0 1 6 ..4 1 8 ..4 1 5 ,.4 1 6 .. 1 1 1 ,.7 12 ,.7 13 ,.8 1 2 ,.2 1 2 ,.5 1 2 ..9 12 ,.8 15 .2 17. 5 13. 6 14. 4 15. 3 15. 7 10. 9 15. 2 13 . 8 16. 1 17. 9 14. 9 16. 7 MM 4 13. 5 13. 9 13 . 8 MS 17. 0 15. 1 15. 9 12. 6 11. 0 13. 7 14. 3 12. 8 13. 9 13. 1 10. 9 17..8 12..3 11..4 16..3 15..5 11..3 14 ..6 13 ..0 1 5 ..1 1 5 .. 6 14 ..3 1 4 ..9 1 6 ..8 1 5 ..9 13 ..4 1 2 ..7 1 5 ..4 1 8 .. 0 1 5 ,.9 1 6 ,. 0 1 2 ,. 1 13 ,.2 13 ,.5 1 5 ,.5 1 2 ,.2 1 2 ,.5 14 ,.6 14 .4 14.,5 11..4 15..2 16..1 9..8 1 5 ..0 12 ..9 1 5 ..4 13 .. 1 14 .3 1 5 ..6 1 6 ,.8 14 ..2 MD 7 1 1 ..9 1 6 ..9 1 5 ,.8 1 7 ..4 1 6 ,. 1 13 ,.8 13 ,.2 13 ,.6 13 ,.1 1 2 ,.2 1 2 ,.9 13 ,.4 14 .4 12..9 13 .,7 15.. 1 14 .3 12 .2 1 4 ..6 1 1 ..5 14 ..8 1 5 ..4 13 ..0 1 6 ..3 1 6 ..3 13 ., 1 1 2 .. 1 1 2 ..8 1 7 ..0 1 8 ..0 1 6 ,.5 1 5 ,. 1 1 1 ,.8 12 ,.3 13 ,.5 12 ,.8 12 ,.0 12 ,.7 14 ,.4 13 .3 11.,8 11.,7 14 .,9 15.,6 13 .,0 13 .,8 12 .,7 14 . 8 1 5 ..1 14 ..9 1 7 ..0 1 6 ..7 1 5 ..3 1 1 ..3 1 1 .,9 17 ..1 1 9 ..0 1 7 ..4 14 ..7 13 ..3 14 .2 13 ..9 13 .1 1 1 ..6 1 2 ..5 13 .3 11..6 11. 3 12 .9 16. 0 14 .9 13 .8 13 . 7 MS 14. 1 16. 7 13 . 0 15. 1 17. 3 15. 4 12. 6 10. 8 14. 6 17. 1 17. 2 12. 0 14 .3 15. 0 15. 1 12. 5 12 . 0 12. 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 1 2 ., 1 13 ..3 1 5 ,.2 1 6 ..3 1 4 ..6 1 2 ..6 1 0 ,.9 1 2 ,.4 1 0 ,.5 14 ,.6 12 ,.2 12 ,.2 13 ,.4 1 2 ,.1 8.,3 12 ..6 14 .,1 13 .,8 1 0 .,1 12 .,9 13 ..5 9..9 1 2 ..9 1 1 ..3 14 .6 1 1 ..8 12 .,1 9..6 13 .9 14 .4 17..0 12 ..8 14 .,0 14 ..7 13 ..2 1 1 ..0 13 .,7 13 .6 13 .1 FD 3 11,.8 13 .7 1 2 ..3 13 .,7 1 0 ..0 1 0 ..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) T A B L E E4 0 (P A G E 1 3 ) : PU P B O D Y W EIG H TS FRO M B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU P S ARGUS 418-020 Page 628 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 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 1465 1472 1474 1476 1477 1480 13.5 13.9 14.2 10.5 13.7 11.2 14.5 14.2 12.9 14.7 15.2 13.9 11.8 13.2 12.7 12.1 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 21.0 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 12.8 15.0 19.0 18.6 18.7 14.6 15.3 13.1 10.2 10.7 12.4 10.8 11.1 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 12.9 12.5 12.6 14.8 18.6 16.2 17.4 13.9 14.6 12.8 14.0 19.4 13.8 10.7 9.0 15.4 12.7 12.1 14.7 15.8 11.1 15.3 13.5 13.9 14.2 17.9 19.9 11.9 14.3 12.1 13.5 MM 6 17.5 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 15.3 MS 11.0 11.7 MM 3 16.4 16.0 MS 16.0 12.9 13.6 17.1 13.0 MD 1 9.7 16.9 12.7 14.1 13.5 15.2 12.8 16.0 12.0 14.6 13.8 16.2 14.8 11.4 13.2 13.1 13.9 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EA N L IT T E R W EIG H T S IN C L U D E O N LY W EIG H TS O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D - D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: 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 # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 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 14.5 14.4 14.9 NOT PREGNANT 16.1 15.8 14.9 15.5 13.5 15.9 20.5 20.8 16.4 13.5 16.3 12.5 14.2 13.3 14.9 12.5 11.6 10.7 17.8 16.6 17.3 13.7 12.6 11.3 16.9 15.9 16.7 13.0 13.4 11.6 10.8 10.7 10.6 18.1 11.9 16.6 NOT PREGNANT 15.2 14.5 14.1 12.2 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 21.6 13.7 13.2 12.3 13.0 13.0 12.7 15.7 16.3 15.9 10.9 13.2 11.2 12.4 14.3 14.0 13.9 15.2 11.3 16.3 14.9 15.8 13.9 15.2 14.7 16.1 21.5 15.0 14.2 10.5 16.9 14.1 17.1 13.3 10.8 17.3 13.1 15.3 19.5 14.4 14.9 12.7 16.6 12.8 16.0 11.3 10.8 15.7 14.5 15.2 17.5 15.3 14.5 13.7 15.9 15.3 12.2 16.1 13.2 12.2 14.8 11.2 12.5 13.8 14.9 14.1 13.8 15.1 18.7 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 13.5 15.3 13.0 14.2 14.6 11.2 11.1 11.6 16.9 12.4 15.3 11.6 11.2 14.0 13.9 13.4 10.5 11.9 16.7 12.5 11.0 14.4 14.5 12.6 17.3 13.7 11.4 14.7 16.6 13.6 14.3 13.9 12.3 10.8 14.3 15.6 MM 5 11.7 10.1 13.9 14.6 10.2 16.9 15.4 12.0 11.5 12.4 16.1 13.5 11.8 14.9 12.4 13.7 13.8 14.0 14.6 13.8 12.8 10.9 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 12.7 17.5 15.5 FD 1 FS 14.2 14.3 UU FS 13.4 12.4 10.2 10.4 8.9 13.4 13.2 13.2 10.7 12.0 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) T A B L E E4 0 (P A G E 15 ) : P U P B O D Y W EIG H T S FROM B IR T H T O D A Y 22 P O S TP A R TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU P S ARGUS 418-020 Page 630 6 10 11P U P # 1 2 3 4 5 7 89 12 13 14 15 R AT/ L IT T E R # M ATERNAL DOSAGE GROUP V 30 M G /KG /D AY POSTPARTUM DAY 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 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 12.1 16.8 14.8 14.1 12.3 12.4 14.2 13.0 12.6 14.6 15.8 16.2 15.7 13.4 13.9 14.3 10.8 11.7 11.6 13.7 11.8 12.8 15.5 15.1 14.6 12.3 12.5 12.1 16.1 14.2 15.8 10.4 11.8 10.9 13.9 14.5 13.5 10.8 9.6 10.3 NOT PREGNANT 14.3 13.2 14.6 16.4 15.1 15.6 18.3 18.4 19.0 11.8 14.1 13.1 15.4 13.0 14.5 13.4 13.9 12.1 12.4 11.1 10.8 13.9 15.2 13.7 19.0 18.9 21.4 12.3 12.7 12.1 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 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 13.1 14.3 14.9 14.7 13.9 13.9 13.0 10.9 10.3 13.0 13.9 13.2 10.3 13.1 10.9 10.9 15.1 15.4 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 13.9 14.9 12.9 14.1 13.4 10.3 14.0 10.8 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 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 14.5 15.1 12.0 13.8 14.1 12.0 14.6 10.3 MD 1 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 12.6 14.7 12.9 14.4 11.6 14.2 11.0 13.4 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 14.3 12.6 12.2 10.4 12.5 11.4 12.0 14.0 FS 11.9 11.5 FS 12.8 12.8 14.9 10.8 11.3 14.3 14.0 10.8 14.7 11.5 14.4 8.6 11.5 FD 6 15.0 10.8 12.1 14.2 11.2 12.1 14.2 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G ) . M EAN L IT T E R W EIG H T S IN C L U D E O N LY W EIG H T S O F L IV E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . 16 201 7 1 8 1 9 12.9 1 3 . 3 F D 3 12.2 PROTOCOL 418-020: 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 1 4 5 6 7 8 c) 10 11 12 13 14 15 16 17 18 19 20 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 22 .3 20. 7 24 .0 22 .7 22 .2 22. 9 20. 7 23 .,4 21. 7 21. 1 22 .8 21. 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 22. 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 20. 4 20. 9 18. 6 20. 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 22 .5 21. 5 22 .,1 21. 3 22 .2 20. 0 19. 8 20. 6 24. 7 22..0 19. 5 23 .3 21. 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 21. 8 24. 4 25 .2 23 .7 25. 7 27. 1 25. 5 18. 4 22 .9 18 .4 21. 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 22 .4 25. 7 21. 5 19. 7 22. 7 29. 1 27. 0 25 .6 24. 1 25. 5 21. 2 22. 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 22. 7 22 .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 CONFIRMED 25. 0 25. 8 25 .9 24. 8 24 .4 24 .3 24 .0 28. 1 25. 9 22 .1 19. 8 27. 9 20. 8 30. 3 MM11 29. 7 26. 2 20. 1 20. 6 27. 9 24 .4 23 .6 24 .7 25. 3 30. 0 25. 3 23 .1 28. 4 30. 0 25. 8 21. 5 23 .5 26. 4 23 .3 27.,7 24.,7 19.,7 23.,1 29.,4 23..3 MM 2 16..4 27..4 27..6 20..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 24,.9 20..9 25..7 24,.4 19.,1 25..7 23 .9 28..5 16..0 29..6 26..9 18..3 21..8 26,.5 28,.1 20,.5 27,.2 26,.6 20,.7 25,.1 28,.5 32 .7 26 .1 24 .6 22 .8 24 .8 23 .7 28..1 26,.7 23 .6 22..3 24..4 26. 1 22 .8 22 .9 24 .5 23,.8 21. 8 28 .5 15,.0 27,.2 29,.7 20,.6 20,.0 29. 4 18. 1 28. 5 19. 2 MM12 24 .6 25 .8 20 .2 24 .6 28 .3 16 .4 28 .0 27 .1 25. 3 26. 1 15. 3 24 .4 27. 1 20. 2 24 .5 29. 8 25 .5 23 .8 24 .5 28 .4 25. 3 16. 4 22. 8 23 .0 23 .9 25. 0 22 .5 19. 5 24 .0 23 .7 25. 9 25..7 26..3 24 .0 24 ,.3 27..6 26. 5 28..6 15..9 16. 9 20.,7 28..6 19..9 18. 7 17,.0 20..5 19. 0 20..0 24 ,.5 25. 4 23 .4 15,.6 18. 7 15..8 26 .6 24 .0 20,.2 19. 4 20,.0 21,.6 24 .5 24 ,.0 25,.5 27. 6 28,.6 20 .5 20,.3 23 .2 22,.4 26. 9 19. 3 FU 26. 5 28,.0 17,.1 22 ,.8 22,.5 FS 23.3 19.8 12.4 17.0 20.4 18.4 21.6 FS FS 18.6 FD10 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 E4 0 (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 10 11 12 13 14 15 16 17 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 1392 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 22.8 30.9 28.3 30.8 23.6 25.8 23.9 20.1 22.2 21.5 26.0 26.6 25.7 21.7 21.3 22.6 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 20.1 23.9 23.1 21.0 28.1 28.7 27.0 24.0 23.3 24.3 26.7 26.1 26.0 21.4 21.7 23.5 21.0 23.7 21.1 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 18.0 25.6 22.8 24.4 23.0 21.5 18.1 20.2 24.5 21.2 FD 3 21.0 22.3 22.1 24.1 19.8 19.0 21.7 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 OF 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 # 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 15 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 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 22.8 21.0 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 22.6 29.6 24.6 25.0 22.9 16.0 22.1 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 21.8 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 26.3 22.5 21.6 30.3 37.5 27.2 27.8 25.1 27.1 20.5 27.9 27.8 25.4 19.4 23.0 27.8 24.9 20.4 28.6 23.0 23.1 22.5 18.7 29.6 24.7 31.1 37.2 27.8 26.5 19.4 22.7 MM 6 35.8 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 21.1 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 21.1 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 21.1 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 21.9 20.4 FD 1 19.0 21.3 26.9 22.0 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 19) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 634 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 IV 10 MG/KG/DAY POSTPARTUM DAY 15 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 22.4 22.3 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 22.1 20.7 32.6 29.7 29.2 24.8 23.4 28.1 30.9 31.0 32.9 19.5 21.7 18.6 21.5 24.3 22.6 30.1 25.2 30.8 NOT PREGNANT 24.9 24.1 24.1 22.1 21.1 21.0 26.3 28.5 29.7 26.6 28.0 26.6 23.3 22.1 24.4 25.3 23.7 24.9 31.1 32.6 30.3 31.3 35.9 18.7 20.2 20.3 28.1 29.8 24.3 23.7 28.4 20.5 20.2 24.9 21.5 22.5 21.5 23.4 23.9 23.3 22.5 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 22.0 31.4 25.6 19.6 28.9 25.4 22.9 23.9 22.8 18.4 27.0 23.1 21.8 22.1 22.8 24.4 24.8 24.3 29.9 30.5 25.0 24.0 22.3 31.7 26.5 27.9 21.4 23.7 28.2 21.1 19.6 28.8 25.3 21.3 27.8 30.4 17.5 22.3 25.1 21.4 22.6 22.6 25.6 23.4 28.0 25.9 28.7 25.5 23.4 21.8 30.8 25.1 29.5 19.0 23.9 25.5 21.9 23.4 31.5 28.6 23.5 24.9 31.4 19.9 27.2 26.8 16.9 22.8 23.6 25.2 23.7 22.3 25.7 32.3 27.7 24.2 25.3 30.4 24.5 27.9 22.1 20.1 28.8 24.2 17.7 27.9 25.6 23.4 22.7 32.0 17.8 24.6 27.6 23.0 24.1 24.1 24.8 21.9 20.4 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 21.5 28.5 21.0 28.9 19.9 22.5 26.8 21.1 20.3 27.9 28.6 24.1 23.2 MD 1 26.1 21.7 28.3 26.7 24.4 23.3 22.3 18.7 20.9 20.2 18.4 21.7 17.5 24.4 18.5 26.5 MS 23.6 21.4 21.9 25.1 18.3 22.1 24.2 29.2 28.3 23.6 22.4 32.8 24.0 29.5 20.3 20.7 27.1 21.7 16.2 24.9 24.2 19.7 22.6 27.7 17.4 25.2 28.2 24.8 20.6 23.5 26.4 20.8 25.5 22.4 24.1 25.5 20.2 29.4 23.5 27.4 19.4 21.0 25.1 23.6 20.7 28.3 26.4 10.5 23.3 27.6 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-6889.6) TABLE E40 (PAGE 20) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ARGUS 418-020 Page 635 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 15 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 26.0 25.1 24.5 31.2 31.8 30.1 22.8 17.5 23.0 19.8 18.5 16.7 25.6 25.1 24.2 23.9 25.9 23.7 20.9 20.1 24.2 22.0 21.4 21.2 27.5 27.2 27.3 22.7 23.1 24.2 19.6 21.1 18.5 22.9 23.4 23.0 23.3 24.9 25.6 22.8 20.6 17.8 27.5 27.6 24.6 21.9 20.3 19.6 22.8 24.7 23.7 21.0 20.7 20.4 NOT PREGNANT 21.5 22.6 20.6 25.8 26.1 23.8 37.1 35.5 33.9 22.7 22.8 20.7 22.6 23.5 25.0 23.0 24.3 24.8 22.4 20.6 22.0 23.4 24.2 18.1 29.7 30.5 28.9 21.2 20.8 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 24.6 31.1 23.7 18.9 19.6 22.7 18.9 21.2 27.1 22.3 21.9 23.4 25.2 17.2 26.1 21.7 26.2 20.1 23.4 32.4 22.9 18.8 25.9 22.8 21.9 22.7 27.9 22.5 19.5 21.8 25.2 21.2 22.5 21.9 24.4 21.2 23.7 31.9 19.6 19.5 23.4 23.1 20.4 20.5 28.2 24.4 MD 7 21.7 24.0 19.8 24.2 18.2 25.5 MM 8 24.2 29.1 17.8 19.6 24.5 22.3 21.0 20.1 25.9 26.1 13.9 22.3 22.7 17.5 27.6 21.6 24.5 MD 7 22.7 31.5 25.2 18.2 23.8 19.8 20.4 20.2 27.9 22.1 19.3 22.2 23.6 15.8 24.5 19.5 22.1 21.1 22.8 25.1 32.0 19.1 26.3 23.3 21.5 21.9 33.3 20.4 23 .4 21.5 MM 3 21.1 21.2 23.2 20.8 21.7 32.7 20.6 22.6 19.2 24.6 21.1 22.9 24.7 18.9 21.4 30.2 19.4 23.5 22.0 25.0 21.7 23.1 24.7 23.1 23.2 18.3 24.9 23.6 24.3 21.4 19.9 25.0 20.8 23.0 17.9 23.6 22.7 21.4 20.8 23.1 24.1 20.1 22.4 19.4 22.6 22.7 30.1 21.3 17.0 23.0 22.0 20.3 19.4 26.6 22.5 16.4 21.2 22.8 19.1 26.5 18.7 23.7 20.1 21.5 25.3 18.2 23.2 23.1 20.0 21.9 18.8 21.1 24.4 29.0 22.2 16.9 24.8 23.1 22.0 20.0 27.5 19.1 20.2 22.0 21.3 19.0 26.3 22.0 24.5 20.6 22.0 26.5 22.2 19.2 24.9 23.0 20.0 21.7 27.6 24.3 17.2 20.1 23.7 21.0 25.2 18.5 23.2 20.8 20.5 19.8 24.6 25.5 20.3 23.6 25.7 19.9 22.7 20.7 24.3 21.4 20.6 20.5 19.7 MD 1 23.2 25.3 FM 2 20.9 17.2 24.9 21.4 19.5 26.6 23.4 20.7 21.7 20.2 24.0 20.1 22.9 19.8 22.4 21.1 24.4 21.3 22.0 17.3 19.2 25.4 FS 9.0 18.0 FS 22.4 20.3 20.1 20.2 20.7 21.7 20.8 18.7 22.5 17.5 22.5 23.8 18.4 18.3 FD 6 25.9 24.4 16.9 19.8 24.4 18.5 19.3 16.0 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 # 12 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 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 34,.8 43 .2 30,.9 32 ,.3 41,.4 38..4 39..0 46,.2 31..8 36..1 46,.7 26..9 28,.5 49,.1 27..0 34..3 47 ,.7 24..0 34,.8 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 37,.4 42,.7 29,.0 40,.3 45,.8 36 .2 38 .6 37 .2 38 .0 23 ,.4 39 .2 40 .3 42 .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 FDIO 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) T A B L E E4 0 (P A G E 2 2 ) : P U P B O D Y W EIG H TS FRO M B IR T H T O D A Y 22 PO S TPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 637 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY POSTPARTUM D AY 22 13 6 2 1363 13 6 4 1367 13 6 8 1371 13 75 13 76 1378 1379 13 8 1 13 8 2 1383 13 8 4 13 8 7 13 8 9 13 9 2 1393 13 9 7 13 9 9 140 1 14 0 4 14 0 7 14 0 9 14 10 14 13 14 15 14 16 14 18 42.5 31.4 32.3 38.9 45.5 41.9 35.4 36.8 NOT 34.6 48.6 36.3 48.8 43.0 33.6 38.9 28.6 43.3 50.7 49.6 45.8 39.5 29.3 46.7 40.3 47.2 39.1 39.2 37.6 42.4 43.3 36.0 31.0 32.3 3 2.7 39.5 39.5 38.3 4 0 .1 31.3 35.9 34.5 36.3 37.6 42.0 P R EG N A N T 39.4 39.7 49.1 49.7 39.1 38.1 47.9 43.2 44.8 41.4 32.4 35.4 32.0 4 1.4 33.1 30.9 43.9 45.8 48.4 48.8 50.3 49.3 42.8 42.3 34.2 38.2 38.0 34.4 48.3 50.2 42.4 40.3 42.3 42.6 36.2 4 1 .1 34.9 3 1 .7 38.8 36.6 42.6 34.4 40.8 40.0 44.2 36.0 34.9 32.3 4 0 .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 3 7.7 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 3 1.1 46.0 38.2 48.3 38.7 36.8 37.9 43.8 34.1 31.5 37.1 37.2 29.5 35.0 36.3 39.6 33.6 32.5 33.5 42.7 31.9 34.3 3 7.7 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 34.5 52.3 36.6 49.5 4 1 .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 39.1 39.4 35.7 31.8 44.6 32.7 45.0 37.6 35.4 35.5 3 7.7 31.2 36.5 36.4 34.7 3 1 .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 4 1 .7 38.4 25.8 30.9 37.9 36.7 40.2 44.4 3 7.7 38.0 26.8 34.9 32.2 39.1 38.3 FD 17 40.2 36.6 36.9 31.9 32.7 38.1 37.9 33.9 FM 14 27.5 30.8 22.1 FD 4 36.0 39.3 39.5 FD 9 28.6 36.7 36.2 43.1 39.3 25.7 33.3 3 1 .1 25.1 FS 24.9 31.6 31.2 33.5 3 7 .2 FM 5 FD 3 FM 3 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S (G ) . M EAN L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L I V E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D AY PO STPARTUM T H E E V E N T O C C U R R ED . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E4 0 (P A G E 23 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO S TP A R TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N P U P S ARGUS 418-020 Page 638 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY POSTPARTUM DAY 22 14 2 1 14 2 4 1426 14 2 8 1430 143 1 14 3 3 1436 14 3 7 1439 14 4 2 1443 1446 14 4 8 1450 14 5 2 1455 14 5 6 1458 14 5 9 146 1 14 6 3 14 6 5 14 6 8 14 6 9 14 72 14 74 1476 1477 14 8 0 34.3 28.8 36.0 37.2 37.6 45.1 42.4 3 7 .7 40.5 54.6 53.5 41.0 NOT 43.9 31.6 34.7 48.7 52.1 NOT 42.0 50.3 37.2 38.5 33.8 37.6 50.3 38.4 41.3 37.4 45.0 33.3 30.2 26.1 27.9 3 3 .1 36.6 40.9 40.9 34.4 32.6 40.3 37.5 39.6 41.2 39.5 37.4 4 1.5 34.0 54.5 52.4 52.8 52.8 43.7 41.8 PREGNANT 43.6 39.3 2 7 .7 32.3 35.4 35.9 50.8 46.8 50.0 50.2 P R EG N A N T 44.5 47.0 44.7 51.1 38.8 36.2 47.9 41.4 35.8 26.2 36.3 39.5 49.5 5 1.1 43.3 4 2.1 39.8 38.5 36.6 26.8 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 4 1 .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 30.0 27.0 34.9 37.7 33.8 42.6 38.3 38.6 38.6 53.2 37.6 28.8 21.8 31.2 41.5 31.3 46.2 36.2 37.0 34.8 48.3 41.4 33.9 24.4 32.9 34.1 30.7 MD 1 31.0 35.3 39.1 FD 1 39.2 MS 27.8 33.7 MD 5 MS 28.8 32.3 MM 3 3 7.7 26.2 33.0 41.9 40.2 30.5 31.6 46.9 46.8 52.4 33.1 44.1 35.5 36.2 47.6 42.3 31.6 34.5 4 7 .1 46.6 45.5 MS 43.9 36.2 35.5 41.3 39.4 MD 1 21.3 41.8 MD 2 50.1 37.2 45.9 34.3 35.7 44.7 42.4 40.2 32.6 44.7 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 3 4 .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 4 7 .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 4 1 .1 21.4 3 7.7 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 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S (G) . M EA N L IT T E R W EIG H TS IN C L U D E O N LY W EIG H TS F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . O F L IV E 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) T A B L E E4 0 (P A G E 2 4 ) : P U P B O D Y W EIG H TS FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 639 PU P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 R AT/ LIT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY POSTPARTUM D AY 22 14 8 2 14 8 3 1486 1488 14 9 0 1491 14 9 4 1496 1497 15 0 0 15 0 2 15 0 5 1507 15 0 8 15 11 15 13 15 14 15 16 15 17 15 19 1521 1523 15 2 4 15 2 7 1528 1531 15 3 3 1534 15 3 7 1539 3 8 .1 NOT 3 7.1 37.4 48.3 36.3 45.4 38.8 43.0 32.7 50.2 28.3 35.4 39.5 NOT 34.5 34.9 43.3 36.8 36.3 43.4 48.2 58.4 32.6 47.6 41.6 36.6 39.0 37.4 41.5 33.8 38.4 P R EG N A N T 3 1 .1 35.8 41.7 40.1 52.3 49.3 36.3 31.3 40.1 46.5 42.1 31.4 55.2 54.0 40.5 40.4 4 7 .1 49.3 34.2 30.8 3 7.7 30.9 42.9 40.5 P R EG N A N T 39.2 40.0 35.4 34.3 47.3 44.4 36.9 36.3 40.8 37.2 42.2 42.7 50.4 50.1 50.5 28.0 25.3 42.2 47.3 46.2 36.3 4 2 .1 38.2 37.7 41.4 37.3 39.2 39.9 39.6 43.5 3 2 .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 36.5 38.4 55.9 30.2 39.5 44.4 50.7 38.2 47.6 29.1 34.5 43.0 39.6 27.5 48.3 36.6 35.4 42.0 31.4 26.1 37.2 38.1 36.9 42.0 38.4 41.5 34.3 31.6 38.8 51.9 35.0 42.2 36.1 49.5 4 3 .1 45.5 32.6 33.8 38.7 36.0 32.6 46.0 33.0 36.3 40.2 48.5 32.3 4 1 .1 34.5 31.0 36.1 36.4 41.8 33.5 32.6 39.9 55.1 36.2 44.4 35.9 49.0 40.8 49.0 30.4 33.1 39.6 37.9 30.6 43.4 32.4 33.6 44.4 51.1 29.5 41.2 46.6 37.3 3 7 .1 24.4 42.4 37.3 33.7 32.7 39.1 52.7 3 0 .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 4 3 .1 38.7 45.6 31.8 30.8 41.5 38.6 32.0 46.8 33.6 38.4 38.7 MD 1 41.7 27.0 51.6 3 1 .7 38.9 43.1 47.0 27.8 43.7 34.5 38.0 36.8 35.5 39.6 26.7 41.5 MS 40.7 35.4 3 1.1 39.3 34.0 31.5 3 7 .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 37.2 36.8 36.9 38.0 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 38.1 33.5 46.8 31.8 35.0 40.8 34.6 36.1 34.0 4 1 .1 3 1.1 29.8 39.9 48.6 MM 5 2 4 . 8 40.5 37.2 39.9 36.8 40.6 42.6 31.2 34.3 35.5 41.0 34.4 33.4 34.3 34.6 34.0 37.0 36.1 29.0 35.2 24.8 43.1 38.9 FD 2 26.5 33.2 FD 2 42.0 31.2 32.6 37.3 34.2 43.7 32.5 30.6 MS 29.2 30.7 36.8 30.5 23.2 21.9 37.4 38.3 39.8 36.1 37.2 24.5 4 1 .1 FD 1 32.6 33.8 UU FS 3 1 .1 30.2 33.2 32.4 30.8 21.6 FS 36.1 FS FS 21.9 3 1.7 23.1 FD 18 27.2 32.9 FD 12 25.2 36.1 FM 6 FD 1 A L L W EIG H TS W ERE R EC O R D ED I N GRAM S ( G ) . M EAN L I T T E R W EIG H T S IN C L U D E O N LY W EIG H T S F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PRESU M ED C A N N IB A L IZ E D ) NU M B ER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPAR TU M T H E E V E N T O C C U R R ED . OF LIV E PUPS. 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) T A B L E E4 0 (P A G E 25) : PU P B O D Y W EIG H T S FROM B IR T H T O D A Y 22 PO S TPA R TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 640 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP V 30 M G /K G /D A Y POSTPARTUM DAY 22 15 41 1544 15 4 5 15 4 6 15 4 8 15 5 0 15 5 2 15 5 5 15 5 7 15 5 8 15 6 0 15 6 4 15 6 5 15 6 6 15 6 8 1571 15 73 1576 1578 15 79 15 8 3 1584 1586 15 8 7 15 8 8 15 8 9 159 1 15 9 3 15 9 8 16 0 0 34.1 47.2 34.7 34.9 33.7 40.2 33.9 27.9 34.4 3 7 .1 33.3 38.8 39.7 35.0 43.9 33.6 39.4 32.7 NOT 36.5 39.0 60.9 34.9 42.3 38.9 26.5 36.0 51.2 31.2 38.7 33.2 33.8 44.8 35.6 39.2 35.5 30.6 31.8 38.4 37.6 40.1 45.5 34.0 40.6 32.8 32.6 34.5 33.0 39.3 35.8 33.0 36.3 35.1 37.4 37.3 39.1 40.5 36.4 45.3 44.9 31.6 32.5 35.4 3 8.1 32.8 33.4 PREGNANT 36.1 36.1 42.4 38.1 58.7 55.1 39.5 37.2 41.9 46.2 39.6 39.5 24.8 26.3 36.8 37.4 51.9 50.6 27.4 23.4 40.8 40.6 31.8 49.5 28.7 31.6 38.4 3 8 .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 36.2 40.7 50.7 41.2 33.6 39.2 23.4 39.4 52.4 29.3 39.9 33.4 45.9 45.0 35.8 3 4 .7 4 1 .1 33.4 32.8 3 2 .1 33.7 36.3 39.6 36.1 26.7 40.6 30.5 3 8 .1 32.7 32.0 4 7 .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 34.5 4 4 .6 35.1 32.1 38.3 3 7 .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 3 1.1 32.0 36.6 35.3 30.9 44.6 28.7 35.9 33.3 33.1 MM 3 34.1 40.4 27.2 46.4 33.6 41.3 33.9 42.1 37.2 33.3 40.8 26.7 35.9 56.3 29.4 42.1 40.3 37.2 37.7 25.9 37.5 56.1 25.0 37.5 34.0 40.5 40.2 28.3 36.8 29.3 35.7 3 7.7 37.6 41.6 25.9 27.8 23.7 34.9 37.6 3 7.7 39.3 25.6 35.0 26.7 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 3 1 .7 36.3 40.0 31.6 37.0 39.7 28.6 3 2 .7 29.0 37.6 33.3 47.2 32.9 28.5 3 1 .1 38.0 31.9 29.1 31.0 37.6 33.1 35.5 40.8 34.6 4 7 .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 41.5 34.5 33.9 38.3 35.5 39.1 24.5 38.7 37.4 38.5 24.6 32.4 23.8 MD 1 29.0 38.2 34.8 FM 2 37.4 32.9 37.3 33.5 25.8 35.6 3 4 .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 3 0 .1 24.8 FD 16 FD 3 A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . M EAN L IT T E R W EIG H TS IN C L U D E O N LY W EIG H T S O F L IV E P U P S . F IR S T L E T T E R - - M -M A LE , F -F E M A L E , U -S E X U N D ET ER M IN A B LE S EC O N D L E T T E R - - S -S T IL L B O R N , U -U N C E R T A IN , D -D IE D , M -M IS S IN G (PR ES U M ED C A N N IB A L IZ E D ) NUM BER FO LLO W IN G "S EC O N D L E T T E R " IN D IC A T E S T H E D A Y PO STPARTUM T H E E V E N T O C C U R R ED . 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) T A B LE E 4 1 (P A G E 1) : PUP V IT A L S TA TU S AND S EX FROM B IR T H TO D A Y 22 POSTPARTUM - IN D IV ID U A L D A TA - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 641 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT/ L IT T E R # M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY 13 0 2 13 0 4 13 0 6 13 0 8 13 10 13 12 13 13 13 16 13 18 13 2 1 13 2 5 1328 1330 1331 13 3 4 13 3 5 13 3 6 13 3 8 1340 1341 13 4 2 13 4 4 13 4 5 1346 1348 13 5 0 1353 13 5 5 13 5 8 13 5 9 MA MA MA MA MA MA MA NOT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA NOT MA MA MA MA MA MA MA MA MA MA MA MA F A MA MA P R EG N A N T 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 PR EG N A N T; MA MA MA MA MA MA MA FA 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 F A MA MA MA MA M A MD 4 MA MA MA MA MA MA MA MA MA F A M A TIN G N O T MA MA FA MA MA MA MA FA FA MA FA MA FA FA MA FA MA FA FA FA MA MA MA M A M A M M 11 FA FA FA MA MA F A MA MA F A MA MA MA MA F A F A MA F A F A MA MA F A MA MA MA MA MA MA FA FA FA MA MA MA MA MA F A MS F A F A MA F A F A MA MS MA MA MA MA MA F A F A FA FA FA C O N FIR M ED FA FA FA FA FA FA FA MA FA MM 2 FA FA FA FA MA FA FA FA FA FA FA MA FA FA FA MA MA 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 MA FA FA FA FA FA FA FA FA FA FA F A .F A FA FA FA F A F A FD 17 FA FA FA FA FA MA FA FA FA FA MM 12 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 FA FA FA MA FA FA FA MA FA FA FA FA 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) T A B L E E 4 1 (P A G E 2) : PU P V IT A L S TA TU S AN D S E X FROM B IR T H T O D A Y 22 PO STPARTU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 642 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 2 0 2 1 22 23 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP I I 1 M G/KG/DAY 13 6 2 1363 13 6 4 13 6 7 1368 1371 13 75 1376 13 78 13 79 13 8 1 13 8 2 1383 13 8 4 13 8 7 13 8 9 13 9 2 1393 13 9 7 13 9 9 14 0 1 14 0 4 1407 1409 14 10 14 13 14 15 14 16 14 18 MA MA MA MA MA MA MA MA NOT 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 P R EG N A N T 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 MA MA MA MA MA MA MA FA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA MA MA MA MA MA FA MA MA MA FA MA MM 4 MA MA MA MS MA FA FA MA MA MA MA MA MA FA MA FA MA MA MA MA MA MA MA FA FA MA MA MA MA MA FA FA FA FA FA MA MA MA FA MA FA FA MA MA MA MA MA MA FA FA FA FA FA FA FA MA MD 7 MA FA FA FA FA MA FA FA MA FA FA FA FA 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 FA FA FA FA FA FA FA FA FA F A FD 17 FA FA FA FA FA FA FA F A FD 4 F A FD 9 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FS FA FA FA FA FA FA FA M A F A F A F A FM 5 FA FA FA FA F A FM 14 F D 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) T A B L E E 4 1 (P A G E 3) : PU P V IT A L S TA TU S AN D S EX FROM B IR T H TO D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 643 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 R A T/ LIT T E R # M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY 1421 14 2 4 1426 1428 1430 143 1 14 3 3 1436 14 3 7 1439 14 4 2 1443 1446 1448 1450 14 5 2 1455 14 5 6 1458 14 5 9 146 1 14 6 3 14 6 5 14 6 8 14 6 9 14 72 14 74 1476 1477 1480 MA MA MA MA MA MA MA MA MA MA MA MA NOT MA MA MA MA MA NOT 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 PREGNANT MA MA MA MA MA MA MA MA MA MA 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 FA MA MA MA MA MA MA MA MA MA MA FA MA MA MA MA MA MA MA MA MA MA MA FA MA MA MA MA FA FA MA MA MA MA FA FA MA MA MA FA FA FA MA MA MA MA FA MA MA MA FA FA FA MA MA FA MA FA MA FA FA FA FA MD 1 MA FA FA FD 1 FA FA MA FA MA MA FA MA FA MA MM 6 FA MS FA MA MD 5 MS FA MA MM 3 FA FA FA FA FA FA FA FA MA FA MA MA MA MA MA MA MA MA FA MA FA MA MA FA MA FA MA MA MA FA MA FA MA FA FA MA FA MA MA MA FA MA FA MS FA FA MA FA MA MD 1 MA FA MD 2 FA FA FA FA MA 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 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 FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 1 FD 1 FA FA FA FA FA FA F A FM 2 FA FA FA F A FD FA FA FA FA FA FA FA FA FA FA FA F A FM 2 F A FM 6 F D 6 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 F A FD 6 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) T A B L E E 4 1 (P A G E 4) : PU P V IT A L S TA TU S AN D S EX FROM B IR T H TO D A Y 22 PO STPARTU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PUPS ARGUS 418-020 Page 644 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 R A T/ L IT T E R # M ATERNAL DOSAGE GROUP IV 10 M G/KG/DAY 14 8 2 14 8 3 14 8 6 1488 14 9 0 1491 14 94 14 9 6 149 7 15 0 0 15 0 2 15 0 5 15 0 7 15 0 8 15 11 15 13 15 14 15 16 15 17 15 19 15 21 15 2 3 15 2 4 15 2 7 15 2 8 1531 15 3 3 1534 15 3 7 1539 MA NOT MA MA MA MA MA MA MA MA MA MA MA MA NOT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA P R EG N A N T MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA 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 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 FA FA MA MA MA FA MA MA FA MA FA MA MA FA MA MA MA F A FA FA FA FA M A MD 1 FA FA FA FA MA MA FA FA FA FA MA MA FA FA MA MA MA MA MA MA MA MA MA MA MA MA FA MD 1 MA MA MA FA FA FA FA MA FA MA FA FA MA MA MA FA MA FA FA MA MA MA FA MS FA FA MA 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 FA FA FA FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA MA FA MM 5 FA FA 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 FA UU FA F S FA FA FA FA FA FA MS FA FA F A FD 12 FA FA FA F A FD18 FA FA FA FA FA FA FS FA FA F A FM 6 FD 1 FA FA FS 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) T A B L E E 4 1 (P A G E 5) : PU P V IT A L S TA T U S A N D S E X FROM B IR T H T O D A Y 22 PO STPAR TU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 645 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT/ LIT T E R # M ATERNAL DOSAGE GROUP V 30 M G /K G /D AY 15 41 1544 1545 15 4 6 1548 15 5 0 1552 15 5 5 15 5 7 15 5 8 15 6 0 15 6 4 15 6 5 15 6 6 15 6 8 15 71 15 73 15 76 15 78 15 79 15 8 3 15 8 4 1586 15 8 7 15 8 8 1589 15 9 1 1593 15 9 8 16 0 0 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA NOT 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 F A MA MA MA MA MA MA MA MA PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA F A MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA MA MA FA MA MA MA FA MA MA MA MA MA MA MA MA FA MA MA MA MA FA MA MA MA FA FA MA MA FA MA MA MA MA FA MA MA MA MA FA FA MA MA FA FA MA MA FA MA MD 7 FA FA FA MA FA MA MM 8 FA FA MA MA FA FA FA FA FA MA FA FA FA FA FA FA FA MD 7 MA MA FA MA MA MA MA MA FA MA MA MA MM 3 MA MA FA MA MA FA MA MA MA FA MA FA FA MA MA FA MA MA MA FA MA FA FA FA MA MA MA MA FA FA FA FA FA MA FA MA FA FA MA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA MA FA MA 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 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA M A MD 1 FA FA F A FM 2 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 FA FA FA FA FA FA FA FS FA FA FS FA FA FA F A FD 6 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 16 FD 3 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) T A B LE E4 2 (P A G E 1 ) : C L IN IC A L O B S ER V A T IO N S FROM B IR T H TO D A Y 22 PO STPARTU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 646 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER D A Y (S) PO STPAR TU M O B S ER V A TIO N S a I 0 13 0 8 22 16 /16 PUPS D E H Y D R A T IO N ; U N G R O O M ED C O A T .b 13 13 16 1/13 PUPS D EH Y D R A T IO N . 1321 10 1 / 1 7 PUPS EM A C IA T IO N ; NO M ILK P R ES EN T IN STOM ACH. 1348 3 2/14 PUPS COLD TO TO U C H . 1350 21 1 7 / 1 7 PUPS D EH Y D R A T IO N . II 1 1404 1-22 1/15 PUPS T H R E A D -L IK E T A I L ; NO A N A L O P EN IN G P R E S E N T . 2-22 1/15 PUPS T H R EA D -LIK E T A IL . 14 18 2 12 12 4/16 1/14 1/14 PUPS PUPS PUPS COLD TO TO U C H . COLD TO TO U C H ; D EH Y D R A T IO N . D EH Y D R A T IO N . III 3 14 2 4 4 1 / 1 7 PUPS COLD TO TO UCH . IV 10 15 17 1 1/15 PUPS COLD TO TO U C H . 15 19 16 17 1/16 PUPS 1/16 PUPS EM A C IA T IO N . D EH Y D R A T IO N . 1523 1 2-22 20-22 22 1/12 1/11 1/11 1/11 PUPS PUPS PUPS PUPS T A I L B E N T ( 0 . 7 CM FRO M B A S E ) . b T A I L B E N T (D ID N O T E X C E E D 3 .2 CM R IG H T E Y E : N O T P R E S E N T .b DO M ED H E A D .b FROM B A S E) .b 1527 22 1/16 PUPS D EH Y D R A T IO N . a . T a b u la tio n r e s t r ic t e d to a d ve rs e o b s e rv a tio n s ; a l l o th e r p u ps a p p e a re d n o rm a l. b . O b s e rv a tio n c o n firm e d a t n e c ro p s y . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B L E E4 2 (P A G E 2) : C L IN IC A L O B S ER V A T IO N S FROM B IR T H TO D A Y 22 PO STPARTU M - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS M ATERNAL DOSAGE GROUP M A TER N A L D O SAG E (M G /K G /D AY) LIT T E R NUM BER D A Y (S) POSTPARTUM O B S ER V A TIO N S a ARGUS 418-020 Page 647 1545 15 1/18 PU PS: EM A C IA T IO N . 1548 1 1/14 PU PS: COLD TO TO U C H . 15 5 0 1-22 1/12 PUPS: NO T A IL P R ES EN T. 15 5 7 8-15 1/13 PUPS: M OUTH: MASS ( D ID N O T E X C E E D 0 . 5 CM X 0 . 2 CM X 0 . 2 C M ) . 15 6 5 2 3 4 -7 1/12 PUPS: 1/12 PUPS: 1/12 PUPS: BACK C O LD BACK C O LD BACK A B R A S IO N ( 0 . 5 CM X TO TOUCH. A B R A S IO N ( 0 . 5 CM X TO TOUCH . SC AB ( 0 . 5 CM X 0 . 2 0.2 CM); 0.2 CM); CM). 15 6 8 1 -7 1/13 PUPS: T A IL A B R A S IO N ( 0 . 3 CM FROM B A S E ) . 15 73 5 1/15 PU PS: COLD TO TO U C H . 15 8 3 5 -7 8-10 11-12 13-21 22 1/11 1/11 1/11 1/11 PUPS: PUPS: PUPS: PUPS: 1/11 PUPS: B A S E O F T A I L : A B R A S IO N ( 0 . 5 CM X 0 . 3 C M ) . T A IL A B R A S IO N ( 2 . 5 CM X 0 . 5 C M ) . T IP O F T A IL B LA C K ; T IP O F T A IL M IS S IN G . T IP O F T A IL M IS S IN G ; T A IL SC AB ( 0 . 2 CM X 0 . 2 C M ) . T IP O F T A IL M IS S IN G . 16 0 0 1 2 -3 1/15 PUPS: 1/14 PUPS: PALE IN APPEAR AN C E. PA LE IN APPEAR AN C E. a . T a b u la tio n r e s tr ic te d to a d ve rs e o b s e rv a tio n s ; a l l o th e r pu ps a p p e a re d n o rm a l. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E4 3 (P A G E 1) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 648 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) I 0 LIT T E R NUM BER 13 0 2 13 0 4 13 0 6 13 0 8 13 10 13 12 13 13 13 18 13 2 1 13 2 5 13 2 8 13 3 0 13 3 1 13 3 4 13 3 5 13 3 6 13 3 8 13 4 0 13 4 1 D A Y (S) PO STPAR TU M 22 22 22 22 22 22 17 22 22 10 22 22 22 22 22 22 22 22 16 22 22 22 O B S ER V A TIO N S A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P : K ID N EY : P E L V IS , D ILA T E D , S LIG H T . A L L OTHER T IS S U ES A P P EA R ED NO RM AL. A L L O T H ER PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL A LL PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NO RM AL. NO RM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L OTH ER T IS S U ES A P P EA R ED NO RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL A LL A LL A LL A LL PUPS PUPS PUPS PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R T H ER E V A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 2 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F2 G EN ER A T IO N PUPS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) I 0 CONT. LIT T E R NUM BER 1342 1344 1345 1346 1348 1350 1353 1355 13 5 9 D A Y (S) PO STPAR TU M 22 22 1 4 22 22 1 22 22 22 22 1 22 O B S ER V A TIO N S A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 2 P U P S : S T ILLB O R N . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED N O RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 2 PUPS: A L L PUPS S T ILLB O R N . A U T O LY S IS P R EC LU D ED EV A LU A T IO N . EX A M IN ED A P P EA R ED N O R M A L. FURTH ER A LL A LL A LL PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NORM AL. NORM AL. 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED N O RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 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) T A B LE E43 (P A G E 3) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F2 G E N E R A T IO N PUPS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) LIT T E R NUM BER D A Y (S) PO STPARTUM O B S ER V A TIO N S ARGUS 418-020 Page 650 13 6 2 13 6 3 13 6 4 136 7 13 6 8 13 71 13 75 13 76 13 79 13 8 1 13 8 2 1383 13 8 4 13 8 7 22 1 4 22 22 22 22 9 22 17 22 1 22 22 22 22 22 22 1 22 A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : S T ILLB O R N . A U T O LY S IS P R EC LU D ED FU R TH ER EV A LU A T IO N . 1 P U P : FOU ND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L OTH ER T IS S U ES A P P EA R ED NO RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O THER T IS S U ES A P P EA R ED NO RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 2 P U P S : S T ILLB O R N . A L L T IS S U ES A P P EA R ED N O RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. 1 P U P : K ID N E Y : R IG H T , P E L V IS , M ODERATE D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 5 P U P S : APPEAR ED NORM AL. A L L O T H ER PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : S T ILLB O R N . A U T O LY S IS P R EC LU D ED EV A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. FURTH ER PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 4 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F2 G EN ER A T IO N PUPS M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) II 1 CONT. LIT T E R NUM BER 13 8 9 13 9 2 1393 13 9 7 13 9 9 14 0 1 14 0 4 14 0 7 14 0 9 14 10 14 13 14 15 14 16 14 18 D A Y (S) PO STPAR TU M 7 22 22 1 22 22 22 22 22 22 22 22 22 22 22 3 22 O B S ER V A TIO N S 1 PUP : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH A L L O TH ER T IS S U ES A P P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : ;S T I L L B O R N , , A L L T I S S U E S A P P E A R E D N O R M A L A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NO RM AL. NO RM AL. NORM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. NO RM AL. 1 PUP : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH A U T O LY S IS P R EC LU D ED FU R T H ER E V A LU A T IO N . A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 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) T A B LE E43 (P A G E 5 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PUPS ARGUS 418-020 Page 652 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) III 3 LIT T E R NUM BER 14 2 1 14 2 4 14 2 6 1428 1430 143 1 1433 14 3 6 143 7 1439 14 4 2 1443 1448 1450 1452 1455 D A Y (S) PO S TPAR TU M 1 22 22 22 22 22 1 22 8 22 22 22 1 22 22 22 1 22 22 22 5 6 22 O B S ER V A TIO N S 2 PUPS: A L L PUPS FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L OTHER T IS S U ES A P P EA R ED NO RM AL. EX A M IN ED A P P E A R E D N O R M A L. A LL A LL A LL A LL PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NORM AL. NO RM AL. NORM AL. 1 P U P : FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R T H ER E V A LU A T IO N . A L L PU PS EX A M IN ED A P P E A R E D N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 2 P U P S : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L OTH ER T IS S U ES A P P EA R ED N O RM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 2 PUPS: A L L PUPS S T ILLB O R N . A U T O LY S IS P R EC LU D ED EV A LU A T IO N . EX A M IN ED A P P EA R ED N O R M A L. FUR TH ER A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L OTH ER T IS S U ES A P P EA R ED N O RM AL. 1 P U P : FOUND D EA D . , C A N N IB A LIZA T IO N P R EC LU D ED FUR TH ER EV A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 6 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A T A - F2 G EN ER A T IO N PUPS ARGUS 418-020 Page 653 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) III 3 CONT. LIT T E R NUM BER 1456 1459 14 6 1 1463 14 6 5 14 6 8 14 6 9 1472 1474 1476 14 77 14 8 0 D A Y (S ) PO S TPA R TU M 22 2 22 22 1 22 22 22 22 22 22 1 22 6 22 22 O B S ER V A TIO N S A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P: FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . 1 PU P: K ID N EY S : B ILA T E R A L , P E L V IS , M ODERATE D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. A L L O TH ER PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 2 PU PS: S T ILLB O R N . A L L T IS S U ES A P P EA R ED NO RM AL. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL A LL A LL PUPS PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 1 PU P: FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O THER T IS S U ES A P P EA R ED NO RM AL. 1 PU P: K ID N E Y : R IG H T , P E L V IS , S LIG H T D IL A T IO N . A L L O TH ER T IS S U ES A P P EA R ED N ORM AL. A L L O TH ER PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P: FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. A L L PUPS EX A M IN ED A P P EA R ED ' N O R M A L. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 7) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F2 G EN ER A T IO N PUPS ARGUS 418-020 Page 654 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) IV 10 LIT T E R NUM BER 14 8 2 14 8 6 1488 14 9 0 149 1 14 9 4 14 9 6 14 9 7 15 0 0 1502 15 0 5 15 0 7 15 0 8 15 13 15 14 15 16 15 17 D A Y (S ) PO STPARTUM 1 22 22 22 22 22 1 22 22 22 1 22 22 22 22 2 22 1 22 12 22 22 22 O B S ER V A TIO N S 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED N ORM AL. 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL A LL PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P E A R E D -N O R M AL. A PPEA R ED NORM AL. A P P EA R ED NO RM AL. A PPEA R ED NO RM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L T IS S U ES A P P EA R ED N O RM AL. A L L PU PS EX A M IN ED A P P E A R E D N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED N ORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NO RM AL. NO RM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O THER T IS S U ES A P P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 8 ) : N EC R O P S Y O B S ER V A T IO N S - IN D IV ID U A L D A TA - F2 G EN ER A T IO N PUPS ARGUS 418-020 Page 655 M ATERNAL DOSAGE GROUP M A TER N A L D O S A G E (M G /K G /D AY) IV 10 CONT. LIT T E R NUM BER 15 19 15 21 1523 15 2 4 15 2 7 1528 153 1 15 3 3 1534 15 3 7 1539 D A Y (S) PO STPARTUM 18 22 22 1 22 22 22 22 1 22 1 22 22 1 22 22 O B S ER V A TIO N S 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R TH ER E V A LU A T IO N . A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . A U T O LY S IS PR EC LU D ED FU R TH ER EV A LU A T IO N . 1 P U P : B R A IN : T H IR D AND L A T E R A L V E N T R IC LE S , M ARKED D ILA T IO N . A L L O TH ER T IS S U ES A P P EA R ED N ORM AL. A L L O TH ER PUPS EX A M IN ED A P P EA R ED N O R M A L. A LL A LL A LL PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED NO RM AL. NORM AL. NORM AL. 2 PU PS: S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P: FOUND D EA D . A L L T IS S U ES A PPEA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 9 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F2 G E N E R A T IO N PUPS ARGUS 418-020 Page 656 M ATERNAL DOSAGE GROUP M A T ER N A L D O S A G E (M G /K G /D AY) V 30 LIT T E R NUM BER 15 4 1 1544 15 4 5 1546 15 4 8 1550 1552 1555 15 5 7 15 5 8 15 6 0 15 6 4 15 6 5 15 6 6 15 6 8 15 71 15 73 15 76 D A Y (S) PO STPARTU M 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 O B S ER V A TIO N S A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED N O RM AL. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O TH ER T IS S U ES A P P EA R ED NO RM AL. 1 PU P: FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O THER T IS S U ES A P P EA R ED NORM AL. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 1 PU P: S T ILLB O R N . A L L T IS S U ES A P P EA R ED N ORM AL. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. A L L PUPS EX A M IN ED A P P E A R E D N O R M A L. 1 PU P: FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A U T O LY S IS P R EC LU D ED FU R T H ER E V A LU A T IO N . A L L PUPS EX A M IN ED A P P E A R E D N O R M A L. A L L PUPS EX A M IN ED A P P E A R E D N O R M A L. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. 1 P U P : FOUND D EA D . A U T O LY S IS P R EC LU D ED EV A LU A T IO N . A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. FURTH ER A LL A LL A LL A LL A LL A LL PUPS PUPS PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NO RM AL. NO RM AL. NO RM AL. NORM AL. NORM AL. 1 PU P: FOUND D EA D . A L L T IS S U ES A P P EA R ED NO RM AL. A L L PUPS EX A M IN ED A P P EA R ED N O R M A L. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) T A B LE E43 (P A G E 1 0 ) : N EC R O P S Y O B S ER V A TIO N S - IN D IV ID U A L D A TA - F2 G EN ER A T IO N PUPS M ATERNAL DOSAGE GROUP M A TER N A L D O S AG E (M G /K G /D AY) V 30 CONT. LIT T E R NUM BER 15 79 15 8 3 1584 1586 15 8 7 15 8 8 15 8 9 15 9 1 15 9 3 1598 16 0 0 D A Y (S) PO STPARTU M 22 22 22 22 22 22 22 22 22 22 1 22 O B S ER V A TIO N S A LL A LL A LL A LL A LL A LL A LL A LL A LL A LL PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED EX A M IN ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED A P P EA R ED NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. NORM AL. 1 P U P : FOUND D EA D . NO M ILK P R ES EN T IN STOM ACH. A L L O TH ER T IS S U ES AP P EA R ED NORM AL. A L L PU PS EX A M IN ED A P P EA R ED N O R M A L. 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) T A B L E E4 4 (P A G E 1 ) : PU P O R G A N W EIG H TS - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 658 M ATERNAL DOSAGE GROUP I 0 M G/KG/DAY R AT/ LIT T E R NUM BER B R A IN MF T S P LEEN MF T THYM US MF T T E R M IN A L B O D Y W EIG H T MF T 13 0 2 13 0 4 13 0 6 1308 13 10 13 12 13 13 13 16 1318 1321 1325 1328 1330 1331 13 3 4 13 3 5 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 13 5 5 1358 1359 1.72 1.6 1 1.66 0.20 1.59 1.55 1.57 0.16 1.42 1.32 1.37 0.16 1.29 1.35 1.32 0.09 1.58 1.48 1.53 0.22 1.75 1.67 1 .7 1 0.20 1.48 1.39 1.44 0.15 NOT PREGNANT 1.69 1.56 1.62 0.24 1.45 1.48 1.46 0.13 1.56 1.45 1.50 0.18 1.56 1.54 1.55 0.17 1.44 1.4 1 1.42 0.11 1.58 1.46 1.52 0.14 1.53 1.50 1.52 0.10 1.52 1.46 1.49 0.14 1.56 1.54 1.55 0.19 1.23 1.30 1.26 0.13 1.05 1.80 1.42 0.15 1.58 1.55 1.56 0.15 1.44 1.36 1.40 0.10 1.56 1.4 7 1.52 0.15 1.53 1.4 7 1.50 0.08 1.57 1.52 1.54 0.09 1.50 1.4 1 1.46 0.13 1.34 1.26 1.30 0.07 1.44 1.52 1.48 0.11 1.63 1.5 1 1.5 7 0.14 N O T P R EG N A N T ; M A TIN G NO T 1.53 1.46 1.50 0.20 0.21 0.15 0.11 0.15 0.30 0.17 0.17 0.20 0.16 0.14 0.12 0.26 0.18 0.16 0.19 0.14 0.22 0.14 0.11 0.16 0.14 0.16 0.08 0.09 0.10 0.12 0.12 0.14 0.11 0.14 0.23 0.14 0.21 0.14 0.16 0.16 0.20 0.09 0.15 0.18 0.10 0.15 0.15 0.14 0.15 0.12 0.12 0.14 0.08 0.08 0.15 0.13 0.14 0.14 C O N FIR M ED 0.17 0.18 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 48.1 45.5 42.0 28.5 45.5 54.7 39.4 52.6 33.4 35.8 43.2 26.6 33.8 3 9 .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 41.5 44.0 39.8 34.3 28.4 44.9 53.2 36.5 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 4 1 .7 40.2 46.0 4 2 .6 38 .2 28 .4 45 .2 54 .0 38 .0 49 .4 33 .4 3 5 .6 42 .5 25.0 30 .3 38.9 4 4 .6 44 .2 2 8 .6 40 .7 46 .4 36.0 4 3 .6 40 .4 41.6 35.2 23 .2 42 .0 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) T A B L E E 4 4 (P A G E 2 ) : P U P O R G A N W EIG H TS - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 659 M ATERNAL DOSAGE GROUP I I RAT/ LIT T E R NUM BER B R A IN MF T S P LEEN MF T 13 6 2 13 6 3 13 6 4 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 14 10 14 13 14 15 14 16 14 18 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 1.4 1 1.49 1.56 1.62 1.59 1.39 1.3 1 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 1.4 1 1.42 1.42 1.54 1.49 1.52 1.55 1.55 1.55 1.6 7 1.61 1.64 1.48 1.40 1.44 1.43 1.48 1.46 1.3 7 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 M = M ALE F = FEM ALE T = TOTAL A L L W EIG H T S W ERE R EC O R D ED IN GRAM S ( G ) . 1 M G/KG/DAY THYM US MF T 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 T E R M IN A L B O D Y W EIG H T MF T 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 3 1 .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 3 7 .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) T A B LE E4 4 (P A G E 3) : P U P O R G A N W EIG H T S - IN D IV ID U A L D A T A - F2 G E N E R A T IO N PU PS ARGUS 418-020 Page 660 M ATERNAL DOSAGE GROUP I I I 3 M G/KG/DAY RAT/ LIT T E R NUM BER B R A IN MF T S P LEEN MF T THYM US MF T T E R M IN A L B O D Y W EIG H T MF T 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 1458 1459 1461 14 6 3 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 1.4 7 1.46 1.49 1.49 1.49 1.56 1.45 1.50 1.59 1.4 7 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 1.5 1 1.49 1.50 1.67 1.56 1.62 N O T :P R E G N A N T 1.56 1.50 1.53 1.5 7 1.53 1.55 1.5 7 1.49 1.53 1.45 1.60 1.52 1.30 1.38 1.34 1.38 1.4 1 1.40 1.55 1.56 1.56 1.5 1 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 2 7 .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 3 1.1 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) T A B LE E44 (PAGE 4) : PUP ORGAN W EIGHTS - IN D IV ID U A L DATA - F2 G EN ER A T IO N PUPS ARGUS 418-020 Page 661 MATERNAL DOSAGE GROUP IV RAT/ L IT T E R NUMBER B R A IN MF T SPLEEN MF T 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 1.5 0 1 .4 1 1.46 NOT PREGNANT 1.4 2 1.4 2 1.42 1 .5 1 1.43 1 .4 7 1.5 2 1.4 8 1.50 1.4 2 1 .7 8 1.60 1.5 6 1.4 2 1.49 1.5 4 1.4 5 1.50 1.4 9 1.4 8 1.48 1.4 5 1 .4 1 1.43 1.6 3 1.53 1.58 1.4 4 1.38 1 .4 1 1.3 9 1.2 9 1.34 1.5 4 1 .5 7 1.56 NOT PREGNANT 1.6 3 1.4 9 1.56 1.3 9 1.3 9 1.39 1.4 8 1.4 4 1.46 1 .5 7 1.4 4 1.50 1.5 2 1.4 6 1.49 1.6 0 1.5 4 1 .5 7 1.53 1.4 4 1.48 1.6 5 -- 1 .6 5 1.3 9 1.2 8 1.34 1.4 9 1.53 1 .5 1 1 .5 7 1 .5 1 1.54 1.4 5 1.4 4 1.44 1.5 0 1.4 9 1.50 1.4 5 1.3 5 1.4 0 1.4 6 1.55 1.50 0.10 0 .1 3 0.12 0.11 0 .1 4 0 .2 5 0.10 0 .1 5 0.10 0 .17 0 .1 4 0 .1 6 0 .1 5 0 .0 8 0.22 0.11 0.11 0 .2 7 0.10 0 .14 0 .1 6 0.21 0 .17 0 .1 4 0.10 0.10 0 .1 8 0.11 0.12 0 .2 6 0.10 0 .14 0 .1 3 0 .1 9 0 .1 6 0 .15 0.12 0 .0 9 0.20 0 .17 0 .1 6 0.21 0.11 0.12 0 .1 6 0 .1 3 0.20 0.11 0.21 0.20 0 .1 6 0.12 0 .1 4 0 .1 4 0 .17 0.10 0 .17 0 .0 9 0.11 0 .1 4 0 .15 -- 0 .0 8 0 .1 8 0 .1 6 0 .1 6 0.11 0.10 0 .1 3 0 .17 0 .1 3 0 .1 9 0.10 0.12 0 .1 5 0 .1 4 0.20 0.10 0.20 0 .1 8 0 .1 6 0.12 0.12 0 .1 4 M = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). 10 MG/KG/DAY THYMUS MF T 0.20 0 .1 9 0.20 0 .0 6 0.22 0 .2 9 0 .1 3 0 .1 9 0 .1 5 0 .1 5 0 .1 8 0 .2 5 0.11 0.21 0.20 0.11 0 .1 6 0 .2 6 0 .0 9 0 .17 0.20 0.21 0 .2 4 0 .1 9 0.21 0 .1 9 0.23 0 .0 8 0 .1 9 0 .2 8 0.11 0 .18 0 .1 8 0 .1 8 0.21 0.22 0 .1 6 0.20 0.22 0 .1 4 0 .1 4 0 .18 0 .1 4 0.10 0 .1 8 0 .2 3 0.21 0.12 0 .2 5 0.20 0 .1 5 0 .1 4 0 .1 6 0 .1 8 0 .1 5 0.11 0.20 0 .1 5 0 .1 4 0 .1 9 0.22 -- 0 .0 8 0 .1 8 0 .1 9 0 .1 8 0 .1 6 0 .1 4 0 .1 6 0 .1 4 0.12 0 .1 9 0 .1 4 0.12 0 .1 8 0.22 0.21 0.10 0.22 0.20 0 .1 6 0 .1 5 0 .1 5 0 .17 TER M IN AL BODY WEIGHT MF T 3 8 .1 3 4 .0 36.0 3 2 .6 4 0 .1 5 2 .3 3 6 .3 4 5 .4 3 5 .3 4 3 .0 4 0 .5 5 0 .2 3 0 .8 3 0 .9 4 2 .9 3 6 .9 3 4 .6 5 2 .7 29 .7 4 4 .0 3 4 .5 4 9 .0 4 2 .8 4 5 .5 3 4 .2 2 9 .7 3 8 .7 3 4 .8 3 7 .4 52.5 3 3 .0 4 4 .7 3 4 .9 4 6 .0 4 1.6 4 7 .8 3 2 .5 30.3 40.8 3 9 .2 3 5 .4 4 8 .3 3 6 .8 3 6 .3 4 2 .2 5 0 .4 5 8 .4 3 2 .6 4 7.6 46 .2 4 2 .1 4 1.4 3 7.4 3 9 .6 3 4 .8 2 9 .8 4 3 .7 3 1.8 3 8 .9 3 8 .7 4 7.0 -- 2 4 .8 4 1.2 4 0 .5 4 0 .7 3 7.1 3 6 .1 4 1.1 3 7 .0 3 2 .6 4 6 .0 34.3 3 7 .6 4 0 .4 4 8 .7 5 8 .4 2 8 .7 4 4 .4 4 3 .4 4 1 .4 39.2 3 6 .8 4 0 .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) T A B LE E44 (PAGE 5 ): PUP ORGAN WEIGHTS - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 662 MATERNAL DOSAGE GROUP V 30 M G/KG/DAY RAT/ L IT T E R NUMBER BRAIN MF T SPLEEN MF T THYMUS MF T TERM INAL BODY WEIGHT MF T 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 1.4 4 1.4 2 1.5 6 1.63 1.6 0 1.58 1.4 8 1.53 1.38 1.4 0 1.3 9 1.48 1.4 0 1.4 4 1.54 1.49 1.52 1.4 4 1.39 1.4 2 1.39 1.35 1 .3 7 1.49 1.4 6 1.4 8 1.4 8 1.55 1.5 2 1.4 0 1.36 1.38 1.42 1.4 6 1.44 1.4 4 1 .2 7 1.36 1.46 1.4 2 1.4 4 1.4 5 1.5 2 1.4 8 1.4 6 1.4 4 1.4 5 1.4 0 1 .3 7 1.38 1 .3 1 1.08 1.20 N O T :P R E G N A N T 1.48 1 .4 1 1.4 4 1 .6 1 1 .5 1 1.56 1.66 1.4 8 1 .5 7 1.43 1.43 1.43 1 .6 1 1.53 1 .5 7 1.38 1 .3 7 1.38 1.39 1.36 1.38 1.5 2 1.50 1 .5 1 1.4 5 1 .4 1 1.43 1.38 1 .3 7 1.3 8 1 .4 1 1.43 1.4 2 0 .1 3 0 .17 0 .1 3 0.12 0.21 0 .1 6 0.12 0 .0 9 0 .0 9 0 .1 6 0 .1 3 0.12 0.12 0.12 0 .17 0.0 7 0 .0 8 0.11 0.11 0 .1 5 0.12 0 .0 9 0 .17 0.11 0 .1 3 0 .0 9 0.10 0 .1 8 0 .0 9 0 .1 5 0.10 0 .1 6 0 .1 5 0.0 7 0 .0 9 0 .1 4 0.12 0 .1 6 0.12 0.10 0 .1 9 0 .1 4 0.12 0 .0 9 0.10 0 .17 0.11 0 .1 4 0.11 0 .1 4 0 .1 6 0.0 7 0 .0 8 0.12 0 .0 9 0 .1 9 0 .2 8 0.10 0.21 0.11 0 .1 5 0 .17 0 .2 8 0 .0 5 0.12 0 .1 4 0 .1 5 0 .2 6 0.12 0 .1 6 0 .1 5 0 .1 3 0.10 0 .2 8 0.0 7 0 .1 4 0.12 0 .17 0.2 7 0.11 0 .1 8 0 .1 3 0 .1 4 0 .1 4 0 .2 8 0 .0 6 0 .1 3 0 .1 6 0.22 0 .1 9 0.10 0.21 0 .18 0 .17 0 .0 9 0.10 0 .14 0 .1 6 0 .15 0 .17 0 .17 0 .2 4 0.11 0 .1 3 0.12 0 .1 5 0 .17 0.12 0 .14 0 .1 9 0 .17 0 .1 4 0.11 0.10 0.20 0 .1 3 0 .17 0 .1 6 0 .0 9 0 .1 8 0.10 0.10 0 .1 3 0 .1 6 0.20 0 .1 6 0.12 0.20 0 .1 8 0 .1 6 0.10 0.10 0 .17 0 .1 4 0 .1 6 0 .1 6 0 .1 3 0.21 0.10 0.12 0.12 0 .1 3 0 .2 5 0 .3 3 0.11 0 .1 9 0 .14 0 .0 9 0 .14 0 .3 3 0 .0 8 0 .1 3 0 .1 6 0.22 0 .2 3 0 .18 0.20 0.11 0 .1 6 0 .1 6 0 .3 2 0 .0 8 0 .14 0 .1 4 0 .2 4 0.28 0 .1 4 0.20 0.12 0.12 0 .1 5 0 .3 2 0.08 0 .1 4 3 3 .2 4 4 .8 a 3 0 .6 3 8 .4 4 0 .2 3 3 .9 3 2 .8 3 4 .4 3 5 .8 3 3 .0 3 5 .1 3 9 .1 3 5 .0 4 6 .8 3 1.6 3 8 .1 3 0 .8 3 6 .2 3 9 .0 6 0 .9 3 4 .9 4 6 .2 3 9 .2 26 .7 3 6 .8 5 1 .2 2 7 .4 4 0 .6 3 4 .8 4 7.2 a 3 1.9 3 1.1 3 7.1 3 3 .6 2 9 .1 3 4 .5 3 9 .4 3 2 .0 3 7.0 3 5 .9 3 0 .9 4 4 .6 2 8 .7 3 4 .2 3 1.7 36.3 4 0 .4 50 .7 3 7.6 4 0 .5 3 9 .3 2 5 .0 3 8 .7 5 0 .6 2 9 .0 3 8 .6 3 4 .0 4 6 .0 a 3 1.2 3 4 .8 3 8 .6 3 3 .8 3 1.0 3 4 .4 3 7.6 3 2 .5 3 6 .0 3 7.5 3 3 .0 4 5 .7 3 0 .2 3 6 .2 3 1.2 3 6 .2 3 9 .7 5 5 .8 3 6 .2 4 3 .4 3 9 .2 2 5 .8 3 7.8 5 0 .9 28.2 3 9 .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) TA B LE E45 (PAGE 1) : AN O G ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATIO N PUPS ARGUS 418-020 Page 663 P U P # 1 2 3 4 5 6 7 8 9 1 0 11 1 2 1 3 1 4 1 5 1 6 1 7 1 8 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 1 POSTPARTUM 1302 1304 1306 1308 1310 1312 1313 1316 1.8 1.8 1.8 1.6 1 .9 2.2 1 .5 / MA 3 .1 / MA 2.6 / MA 2 .5 / MA 2 .5 / MA 2 .5 / MA 3 .0 / MA 2.2 NOT MA MA 2.8 2.6 MA MA 2.4 2.6 MA MA 2.4 2.4 MA MA 2.5 2.5 MA MA 2.6 2 .7 MA F A 3 .2 1.1 MA MA 2.1 2 .5 PREGNANT MA 2.6 MA 2 .5 MA 2 .4 MA 2 .5 MA 2 .3 FA 1 .3 MA 2.6 MA 2 .3 MA 2 .4 MA 2.6 MA 2 .5 MA 2 .5 MA 2 .3 FA FA FA FA FA FA 0 . 9 1 . 1 1 . 1 1.0 1 . 3 1.0 MA FA F A FA F A F A F A 2 . 4 1 . 2 1 . 1 1 . 1 1.0 1.0 1 . 3 MA MA MA F A F A F A F A F A F A F A F A 2 . 3 2 . 5 2 . 5 1.0 1.0 1 . 1 1 . 1 1.0 1 . 1 1 . 1 1.0 MA FA F A FA FA F A F A F A FA F A F A 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 F A F A F A F A F A 2 . 5 2 . 2 2 . 3 2 . 5 1 . 1 1.0 1.0 1.0 1.0 FA FA FA 1.0 1.0 1 . 1 FA FA 1.0 1 . 1 FA 1.1 FA FA 1.0 1 . 1 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 2.1 1.8 1 .7 1 .9 1 .7 2.0 2.0 2.0 1.8 1.6 / MA 3 .0 / MA 2 .4 / MA 2.8 / MA 2 .5 / MA 2 .5 / MA 2 .3 / MA 2 .7 / MA 3 .2 / MA 2 .5 / MA 2 .5 MA 3 .0 MA 2 .5 MA 2 .4 MA 3 .2 MA 2 .5 MA 2 .7 MA 2 .5 MA 2.6 MA 2 .4 MA 2 .5 MA 3 .0 MA 2 .4 MA 2.6 MA 2 .5 MA 2 .3 MA 2 .3 MA 2.6 MA 2 .9 MA 2.8 MA 2.6 MA 2 .7 MA 2 .5 MA 2 .4 MA 2.6 MA 2 .7 MA 2 .5 MA 2 .5 MA 3 .0 MA 2 .7 MA 2 .3 MA 2.8 MA 2 .4 MA 2 .5 MA 2.6 MA 2.6 MA 2.2 MA 2.6 MA 2.6 MA 2 .5 MA 2 .4 MA 2.8 MA 3 .0 FA 1.0 MA 2 .5 MA 2.6 MA 2 .5 MA 2 .3 MA 2 .7 MA 2 .7 MA 2.6 MA 2 .5 MA 2 .5 FA 1.1 MA 2 .5 MA 2 .7 MA 2.1 FA 0 .7 FA 1.2 MA 2.6 MA 2 .4 MA 3 .0 MA 2 .5 FA 1.1 FA 1.1 FA 1.1 MA 2 .5 FA 1.0 FA 1.0 FA 1.1 MA 1.2 MA 2 .7 FA 1.0 FA 1.1 FA 1.0 FA 1.0 MA 2.6 FA 1.0 FA 1.0 FA 1.2 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.1 FA 1.0 MA 2 .4 FA 1.2 FA 1.1 FA 1.0 FA 1.1 FA 1.1 FA 1.0 FA 1 .4 FA 1.2 MA 2.1 FA 1 .3 FA 1.1 FA 1.0 FA 1.1 FA 1.0 FA 1.0 FA 1.1 MA 2 .3 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 1.2 FA 1.1 FA 1.1 FA 1 .1 FA 1.2 FA 1.0 FA 1.2 FA 1.0 FA 1.1 FA 1.0 FA 1.1 FA 1 .1 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 1.1 FA 1.0 FA 1.2 FA 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) TA B LE E45 (PAGE 2 ) : A N OG ENITAL DISTANCE - IN D IV ID U A L DATA - F2 G EN ERATIO N PUPS ARGUS 418-020 Page 664 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 1 POSTPARTUM 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 2.0 1.5 1 .9 1.8 1 .7 2.0 2.0 2 .3 1.8 1 .5 / MA 2.6 / MA 2.6 / MA 2 .7 / MA 2 .7 / MA 2.8 / MA 2 .9 / MA 2 .7 / MA 2.6 / MA 2.2 / MA 2 .5 NOT MA MA 2 .7 2.8 MA MA 2 .4 2.2 MA MA 2.5 2.5 MA MA 2 .7 2.6 MA MA 3.0 2 .7 MA MA 2.9 2.5 MA MA 3.3 2 .7 MA MA 3 .0 2.6 MA MA 2 .7 2.8 MA MA 2 .7 2.4 PREGNANT; MA 2 .5 MA 2 .5 MA 2 .3 MA 2 .5 MA 3 .0 MA MA 2.6 FA 1 .3 MA 2 .5 MA 2 .4 MA 2.8 MA 2.6 2.6 MA MA 2.8 2.5 MA MA to 2 .5 MA MA 2.8 2 .4 MA FA 2 .7 1.1 MATING NOT MA MA 2 .7 2 .7 FA FA 1.0 MA 2 .5 MA 2.6 MS 1.0 MA 2 .7 MA 2 .5 FA MA 2 .4 MA 2 .7 MA 2 .5 MA 2 .4 FA 1.0 FA 0 .9 MS MA 2 .5 FA 1.2 FA 1.0 1.1 C O N FIR M ED MA 2 .9 FA 1.0 MA 2 .5 FA 1.1 FA 1.0 FA 0 .9 MA 2 .5 MA 3 .0 FA 1.0 FA 1.1 FA 1.1 FA 1.2 MA 2.2 FA 1.1 FA 1.1 FA 1.0 MA 2 .4 MA 2 .5 FA 1.1 FA 1.2 FA 1.0 FA 1.1 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1 .3 MA 2 .4 FA 1.1 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.2 MA 3 .4 FA 1.0 FA 1.1 FA 1.1 FA 1.0 FA 1.1 FA 1.1 FA 1.2 FA 1.2 MA 2 .5 FA 1.0 FA 1.0 FA 1.2 FA 1.0 FA 1.1 FA 1.1 FA 1.1 MA 2 .5 FA 1.1 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FU FA 1.1 FA 1.0 FA 1.0 FA 1.2 FA 1.1 FA 1.2 FA 1.1 FA 1.2 FS FS FA 1.2 FA 1.1 1359 / MA 1.6 2.6 MA 2 .4 MA 2 .4 MA 2 .7 MA 2.8 FA 0 .9 FA 0 .9 FA 1.1 FA 1.0 FA 1.1 FA 1.0 FA 1.0 FA 1.2 FS FIR S T LET T ER -- M -M ALE, F-FEM A LE, U -SEX UNDETERMINABLE SECOND LE T T E R -- A - A L I V E , S -STILLB OR N, U -UNCERTAIN, D -D IED , A L L DISTANC ES WERE RECORDED IN M ILLIM ETER S (MM). M -M IS S IN G (PRESUMED C A N N IB A LIZ E D ), X-M ISSING; S A C R IFIC ED 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) T A B L E E45 (PAGE 3) : A N O G E N I T A L D I S T A N C E - I N D I V I D U A L D A T A - F2 G E N E R A T I O N PUPS ARGUS 418-020 Page 665 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I I 1 MG/KG/DAY DAY 1 POSTPARTUM 1362 1363 1364 1367 1368 1371 1375 1376 1378 / MA MA MA 2.1 3 .1 2.9 2 .7 / MA MA MA 1.6 2 .5 2.2 2.2 / MA MA MA 1 .7 2.6 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 .7 MA 2 .5 MA 2.6 MA 2 .9 MA 2.6 MA 2.6 MA 3 .1 MA 2.6 FA 1.1 MA 2.6 MA 2 .5 MA 2 .7 MA 2 .5 MA 2 .3 MA 2.6 MA 2 .4 FA 1.0 MA 2 .5 MA 2 .3 MA 2 .4 MA 2.8 MA 2 .7 MA 3 .0 MA 2.6 FA 1.1 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 0 .9 FA 1.0 FA 1.1 FA 1.2 FA 1.0 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FS 1379 1381 1382 1383 1384 1387 1389 1392 1393 / MA 1.8 2 .5 / MA 2.0 2 .7 / MA 1 .7 2.3 / MA 1.9 2.5 / MA 1.8 2 .5 / MA 1.9 2.5 / MA 1 .7 2.3 / MA 1.8 2 .5 / MA 1 .7 2.6 MA 2 .5 MA 2 .9 MA 2 .5 MA 2 .4 MA 3 .1 MA 2.6 MA 2 .5 MA 2 .4 MA 2 .5 MA 2.6 MA 3 .0 MA 2.8 MA 2 .3 MA 2.6 MA 2 .7 MA 2.6 MA 2.6 MA 2 .4 MA 2 .7 MA 3 .1 MA 2.8 MA 2 .5 MA 2 .4 MA 2 .5 MA 2 .4 MA 2.6 MA 2 .5 MA 2 .4 MA 2 .9 MA 2 .7 MA 2 .5 MA 2 .7 MA 2.6 MA 2.6 MA 2 .5 MA 2 .7 MA 2.6 MA 2.8 FA 1.1 MA 3 .2 MA 2.8 MA 2 .7 MA 2 .4 MA 2.2 MS FA 1.1 FA 1.2 FA 1.2 FA 1.0 FA 1.1 MA 2.8 MA 2 .3 MA 2 .4 FA 1.0 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.1 MA 2 .7 MA 2.2 MA 2 .5 FA 1.0 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.2 MA 2 .5 FA 0.9 MA 2 .5 FA 1.0 FA 1.0 FA 1 .3 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 0 .9 FA 1.2 FA 0 .9 FA 1.2 FA 1.2 FA 1.1 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1 .3 FA 1.2 FA 1.1 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 1.1 FA 1.1 FA 0 .9 FA 0 .9 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FS FA 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) T A B L E E45 (PAG E 4) : A N O G E N IT A L D IS T A N C E - I N D IV I D U A L D A T A - F2 G E N E R A T IO N PUPS ARGUS 418-020 Page 666 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I I 1 MG/KG/DAY DAY 1 POSTPARTUM 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 2.0 1 .9 1.8 2.1 1 .7 1.8 2.0 1.8 1 .9 1 .4 1.6 / MA 2 .7 / MA 2 .7 / MA 2.8 / MA 2.2 / MA 2.6 / MA 2 .4 / MA 2 .5 / MA 2.2 / MA 2 .3 / MA 2 .4 / MA 2.8 MA 2 .5 MA 3 .1 MA 2.8 MA 2 .5 MA 2 .4 MA 2.2 MA 2 .3 MA 2 .4 MA 2 .4 MA 2 .3 MA 2.6 MA 2.6 MA 2 .9 MA 3 .1 MA 2 .3 MA 2 .3 MA 2 .4 MA 2 .5 MA 2.2 MA 2 .5 MA 2 .4 MA 2 .3 MA 2.8 MA 2 .7 MA 2.8 MA 2 .5 MA 2 .5 MA 2.6 MA 2 .3 MA 2 .4 MA 2 .5 FA 1.2 MA 2.2 MA 2.6 FA 1.1 MA 2.8 MA 2 .5 MA 2 .5 MA 2 .5 MA 2 .4 MA 2 .5 MA 2 .5 FA 1.0 MA 2 .5 MA 2 .7 FA 1.2 FA 1.1 MA 2.2 MA 2 .3 MA 2 .5 MA 2 .3 MA 2.6 MA 2.8 FA 1.1 MA 2.6 MA 2.8 FA 1 .3 FA 1.0 MA 2.2 MA 2.6 MA 2 .5 MA 2 .5 MA 2 .3 MA 2.6 FA 1.2 FA 1.0 FA 1.1 FA 1.2 FA 1.0 MA 2 .4 FA 1.1 FA 1.0 MA 2 .3 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.2 FA 1.1 MA 2 .5 FA 1.0 FA 1.2 MA 2.2 FA 1.0 FA 1.1 FA 1.1 FA 1.2 FA 1.1 FA 1.2 FA 1.0 MA 2.6 FA 1.0 FA 1.0 MA 2 .3 FA 1.1 FA 1.2 FA 1.1 FA 1.0 FA 1 .4 FA 1.1 FA 2 .5 FA 1.0 FA 1.0 MA 2.2 FA 0 .9 FA 1.0 FA 1.1 FA 1.2 FA 1 .4 FA 1.2 FA 1.2 FA 1.1 FA 1.0 MA 2 .5 FA 1 .3 FA 1.0 FA 1.1 FA 1.1 FA 1 .3 FA 0 .9 MA 2 .5 FA 0 .9 FA 1.2 FA 1.3 FA 1.0 FA 1.2 FA 1.0 FA 1.2 FA 1.0 FA 1.2 FA 1.1 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FIR S T LE T T E R - - M -M ALE, F-FEM A LE, U-SEX UNDETERMINABLE SECOND LET T ER -- A -A L IV E , S-STILLB O R N , U-UNCERTAIN, D -D IED , A L L D I S T A N C E S W E R E R E C O R D E D I N M I L L I M E T E R S (MM) . M -M IS S IN G (PRESUMED C A N N IB A LIZ E D ), X-M ISSING; S A C R IFIC ED 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) TA B LE E45 (PAGE 5 ): A N OG ENITAL DISTANCE - IN D IV ID U A L DATA - F2 G ENERATION PUPS ARGUS 418-020 Page 667 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I I I 3 MG/KG/DAY DAY 1 POSTPARTUM to 00 to 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 2.0 1.8 1.8 1 .7 1.6 2 .0 1.8 2.1 2.0 2.2 2 .3 2.1 / MA 2 .7 / MA 2 .5 / MA 2 .3 / MA 2 .7 / MA 2.6 / MA 2 .4 / MA 2 .7 / MA 2 .9 / MA 2 .7 / MA 2 .7 / MA 3 .5 / MA 2.8 NOT MA 2 .5 MA 2 .5 MA 2.2 MA 2 .5 MA 2.6 MA 2 .5 MA 2 .7 MA MA 2 .3 MA 2.2 MA 2 .5 MA MA 2 .5 MA 2 .4 MA 2 .7 MA 2.6 MA 2 .7 MA 2.6 MA 2 .3 MA 2.8 2.8 MA MA 2.8 3 .2 MA MA 2 .7 3.2 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 .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 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 1.2 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 1.0 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 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.1 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 MA 2.6 FA 1.1 FA 1.2 FA 1.1 FA 1.6 FA 1.2 FA 1 .3 FD1 FA 0 .9 FA 1.2 FA 1.1 FA 1.0 1448 1450 1452 1455 1456 1 .7 1 .5 1.8 1 .9 2.1 / MA 2.2 / MA 2 .5 / MA 2 .4 / MA 2 .7 / MA 2 .5 MA MA 2 .3 MA 2 .4 MA 2 .5 MA 2 .7 MA 2.6 MA 2.6 MA 2 .5 MA 2 .5 MA 2 .5 MA 2 .5 MA 2.8 MA 2 .3 MA 2 .7 MA 2.8 MA 2 .5 FA 1.2 MA 2.2 MA 2 .5 FA 1.2 MA 2 .3 FA 1.1 MA 2.2 MA 2 .4 FA 1.0 MS FA 1.0 MA 2 .5 MA 2.6 MS FA 1.1 MA 2 .4 MA 2.8 FA 1.2 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 0 .9 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 0 .9 FA 1 .3 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FA 0 .9 FA 0 .9 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 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) TAB LE E45 (PAGE 6 ) : ANOG ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 668 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 2 0 2 1 22 23 RAT # MEAN DOSAGE GROUP I I I 3 MG/KG/DAY DAY 1 POSTPARTUM 1458 NOT PREGNANT 1459 1461 1463 1465 1468 1469 1472 1474 1476 1477 1480 2.0 1.6 1 .7 1.8 1.6 2.2 2.0 2.1 1.6 1.8 1.6 / MA 2 .7 / MA 2 .7 / MA 2 .5 / MA 3 .0 / MA 2.8 / MA 2.6 / MA 3 .0 / MA 2 .5 / MA 2.2 / MA 2 .4 / MA 2 .9 MA 2.2 MA 2 .5 MA 2.1 MA 3 .0 MA 2 .5 MA 2 .5 MA 2 .9 MA 2 .4 MA 2 .3 MA 2.6 MA 2 .9 MA 2 .7 MA 2 .4 MA 2 .3 MA 3 .1 MA 2.8 MA 2 .5 MA 3 .0 MA 2 .4 MA 2 .5 MA 2 .5 MA 3 .2 MA 2 .5 MA 2 .5 MA 2 .5 MA 3 .0 MA 2 .5 MA 2 .5 MA 2 .7 MA 2 .7 MA 2 .2 MA 2 .4 FA 1 .4 MA 2 .5 FA 1.2 MA 2.2 MA 3 .1 MA 2 .7 MA 2 .4 MA 2 .7 MA 2 .7 MA 2 .5 MA 2 .9 FA 1 .3 MA 2 .4 FA 1.1 MA 2 .1 MA 2 .5 FA 1.1 MA 2.6 FA 1 .3 MA 2 .5 MA 2.6 MA 2 .4 FA 1.2 MA 2 .4 FA 1 .4 MA 2.2 FA 1.1 FA 1.1 MA 2 .5 FA 1.1 MA 2 .4 MA 2 .3 MA 2 .5 FA 1.2 MA 2.2 FA 1.2 MS FA 1.2 FA 1.0 MA 2 .7 FA 1.1 MA 2 .5 MD1 MA 2.6 FA 1.2 MA 2 .5 FA 1.1 FA 1.0 FA 1.1 FA 1.0 MA 2 .3 FA 1.2 MA 2 .5 FA 1.1 FA 1.2 FA 1.2 FA 1 .3 FA 1.0 FA 1.0 FA 1.1 FA 1.2 FA 1.0 FA 1.2 MA 2 .5 FA 1.0 FA 1.0 FA 1.2 FA 1 .4 FA 1.1 FA 0 .9 FA 1.1 FA 1.0 FA 1.1 FA 1.1 FA 0 .9 FA 1.1 FA 1.2 FA 1 .3 FA 1.0 FA 1.1 FA 1.1 FA 1.1 FA 1.0 FA 1.1 FA 1.3 FA 1.3 FA 1.2 FA 1.0 FA 1.2 FA 1.0 FA 1.2 FA 1.2 FA 0.8 FA 1 .3 FA 1 .4 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FS FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 1 .3 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FA 1.1 FIR S T LET T ER -- M-MALE, F-FEM A LE, U -S EX UNDETERMINABLE SECOND LETTER -- A -A L IV E , S-STILLB O R N , U-UNCERTAIN, D -D IED , A L L DISTANC ES WERE RECORDED IN M ILLIM ET ER S (MM). M -M ISSIN G (PRESUMED C A N N IB A LIZED ), X-M ISSING; S A C R IF IC E D 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) TA B LE E45 (PAGE 7) : A N OG ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GEN ERATIO N PUPS ARGUS 418-020 Page 669 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 1 POSTPARTUM 1482 1483 / MA MA MA MA MA MA F A F A F A F A F A F A FA F A FD 1 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 2.1 2.8 2 .9 3.0 / MA MA MA 1 .9 2.8 2.8 2 .5 / MA MA MA 2.6 3 .2 3 .0 3.6 / MA 1.4 2.4 MA 2 .4 MA 2 .5 / MA 1.9 2.4 MA 2 .4 MA 2.6 / MA 1 .9 2.8 MA 2 .7 MA 3 .0 / MA 1.6 2 .5 MA 2.6 MA 2 .7 / MA 1.9 2 .7 MA 2 .3 MA 2.6 / MA MA MA 1 .4 2.3 2.2 2.5 / MA MA MA 1 .7 2.4 2.5 2.5 / MA MA MA 1.8 2.5 2 .7 2.4 / MA MA MA 1 .5 2.6 2.8 2 .4 NOT PREGNANT MA 3 .0 MA 2 .3 MA 3 .5 MA 2 .5 MA 2.6 MA 2.6 MA 2 .7 MA 2 .4 MA 2.6 MA 2 .3 MA 2 .4 MA 2 .5 MA 2 .9 MA 2 .7 MA 3 .0 FA 1.2 MA 2 .5 MA 2 .9 FA 1.0 MA 2 .5 FA 1.0 MA 2.6 MA 2.1 FA 1.1 MA 2 .9 MA 2 .5 MA 2 .7 FA 1.0 MA 2 .4 MA 2.6 FA 1.1 MA 2.2 FA 1.0 MA 2 .5 MA 2 .4 FA 1.0 MA 2 .7 MA 2 .4 MA 3 .1 FA 1.0 MA 2 .7 MA 2 .5 FA 1.1 MA 2.2 FA 1.0 MA 2 .5 MA 2 .3 FA 1.1 MA 2.8 MA 2.8 FA 1.2 FA 1.1 MA 2.6 FA 0 .9 FA 1.2 MA 2.2 FA 1.0 FA 1.1 MA 2 .5 FA 0 .9 MA 2 .5 FA 1.0 FA 1.3 FA 1.0 MD1 FA 1.0 FA 1.2 MA 2 .4 FA 1.1 FA 1.2 MA 2 .4 FA 1.0 FA 1.1 FA 1.2 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 0 .9 FA 1.2 FA 1.1 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 1.0 FA 0 .9 FA 1 .3 FA 1.2 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FA 1.1 FA 1.0 FA 1.0 FA 1.2 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FA 0.9 FA 1.2 FA 1.0 FA 0 .9 UU FA 0 .9 FA 1.0 FA 1.0 FA 0.9 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FS FA 1.1 FA 0 .9 FA 1.2 FA 1.1 1513 1514 1516 / MA MA MA MA MA MA MA MA MA F A F A F A F A 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 F A F A F A FA FA F A F A F A 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 F A F A 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) TA B LE E45 (PAGE 8 ) : A N O G EN ITA L DISTANCE - IN D IV ID U A L DATA - F2 GEN ERATIO N PUPS ARGUS 418-020 QO (N Page 670 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 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 2.0 4 .1 / MA 1.9 2 . 8 / MA 2.0 2.6 / MA 1 .9 2.6 / MA 3.6 3.6 / MA 1 .9 2.5 / MA 1.9 2 . 6 / MA 1 .9 2.4 / MA 1.6 2.8 / MA 2.0 2 .7 / MA 2.1 2 .7 / MA 2.1 2 .7 MA 2.6 MA 2 .7 MA 2 .5 MA 2 .4 MA 3 .7 MA 2 .5 MA 2 .4 MA 2 .4 MA 2 .5 MA 2 .9 MA 2 .5 MA 2 .5 MA 2.6 MA 2 .7 MA 2 .3 MA 2 .5 MA 2.2 MA 2 .7 MA 2 .5 MA 2.8 MA 2 .9 MA 2.6 MA .2.7 MA 2 .4 MA 2 .3 MA 2 .5 MA 2 .5 MA 2.8 MA 2 .4 MA 2.6 MA 2.6 MA MA 2 .7 MA 2.6 MA 2 .4 MA 2 .9 MA 2 .5 MA 2 .4 MA 2 .7 MA 2.6 MA 2 .7 MA 2 .9 MA 2.6 MA 2 .5 MA 2.5 t 00 MA 2 .9 MA 2 .5 MA 2 .7 MA 2.2 MA 2 .4 MA 2 .4 MA 2.2 MA 2 .5 MA MA 2 .5 MA 2.6 MA 2.6 MA 2.8 MA 2 .7 MA 2.2 MA 2.8 MA 2 .9 FA 1.3 MD1 FA 1 .3 FA 1.2 FA 1.2 FA 1.0 FA 0.8 FA 1.0 FA 1.2 FA 1.1 FA 1.1 FA 1.2 FA 1.1 FA 1 .3 FA 0 .9 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.0 FA 1.2 FA 1.0 FA 1.1 MA 2 .7 FA 1.0 MA 2 .4 FA 1.1 FA 1.0 MA 2.8 MA 2.5 MA 2.1 FA 1.0 MA 2.6 FA 1.1 FA 1 .3 MA 2 .5 MA 2.6 MA 2.0 FA 1.0 MS FA 1.0 FA 1.0 MA 2 .5 MA 2.9 MA 2 .4 FA 1.1 FA 1.0 FA 1.1 FA 1.0 MA 2 .5 FA 1.1 MA 2 .7 FA 1.1 FA 1.1 FA 1.2 FA 1.0 FA 1.1 FA 1.0 FA 1.1 FA 1.0 FA 1.2 FA 1.0 FA 1.1 FA 0 .9 FA 1.0 FA 0 .9 FA 1.0 FA 1.0 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FS FA 1.0 FS FA 1.1 FA 1.0 FA 1.1 FA 1.0 FA FD1 1.0 FIR S T LETTER -- M-MALE, F-FEM A LE, U -S EX UNDETERMINABLE SECOND LETTER -- A -A L IV E , S -STILLB O R N , U-UNCERTAIN, D -D IED , A L L DISTANC ES WERE RECORDED IN M ILLIM ET ER S (MM). M -M IS S IN G (PRESUMED C A N N IB A L IZ E D ), X -M IS S IN G ; S A C R IF IC E D 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) T A B L E E 4 5 ( P A G E 9) : A N O G E N I T A L D I S T A N C E - I N D I V I D U A L D A T A - F 2 G E N E R A T I O N P U P S ARGUS 418-020 Page 671 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 2 1 2 2 23 RAT # MEAN DOSAGE GROUP V 30 M G /K G /D A Y DAY 1 POSTPARTUM 1541 1544 1545 1546 1548 1550 1552 1555 557 1558 1560 1564 1565 1566 1568 1.5 1 .7 1.8 1 .9 1 .4 1.8 1.8 1 .7 1.6 2.1 1.8 1.8 1 .7 1 .4 2.2 / MA 2 .5 / MA 2 .7 / MA 2 .5 / MA 2 .5 / MA 2 .4 / MA 2 .9 / MA 2.2 / MA 2 .4 / MA 2 .7 / MA 3 .2 / MA 2 .5 / MA 2 .5 / MA 2.2 / MA 2.6 / MA 3 .3 MA 2 .9 MA 2 .7 MA 3 .1 MA 2 .5 MA 2 .4 MA 3 .1 MA 2.6 MA 2.6 MA 2.8 MA 2 .5 MA 2.6 MA 2 .5 MA 2.2 MA 2 .9 MA 2 .5 MA 2 .4 MA 2 .3 MA 2 .3 MA 3 .1 MA 2 .4 MA 2 .7 MA 2 .7 MA 2 .3 MA 2 .7 MA 2.6 MA 2 .5 MA 2.6 MA 2 .4 FA 1.1 MA 3 .2 MA 2 .5 MA 2 .5 MA 2 .7 MA 2 .5 MA 2 .5 MA 2 .3 MA 2.8 MA 2.1 MA 2 .5 MA 2.8 MA 2 .7 MA 2 .3 MA 2 .4 FA 1.1 MA 3 .1 FA 1.1 MA 2 .4 MA 2 .9 MA 2 .7 FA 1.0 MA 2 .4 MA 2 .3 MA 2 .4 MA 2.2 MA 2.6 MA 2.2 MA 2 .5 MA 2 .5 FA 1.1 MA 3 .2 FA 1.1 MA 2 .5 MA 2 .7 MA 2 .5 FA 1.0 FA 1.1 MA 2 .7 MA 2.6 FA 1.1 MA 2 .7 MA 2 .5 MA 2 .9 MA 2 .3 FA 1 .3 MA 3 .1 FA 1.1 FA 1.2 MA 2 .4 MA 2 .7 FA 1.0 FA 1.6 MA 2 .7 MA 2 .7 FA 1.1 MA 2 .4 MA 2.6 FA 1.2 FA 1.0 FA 1.2 MA 2.6 FA 1.0 FA 1.0 MA 2 .5 MA 2 .5 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.0 MA 2.8 FA 1.2 FA 1.0 FA 1.1 FA 1.2 FA 1 .3 FA 1.2 FA 1.1 MA 2 .5 FA 1.2 FA 1.0 FA 1.2 FA 1.0 FA 0 .9 FA 1.0 MA 2 .5 FA 1.0 FA 1.0 FA 0 .9 FA 1.1 FA 1 .5 FA 1.2 FA 1.2 FA 1.1 FA 1.0 FA 1.0 FA 1.1 FA 1.1 FA 1.1 FA 1.1 MA 2 .7 FA 1.1 FA 1.0 FA 1.1 FA 1.3 FA 1 .4 FA 1.1 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FA 1.2 FA 0 .9 FA 1.0 FA 1.1 FA 1 .4 FA 1.2 FA 1.2 FA 1.2 FA 1.0 FA 1 .4 FA 1.1 FA 1.1 FA 1.1 FA 1.1 FA 1.0 FA 1 .3 FA 1.0 FA 1.1 FA 1.0 FA 1.2 FA 1.1 FA 1.1 FA 1.0 FA 1.1 FA 1.2 FA 1.0 FA 1.0 FA 1.0 FA 1.1 FA 1 .1 FA 1.0 FA 1.1 FA 1.1 FA 1 .3 FA 1.2 FA 1.2 FA 1.0 FA 1.2 FA 1.0 FS FA 1.1 FA 1.1 FS FA 1.0 FA 1.1 FA 1.2 FA 1.1 FA 1.2 FA 1.2 FA 1.0 FA 1.0 FA 1.1 FA 1.0 FA 1.1 FA 1.1 FA 1.0 FA 1.2 FA 1.1 FA 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) TA B LE E45 (PAGE 10) : AN O G ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 672 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP V 30 M G / K G / D A Y DAY 1 POSTPARTUM 1571 1573 1576 1578 1.8 1 .9 2.0 / MA 2.6 / MA 2 .7 / MA 2 .5 NOT MA MA 2 .5 2.3 MA MA 2.8 2.6 MA MA 2.2 2 .9 PREGNANT MA 2 .5 MA 2 .4 MA 2.6 MA 2.8 MA 3 .2 MA 2 .3 MA 2.6 MA 2.8 MA 2 .5 FA 1 .4 MA 2.8 MA 2 .7 FA 1 .3 FA 1.2 MA 2 .5 FA 1.2 FA 1.3 FA 1.0 FA 1.2 FA 1.0 FA 1.0 FA 1 .4 FA 1.2 FA 1 .3 FA 1.1 FA 1.1 FA 1.0 FA 1.2 FA 1.1 FA 1.0 FA 1.2 FA 1.1 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 2.0 1 .7 2 .5 1 .9 1 .7 1 .5 1 .7 2.0 2.0 1.8 2.2 / MA 3 .0 / MA 2.8 / MA 2.8 / MA 2 .5 / MA 2.8 / MA 2 .5 / MA 2 .5 / MA 2.6 / MA 3 .3 / MA 3 .0 / MA 2 .5 MA 2 .7 MA 2 .7 MA 3 .0 MA 2.6 MA 2 .4 MA 2.8 MA 2 .5 MA 2.8 MA 3 .0 MA 2.8 MA 2.6 MA 2.6 MA 2 .4 MA 2 .9 MA 2 .4 MA 2 .5 MA 2.8 MA 2 .5 MA 3 .2 FA 1 .5 MA 2 .7 MA 2.6 MA 2.8 MA 2 .3 FA 1.2 MA 2.6 MA 2.6 MA 2 .4 MA 2.6 MA 2 .3 FA 1 .4 MA 2 .7 MA 2 .4 MA 2 .9 MA 2 .7 MA 2 .7 MA 2.6 FA 1.1 MA 2.6 MA 2 .4 FA 1.6 MA 2 .5 MA 2 .3 MA 2.8 FA 1.2 MA 2.6 FA 1.0 FA 1.0 MA 2 .4 MA 2.0 FA 1 .5 MA 2 .7 MA 2 .7 MA 2.8 FA 1.0 MA 2 .5 FA 1.0 FA 1.0 FA 1.2 MA 2 .4 MA 2 .5 MA 2.6 MA 2 .9 FA 1.2 FA 1.2 FA 1.0 FA 1.1 FA 1.0 MA 2.2 FA 1.1 MA 2.8 FA 1.1 FA 1.1 FA 1.0 FA 1.0 FA 1.1 FA 1.1 MA 2 .5 FA 1.2 MA 2.6 FA 1.0 FA 1.1 FA 1.2 FA 0 .9 FA 1.1 FA 1.0 MA 2.2 FA 1.0 MA 2 .9 FA 1.1 FA 1.2 FA 1.1 FA 1.0 FA 1.2 FA 1.0 FA 1.1 FA 1.0 MD1 FA 1.1 FA 1.0 FA 1.1 FA 1.1 FA 1.2 FA 1.0 FA 1.1 FA 1.1 FA 1.1 FA 1.1 FA 0 .9 FA 1.2 FA 1.0 FA 1.3 FA 1.1 FA 1.0 FA 1 .4 FA 1.1 FA 1 .4 FA 1.1 FA 1.0 FA 1.2 FA 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) TA B LE E45 (PAGE 11) : ANO G ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATIO N PUPS ARGUS 418-020 Page 673 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 22 POSTPARTUM 1302 / MA MA MA MA MA F A F A F A F A F A F A 11.2 13 .6 13 .5 14 .5 1 5 .1 15 .2 8.5 7 .9 8 .7 8.1 9 .1 8.8 1304 / MA MA MA MA MA MA F A F A F A F A F A F A 1 1 .9 1 5 .9 15 .2 1 4 .9 14 .5 1 5 .2 1 3 .2 8.1 8.3 9.2 10.0 9.0 9.5 1306 / MA MA MA MA MA MA MA MA F A F A F A F A F A F A F A F A 10 .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 F A F A F A F A F A F A F A F A F A F A 9.0 12.8 12.0 1 1 .9 11.8 1 2 .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 F A F A F A F A F A 1 1 .7 1 4 .6 1 3 .3 1 3 .0 13 .4 1 3 .4 1 4 .3 1 2 .9 1 3 .3 1 3 .8 8.6 8.0 8.2 8.6 8 .7 1312 / MA MA F A FA 1 2 .5 1 4 .8 1 5 .0 10 .3 9.8 1313 / MA MA MA MA MA F A F A F A F A F A F A F A F D 1 7 1 1 .3 13 .3 1 4 .0 1 5 .0 1 5 .6 1 6 .0 9 .1 9.3 9.9 7 . 1 8.1 9 .1 9 .2 1316 NOT PREGNANT 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1 2 .3 9.8 9 .6 1 1 .7 9 .0 1 1 .4 1 2 .3 1 1 .5 11.6 1 0 .3 / MA 1 6 .3 / MA 1 3 .6 / MA 1 1 .7 / MA 1 4 .6 / MA 12.0 / MA 1 2 .5 / MA 1 5 .2 / MA 1 5 .6 / MA 1 5 .0 / MA 13 .7 MA 1 4 .6 MA 1 3 .9 MA 14 .1 MA 15 .1 MA 12.6 MA 1 3 .0 MA 1 3 .9 MA 14 .2 MA 1 4 .0 MA 1 2 .4 MA 1 3 .5 MA 12.8 MA 12.0 MA 1 2 .9 MA 12.2 MA 12.0 MA 1 3 .8 MA 14 .6 MA 1 4 .3 MA 10 .7 MA 14 .7 MA 13 .7 MA 11.3 MA 14 .1 MA 11.8 MA 1 3 .2 MA 14 .9 MA 1 3 .0 MA 1 4 .9 MA 1 4 .0 MA 14 .9 MA 12.0 MA 11.2 MA 14 .4 MA 1 1 .5 MA 12 .7 MA 1 5 .2 MA 14 .2 MA 1 3 .8 MA 14 .1 MA 1 5 .0 MA 12.6 FA 7.2 MA 1 5 .3 MA 11.6 MA 12 .7 MA 13 .5 MA 14 .0 MA 14 .5 MA 12 .4 MA 1 5 .5 MA 11.8 FA 7 .5 MA 14 .2 MA 1 1 .7 MA 1 1 .9 FA 7 .8 FA 9 .0 MA 1 5 .5 MA 1 2 .4 M A MM2 1 6 .3 MM11 F A 7.0 FA FA 8.4 7 .9 FA FA 7 .8 9.8 FA FA 6.9 7 .0 MA MA 11.9 12.4 FA FA 8.5 7 .8 FA FA 8.3 8.8 FA FA 9.2 8 .7 MA F A 12 .9 6.4 FA 8.6 FA 7 .1 FA 7 .2 FA 8.1 FA 6 .9 MA 1 3 .3 FA 8.6 FA 9 .2 FA 8 .7 FA 9 .2 FA 6.8 FA 7 .6 FA 8.6 FA 7 .4 MA 13 .2 FA 8 .3 FA 9 .4 FA 7 .9 FA 8.2 FA 7 .2 FA 8 .5 FA 6 .9 FA 8.6 FA 6 .3 MM12 FA 8 .4 FA 6.8 FA 7 .1 FA 9 .1 FA 8 .7 FA 8 .4 FA 8.2 FA 8 .4 FA 8 .7 FA 7.2 FA 6.2 FA 8 .3 FA 9 .4 FA 7.2 FA 7.9 FA 7.6 FA 6 .9 FA 7.9 FA 9 .1 FA 8 .4 FA 6.6 FA 6.8 FA 8.2 FA 7 .0 FD10 FD16 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) TA B LE E45 (PAGE 12) : AN O G ENITA L DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 674 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY DAY 22 POSTPARTUM 1340 / MA MA MA MA MA MA MA MA F A F A F A F A F A F A 12.2 1 3 .2 1 3 .1 1 5 .5 1 4 .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 F A F A F A F A F A F A F A F A 1 1 .4 1 6 .0 1 5 .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 F A F A F A F A F A F A F A 11.6 1 4 .4 1 5 .2 1 5 .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 F A F A F A F A F A F A F A F A 1 0 .9 1 5 .2 1 4 .7 1 4 .5 1 4 .6 1 3 .2 1 3 .2 1 3 .5 8.0 7 .2 8 .4 7 .5 9.3 8.0 8.4 8.0 1345 / MA MA MA MA MD4 MS F A F A F A F A F A F A F A F A F A F S 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 F A F A F A F A 11.6 13 .6 13 .0 14 .4 14 .0 14 .5 1 4 .1 8.5 7 .5 9.2 7 .4 1348 / MA MA MA MA MA MA MS MA MA F A F A F A F A F A F A F S 11.2 13 .3 1 4 .1 14 .6 13 .2 14.3 13 .4 1 4 .2 1 4 .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 F A F A F A F A 1 0 .5 12.8 11.6 12.2 1 2 .7 1 1 .5 1 2 .5 11.1 9 .8 1 0 .9 12.8 1 1 . 4 1 1 .3 12.2 6.3 6.2 6 .3 7 . 7 1353 / MA MA MA MA MA MA F A F A F A F A F A F A F A F U 10.6 1 4 .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 F A F A F A F A F A F A F A F A F A F A F A 1 0 .4 1 4 .6 1 5 .2 1 4 .6 1 5 .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 F A F A F A F A F A F A F A F A FS 10.8 1 4 .4 1 4 .5 13 .3 14 .9 13 .6 8.5 8.5 9.0 8.6 9.2 7 .8 8.8 8.8 FIR S T LET T ER -- M -M ALE, F-FEM A LE, U -SEX UNDETERMINABLE SECOND LE T T E R -- A -A L IV E , S-STILLB O R N , U-UNCERTAIN, D -D IED , A L L D I S T A N C E S W E R E R E C O R D E D I N M I L L I M E T E R S (MM) . M -M IS S IN G (PRESUMED C A N N IB A LIZE D ), X-M ISSING; S A C R IFIC ED 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) T A B LE E45 (PAGE 13) : A N O G EN ITA L DISTANCE - IN D IV ID U A L DATA - F2 GENERATIO N PUPS ARGUS 418-020 Page 675 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I I 1 MG/KG/DAY DA Y 22 POSTPARTUM 1362 / MA MA MA MA F A F A F A 1 1 .9 1 4 .4 14 .9 1 4 .7 13 .6 8.8 8.5 8.5 1363 / MA MA MA MA MA MA MA F A F A F A F A F A F A F A F A F A FD4 F S 1 0 .4 1 3 .1 13 .5 1 2 .9 15 .6 1 2 .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 F A F A F A F A F A F A F A F A 10 .4 1 4 .1 14 .0 1 3 .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 F A F A F A F A F A 11.6 13 .3 13 .5 1 3 .7 1 4 .4 14 .3 1 4 .4 13 .4 13 .3 8.8 8.5 7 .6 8.2 7 .6 1368 / MA MA MA MA MA MA MA MA F A F A F A F A F A F A F A 1 1 .5 15 .4 13 .6 1 3 .5 1 4 .9 15 .3 1 3 .4 1 4 .0 1 4 .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 F A F A F A F A F A FD9 11.2 13 .3 12 .5 13 .6 13 .0 13 .3 12.1 12.2 1 2 .7 1 1 .3 13 .6 1 1 .9 7 .7 8.1 7 .4 8.9 7 .8 1375 / MA MA MA MA MA MA MA MA MA F A F A F A F A F D 1 7 12.2 15 .4 1 4 .1 13 .0 14 .6 14 .3 1 4 .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 F A F A F A F A F A 1 1 .5 1 3 .0 1 2 .9 1 3 .9 1 2 .7 1 3 .5 1 3 .0 1 2 .4 1 2 .9 1 3 .6 12.6 7 .8 8.3 8 .7 8.9 8.5 1378 NOT PREGNANT 1379 1381 1382 1383 .1384 1387 1389 1392 1393 1 0 .5 1 2 .3 10 .7 11.9 10.6 11.3 10.0 9 .6 11.3 / MA 12.6 / MA 16 .1 / MA 1 4 .5 / MA 14 .7 / MA 1 4 .2 / MA 13 .7 / MA 12.2 / MA 10.8 / MA 14 .7 MA 14 .1 MA 1 5 .4 MA 1 3 .5 MA 1 5 .2 MA 14 .2 MA 1 3 .6 MA 1 3 .0 MA 11.6 MA 1 5 .0 MA 12.6 MA 1 5 .0 MA 1 4 .3 MA 1 5 .5 MA 15 .0 MA 1 3 .4 MA 1 3 .9 MA 11.8 MA 14 .8 MA 1 3 .4 MA 1 5 .2 MA 1 3 .8 MA 14 .1 MA 1 4 .6 MA 1 2 .9 MA 1 3 .0 MA 11.8 MA 1 5 .5 MA 13 .2 MA 16 .0 MA 14 .9 MA 1 3 .8 MA 1 3 .0 MA 1 3 .0 MA 15 .1 MA 11.8 MA 15 .4 MA 13 .7 MA 16 .1 FA 9 .2 MA 14 .9 MM4 MA 1 4 .3 MA 13 .4 MA 11.6 MS FA 7.8 FA 8.1 FA 8 .4 FA 8 .5 FA 8 .3 MA 13 .1 MA 11.5 MA 11.3 FA 8.0 FA 7 .9 FA 9 .2 FA 8 .4 FA 7 .6 FA 7 .7 MA 14 .7 MD7 MA 1 2 .5 FA 8.1 FA 6.8 FA 9 .7 FA 8.8 FA 8 .5 FA 8.0 MA 1 4 .3 FA 7 .7 MA 1 2 .4 FA 7.6 FA 8 .3 FA 9 .4 FA 8.0 FA 9 .4 FA 7 .2 FA 8 .5 FA 7 .0 FA 7 .5 FA 9 .0 FA 8.0 FA 8.6 FA 8.3 FA 9.0 FA 7.4 FA 8 .5 FA 7.3 FA 7.4 FA 8.1 FA 7.4 FA 9 .0 FA 8.6 FA 9 .0 FA 8 .3 FA 7 .8 FA 7.2 FA 8 .3 FA 8.8 FA 8.0 FA 8.1 FA 6.8 FA 7.2 FA 8.1 FA 7 .1 FA 7 .8 FA 8 .7 FA 8.0 FA 7 .0 FA 8.2 FA 6.8 FA 7 .0 FS FA 6 .5 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) TA B LE E45 (PAGE 14) : AN O G ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 RAT # MEAN DOSAGE GROUP I I 1 MG/KG/DAY DAY 22 POSTPARTUM 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 1418 / MA 1 3 ..2 1 6 . 0 / MA 1 2 .. 1 1 6 . 5 / MA 1 0 .. 9 1 4 . 0 / MA 1 1 ..6 1 3 . 5 / MA 10 .4 12.0 / MA 13 .3 16 .8 / MA 12 .9 14 .8 / MA 1 1 .7 14 .8 / MA 1 0 .. 2 1 2 . 5 / MA 9,.1 1 4 . 4 / MA 10 .4 1 3 .6 MA 15 .0 MA 16 .6 MA 15 .0 MA 12.1 MA 1 3 .3 MA 1 5 .9 MA 14 .1 MA 13 .8 MA 12 .7 MA 12.8 MA 15 .5 MA 1 5 .6 MA 17 .1 MA 1 3 .4 MA 12.8 MA 1 2 .9 MA 16 .6 MA 1 3 .3 MA 1 4 .3 MA 12.6 MA 1 3 .0 MA 1 3 .6 MA 1 5 .5 MA 1 4 .4 MA 15 .7 MA 13 .4 MA 13 .1 MA 1 5 .0 MA 14 .8 MA 1 2 .2 MA 1 1 .9 FA MA 1 6 .3 FA 9 .7 MA 1 4 .6 MA 12.1 MA 12.1 MA 1 5 .5 MA 1 3 .8 MA 1 5 .3 MA 12 .7 FA 8.1 MA 11.5 8.1 MA 1 5 .4 MA 16 .9 FA 9 .8 FA 8 .4 MA 1 3 .6 MA 1 3 .5 MA 1 6 .3 MA 14 .2 MA 1 3 .8 MA 12.2 FA 8.0 MA 1 3 .0 MA 1 5 .6 FA 9.3 FA 8 .4 MA 1 3 .6 MA 12.2 MA 1 5 .8 MA 14 .0 MA 14 .5 MA 11.5 FA 7.3 FA 8.8 FA 9 .9 FA 9 .4 FA 8.0 MA 1 5 .0 FA 8 .7 FA 8 .9 MA 16 .2 FA 8.8 FA 8.0 FA 8.1 FA 8.2 FA 9 .6 FA 9.0 FA 7 .2 MA 1 3 .0 FA 7 .7 FA 9.8 MA 1 3 .0 FA 8.0 FA 6.8 FA 7 .6 FA 7 .8 FA 9 .7 FA 9.6 FA 8.8 MA 1 3 .5 FA 8.8 FA 9 .4 MA 1 3 .9 FA 8.1 FA 8.0 FA 8 .5 FA 7.3 FA FA 9 .1 9.3 FA 8 .5 MA 8 .7 FA 8 .4 FA 9 .6 MA 1 3 .0 FA 9 .4 FA 8 .5 FA 7 .9 FA 7 .1 FA 9 .2 FA 8.2 FA 8 .7 FA 10.0 MA 1 3 .8 FA 9.3 FA 7 .3 FA 8.0 FA 6.1 FA 9 .2 FA 8.1 MA 14 .4 FA 9 .3 FA 7 .7 FA 8.0 FA 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 F A FM 5 7 .9 FM 3 FIR S T L E T T E R -- M -M ALE, F-FEM A LE, U -SEX UNDETERMINABLE SECOND LE T T E R -- A -A L IV E , S -STILLB O R N , U-UNCERTAIN, D -D IED , A L L D I S T A N C E S W E R E R E C O R D E D I N M I L L I M E T E R S (MM) . M -M ISSIN G (PRESUMED C A N N IB A LIZ E D ), X-M ISSING; S A C R IFIC ED WHEN FOUND ARGUS 418-020 Page 676 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) TA B LE E45 (PAGE 1 5 ): AN O G ENITA L DISTANCE - IN D IV ID U A L DATA - F2 G ENERATION PUPS ARGUS 418-020 Page 677 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP I I I 3 MG/KG/DAY DAY 22 POSTPARTUM 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 10 .5 9 .0 10 .4 10.6 9 .5 12.8 1 1 .4 1 1.7 10.6 13 .9 13 .0 1 1 .4 / MA 11.9 / MA MA 12.8 MA MA 1 1 .4 MA 10.6 / MA 11.3 / MA 1 3 .8 / MA 1 3 .3 / MA 16 .2 / MA 1 4 .6 / MA 1 2 .5 / MA 1 3 .3 / MA 1 5 .4 / MA 1 7 .0 / MA 1 3 .8 NOT 10.6 11.2 MA MA 12.6 12 .5 MA MA 14 .6 13.3 MA MA 13.2 13.8 MA MA 14 .8 15.2 MA MA 14 .4 13.3 MA MA 13.4 13.9 MA MA 13 .5 12.1 MA MA 15.8 1 6 .7 MA MA 15.4 15.6 MA MA 14.6 14 .2 PREGNANT MA 1 2 .5 MA 1 2 .5 MA 1 4 .4 MA 14 .7 MA 12.8 MA 1 5 .0 MA 1 3 .8 MA 12 .7 MA 1 3 .2 MA 1 5 .8 MA 1 4 .2 MA 1 3 .9 MA 1 1 .9 MA 10.8 MA 12.6 MA 1 5 .0 MA 1 1 .9 MA 1 4 .9 MA 13 .1 MA 1 3 .6 MA 1 4 .3 MA 1 6 .3 FA 10 .7 MA 1 4 .3 MA 1 2 .3 MA 1 0 .9 MA 1 3 .4 MA 12.6 MA 1 3 .6 MA 1 5 .4 MA 1 3 .8 MA 1 3 .3 MA 1 2 .9 MA 1 4 .9 FA 9 .0 MA 13 .1 MA 11.6 MA 12.0 MA 1 2 .3 FA 7 .8 FA 6 .7 MA 1 6 .5 MA 1 3 .5 MA 1 2 .4 MA 13 .7 FA 10.6 FA 9.0 MA 15 .1 MA 11.8 MA 10.1 FA 7 .6 FA 8.8 FA 8.6 MA 14 .9 MA 12 .7 MA 1 3 .5 MA 1 3 .0 FA 9.9 MA 12.0 MA 1 1 .7 MA 10.2 FA 6 .9 FA 8.2 FA 8 .4 MA 1 3 .9 MA 14 .1 FA 8.8 MA 12 .7 FA 9.5 FA 7 .5 MA 1 2 .5 FA 6.6 FA 8 .4 FA 7.8 FA 7 .4 MD1 MA 13 .1 FA 8.8 FA 6.6 FD1 FA 8.6 FA 8.1 FA 6 .5 FA 7 .1 FA 8.6 FA 6 .9 FA 7 .9 FA 8.0 FA 8 .4 FA 8.0 FS FA 7.4 FA 6 .7 FA 6 .7 FA 8 .7 FA 7 .7 FA 6 .7 FA 7.8 FA 8.6 FA 8 .7 FA 8.8 FS FA 8 .9 FA 8 .3 FA 6.6 FA 7 .7 FA 8.8 FA 8 .9 FA 9 .4 FA 9 .0 FA 6.8 FA 8 .7 FA 7.0 FA 6.8 FA 8.6 FA 7 .7 FA 9 .1 FA 8 .7 FA 6 .4 FA 8.0 FA 7 .5 FA 7.4 FA 8.6 FA 6 .5 FA 8 .7 FA 8.2 FA 6.2 FD1 FA 7 .1 FA 7 .7 FM2 FA 7 .5 FA 8.6 FD1 FA 6 .7 FA 7 .3 FA 8 .3 FD8 1448 1450 1452 1455 1456 10.2 9 .3 10.6 10 .9 12.2 / MA 1 3 .8 / MA 12.8 / MA 1 0 .9 / MA 1 3 .5 / MA 12.6 MA 1 3 .5 MA 12.1 MA 11.6 MA 1 3 .8 MA 1 2 .3 MA 14 .5 MA 1 2 .4 MA 1 2 .4 MA 1 3 .8 MA 14 .2 MA 13 .1 MA 1 3 .6 MA 1 2 .9 MA 1 4 .6 MA 1 5 .9 MA 13 .7 FA 7 .9 MA 11.8 MA 12 .7 FA 9 .1 MA MS MS 12.8 FA 8 .4 MA 1 2 .5 MM6 FA 8.1 MA 12.6 MD 5 FA 7 .7 MA 11.6 MM3 FA 9 .4 FA 7 .1 FA 7.3 FA 9 .4 FA 8.0 FA 8.8 FA 7 .7 FA 8.0 FA 8.6 FA 8.1 FA 8.8 FA 8 .5 FA 7 .9 FA 7 .6 FA 8.2 FA 7 .9 FA 7.8 FA 8 .3 FA 7.4 FA 7.2 FA 8 .3 FA 6.8 FA 7.4 FM2 FA 8.1 FA 7 .0 FM 6 F D 6 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) TA B LE E45 (PAGE 1 6 ): A N OG ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 678 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP I I I 3 MG/KG/DAY DAY 22 POSTPARTUM 1458 NOT PREGNANT 1459 1461 1463 1465 .1468 1469 1472 1474a 12.1 12.1 10.8 11.1 9 .2 11.8 1 2 .4 / MA 1 3 .6 / MA 15 .1 / MA 1 3 .4 / MA 14 .1 / MA 12 .7 / MA 1 3 .8 / MA 14 .6 MA 14 .7 MA 1 5 .5 MA 14 .1 MA 16 .1 MA 1 3 .3 MA 1 3 .2 MA 16 .1 MA 14 .7 MA 15 .8 MA 1 2 .4 MA 1 4 .5 MA 1 1 .4 MA 14 .2 MA 15 .0 MA 1 5 .0 MA 1 4 .6 MA 1 3 .2 MA 15 .4 MA 12 .7 MA 12.6 MA 1 4 .5 MA 14 .1 FA 10.0 MA 1 3 .6 MA 14 .0 MA 1 3 .4 MA 12.0 MA 15 .1 MA 1 4 .3 FA 10 .4 MA 1 3 .5 MA 15 .5 FA 6 .3 MA 12 .4 FA 9 .8 MA 1 5 .9 FA 10.2 MA 14 .0 FA 9 .3 FA 8 .5 MA 11.6 FA 10.2 MA 1 4 .0 FA 10.1 MS FA 9 .5 FA 8 .3 MA 12.6 FA 9 .7 MD2 FA 10.1 FA 8 .4 FA 9 .0 FA 7 .7 MA 1 3 .0 FA 8.3 FA 10.0 FA 10.2 FA 8.0 FA 8.0 FA 8.6 FA 8.6 FA 11.2 FA 9 .0 FA 1 0 .9 FA 7.3 FA 8.8 FA 7 .7 FA 8.3 FA 7 .7 FA 7 .1 FA 8 .7 FA 7 .9 FA 9 .0 FA 7 .0 FA 8.2 FA 8 .7 FA 7 .2 FA 7 .0 FA 7 .3 FA 8 .5 FA 7 .5 FS FA 8 .5 FA 6.1 FA 9 .3 FA 7 .5 1476 / MA MA MA MA MA MA MA MD1 F A F A F A F A F A F A F A F A F A 9.9 1 1 .9 13 .6 12 .9 1 1 .3 13 .3 1 2 .4 12.0 8.6 8.0 7 .7 8.0 7 .7 8 .7 8.2 7.0 7 .1 1477 / MA MA MA MA MA MA MA MA F A F A F A F A F A F A F A F A F D 6 9.6 14 .3 1 2 .9 10 .3 9.2 1 1 .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 F A F A F A F A F A F A F A F A F A F A 10.1 1 4 .1 1 4 .4 16 .0 8.8 9 .1 8.8 8 .7 7 .9 7 .6 8 .4 9.0 9 .1 9.0 FIR S T LET T ER -- M-MALE, F-FEM A LE, U -S EX UNDETERMINABLE SECOND LE T T E R -- A -A L IV E , S -STILLB O R N , U -U NCERTAIN, D -D IED , A L L DISTANC ES WERE RECORDED IN M ILLIM ET ER S (MM). a . A n o g e n ita l distances fo r l i t t e r 1474 were n ot recorded. M -M IS S IN G (PRESUMED C A N N IB A LIZ E D ), X-M ISSING; S A C R IFIC ED 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) TAB LE E45 (PAGE 17) : AN OG ENITAL DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 679 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 2 0 2 1 2 2 23 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 22 POSTPARTUM 1482 / MA MA MA MA MA MA F A F A F A F A F A F A F A F A F D 1 F S 1 0 .4 1 3 .4 1 2 . 6 1 2 .9 13 .4 1 4 .4 1 2 . 6 8.0 8 .9 9 .1 7 .8 8 .5 7 .8 8 .6 7 .3 1483 NOT PREGNANT 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 11.5 12 .7 14 .4 9 .4 1 1 .9 11.0 11.3 1 1 .9 11.0 9 .1 10.2 9 .9 / MA 1 3 .3 / MA 15 .2 / MA 16 .1 / MA 1 3 .9 / MA 1 4 .6 / MA 1 3 .8 / MA 1 2 .9 / MA 1 2 .5 / MA 14 .7 / MA 11.0 / MA 1 2 .9 / MA 1 2 .7 NOT MA MA 12.2 14 .8 MA MA 15 .5 15 .0 MA MA 15 .4 15.5 MA MA 13 .8 12.1 MA MA 13.0 14 .9 MA MA 13.6 12.9 MA MA 1 4 .7 14 .6 MA MA 13.3 14 .3 MA MA 1 5 .7 16 .2 MA MA 12.6 11.5 MA MA 12.3 1 1 .7 MA MA 14 .3 13.0 PREGNANT MA 1 3 .2 MA 1 6 .8 MA 1 7 .7 MA 12.2 MA 13 .7 MA 1 3 .6 MA 1 6 .3 MA 1 3 .8 MA 1 6 .0 MA 9.0 MA 1 2 .4 MA 1 4 .4 MA 1 4 .9 MA 16 .6 MA 1 7 .6 FA 7 .5 MA 1 5 .8 MA 15 .1 FA 9 .2 MA 13 .7 FA 8 .9 MA 11.0 MA 1 3 .4 FA 8.2 MA 12.8 MA 15 .1 MA 16 .6 FA 8 .3 MA 14 .1 MA 1 3 .9 FA 9 .9 MA 1 5 .0 FA 7 .5 MA 12.0 MA 11.9 FA 8 .5 MA 14 .1 MA 16 .9 MA 1 7 .3 FA 8 .4 MA 14 .1 MA 12.8 FA 10.0 MA 13 .1 FA 9 .4 MA 11.3 MA 1 2 .5 FA 7 .4 MA 1 3 .6 MA 12.6 FA 9 .5 FA 7 .7 MA 12 .7 FA 8 .5 FA 9.5 MA 14 .4 FA 9.3 FA 7 .7 MA 12.0 FA 8.2 MA 1 2 .4 FA 9 .6 FA 9 .3 FA 8.1 MD1 FA 7 .8 FA 9 .3 MA 14 .8 FA 9 .2 FA 7 .8 MA 11.6 FA 7 .9 FA 8 .9 FA 9 .4 FA FA 8.2 FA 10.0 8.6 FA 8 .5 FA 8 .5 FA 7 .1 FA 8 .7 FA 9.0 FA 7 .5 FA 6.2 FA 7 .5 FA 9 .0 FA 7 .8 FA 8 .3 FA 8 .3 FA 9 .0 FA 8.1 FA 8.1 FA 8 .3 FA 7 .9 FA 7.9 FA 7 .9 FA 8 .7 FA 8.8 FA 8.8 FA 8 .4 FA 8 .3 FA 8 .9 FA 7 .6 FA 8.0 FA 7 .7 FA FA FA 8.9 9 .1 8.4 FA FA FA 9.4 10.0 10 .4 FA FA UU 7 . 7 6.9 FA FA 7 .0 8.8 FA 7 .2 FA 8.1 FD2 FA 7.8 FS FA FA FA 7.2 7 .7 7 .7 FA FA FA 7 .3 8.3 7 .0 FD2 FA 6.6 FA 7.2 1513 / MA MA MA MA MA MA MA MA MA F A F A F A F A MS 1 1 .9 12 .5 1 3 .7 14 .3 13.3 1 3 .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 F A F A F A F A F A F A F A 1 1 .3 1 4 .8 1 5 .0 1 3 .8 14 .0 1 3 .1 1 4 .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 F A F A F A F A 1 2 .3 1 3 .4 1 4 .5 1 3 .0 14 .3 1 3 .9 15 .2 1 4 .4 1 3 .4 1 4 .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) T A B LE E45 (PAGE 18) : AN O G ENITA L DISTANC E - IN D IV ID U A L DATA - F2 GENERATIO N PUPS ARGUS 418-020 Page 680 PUP # 1 2 34 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY DAY 22 POSTPARTUM 1517 1519 1521 1523 1524 1527 1528 1531 1533 1534 1537 1539 9. 6 1 0 ,. 6 1 1 ..0 1 2 .. 4 1 7 . ,5 9 . .2 1 1 ,. 6 1 1 ,. 8 9,.9 1 0 ,. 2 / MA 1 2 .4 / MA 13 .7 / MA 12 .7 / MA 1 4 .8 / MA 1 8 .4 / MA 11.1 / MA 1 4 .4 / MA 1 3 .3 / MA 13 .7 / MA 12.6 / MA 1 0 .6 1 2 .0 11.8 / MA 14 .8 MA 1 1 .7 MA 14 .5 MA 1 3 .0 MA 1 4 .9 MA 16 .6 MA 11.3 MA 14 .1 MA 14 .4 MA 1 4 .6 MA 12 .7 MA 12.0 MA 1 4 .0 MA 11.8 MA 1 3 .5 MA 14 .0 MA 1 5 .2 MA 10.8 MA 1 5 .0 MA 1 5 .0 MA 1 3 .8 MA 1 4 .4 MA 12.1 MA 1 4 .9 MA 11.6 MA 14 .1 MA 1 3 .6 MA 1 4 .3 MA 1 2 .4 MA 14 .0 MA 14 .8 MA 11.0 MA 12 .7 MA 11.6 MA 14 .1 MA 1 2 .9 MA 11.8 MA 12.0 MA 12.1 MA 11.3 MA 1 3 .5 MA 1 3 .4 MA 1 2 .9 MA 12 .7 MA 1 2 .9 MA 1 3 .6 MA 1 1 .5 MA 14 .2 MA 13 .0 MA 15 .0 MA 11.6 MA 13 .1 MA 12 .9 MA 12.0 MA 1 2 .4 MA 1 3 .4 MA 14 .3 MA 1 0 .9 MA 1 3 .6 MA 1 2 .5 MA 1 5 .5 MA 11.6 FA 8.2 MA 13 .7 FA 8.6 FA 8.0 MA 1 0 .5 MA 1 5 .2 MA 10.6 MA 1 3 .4 FA 8.8 MD1 MA 12 .7 FA 7.8 MA 1 3 .9 FA 8.0 FA 7 .1 MA 12.0 MA 1 3 .3 FA 7.2 FA 8.0 FA 8.6 FA 9.4 MA 10.0 FA 8.2 MS FA 8.0 FA 7.3 MA 11.6 MA 13 .1 FA 6 .9 FA 6.3 FA 8.3 FA 8 .4 MA 9.2 FA 8.0 FA 9.3 FA 6 .9 FA 7.5 MA 1 2 .4 FA 8.1 FA 8.0 FA 8.0 FA 7 .7 FA 8.0 MM5 FA 8 .3 FA 9 .1 FA 7 .9 FA 7 .5 FA 8.1 FA 7 .0 FA 7 .1 FA 8 .4 FA 8.8 FA 6 .5 FA 9 .0 FA 8.1 FA 7 .5 FA 7.3 FA 7 .9 FA 7 .2 FA 7.0 FA 6.8 FA 5 .9 FA 8 .9 FA 7 .7 FA 8 .3 FA 6 .9 FA 8.2 FA 5.5 FA 9 .2 FA 7.3 FA 6.1 FA 8 .9 FA 6 .9 FA 6 .4 FA 5 .1 FS FA 7.5 FS FD18 FA FA 6.4 5 .7 FA 8.6 FA 9 .0 FM6 FD1 FIR S T LETTER -- M-MALE, F-FEM A LE, U -S EX UNDETERMINABLE SECOND LETTER -- A -A L IV E , S -STILLB O R N , U-UNCERTAIN, D -D IED , A L L DISTANC ES WERE RECORDED IN M ILLIM ET ER S (MM). M -M IS S IN G (PRESUMED C A N N IB A LIZED ), X-M ISSING; S A C R IFIC E D 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) TA B LE E45 (PAGE 19) : A N O G EN ITA L DISTANCE - IN D IV ID U A L DATA - F2 GENERATIO N PUPS ARGUS 418-020 Page 681 P U P # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7 18 19 20 2 1 22 23 . RAT # MEAN DOSAGE GROUP V 30 M G /K G /D A Y DAY 22 POSTPARTUM 1541 / MA MA MA MA FA F A F A F A F A F A F A F A F A F A 9..7 1 2 .4 1 3 .9 1 3 .8 1 3 .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 F A F A F A F A F A F A FM2 F S 1 1 .. 4 1 4 . 6 1 2 . 4 1 3 . 9 1 6 . 0 1 2 . 5 1 5 . 0 9 . 1 8 . 9 8 . 3 8 . 7 9 . 1 8 . 7 1545 / MA MA MA MA MA MA MA MA MA F A F A F A F A F A F A F A F A FD 16 FD3 9 . .8 1 2 . 0 1 1 . 8 1 2 . 7 1 1 . 4 1 4 . 3 1 2 . 8 1 2 . 3 1 0 . 6 1 0 . 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 F A F A F A F A F A F A F A 9 . .6 1 2 . 4 1 1 . 7 1 2 . 3 1 1 . 8 1 2 . 6 1 2 . 2 1 2 . 3 1 0 . 8 7 . 3 7 . 1 7 . 2 6 . 8 6 . 6 6 . 3 6 . 9 1548 / MA MA MA MA F A F A F A F A F A F A F A F A F A FS 9 ..6 1 2 . 3 1 4 . 5 1 3 . 3 1 3 . 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 F A F A F A F A F A F A F A 1 0 .5 1 3 .4 1 3 .1 1 4 .4 1 4 .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 F A F A F A F A F A F A F A 1 0 .. 2 1 3 . 0 1 3 . 2 1 3 . 4 1 3 . 4 1 2 . 6 1 1 . 6 1 2 . 0 7 . 9 7 . 7 8 . 1 7 . 7 6 . 8 7 . 9 6 . 8 1555 / MA MA MA MA MA MA MA F A F A F A F A F A F A F A F D 6 9,.5 1 1 . 5 1 2 . 3 1 1 . 8 1 1 . 7 1 1 . 6 1 2 . 2 1 2 . 5 7 . 3 7 . 1 6 . 7 7 . 6 7 . 2 7 . 0 6 . 2 1557 / MA MA MA MA MA F A F A F A F A F A F A F A F A 1 0 ,. 3 1 4 . 0 1 3 . 8 1 3 . 1 1 3 . 5 1 2 . 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 F A F A F A F A F A F A 1 1 ,. 4 1 3 . 1 1 3 . 8 1 4 . 4 1 3 . 4 1 2 . 9 1 4 . 2 1 3 . 4 1 3 . 9 1 2 . 5 1 4 . 2 9 . 0 8 . 1 7 . 2 8 . 7 7 . 1 7 . 0 1560 / MA MA MA MA MA MA MD 7 F A F A F A F A F A F A F A F A 9 .2 1 2 . 6 1 1 . 7 1 2 . 0 1 1 . 8 1 2 . 5 1 1 . 8 7 .0 8.0 6 .4 7 .0 8.8 6.3 6.3 6.0 1564 / MA MA MA MA MA MA F A F A F A F A F A F A F A 10 .3 1 3 . 1 1 3 . 0 1 3 .3 1 2 . 4 1 3 .0 1 3 .3 8 . 1 7 . 2 8 . 1 7 . 9 8 .3 8.2 7 . 5 1565 / MA MA MA MA MA MA F A F A F A F A F A F A 1 1 .8 1 4 . 9 1 4 . 0 1 4 . 2 1 4 . 5 1 3 . 8 1 4 . 9 9 . 6 9 . 4 8 . 5 9 . 1 9 . 1 9 . 4 1566 / MA MA 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 1568 8 .3 1 3 . 1 1 2 . 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 / MA MA MA MA MA MA MA F A F A F A F A F A F A 11 . 9 14 .3 15 .0 1 4 .7 13 .0 14 .2 15 .6 1 4 .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) TA B LE E45 (PAGE 2 0 ): AN O G ENITA L DISTANCE - IN D IV ID U A L DATA - F2 GENERATION PUPS ARGUS 418-020 Page 682 PUP # 12 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 1 7 18 19 20 2 1 22 23 RAT # MEAN DOSAGE GROUP V 30 M G/KG/DAY DA Y 22 POSTPARTUM 1571 / MA MA MA MA MA MA F A F A F A F A F A F A F A 9 .7 12:2 1 1 .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 F A F A F A F A F A F A F A F A 11.0 1 5 .1 13 .3 1 3 .6 1 4 .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 M A M A M A M A M A MM 8 MD 7 F A F A F A F A F A 10.2 12.0 12 .4 13 .0 1 1 .7 12 .4 12.0 7 .0 7 .4 8.5 8.2 7 .5 1578 NOT PREGNANT 1579 1583 1584 1586 1587 1588 1589 1591 1593 1598 1600 10 .5 10 .7 1 6 .3 11.4 10 .7 10.1 9 .0 11.6 11.3 8 .7 11.2 / MA 1 4 .0 / MA 1 4 .0 / MA 1 8 .4 / MA 13 .7 / MA 1 4 .0 / MA 1 2 .9 / MA 11.0 / MA 1 2 .5 / MA 1 5 .2 / MA 11.8 / MA 1 3 .6 MA 12 .7 MA 14 .1 MA 1 7 .9 MA 15 .0 MA 1 3 .9 MA 1 3 .5 MA 11.2 MA 1 3 .2 MA 15 .0 MA 11.5 MA 1 3 .4 MA 14 .5 MA 14 .6 MA 1 8 .9 MA 1 2 .4 MA 14 .1 MA 1 3 .9 MA 11.8 MA 1 3 .2 FA 9 .8 MA 10 .7 MA 14 .0 MA 1 3 .0 MA 14 .7 FA 10.1 MA 1 3 .3 MA 12.8 MA 1 2 .5 MA 11.2 MA 1 3 .2 FA 8.6 MA 12.0 MA 1 3 .8 MA 12.8 MM3 MA 1 2 .9 MA 12.2 FA 9 .3 MA 1 2 .4 MA 14 .6 FA 9 .3 MA 11.6 MA 12.8 MA 13 .7 FA 8 .4 MA 1 4 .9 FA 9.5 FA 8.6 MA 12.0 MA 1 3 .0 FA 9 .8 MA 11.6 MA 12 .7 MA 11.5 FA 9.0 MA 1 2 .3 FA 8 .9 FA 7 .9 FA 8.1 MA 12.1 MA 11.8 MA 12.2 MA 1 3 .6 FA 8.8 FA 8.2 FA 9 .0 FA 9 .2 FA 7.0 MA 12 .7 FA 5 .9 MA 12.2 FA 8.2 FA 8.8 FA 8 .4 FA 8 .3 FA 8 .4 FA 6 .7 MA 1 3 .4 FA 7.4 MA 11.3 FA 7 .1 FA 9.0 FA 8.8 FA 7 .6 FA 8.0 FA 7 .6 MA 1 2 .3 FA 7.6 MA 12.1 FA 7.4 FA 8 .5 FA 9 .1 FA 7.8 FA 8 .9 FA 6 .9 FA 8.0 FA 6.6 MD1 FA 7.5 FA 8.0 FA 9 .4 FA 9 .0 FA 7 .0 FA 6.9 FA 6.6 FA 8.2 FA 8.1 FA 9 .3 FA 8 .7 FA 6 .4 FA 7 .7 FA 6.8 FA 7 .1 FA 5 .9 FA 6 .3 FA 9 .0 FA 7.2 FA 6.6 FA 7.3 FA 5 .9 FA 6 .9 FIR S T LE T T E R - - M-MALE, F-F E M A LE , U -S EX UNDETERMINABLE SECOND LET T ER -- A -A L IV E , S-STILLB O R N , U-UNCERTAIN, D -D IED , A L L DISTAN C ES WERE RECORDED IN M ILLIM ET ER S (MM). M-M ISSING (PRESUMED C A N N IB A LIZED ), X-M ISSING; S A C R IFIC E D WHEN FOUND ARGUS 418-020 APPENDIX F PROTOCOL AND AMENDMENTS Page 683 ARGUS 418-020 OPrimedica Argus Research Laboratories. Inc. 905 Sheehy Drive. Building A Horsham. PA 19044 Telephone: (215)443-8710 Telefax: (215)443-8587 PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 STUDY TITLE: ORreaplro(Gdauvcatiogne)STtwudoy-Goef nAemramtioonniu(mOnPeeLriftltueorrpoeorctGaneonaetreation) (APFO) in Rats PURPOSE: The purpose of this study is to provide information c(AoPncFeOrn) ionng tthhee mefafelectasnodf fAemmmaloenrieupmroPdeurcftluivoerosoycsttaenmosatine fCurnl:cCtiDon,(SesDtr)oIGuSs cByRcleVsA, Fm/Patluinsgbreahtsa,viinocr,lucdoinngcegpotinoand, al parturition, lactation, weaning and the growth and dpmeroovrvetiadloleiptyminaefnondrtmpoafrteoiolfimnfspianrbainorgyu.tdeaTfthfaeecotsnstupodonytenisnetoaianlslaoptardel enmsaoitgarnbleiddityto, developmental toxicity, as well as to serve as a guide for use in the design of subsequent tests. ddiFneeocvvroeefrulplooroppthrmmaeteerenndintt,afionlarttdomodxtaihittciieooitnnyparaolonntsodtfucudodnelycvbtseiaoelsongepamdml edoenenntfstitachcileeannngecuubieiredosetoalixnnidecsityf.or TESTING FACILITY: A90rg5uSshReeesheyaDrcrhiveL,aBbouriladtionrgieAs, Inc. TTHeeollreespfhahaxom:n,eP: en((22n11s5y5l))v44a44n33ia--8857181970044-1297 STUDY DIRECTOR: RAraasyysmmocooinnaddte.yGDo.rikrYe@ocrtpkor,rimPofhe.dRDiec.,sae.DcaAormcBhT SPONSOR: 3M Corporate Toxicology 3SMt. PCaeunl,teMr,inBnueilsdointag 252501-424E--100200 Page 684 ARGUS 418-020 STUDY MONITOR: J33oMMhnCMoBerdupitcoearnalhtDeoefTfp,oaPxrhitcm.oDel.on,gtDyABT, CIH 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; SRuebpsrotadnuccetison(OaPnPdTFSe)rt8ili7ty0.E38ff0e0ct,sA. uOguffsict,e 1o9f9P8r.evention, Pesticides and Toxic U.S. Environmental Protection Agency (1997). Toxic Substances Control Act (TSCA) TreefsetreGnucieddeltinoeOs;PFPiTnSal 8R7u0le.3.80R0e)p.roFdeudcetiroanl RanedgisFteerr,tilAityugEuffsetc1ts5,, 719999.79.380 (crossAUFic.nSta/.TlEoRxnuivcleirS.onu4mb0setCanFntaRclePPsraCorttoen1ctt6rioo0nl/PAAacgrtte(7nF9cI2Fy..RAF/eTdSeCraAl);InGseocotdiciLdaeb, oFruantogriycidPeraacnticdeRSotdaenndtaicriddse; OPrrignacnipizleastioonf GfooroEdcLoanboomraictoCryooPprearcatticioens a[nCd(9D7e)1v8e6lo/Fpminaeln].t (1998). The Revised OECD REGULATORY COMPLIANCE: This study will be conducted in compliance with the Good Laboratory Practice (GLP) regulations cited above. ADlilrecchtaonrgaensdothr ereSvipsoionnssoro,fdthaitsedpraontodcmolasinhtaallinbeeddwoicthumtheenpterodt,osciogln. ed by the Study TaatnhtdehetTheeTsetrisentpginogrFt,aFacainlcidtiyli'twsyiQlilnuinaasclpictyeocrAdt sacsnruictirecaanwlciptehhUathsneeitsS(QotafAntUhdo)asrwdeillOpaopuretdiroiatnttishnegofpPtrhrooetcosectdouuld,ryethsceoonrfadAwurcgdtueasdta Research Laboratories, Inc. Should any portion of the study be conducted by a subcontractor or by the Sponsor, the QanAdUrefoprotrhtsatfofar cthiliatyt swtuilldcyopnodruticotncaricticcoarldpinhgasteo tinhsepSeOctPiosnsofatnhdatafuadciitlitrye.spSeucctihvecrrieticsaullts 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 QAU Statement generated by that facility and provided to the Testing Facility for inclusion in the final report. Tthheerfeinpaolrtreapcocurtrawtielllyinrcelufldeectsa tchoemrpalwiandcaetasotabtteamineendtdsuigrinnegdthbey tpheerfSortmudaynDceireocfttohrethsatutdy Page 685 ARGUS 418-020 Protocol 418-020 Page 3 and that all applicable GLP regulations were followed in the conduct of the study. Should significant deviations from GLP regulations occur, each will be described in detail, together with how the deviation might affect the quality or integrity of the study. SCHEMATIC OF STUDY DESIGN AND STUDY SCHEDULE: See ATTACHMENT 1 to the protocol. TEST SUBSTANCE AND VEHICLE: Identification: Test Substance: Ammonium Perfluorooctanoate (APFO), Lot 332. TidheentSityp,ocnosmorpwosillitiporno,vimdeetthootdheofTseysnttinhgesFisa,csiltirtyendgotchuamnednptautrioityn oofrtcheerttiefisctastiuobnsotafnthcee. Vehicle: Reverse Osmosis Membrane Processed Deionized Water (R.O. deionized water). tNoebiteheprrethseenStpinonthseorvneohricthleethSatut dwyoDulidreicnttoerrfiesraewwaitrhe tohfearneysuplotsteonftitahliscosntutadmy.inTahnetsrelifkoerely, no analyses other than those mentioned in this protocol will be conducted. Safety Precautions: tGaolhobavelef-wsf,aocdrneusdrteu-msripnisigrta/fHtooErrmPwuAilll-afbtilietoenwreopdrrnempaaansrdakt,pioarnepppaarnordaptrdiioaontseawegilyele.bepInrcoaotedncddtiuitoicontnea,dnTidynvuaenkcifhoselremme/ivclaeabsl fcauonmadte hood when using the bulk test substance. The Material Safety Data Sheet (MSDS) is attached to the protocol (ATTACHMENT 2). Storage: VBPeurehlkpicaTlreee:sdt Substance: Formulations: RRRooeoofmmrigtteeermmatppeeedrr,aapttuurorreete.. cted 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. FORMULATION: Frequency of Preparation: Formulations (solutions) are prepared weekly at the Testing Facility. Detailed preparation procedures are attached to this protocol (ATTACHMENT 3). Adjustment for Purity: Tcahlecutelastitosnusb.stance will be considered 100% pure for the purpose of dosage Testing Facility Reserve Samples: T5hmeLTseasmtinpgleFoafcvileityhiwcliell uresseedrvdeurain1g gthseacmopulreseofoefathche slottudoyf .buSlkamtepsltessuwbsilltabnecestoarnedda under the previously cited conditions. ANALYSES: sRteusduyltrsepoof rrte. quired analyses will be provided to the Testing Facility for inclusion in the Samples additional to those described below may be taken if deemed necessary during the course of the study. Bulk Test Substance Sampling: 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 41P8a-g0e205 This sample will be sent to: 3KMrisEJn. vHiraonnsmeenn, tPahl .TDe.chnology & Safety Services 9BS3tu.5ilPdBainuugsl,h2M-A3invEen-n0eu9soeta 55133-3331 TTeelleefpahxo:ne: ((665511)) 777788--66017168 The recipient will be notified in advance of sample shipment. Analyses of Prepared Formulations: Concentration: Csdrureetanoumqydnduseacyerie.onstnftihnDtpoerguarfepptstipholraiecaenmvaraiSotpoetfpliueotosshsnanley.wsmocpiOplrilrt.lneeebepdseaswcrreaeoiltmdnladbipfnioelteeirotmdanokuasfelseaanatbnicofadrhnocdskmdiusuwpcepialallsirccabdahmeetedcpvoelsaenretsicftt.iehewnedBitlrlaTdacbeutkeisrouitnnsipnghogsiptnahFpmeteahpdcceilolefifuotisyrrrsswuatepinallooanbnfldyetsthlhaisissest;ottrheed Stability: dSutapbliicliatyteosf athmeppleresp(a2remdLfoeramchu)lafrtioomnsewaicllhbceodnocecunmtraetniotendwdilul rbinegtathkeisnsotundtyh.eTfiwrsot dseatysooff wsppptrrrioeleelrpppebaaaderrraaaruttteniiioootdannnei.n.raetTsOdhhnepaeeotpsstsersheaiebsvmailToepmuelaespsnltlyoeidnfscgteiewtaeFnicdlaldhcbcaieldoyitunsyapdnaaliitafscitolaeybntrzaesetchdsakeenuatfdptiwrtsdshitlailesambcnfaeoparllldseloyhesswi.dipsinp.aBgetaTdttchihmkoeeunepTrtepehsmoseatianmidnitnsagp:iylneFgosaafscswiasliilmtolyobpnuelepasofnter the request of the Sponsor. Shipping Instructions: Samples 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 DISPOSITION: Prepared formulations will be discarded at the Testing Facility. All remaining bulk test substance will be returned to: Nelda Marecki, Ph.D. 33BSMMtu.ilPdCSaiMenungMl,te2GMr3N6E-H15SB51-&14R04-1000 TEST SYSTEM: Species/Strain and Reason for Selection: TTda1)neehdvstehetidiCnlsoegrpslv:mtCeFralaDeoicnnpitmlia(otSylef 1Dtnr1oa't)3xatI5Gi;lnhatSasonsxadBibncR3edit)yeVhtnheAaevdsFaet/belPmueslaueottsnniaosrnwttirscriada;letet2elw)diysahutpsoisshtesbaodeerrlmiectshcaaertlcnoedosudaligottaihavgsoeicatuahtntoledliynrTeedaexpucpsrstotietvdrrSeyiueycfinsnottcirevtehemreeeapxbsnrieopsdcdteaucauictesttsiheve:eand strain. Number: P Generation: PInoitpiaullaptoiopnulsaetiloenctaecdcfliomrastteudd:y: s11e56x05 pvveiirrggr iignnrommuaapll)ee. rraattss aanndd 116550 vviirrggiinn ffeemmaallee rraattss.(30 per 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: Both male and female rats will be evaluated. Protocol 418-020 Page 7 Source: P Generation: Charles River Laboratories, Inc. TLahbeorraattsorwieilsl ,beIncs.h,iptopethdeinTefisltteinregdFcaacriltiotyn.s by air freight and/or truck from Charles River F1 and F2 Generations: Odaffmspsriinngthwisillsbtueddy.elivered at the Testing Facility by the pregnant P or F1 generation Identification: P Generation: Rats are permanently identified using Monel self-piercing ear tags (Gey Band and Tag Co., Inc., No. MSPT 20101). Male and female rats will be assigned temporary numbers astturdeycebiepftoarendadgmiveinnisutrnaiqtioune opfetrhmeafniresnttdiodseangtieficoaftitohne nteusmt bseurbsstwahnecne.assigned to the F1 and F2 Generations: Pups will not be individually identified during the postpartum period; all parameters will cboenetivnauleudateodbsienrtveartmiosn owfitllhbeelitidteern. tiAfiet dwewaitnhinag,MeoancehlF1seglfe-npeierractiinogn eraatrstaegle.cted for ANIMAL HUSBANDRY: All cage sizes and housing conditions are in compliance with the G uide fo r the Care a n d U se o f L a b o ra to ry A nim als{4). Page 690 ARGUS 418-020 Protocol 418-020 Page 8 Housing: P Generation Rats/F1 Generation Litters: ePxgceenpet rdautiroinngrtahtes wcoilhl abbeitiantdioivnidaunadllyphoostupsaerdtuimn sptearinioledsss. sDteueriln, gwciroeh-baobtittoamtioend, ceaagchespair opdarfemrsautasmnwedidlldbgeeelivshetaoretuiodsnel,idttfeeinrmwtahilelel bmreaathlseowuraisllte'sbdecianingadei.cvoidBmueamgllioynnnhinnogeussnteiondglainbteonrxetshdtauinnrgindgbaoytxh2ee0sp.oofEstapcahrtum 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 hPoguesneedraatfitoenr craothsa. bBitaetgioinnn.inTghneosalamteer tthyapne odfayca2g0inogf wprilel sbuemuesdedgeasstadteiosnc,rifbeemdafloer rtahtes whoillubseedinindivaidcuoamllmy ohnounseesdtiningnbeosxtindgurbinogxethse. pEoascthpadratummapnedridoedl.ivered litter will be 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: T1h00e%anfrimesahl raoior mthaist hinadsebpeeenndepnatslysesdupthprlioeudgwhit9h9a.9t7le%asHtEtePnAcfhilatenrgse. sRpoeormhoteumr opferature will be maintained at 64F to 79F (18C to 26C) and monitored constantly. Room humidity will also be monitored constantly and maintained at 30% to 70%. Light: 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 (PMI Nutrition International), available a d libitum from individual feeders. Page 691 ARGUS 418-020 Protocol 418-020 Page 9 Water: Water will be an automatic available watering aacdcelibssitusmysftreomm. individual All water bottles will be attached to from a local the cages or from source and passed through a reverse osmosis membrane before use. Chlorine will be added to the processed water as a bacteriostat; processed water is expected to contain no more tbhaacnte1ri.a2l pcpomntacmhlionraintieonatatnhdettwimicee oafnannuaallylysifso.r Wpoastseibr lies achneamlyziceadl cmoonntathmlyinfaotriopno.ssible Contaminants: Neither the Sponsor nor the Study Director is aware of any potential contaminants likely twcroooounbutdeilnduepcilrntyeetesdper.efnerftroeirnmwtheitehd tcbheyertthirfeieesdfueldtesideots,futthhpeipsldisertriunodkryin.thgoTwsheaetremerfeoonrretit,ohnneeondaeinsnatitnlhygsisemsparootetthoriecaorlltahwtailnlel vbtheelosstehat DAY NUMBERING SYSTEM: Gestation day 0 vaginal contents is defined as the day spermatozoa and/or a copulatory plug observed are observed in situ. in a smear of the The day of birth is designated lactation day 0 (postpartum day 0) in the Health Effects TapFnoeadssctitlpTiGtaoyr.uxtuiidcTmehSlriu(nodbeuassgytha-1onRucoetefptslhraoi8csd7taup0tcr.ioo3titn8oo)0nc0iona,ln,tAhdtuhegFeSuedsrtaatti,lnyitd1yo9afE9rbd8ffi)reO.tchptTswehri(ailOlstbifnsfeiagcmedPeeorsofidgcPaneryadetuivseerdednsetdisooainfyg,tnh1PaepteeoTsdsteitcsdpitadainyergtsu1m l(adcatyat1ioonfplaecritoadtiowni)llabneddaelltesrumbisneeqduaenndt acgiteesd oafctchoerdFin1gglye.neration rats and days of the 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 tghreoubpassibsaosfepdhoynsiccaolmappupteear-rgaennceeraatneddb(owdeyigwhet-iogrhdte. reTdh)erarantdsowmililzbaetioansspigronceeddutoredso.sage 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 P41a8g-e02100 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. wDhaiych1 aolfl lpaucptastiionna(plitotestrpaarretuimnd)ivisiddueaflilnyewdeaigshtehde (dpauypobfobdirythwaenigdhtiss awlsillobteherefcirosrtddeady on 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. Avilal bFi1litygeonfethraetsioenpruaptss,woinll beeithweeradnaeyd2a2t pthoestspaamrtuema,goe,r ibfarseeqduiroend,obdsaeyr2ve9dpgorsotpwathrtuamnd. oSbhsoeurlvdaittiobneanl eincteesrvsaalrsywtoillebxeteanddjuthsetedlacatcactioorndinpgelryio.d to day 29 postpartum, all affected At weaning, a table of random units or a computer-generated randomization procedure waitlol tbael oufse3d00torastesle(1ct5030ramtsalpeear nsdex3)0chfeomseanlefoFr1cgoenntienruaetidonevpaulupastipoenr. gArotulpe,asret sounletinmgainle tdpchoeuanpstctitarnhinbuedeesddotunfoodenryftsehbtmueedaeFylx1e.tepgnuedpneepdreatrtoioliitnntecwrl,uildwl ebheeanuthspeiroddssfgoiberlnese,erwlaeticiloltinboe,ntshoeefleFpc2rtoegcdee.ndeuIfrraeretsiospunrltepsvuwipoasursrlaynt oIFfr1stbtrueodarytmFr2eebsnutl-ilttrtseelrsasht.eoduIfladplrtwoeardarurtciaotninotsn(eino.gfl.ia,ttepsreoscoiorznered),plpritoatedrreucnisttiaodlnepepameirersfdomrnmaeyacnebcesesraeinrmyt,hatetheedcostnoetcrpoorlnodgdruocuep cohabitation period will be scheduled approximately one to two weeks following weaning of the F1a or F2a litters. ADMINISTRATION: Route and Reason for Choice: Tdiheetaoryrarlo(ugtaev,athgee)erxoauctet dwoassagseelceacntedbefoarcucsuerabteelcyaaudsme:ini1s)teirnedco; manpdar2is)oitniswoitnhethe 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. Dosages will be adjusted based on the most recently recorded body weight and given at approximately the same 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 tero exposure) or via maternal milk during the postpartum period. F1 generation rats will be given the same dosage level of the test substance as their respective P generation sires and dams. Dosages will be given once daily, beginning at weaning (approximately 70 days before cohabitation) and continuing until the day before sacrifice. Dosages will be adjusted at least weekly for body weight changes and given at approximately the same time each day. F2 Generation: pPeurpiosdm. ay be exposed in tero during gestation or via maternal milk during the lactation Rationale for Dosage Selection: Dosages 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 olleebvvseeell riivssaeebxxlepp-eeaccdtteevdderttsooep-perrofofdeduuctcceelevnmeoilne(imNviOadleAonEbcLes)e]o.rvf aebitlheetrosxyicsteefmfeicctso,rwrehpilreotdhuectliovweetostxidcoitsya[gneo- Dosage Levels. Concentrations and Volumes: Dosage Group I Number of Rats per Sex 30 Dosage (mq/kg/day) 0 Concentration (mg/mL) 0 Dosage Volume (mLTkq) 5 Argus Batch Number B-418-020-A(Day.Month. Year) II 30 1 0.2 5 B-418-020-B{Day.Month.Year) ill 30 3 0.6 5 B-418-020-C(Day.Month.Year) IV 30 10 2 5 B-418-020-D(Day.Month.Year) V 30 30 6 5 The test substance will be considered 100% pure of the purpose of dosage calculations. B-418-020-E(Day.Month. Year) Page 694 ARGUS 418-020 TESTS. ANALYSES AND MEASUREMENTS - P GENERATION: Protocol P41a8g-e02102 Viability - Male and Female Rats: All Periods: At least twice daily. Clinical Observations and/or General Appearance - Male and Female Rats: Acclimation Period: Weekly. Dosage/Exposure Period: bDeairlyecboerfdoered adopsparogxei.maPtoeslytd6o0sag1e0 ombisneurtveastiaofntesrwill administration. Maternal Behavior: Days 1, 5, 8, 15 and 22 postpartum. Observed abnormal behavior recorded daily. CaplipnricoaplrioabtesebryvathtieonSstumdayyDbierercetocroradnedd/omr oSrteudfryeqMuoennittolyr.than cited above if deemed Body Weiahts - Male Rats: Acclimation Period: Dosage/Exposure Period: Day of Sacrifice: Weekly. Weekly. Prior to sacrifice. Body Weiahts - Female Rats: Acclimation Period: Weekly. Precohabitation Period: Weekly. Cohabitation Period: Weekly. Gestation Period: Days 0, 7, 10, 14, 18, 21 and 25 (if required). Postpartum Period: Days 1, 5, 8, 11, 15 and 22 (terminal body weight recorded). Feed Consumption Values - Male Rats (recorded and tabulated): Dosage/Exposure Period: Weekly. Page 695 ARGUS 418-020 Protocol 418-020 Page 13 Feed Consumption Values - Female Rats (recorded and tabulated): Precohabitation Period: Weekly. Gestation Period: Days 0, 7,10,14,18, 21 and 25 (if necessary). Postpartum Period: Days 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 Consumption Values - Male and Female Rats: vcnFaaeelgceueedesswcsoiawtnhriylsloutnnomoetrpefbteipeoelendrnevjicasaohrl,urdterheesedpmlfeoeanreyitdsa.bhbemuDlerauentrcetinodogr.fdctehodehmafeboeirtdaetjifaorernsq, uwweihlnletblnyettwdhoaocnruacmtisteeondcteacdbu.opvyIenthdifeivitisdiausmale Estrous Cycling and Mating: Estrous cycling will be evaluated daily by examination of vaginal cytology beginning 2od1busrdienargvyesthdbeeincfooarhesambthieteaatsrioconhfeptdheuerlieovdda.gcionhaal bcoitanttieonntspaerniodd/oranadcocopnutlaintuoirnygpulungtilisspoebrsmeravteodzoian are situ 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 Observations: Litters will be examined after delivery to identify the number and sex of pups, stillbirths, live births and gross alterations. Fertility Parameters: 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 P41a8g-e02104 Number of implantation sites. General condition of dam and litter during the postpartum period. Utter 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 MEASUREMENTS - F1 GENERATION: Viability: Preweaning Period: Postweaning Period: ddLaaittiilleyyr..s Twhilel bpeuposbsinerevaecdhfolirttedreawdillpbuepscoautnlteeadstotnwciece Twice daily. Clinical Observations and/or General Appearance - Male and Female Rats: Preweaning Period: Daily. Postweaning Period: Daily before dosage.Postdosage observations will baedmreinciosrtdraetdiona.pproximately 60 10 minutes after Maternal Behavior: aDbanyosrm1,a5l,b8e,h1a5viaonrdre2c2orpdoesdtpdaaritluym. . Observed 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: Days 1 (livebom pups), 5, 8, 15 and 22 postpartum. Postweaning Period: Weekly. Page 697 ARGUS 418-020 Protocol P41a8g-e02105 Presumed Gestation Period (Female Rats): L(FaecmtaatiloenRPaetsri)o:d Day of Sacrifice: Days 0, 7, 10, 14, 18, 21 and 25 (if required). Days 1, 5, 8, 11, 15 and 22. Prior to sacrifice. Feed Consumption Values - Male and Female Rats: Postweaning to Cohabitation: Weekly. P(MoasltecoRhaatbsi)t:ation Period Weekly until sacrifice. G(FeesmtaatlieonRPatesr)i:od Days 0, 7, 10, 14, 18, 21 and 25 (if required). L(FaecmtaatiloenRPaetsri)o:d feDnexoaeptydets.acb1teu,d5la,tthe8ad, t1ap1futeaprnsddwa1iyl5l .1b5eFgpeinoesdttopcacorontunsmsuum,mpwethioemnnavittaeilrsuneasl Fneeceedscsoanrysutomrpetpiolennvisahlutehsemfeaeyd.beDruercinogrdceodhmaboirtaetiforenq, uwehnetlny ttwhaonractisteodcacbuopvyethifeitsiasme wcailgl enowtitbheorneecofredeeddjaorr,tarebpulleanteisdh.ment of the feed will be documented. Individual values Postweaning Developmental Observations: Sexual Maturation: pFoesmtpaalerturamts. wMilal lbeereavtsalwuialltebde feovratlhueataegdefoorf tvhaegiangael poaf tpernecpyu,tibael gsienpnainragtioonn,dbaeyg2in8ning 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 doubrsienrgvethdeincoahsambiteaatiroonf ptheeriovda.ginal contents and/or a copulatory plug is observed in situ 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 P41a8g-e02106 Duration of Gestation: As cited above for P generation rats. Litter Observations: As cited above for P generation rats. Fertility Parameters: As cited above for P generation rats. Litter Data: As cited above for P generation rats. TESTS. ANALYSES AND MEASUREMENTS - F2 GENERATION: Viability: Preweaning Period: Litters will be observed for dead pups at least twice ddaaiillyy.. The pups in each litter will be counted once Clinical Observations and/or General Appearance: Preweaning Period: Daily. Body Weights: Preweaning Period: Days 1,5, 8, 15 and 22. Preweaninq 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 Protocol P41a8g-e02107 GROSS NECROPSY AND HtSTOPATHOLOGY: Adult P and F1 generation rats will be necropsied and examined for gross lesions. Gross lesions will be retained in neutral buffered 10% formalin and examined histologically. Tissue trimming and histopathology 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 samples (approximately 4 mL per rat) will be creoslluelctitnegd sfreormumthweillinbfeeriiomrmveendaiatcealyvafroinzteonseornumdryseicpeaarantdormtuabinetsaiannedd cfreonzterinfu(g<e-d70. TCh)e until shipment to the Sponsor for analysis. The liver will be excised, weighed, and a sSapmonpsleorsfeocrtiaonna(lylastiesr.al lobe) frozen and retained at <-70C until shipment to the After completion of sample collection, serum and liver section samples will be shipped (rfercoizpeiennot nanddrythicee)SttoudKyriMs oJ.niHtoarnwseillnb, ePnh.oDti.f,ieadt tinheadpvreavnicoeusolyf scaitmedplaedsdhreipsms.enBt.oth the wGoririllfoicsbesesne, exacasrmowpineselyldaw:silelaxinntecinrluntedarelnaaanlndeixninaittmiearlinnpaahltiyposonicrtoaiofl nteissxsaoumfeaisnllaahtnioodlnlooowrgf aoernxgsteainrnnsa;slitthsueu. refTaxhcteeersfnoaallnlodwianlgl 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. hSiesetoAloTgTicAaCl eHvMalEuaNtTion4sfotor abdedcitoionndaulcttiessdu; easll toothbeerwtisesiguheesdwailnl dberedtiasicnaerdd,eadn.d Adult Rats Found Dead or Moribund - P and F1 Generation Rats: 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 Uteri of apparently nonpregnant rats will ibneu etexrai mwiilnl ebde examined to the extent possible. while being pressed between glass plates to confirm the absence of implantation sites. See ATTACHMENT 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 Rats: gaArsfotsesersscsnoetmhceprolepptosiotyennootfiafthlthetoetxhciocoirthayacobicfit,athatiebodnteopsmteirsniuoabdl ,satnaaddnucpletemlovniacltevhiesracmtesraawleiwllriebllepbresoadpcuercirftfiiocvreemds,eydas.ntedTmao, the following endpoints will be evaluated: Sperm Evaluations: AsMpopetorilmrittyiocwnoinlolcfbetehneteravletaifoltuncaataeundddabmyeopthtiideliitdyHyuamsmiisnilgtwocnilloTbmhepouumsteeerd-IaVfsoOsriSsetvebadylucsaoptleiloernmctiooafnncaaolufysdaiassae(CmpiAdpSildeAyf)mr.oaml tteHhisvaesamullueeilafttowtecneasiTugphhdeotar)mm.eepSmidpIoVeidrOrpymShmomifsloo.orgryTaphhadeoneldtoreegtrmoymaepinivrnaeaitpnliuoaganrelteioofaftnscshpaoweumirdlmloaignececopnluniaddctieedenyttmhotreaibstfeioowlneliolvl(wasblipeuneagurt:msee1d)dpbetyor tgmhreaamnuoaflly determination of the percentage of normal sperm in a sample of at least 200; and 2) qaubanloitramtiavel taeivl,aalunadtioanbnooframbanlohrmeaadl sapnedrmta,il.including such categories as abnormal head, Organ Weights: The following organs will be individually weighed: right testis, left testis, left epididymis p(wrohsotlaetea.nd cauda), right epididymis, seminal vesicles (with and without fluid) and Histopatholoov: Tveevhsaeilcurlaeetmsioawni.inllinTbgheepfioxteretsidoteninsonwfeitlhul etbraelelffibtxueefdpfeidirneiddByom1u0isi%n,'stfhoseromrluiagtlihiontnefofporidrpi4do8ysmstoibis9l,e6phrhiosostuotarpstaeathanondldothgseiecnmalinal retained in neutral buffered 10% formalin for possible histopathological evaluation (see ATTACHMENT 4). tShheocuoldhaabsiteactioonndpleitrteiordbfeordteheemseedconnedcelisttsearr,ye,xmteanledinragtsthweilsl tnuodtybbeysaapcprirfoicxeimd autnetliyl after 14 weeks. Scheduled Sacrifice - P and F1 Generation Female Rats: 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 P41a8g-e02109 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. Dams with No Surviving Pups - P and F1 Generation Female Rats: Dams 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. PF1/F2 Generation ups Found Dead on Day 1 Postpartum: Pups that die before examination of the litter for pup viability will be evaluated for vital sstinaktuwsilaltbbeiritdhe. nTtihfieedluansgsstiwllbillobrne; rpeumposvweidthalnudngims mtheartsfelodaitnwwilal tbeer.idPeunptifsiewditahslulinvgesbothma,t and to have died shortly after birth. Pups with gross lesions will be preserved in Bouin's esovalulutioantiofnosr,piot swsililbbleefuntoutreedeinvathlueatnioenc.roSpshyoudladtap.ostmortem autolysis preclude these PF1/F2 Generation ups Found Dead or Moribund on Days 2 to 22 Postpartum: Pups found dead or sacrificed due to moribund condition will be examined for gross fleosuinodnsonanddayfosr2thteo c5apuossetpoafrtthuemmwoilrlibbuenpdrecosenrdvietiodninoBr doeuainth's. soPluuptisonwiftohr gproossssiblelesifountusre enevevaaulltuuraaalttiiboounnf;sfegirtreowdsilsl1bl0ee%sinofoontrsemdoafilnipnut.hpesShnfooeuucnrldodpposonysddtmaatyoasr.te6mtoa2u2toplyossitspaprrteucmludweillthbeespereserved in F1/F2 Generation Pups Not Selected for Continued Observation: Awlilllpbuepsracnudlolemdlyonsedlaeycte22d paondstpeaxratumminewdillfobregsraocsrsifilceesdio,nasn;dgrtohsreselepsuiopnsspwerillsbeex per litter preserved in neutral buffered 10% formalin. Necropsy will include a single crosstcbshreueocffstteishor-rensedeeocf1stit0eoh%lneeecfhdoteerbadmrdaapialunintpftsofhorepraeplperovpsseaeslrxiebopnlfeetthrhhelyiistdfttreoroorlnocwtgeaiiplcll-hapbalaeleyrwiv.eaetTaliuglisahssteuiuodtenusa.ren(AdsaHenreedretAaemiTxnaaTeimnAdiCniningHantMpioeuEnupNtsroaTfwlt4ihll)ebfreom discarded without further examination. Page 702 ARGUS 418-020 Protocol 418-020 Page 20 PROPOSED STATISTICAL METHODS15-111: Averages and percentages will be calculated. Litter values will be used where appropriate. Additional procedures and/or analyses may be performed, if appropriate. Type of Test3 I. Parametric A. Bartlett's Testc II. Nonparametrict A. Kruska(<l-7W5%allitsieTse) st Significant at p<0.001 Not Significant Significant at p<0.05 Not Significant Nonparametric Analysis of Variance Dunn's Test Significant at p<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 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 703 ARGUS 418-020 Protocol 418-020 Page 21 DATA ACQUISITION. VERIFICATION AND STORAGE: Data generated during the course of this study will be recorded either by hand or using the Prim ed Vivarium T ica em Argus peratu A re uto an m d ated R e la D a ta tive H Co um llection and idity M onito M rin a g nageme S y s te m natnSdytshteemH, the am ilto n tThheoPmreimIeVdOicSa. Vivarium Tem All data will be tabulated, summarized and/or statistically analyzed Argus peratu A re uto an m d ated R e la D a ta tive H Co um llection and idity M onito M rin a g nageme S y s te m ,n t System, M icrosoft the Exc e l using [part of Microsoft Office 97 (version SR-2)] and/or The SAS System (version 6.12). pReercsoorndnsewl iwllitbheinre2v1iedwaeyds abyftethregeSnteurdaytioDnir.ecAtollroaringdin/oarl arepcporrodpsriwatiell bmeasntaogreedmienntthe archives of the Testing Facility. All original data will be bound and indexed. A copy of tasrhetlloeprrsoaeerwdt,madaataftttteeharreiwawTlihslel.icsbhteintsigmuFpepatlchieielidtyStoaptothnneosoScrhpwaoirnlgl seboefrocuroponontnaecryteeeqdauretosatfd.teePrtemrremasieilnirnevgetdhoeftitsdhsiesupedorsaswifttiiolflinnbaeolf RECORDS TO BE MAINTAINED: Protocol and Amendments. TARenasinmtdSaolumAbizscatqatuinoiscnieti,oSVnc.heehdiculelesa.nd/or Reagent Receipt, Preparation and Use. Mating History. TGreenaetmrael nCto(mif mpreenstcsr.ibed by Staff Veterinarian). CBBloloindoiycdaWSl eOaimgbhspetlser.vCatoiollencstiaonnd, /PorroGceesnseirnagl AanpdpeSahraipnmcee.nt. GFeeesdtaCtioonnsLuemngptthio.n Values. GSLiprttoeesrrmsONbEesvcearrlouvpaasttiiyoonnOsb(.mseortviliatyti,oncos.ncentration and morphology). Organ Weights. SFHetiusetddoyloaMgnidacianWlteOantbeasrnecArevnaa(trliyoosonemss..and environmental records). 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, ATS Director of Research: Alan M. Hoberman, Ph.D., DABT Associate Director of Research and Study Director: Raymond G. York, Ph.D., DABT DDMDiiiarrreeencccatttgoooerrrroooofff fOSLAatpunbediomryaraatMitlooaOnrnyspaOeagrnpeademtiroCeanntoisotm:napsnVl:idaalnJCeocrhehiea:niArpFB..eaSrBrsbhaoaarnrrnpa,eeItJntr.,,sPBtMita.u.SSttt.ie.ornsaolnA, nBi.mA.al Care and Use CCoonmsmulittatenet,: VDeetenrainCa.ryLePbaoth, oVlo.Mgy.D: .W. Ray Brown, D.V.M., Ph.D., ACVP REPORTS: TuDphradefatStestuus.mdymSDtaairrtyeiscttaitcobarlelwasilnloapflryuosnveaisduedwipitlelednriooctdobimcepupupetderafro-treremsceoodfrdsoetnuddtdhyaeptsareomginraeteysrsaimctocdotahmteap.Sanpyonthseosr.e Afboelclofoiwnmainpligrze:ehdefnoslliovewidnrgafctofinnsaulltraetpioonrtwwiitlhl btheepSreppoanrseodr.onThcoemreppleotriot nwiollfinthcelusdteudthyeand will SEuxpmemrimareynatanldDCeosnigcnluasniodn.Method. AEGDpvaLaptPaleu,nCaPdtoiriomconetposloc:iafonTlFcaeigensudtSreRtAases,tsesSumoluctesmia.nmtte, adRryeApmaonerdtnsdIonmdfeiSvniudtpsupaaolnrTdtianDbgeleDvsiaaSttaiou(nmifsm,apaSprtiurzodinpygriDathitreee)cAatobnrod'sve QAU Statement. tAhnroiungtehrimwesaunminmg aorfythreepFo1rt gceonveerraintgionthweilplearlisood bfreomissiuneitdia.tioTnhiosfrteepsot rdtiwetillebxpeoisduernetical 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 CARE AND USE COMMITTEE STATEMENT. TInhsetitpurtoiocneadluArensimdaelsCcraibreedanind tUhissepCrootmocmoilttheaev.eAblel epnrorceevdieuwreesddbeyscthriebeTdesintinthgisFparcoiltiotyc'sol 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. Tests. Environmental Protection (1982). Agency, IWn aVsivhoinRgetopnr,o dDu.Cc t.ivNe aatinodnaMl uTteacghennicicaitly Information Service, U.S. Department of Commerce, Springfield, VA 22161. 2. Cnahlrtirsetxiaonn,eM(P.Sr.oc(1e9e8d4in).gsRoefpNroadlturectxivoenetoSxyicmitypoasnidumte,raNteowlogYyorekvaAlcuaadtieomnsy ooff Sciences, November 7, 1983), J. Clin. Psychiat. 45(9):7-10. 3. LICnaocn.n,gt,WroPlil.DmL.aint(ag1t9ion8n8t,h).Me AECmh0ab1rrl8ye8os7aR-0niv6de3Fr0eC. tra(l:DlCDaDetavebBlaoRspeRmapetr.notvaCildhTeadorlxebiscyitRAy irv(gTeuersrLaRatobelosoergaaytr)ocrhies, Laboratories, Inc.) 4. Institute of Laboratory Laboratory Animal Anim als. National RAecasoduermceysP(r1e9s9s6, )W. aGshuiidnegtofonr,thDe.CC. are and Use o f 5. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. S tatistical M ethods, 6th Edition, Iowa State University Press, Ames, pp. 240-241. 6. Sokal, B io m e trRy.,RW. a.Hn.dFRreoehlmf,aFn.Ja.n(d19C6o9.),. Bartlett's test of homogeneity San Francisco, pp. 370-371. of variances. 7. SMneethdoedcso,r,6Gth.WEd. iationnd,CIoowcharaSnta, tWe .UGn.iv(1e9rs6it7y).PrAensas,lyAsims eosf,Vpapr.ia2n5c8e-.27S5t.atistical 8. tDreuantnmeettn, tCs.wWit.h(1a9c5o5n).troAl. mJu. lAtipmleerc.oSmtapta. rAissosnocp.ro5c0e:1d0u9re6-f1o1r2c1o.mparing several 9. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biom etry, 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). N onparam etric S tatistics for the B ehavioral Sciences, McGraw-Hill, New York, pp. 96-104. Page 706 PROTOCOL APPROVAL: FOR THE TESTING FACILITY ARGUS 418-020 Protocol 418-020 Page 24 ADliarencMto.r HofoRbeersmeaanrc,hPh.D., DABT V ^. Rymohd G. York. ^hX)., tf)ABT ASstusdoyciDatiereDctiorerctor pf^Re^earch ____________ fbena C. Lebo, V.M.D. Chairperson, Institutional Animal Care and Use Committee FOR THE SPONSOR John Butenhoff, Ph.D., DABT, CIH Study Monitor Sponsor's Representative C 7 - s V l \/ ~ < -c Date A ~ 7 b ' i ' L Date 07Date & g - A ffi/ - 0# Date Page 707 ARGUS 418-020 ATTACHMENT 1 SCHEMATIC OF STUDY DESIGN AND STUDY SCHEDULE Page 708 ARGUS 418-020 ATTACHMENT 1 ProtocPoalg4e181-0o2f 03 TWO-GENERATION REPRODUCTION STUDY3 First Day of Test Substance Exposure P Gene1rationPremating PMGaeleneRraattison 10 weeks PFeGmeanleeraRtaiotsn 10 weeks Cohabitation6 LaPsESGtxuDepbnaosyestauroanrfetcieoT-ne'st 2 weeks PGreesstuamtioend DNealtivueraryl I Lactation 3 weeks 3 weeks F1 GRenaetsration F1 GeRnaetsration Postpartum 3 weeks PWoDseatapyan2rint2ugm' Postweaning I Cohabitation61 PGreesstuamtioend LFa1sEStGxuDpbeaosnysteauronrafectiTeo-ens6t Lactation 10 weeks 2 weeks 3 weeks F2 Generation Rats 3 weeks Postpartum 3 weeks PoDstapyar2t2um0 Dosage Period a. For additional details see "Tests, Analyses and Measurements" section of the b. pMraolteocroalt.s sacrificed after determination of sufficient number of pregnancies; c. sPpgeermneeravtaiolunafteiomn.ale rats and F1 generation rats not selected for continuation on study sacrificed. d. F1 generation dams and F2 generation litters sacrificed. Page 709 ARGUS 418-020 ATTACHMENT 1 07 NOV 00 SCHEDULEa.b.c ProtocPoalg4e182-o0f203 PBeGgeinnseration Animal Receipt - Acclimation 13 NOV 00 21 JAN 01 PM - 04 FEB 01 AM 0242 JFAENB 0011 12 FEB 01 01 MAR 01 16 FEB 01 01 MAR 01 12 FEB 01 SPtaGret noef rTaetisotnSRuabtsstance Exposure - PleaGset n7e0radtaioyns oCfotheasbt istautbiosntaPnceerioedxp(Aosftuerrea).t FLairsstt PPoossssiibbllee DDaayy 00 ooff PPrreessuummeedd GGeessttaattiioonn.. L(F(DDairaassyytt PP221o5ossoossffiibbpplleerreeDDssuueemmlliivveeeeddrryygg--eeFssFtt11aattGGiiooeennnn))..eerraattiioonn Litters Litters LFFFaieerssmmtt aaPPlleeoossRRssaaiibbttlleeSSaaDDccaarriiyyffiicc22ee55.. of of Presumed Presumed Gestation Gestation (SEcahrelideustlepdosSsaibcrleificdeat-e)P. Generation Male Rats 05 MAR 01 22 MAR 01 F(Sirasct rPifiocsesiobflePDgaeyn-e2r2atPioonstdpaamrtusmanWd eaning oLF1abssgteerPvnoaestrisaoitnbio)le.n pups not selected for continued Day-22 Postpartum Weaning. 06 MAR 01 F1 Generation Postweaning Observations Begin (Details of tests cited in protocol). ab.. c. fATTwTToeo(Podxffhhhhdraraotteeelrdrehatyotrheenaecsiduen1ncstntaga-uldtitaoolFyiht,idouifcf1nooetynomthlnuaafwaipiA)tstncbni1ootogtiiihdtnsa0urrniettaittlhisutFtidnotohopidc2nopnieebsyytnr)rhgeooiSdm(oeeafdtEcetodnntaaaoPsPhcedntywnioeeAegrddaalibsn),lasilu.lttesalitirtobccuhdtstTeetniehdeudehxOdseybeddtdi.sepspewdaAaneeotasyiecsdlqrsalyacsreoutmrmotnetdfeeihnraseiqbndnetgstuoitaierdmniStalPdrahigenegtdyruaocwneatadoilnctsysuipyledlGtdpo0dhdbDecurfeeueo(iiitsdtrardhxepeeidageiedrtcmseyhonlitsFnioacaao0ri1edecrgtfteeocsdnstgdghlofuiayogeeerlrtdadfnn4eneTacitse2desnhyterragteawdadshtl1teyttaieeiUoio.osypeFn.pncnokSa)1rr;ssc.oirib.tpnaistEpleoiutotasnIydccsfr.vohtatrppiulern.raaomsdernuvtsmudl(ittodumaseuadynysystlay1l Page 710 ARGUS 418-020 ATTACHMENT 1 Protocol 418-020 Page 3 of 3 31 JUL 01 Interim Status Report - Draft Mail Date. Estimated Dates3 06 MAR 01 SF1taGrt eonfeTreastitoSnuRbasttsance Exposure - 28 MAY 01 PM -18 JUN 01 AM lFe1asGte7n0edraatyiosnoCf toehsat bsiutabtsiotannPceereioxdpo(Asuftreer).at 2198 MJUANY 0011 First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation. 19 JUN 01 13 JUL 01 First Possible Delivery - F2 Generation Litters (LDaasyt P21ososfibplereDsuemliveedryg-esFt2atGioenn).eration Litters (Day 25 of presumed gestation). 23 JUN 01 13 JUL 01 First Possible Day 25 of Presumed Gestation FLaesmtaPleosRsaibtleSaDcariyfic2e5. of Presumed Gestation Female Rat Sacrifice. 26 JUN 01 F1 Generation Male Rats Sacrificed after Day 21 of Cohabitation Period - Earliest Approximate Date. 10 JUL 01 03 AUG 01 F(Fir1stgPenoessraibtiloenDdaaym2s2 aPnodstFp2argtuemneration litters sLaacsrtifPicoesds)i.ble Day 22 Postpartum. 12 DEC 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--OCT--2000 09 :14 3M Fax Message ARGUS 418-020 Page 2/17 MATERIAL SAFETY DATA SHEET 3M 3M Center 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 .: 98-0211-0008-0 00-51135-09138-8 98-0211-0891-9 98-0211-5489-7 00-51135-02941-1 9B-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 PERFLU0R00CTAN0ATE............ AMMONIUM PERFLU0R0HEXAN0ATE............ AMMONIUM PERFLU0R0HEPTAN0ATE........... 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:... PH:................ 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. Mes s a g e ARGUS 418-020 Page 3/17 MSDS: 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: Water, Carbon dioxide, Dry chemical, Foam SPECIAL FIRE FIGHTING PROCEDURES: Near 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 714 31--OCT--2000 09:14 3M Fax Message ARGUS 418-020 Fage 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 Water 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 & Exempt Solvents: N/A. Since regulations vary, consult applicable regulations or authorities before disposal. U.S. EPA Hazardous Waste 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 715 31-OCT-2000 09 :14 3M Fax Message ARGUS 418-020 Page 5/17 MSDS: FC-143 FLUOHAD 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: Xnunediately 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. Wear 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 3M fa x message ARGUS 418-020 fage o// 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. Wash exposed areas thoroughly with soap and water. Wash hands after handling and before eating. RECOMMENDED STO RAG E: 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.) EXPOSURE LIMITS INGREDIENT VALUE UNIT TYPE AUTH SKIN* AMMONIUM PERFLUOROOCTANOATE........ AMMONIUM PERFLU0R0HEXAN0ATE........ AMMONIUM PERFLUOROHEPTANOATE....... HEPTADECAFLU0R0N0NAN0IC 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 3M Fax Bassaga ARGUS 418-020 rage / / j . j MSDS: FC-143 FLUORAD 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 PERFLU0R00CTAN0ATE (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--O C T -- 2000 0 9 z14 3M Bax Message ARGUS 418-020 vage tt/i/ MSDS: FC-143 FLUOHAD 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 3U Fax Message MSDS: FC-143 FLUORAD Brand Fluorochemical Surfactant. August 25, 2000 ARGUS 418-020 ra g e y /x / 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-OCZT-2000 09 :14 3M Fax Message ARGUS 418-020 F age lu/iv MATERIAL SAFETY DATA SHEET 3M 3M Center 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 FLU0RAD 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-0002-0378-4 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 PERFLU0R00CTAN0ATE............ AMMONIUM PERFLUOROHEXANOATE............ 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:... PH:................ VISCOSITY:......... N/A N/A N/A N/A apprec. 0.4 - 0.5 Water=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 vage li/i/ MSDS: 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 3M Fax Message ARGUS 418-020 P a g e 12/1'/ USDS: FC-143 FLUOEAD 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 Water 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. V0C Less H20 & Exempt Solvents: N/A. Since regulations vary, consult applicable regulations or authorities before disposal. U.S. EFA Hazardous Waste 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 3M Tax M e s s a g e ARGUS 418-020 Tage 13/iy 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: 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. Wear vented goggles. SKIN PROTECTION: Avoid skin contact. Wear 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 724 31--OC T --2000 09 :14 3M Fax Message ARGUS 418-020 Page 14/1 M5DS: 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 POHDER FREE FLOHING.** 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 THA 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 Pax Message ARGUS 418-020 Page 25/1 MSDS: FC-143 FLUORAD 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 PERFLU0R00CTAN0ATE (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 Fax message ARGUS 418-020 Pa g e le/17 MSDS: 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 Page 727 31--OCT--2000 09:14 3M Fax Message MSDS: FC-143 FLUORAD Brand Fluorochemical Surfactant August 25s 2000 ARGUS 418-020 vage 1 //1 / 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 728 ARGUS 418-020 ATTACHMENT 3 TEST SUBSTANCE PREPARATION PROCEDURE Page 729 ATTACHMENT 4 ARGUS 418-020 Protocol 418-020 Version: 418-020(04 NOV 001 TEST SUBSTANCE PREPARATION PROCEDURE Page 1 of 2 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 APFO 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 asnpnuedmcbsifteyorr,tahcgeoenpccrooetnnodtcriaotitolionnnus,.mdboesra,gteesltesvuebl,sptarenpcaeraidtieonntifdicaateti,oenx, pAirragtuiosnbadtacthe 2. __S__o__lutioODnnsaciewlyipllrbioer tporedpoasrXiendg: Weekly ____For _BydaSypsoonfsuosre 3. Solutions will be administered ata final dosage volume of _5_ mL/kg/day. 4. __SXX__XaXfety:GDTWHFyuulaoovlsllvfr-et-keF-FkMsaian,scicslueeaetneRRcRivfhoeeeeerssssmmppp(ii/wriirlrcaaaahatbttooelornrfcru/o(Pfmuaoostres,insigthgoivooletugohtgdeiPoleranbesnuspdolskrreuumsrpseaaeafrHteaaetotryihiooaagdnl)llafa-sfnasdceesdoraesnsindpgifr)aactoesr hwieheldn using the bulk TA/S only 5. Dosage solutions adjusted for % Activity/Purity or Correction Factor ______YeAsctivity _____X_ %NoPu(Critaylculatio_n_s_baCsoedrreocntio1n00F%a)ctor 6. Sampling requirements: Cited in protocol. 7. Storage: Cited in protocol. Page 730 ATTACHMENT 4 ARGUS 418-020 Protocol 418-020 Version: 418-020(04 NOV 00) TEST SUBSTANCE PREPARATION PROCEDURE Page 2 ot 2 C. Dosage Solution Preparation: 1. Weigh out the required amount of the test substance in an appropriately sized, labeled container (see PREPARATION CALCULATIONS). 2. Add approximately 80% of the required amount of vehicle to the container aCnAdLCmUixLwAiTthIOaNsSti)r.bar and magnetic stir plate (see PREPARATION 3. Oarennqcauepirepthdroevptoreilausttmesleyubs(ssizetaeendPcgeRraEisdPucAoaRtmeAdpTlecIOyteliNlnydCdeiArs.sLoCQlvUSeLdaA,dTtrwIaOintNhsSfve)er.hthicelestooluthtioen to 4. Stopper the graduated cylinder or cover with parafilm and mix by inversion tcsoeovnaetnardainldetuirmrwineigtshattohliqeeunsosttuitrirnbegap,r.rdooPpselaargcmee ioaxnidnmga.inmRisategrtanuteriontincthasentirsdop/olluarttsieoanamntpodlintahgge.italatbeepleridor 5. Repeat steps (1) through (4) for each concentration. Written By: 'h ia J L U . U ^ v Page 731 ARGUS 418-020 ATTACHMENT 4 NECROPSY, ORGAN WEIGHTS AND HISTOPATHOLOGICAL EVALUATION Page 732 ATTACHMENT 4 ARGUS 418-020 ProtocPoalg4e181-0o2f 02 NECROPSY, ORGAN WEIGHTS AND HISTOPATHOLOGICAL EVALUATION Organ Weights 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 thymus target organs (if identified by amendment) liver adrenal glands pituitary uterus with oviducts and cervix epididymides 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 thymus Tissue Retention The following tissues will be collected from all P and F1 generation parental male and female rats at necropsy and retained in neutral buffered 10% formalin for possible histological evaluation: pituitary target organs (if identified by amendment) adrenal glands gross lesions (including tissue masses) Female Rats vagina uterus with oviducts, cervix and ovaries Male Rats testis (right) seminal vesicles (with coagulating gland) epididymis (right) prostate Note: Testes will be fixed in Bouin's solution for 48 to 96 hours before being retained in neutral buffered 10% formalin. 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% formalin 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 intermediate 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 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 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 primordial and growing follicles as well as the large corpora lutea of lactation. Histopathological examination should detect qualitative depletion of the primordial follicle population. A quantitative evaluation of primordial follicles should be conducted for F1 female 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 primordial 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 intermediate 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, motility 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 intermediate 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.November 7, 2000 Page 734 GPrimedo. ARGUS 418-020 Aigus 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 1-18 December 2000 1. Body 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) F1generation 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 F1generation 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 418-020 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 inteimediate 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 IDENT 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 Page 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 Puns 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 F1 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 418-020 Amendment 1 Page 4 Z A ip fa j c / HJena 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 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: 1February 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. Theresa H. Woodard, D.V.M. Date John Butenhoff, Ph.D., DABT, CIH Date Chairperson, Institutional Animal Care Study Monitor and Sponsor's Representative and Use Committee 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 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 3-20 July 2001 1. Gross Necropsy and Histopathology (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. Alan M. Hoberman. Ph.D., DABT Director of Research ^ Date Valerie A. Sharper, M.S. Director of Study Management for Raymond G. York, Ph.D., DABT Associate Director of Research and Study Director y jis f I Date Theresa H. Woodard, D.V.M. Date John Butenhoff, Ph.D., DABT, CIH Date Chairperson. Institutional Animal Care Study Monitor and Use Committee Any revisions to this finalized amendment must be made by subsequent amendment. "Page 740 ARGUS 418-020 TT9Hd0doe5erpsfSohhhccoemne(e2hP:1yA(5D2)1r41i54v9)e3044-B48435ld-8g87.7A10 A R G U S RESEARCH C hales R iva Laboratories Discovery a id Developm ent Services PROTOCOL 418-020 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). Theresa H. Woodard, D.V.M. Date John Butenhoff, Ph.D., DABT, CIH Date Chairperson, Institutional Animal Care Study Monitor and Use Committee 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 FACILITY 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) Study3 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 DL 11 13837,13850, 13853, 13858 III 3 DL 8 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 02 01 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 III 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 JUN 01 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 JUN 01 12 JUN 01 19 JUN 01 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 02 01 02 01 03 02 01 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 JUN01 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 -1 +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 III 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 Dosage Day of Group (mg/kg/day) Study Date I 0 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 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 10. Observations for pups were not recorded for the following litters. Generation FI Dosage Group III 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. 11. 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. 12. Predosage observations, dosage volumes and postdosage observations were not recorded for the following rats. Generation FI Dosage Group III 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. 13. 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. Page 750 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 18. 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. 19. 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 JUL 01 25 JUN 01 07 JUL 01 21 JUN 01 23 JUN 01 25 JUN 01 28 JUN 01 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. 20. 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 DL4 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. 21. 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. Page 752 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 III 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 JUL 01 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 1378a 1458 1446a 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 Phone: (814) 231-8032 State College, PA 16801 Fax: (814) 231-1253 or (814) 231-1580 Purity' 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 1 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 (NM R) Total % Impurity (LC/M S) Total % Impurity (GC/M S) Residual Solvents (TGA) Purity by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nitrite 6. Phosphate 7. Sulfate Organic A cids-1(IC) 1. TFA 2. PFPA 3. HFBA 4. NFPA Elemental A nalysis3: 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine Ammonium Analysis3 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 w t./w t.% 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 wt./wt.% 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 wt./wt.% 6. <0.006 wt./wt.% 7. <0.040 wt./wt.% 1. <0.1 wt./wt.% 2. <0.1 wt./wt.% 3. <0.1 wt./wt.% 4. <0.25 wt./wt.% 1. 18.9w t./w t.% 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 1 o f 2 ARGUS 418-020 Centre Analytical Laboratories. Inc. 3046 Research Drive 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: < -10 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 gF isO rt^iH ^ (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 - c6Identity C7 homologue/Fu 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: favid S. Bell Date Scientist, Cenfre Analv^cgfLaboratories Reviewed By: ft) '/f/o r /J o h n Flaherty Date Laboratory Manager, Centre Analytical Laboratories COA023033-37.doc Page 2 o f 2 Page 757 ARGUS 418-020 APPENDIX I ANALYTICAL REPORT Page 758 3M Medical Department Study: T-6889.6 -- -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 3M Medical Department Study: T-6889.6 LIMSAnalytical Report: FA CT TOX-164 00-2738 Study Title Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Periluorooctanoate (APFO/PFOA) in Rats q ^^ -Q 2-D 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 Sera Extractions 3M Environmental Laboratory Building 2-3E-09,935 Bush Avenue St. Paul, MN 55106 Pace Analytical Services, Inc.--Tier2 Facility 1700 Elm Street S E , Suite 100 Minneapolis, MN 55414 Project identification 3M Medical Department Study: T-6889.6 Argus In-Life Study: 418-020 Analytical Report: F A C T TO X-164 3M LIMS No. E00-2783 Total Number of Pages 110 /3A4 F n v irn n m a n ta l I a h n ra tn rv 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 Report: FACT TOX-164 LIMS E00-2738 Analytical Report: FA CT TOX-164 LIMS E00-2738 This page has been reserved for specific country requirements. O l C m. 4 3M Environmental Laboratory Page 760 D m na O Page 2 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Ana1ytica.ReAp S t W M 6 4 LIM S 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 Fluorochemical in Rat Sera Samples Study Identification Numbers: T-6889.6, FACT TOX-164, LIMS EOO-2738 TAhgiesnsctyud(EyPwAa)sGcooondduLcatebdoriantocroymPprlaiacnticcee w(GitLhPU)nSitteadndSatardtess4E0nCvFirRonPmaernt t7a9l2P,rwotitehcttihoen exceptions in the bulleted list below. Exceptions to GLP compliance: There were two study directors in this study. This study was designed as two tsheepagreanteersattuiodnieasn. dTshheipinm-elifnet pohf aspseec(iAmregnuss.#T41h8e-0a2n0a)lywticaasl csotundsyid(e3rMedFtoACenTd-TaCtX164) was considered to start at the receipt of these specimens for analysis. This sretusduylt.edHionwheavveinr,gstiwncoestehpeatreactehnsitcuadlypdeirrfeocrmtoarsn,coenoeffeoarcehacphhapsheasweasofetnhteireslayme 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 D irector Date -------------- ----------------- David Sanders, Ph.D., Sponsor Representative M o -l * Date y,* A. C Lua________ _____________ Qijpjika Lisa Clemen, Principal Analytical Investigator Date William Reagen, Ph.D., Laboratory Management Date 3M Environmental Laboratory 3M Environmental 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 EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 GLP 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 EOO-2738 TdUihrneiistc(tsQoturAdaUyn)dhaalsasbibnoedraeicntaotrienydsmpineacntthaeegdefobmylleotnhwtei.n3gMtaEblnev.iroTnhme efinndtainl gLsabwoeraretorreypQoruteadlitytoAtshseusratundcye Inspection Dates Phase Date Reported to Management Study Director 5/30/01 Protocol 05/30/01 05/30/01 6/27/01 Analysis 06/27/01 06/27/01 6/26/01 091/205/0/011/0-019-1/208/0/021/0a1nd 11/07/01-11/08/01 Sample Dilutions Data Draft report 06/26/01 10/03/01 11/09/01 06/26/01 I 10/03/01 ! 11/09/01 QAU Representative i/ n lo z . Date 3M Environmanta/ Laboratorv 3M Environmental Laboratory Page 762 Paae 4 Page 4 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TQX-164 LIMS EOO-2738 Analytical Report: LFIAMCSTETOOOX-2-176348 Table of Contents 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 SamSDeporlseaeAPCrneoapnlyafisrrmaetsaio.t.ni.o..n.a..n.a.d.n..dA...nS..a.t.al.y.b.s.i.li.is.t.y......A.....n.....a....l..y....s....e.....s.....................................................................................................................................................................................................................................111111 MethPordepSaurmatmoryarMieest.h..o...d.....................................................................................................................................................................................................................1122 AAnnaallyyttiiccaall MEqeuthipomd.e..n..t................................................................................................................................................................................................................1132 Deviations/Amendments..................................................................................................... . 14 Data Quality Objectives and Data Integrity................................................................................ 14 Data Summary, Analyses, and Results.......................................................................................14 SSSuutammtemmmaaerrnyytooofffSQDauamatalpityQleCuRoaenlisttryuo.l.lt.s.A....n....a.....l.y....s....e....s......R......e.....s...u.....l.t..s....................................................................................................................................................................................................................111665 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 fEroTmS-S8-e4r.u1m, EfoxtrraAcntiaolnysoisf PUesrinflugoHroPoLcCta-nEelescutrlfoosnpartaeyo/Mr aOstsheSrpFeicutororomcehterym,ic(1a4l Cpoamgepso)u..n..d..s.....37 ETS-8-4.2, Extraction of Fiuorochemical 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 SEeTrSu-m8-5E.x2t,raAcntsalyUssisinogfHPPoLtaCs-sEiulemctProesrpflruaoyr/oMoacstasnSepseuclftoronmateetoryr,O(1t1hepraFglueosr)o..c..h..e..m....i.c..a..ls....in... 76 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 [' Department Study: T-6889.6 ------ ;:r -- - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 3M Medical Department Study: T-6889.6 Analytical Report: FA CT TOX-164 LIMS EOO-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. 1S4pNeocvimemenbserr,e2ce0i0v0ed...f.r.o..m.....A...r.g..u..s...R...e..s..e..a...r.c..h...L..a..b...o..r.a..t.o..r.y...S...t.u..d..y...(..4..1..8..-.0..2...0..)..o..n.............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-TO X-16 4 ................................................................................................................ 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 FACTTOX-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. TO X 164 Data Summary of PFOA Concentration--Rat Serum (pg/mL)..............89 Pnvirnnm antal / ahnratnrv 3M Environmental Laboratory Page 764 Pano A Page 6 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Study Personnel and Contributors -- - -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-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 Chemistry Laboratories 3SMeraEAnvniraolynsmeesntal Laboratory (3M Lab) Lisa Clemen, Principal Analytical Investigator Sponsor 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 ST. Paul, MN 55144 David Sanders, Ph.D., Sponsor R e p re s e n ta tiv e PSaecrae EAxntaralycttiicoanlsServices, Inc.--Tier2 Facility 3M Lab Contributing Personnel Rhonda Dick* Kristen J. Hansen, Ph.D. Marlene M. Heying* Harold O. Johnson ' Contract lab professional 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 ll C M iriiv iiim n n fe / I o K /iro fn n / 3M Environmental Laboratory Page 765 Pano 7 Page 7 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 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 2p0re0s1e.nted in this report. The analytical portion of this study was initiated on 07 June, Specimen Receipt and Maintenance The 3M Environmental Laboratory received dosage solution/suspension specimens collected at the end of the in-life study #418-020 on 14 November, 2000, 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 wseerrae/liimvemr sepdeiactiemlyetnrasnwsefererreredcteoivsetodrafrgoezeant i-n20goCodc1o0ndCit.ioSnpoencidmryenicset.haAtllwsepreeceimxterancsted at Pace Tier2 were shipped frozen on dry ice. Table 1. Specimens received from Argus Research Laboratory Study (418-020) on 14 November, 2000 Specimens Dosage Solution/Suspension H m epolnt Day 0 Stability Day 10 Stability Concentration Total# 5 5 5 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 EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 Table 2. Specimens received from Argus Research Laboratory Study (418-020) on 18 April, 2001 Specimens Gender Group Total* Serum and Liver Female I 26 It 26 III 29 IV 29 V 28 Male I 30 II 30 III 30 IV 30 V 29 Table 3. Specimens received from Argus Research Laboratory Study (418-020) on 13 July, 2001 Specimens Dosage Soiution/Suspension Timepoint | Total # Concentration I 5 Table 4. Specimens received from Argus Research Laboratory Study (418-020) on 09 August, 2001 Specimens Serum and Liver Gender Female Male # Group I II III IV V I II III IV V Total# 28 28 27/28 28 29 30 29 30 30 29 QM Pnvim nm antal I ahnratnrv 3M Environmental Laboratory Page 767 Pace 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 GEnLvPirorenqmueirenmtaleLnatsb.oratory will be stored and maintained at the laboratory according to Chemical Characterization of the Reference Substance Ammonium periluorooctanoate CAS Number: 3825-26-1 Chemical Formula: C7F15COO'NH4+ Molecular Weight: 430.9 Cpehreflmuoicroaol cchtaanroaactteeruizsaetidonininthfoisrmstautdioynisopnrtehseenretefedreinnctaebsuulabrsftoarnmcebaemlowm.onium Table 5. Characterization of the Analytical Reference Substance in Study FACT TOX-164 Location 3M Lab Substance PFOA TCR-99030-030 (STStHuarPnrodFgaOardSte) TCR0-0505017- Source NA SynQuest Laboratory Expiration Date 10/31/2006 NA Storage Conditions -20C 10C -20C 10C Chemical Lot Number 332 Q75-91 Physical Description Purity White powder 95.0% * White powder NA NA--Not available *S e e Certificate of Analysis from Centre Analytical Laboratories in A pp en d G . 3M Environmental Laboratorv 3M Environmental Laboratory Page 768 Paae 10 Page 10 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 Sample Preparation and Analysis -- -- - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analytical Report: FACT TOX-164 LIMS E00-2738 Dose Confirmation and Stability A nalyses 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, t2ph7reosNceeodvsuearmme,bpEelerTs, S2w-08it0h-04,M.1a.ilnlid-FQoornwoeantreeer-d,eotxhsteeransceotioxlutnrtiaopcnetirncfoogrnmthceeendstraoamntiop1nl7essJaaumnsuipnalgery,t,ha2em0i0oa1ntrbipxyasidrpiliuketinwgas 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 HETPSL-C8--E5.S1/MwSe/rMe Sus. eTdhfeorindsotrsuemseonlutatiol npaarnaamlyesteerss. aDnedtaainleadlydticeaslccriopntiodnitisonosf tdheesmcreibtheoddisn used are located in Appendix C. Sera A nalyses AansdpGerrothuepsVtuwdeyrperoatnoaclyozl,eodnilny tsheisrupmhassaemsptluedsyfr(oSmeethTeabPleG6enfoerramtioorneGinrfoourmp aI,tGionro)u. pAInV, 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-ierf-butyl ether (MtBE). Sample extracts were analyzed using highEpeSrMfoSrmMaSn)cien tlihqeuimd cuhltirpolme aretoagcrtaiopnhmy-oedleectvroesrspurasya/tnanedxetrmactmedasssersapeccutrrvoem. ePtrFyO(HAPleLvCe-ls were quantitated by external calibration. Table 6. P Generation Rat Samples Analyzed in Study FACT-TOX-164 Dosage Group Group 1 Group IV Group V Gender Male Female Male Female Male Female T o ta l# 3 3 10 10 10 10 3M Environmental Laboratorv 3M Environmental Laboratory Page 769 Pane 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 E00-2738 Analytical Report: FACT TOX-164 UMS E00-2738 Method Summaries 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 ental Laboratory Preparatory Method ETS-8-4.1, "Extraction of Potassium Perfluorooctanesulfonate or Other SFipueocrotrcohmeemtriyc"al Compounds from Serum for Analysis using HPLC-Electrospray/Mass ETS-8-4.2, "Extraction of Fiuorochemical Compounds from Serum for Analysis using HPLC-Electrospray/Mass Spectrometry" Analytical samples were extracted using an ion-pairing extraction procedure. An ionppaarirtiintiognreedaginetnot mwaesthaydl-dfee/dt-btoutayl-laebthoerar t(oMrytBsEa)m. pTleheanMdtBthEepahnaaslyetewaiosnrpeamirowveads and put irnetcooansntiittruotegdenine1va.0pmorLatoofrmunettihl adnryo.l aEnadchfilteexrteradcutesdinlgabao3ramtoLrypslaasmticplseywrinagse attached to a 0.2 pm nylon filter into glass autoviais. 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" AsFainonnaraglellyyexssaipesmrs,imwpwlaaeesr,ryefmrioapongelemrcfcoheuranmlarteaer dcdiotefnbury4rist1mhti3eco,ronstfioetoalperiprcnoatgedrdtuoiccnaueeslaiootrhrnfeimu1poo6rrr9iomec(apChrre3yoFmdi7ou*icn)c.atflToiouhrnsePsinFcsghOeaHAlerPac(LCcteCt7edF/rEfi1sr5SotCim/cMOioOSan/*M) S. 169 was monitored for quantitative analysis. "ihA ^nt/irrtnmonfal I ahnratnrv 3M Environm ental Laboratory Page 770 P an a 19 Page 12 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 E00-2738 Analytical Equipment The following is representative of the settings used during the analytical phase of this study. Liquid Chrom atograph: Hewlett-Packard9 Series 1100 Liquid Chromatograph system Analytical column: Keystone BetasilTM C182x50 mm (5 pm) Column temperature: 30C Mobile phase components: CCoommppoonneenntt AB:: 2mmeMthaanmolmonium acetate SIFnloojelwvcetirnoatnteGv:ro3al0ud0miepneLt::/1m80.0inpmL inutes Time (m0i.n0utes) 1%0B% 1.0 10% 5.5 95% 78..50 9150%% Maas Spectrom eter: Micromass API/Mass Spectrometer Quattro IITMTriple Quadrupole system Software: Mass LynxTM 3.4 MCCooonldliees:ioVEnolleGtacagtrseo:sEp1nr5ea-ry6g0yN:Ve2g0a-t5iv0e eV Source Block Temperature: 150C 10C AEnleacltyrsoidseT:yZp-es:pMrauyltiple Reaction Monitoring (MRM) Table 7. Target Ions M onitored in 3M Laboratory Analyses Target Analyte Primary Ion (amu) Product Ion (amu) PFOA 413.0 169.0 THPFOS 427.0 80.0 3M Environmental Laboratory 3M Environmental Laboratory Page 111 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: LFIAMCSTET0O0X-2-176348 D eviations/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: a Linearity: The coefficient of determination (r2) equal to or greater than 0.990 using 1/x weighting. tLhiemcitasliborfaQtiounancutirtvaeti,odnef(iLnOedQa):sTthhee lLoOwQesitssetaqnudaal rtdo tthhaetloiswbeosttha2cctiempetasbtlheesmtaantdriaxrd in 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. cDhermomoantsotgraratipohnicorfeStepnetiocnifitcimitye: PFOA identification will be (approximately 7 minutes), substantiated by 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 tEhneveirxocnempetinontasl Lnoatbeodraintotrhyisprroetpoocrot.l for FACT TOX-164 (see Appendix B) were met with AM Fnvimnm&ntal / ahnm tnrv 3M Environm ental 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 EOO-2738 Analytical Report: FA CT TOX-164 LIMS EOO-2738 Summary offQ uality Control A nalyses R esults Linearity: The coefficient of determination (r*) 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 tmhaotstoaf tphperoepxrtiraatcetitoonthbeladnaktsa.weLroewdceuarcvteivaptoeidnttsowdiitshqpueaalikfyaaredaastalersasngtheatnhatwt omtaimy ehsave been significantly affected by background levels of the analyte. Occasionally, a single mid-range curve point that was an obvious outlier may have been deactivated. Quantitation of each analyte was based on the response of one specific product ion AusnianlgyttihcaelmMueltthipoledsr)e.sponse-monitoring mode of the instrument (see Appendix C, Lim its of Q uantitation (LOQ): The LOQ is equal to the lowest acceptable standard in tisheatclaelaibsrtattwioontcimurevseth(deeafinneadlytaespaeasktaanrdeaarddewtiethcitned3in0%theoef xthtreacthtieoonrebtliacnakl sv,al(usee)e, and 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 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%. Mssptaeuamrdftorypir,xlmebSseepdc(raiakputerssisoee:rrttuhAomeltthh)e;oextutwsrgatohacrmtmet odaaftrmtsrixiaxasmtsrpippxikilkeceeuestrexvwstertaesscrwewtioeennrroee/tappanreaeqrlpfuyoasarrimlseitydetodcino.dnetThttreheorelmscfaiiornmsmetepteemoxsntarteatwrncixattisooanfsththise 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 Report: FACT TOX-164 LIMS E00-2738 Analytical Report: FACT TOX-164 LIMS E00-2738 Table 9. M atrix Spike Recoveries in the Analyses of Rat Sera Extracts Concentration RUenceoxvteraryctveedrsCuusrvaen ExRtreaccotveedryMvaetrrsixuCsuarnve ASPnaraimolyrpsteloes AfAtenraSlyasmesple 25 ng/mL 500 ng/mL 50 ng/mL 1500 ng/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 wfdaiedilurenreod.tilvuTatheryedms1u:o5rrr0eoogtharat1en:1r0e50s0p0%osnhfsrooewmoefdtheseaucmrhroeagananatelwytiditcheaivnliareutainocnhwsaalsonwavleeyrtriifctiheaadl nrtuo5n0d.%eEt.exrtSmrainicnctesetwthhhaeitcshiet were consistently low, these outliers will not affect the outcome of this study. Statem ent of Data Quality It is not possible to verify true recovery of endogenous analyte from tissues without radiolabeled 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. Sum m ary of Sam ple R esults PFOA results (those obtained using lot # 332) have been corrected for purity of the analytical reference material. Dose C onfirm ation and S tability Analyses: PFOA 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. % Samples from C ontrol Anim als: Low levels of PFOA were detected in the male sera of the control animals. % Samples from Dosed Anim als: In general, PFOA levels found in female sera of the treesmt aainniemdatlhseinscarmeaesebdetwfroemenddoosseeggrroouupp44toangdro5u.pS5i.gnPifFicOaAntldeivffeelrsefnocuensdbinetmweaelensera male and female PFOA levels were observed in these data. Detailed sample data tables are presented in Appendices D and E. 3M Environmental Laboratorv 3M Environmental Laboratory Page 774 Pane 1fi Page 16 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 E00-2738 Statistical Methods and Calculations Statistical methods were limited to the calculation of means and standard deviations. See TAOppXe-n16d4ix. F for example calculations used to generate the serum sample data in FACT Statement of Conclusion sUenrdaeorfthaell craotnsdditoiosnesd owfitthhethperetessetnstusbtusdtaiensc,ethdeurfilnugortohcehienm-liifceapl hPaFsOeAofwtahse osbtusdeyr.ved in the References None Fru/irnnm antal I ahnratnrv 3M Environmental Laboratory Page 775 Paria 17 Page 17 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ~ -".***-- -- -- - ARGUS 418-020 Analytical Report: FACT TOX-164 LIM S EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 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 Conditions Chemical Lot # Physical Description Sigma-Aldrich 02/14/06 Frozen -20C 019H89291 Rat Serum Table 11. Characterization of Test Substance in Study FACT-TOX164 Chemical Name Source Expiration Date Storage Conditions C hem ical L o t # Physical Description Purity Test Substance PerAfAlPumoFmrOooo/PncFtiuaOmnAoate TCR-99030-030 NA 10/31/2006 -20C10C 332 White powder 95.0%* N A -- N o t available ` S e e the Certificate of Analysis from Centre Analytical Laboratories in App en dix G . 3M Environmental Laboratory 3M Environmental Laboratory Page 776 Page 18 Page 18 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 UMS E00-2738 Appendix B: Protocol, Amendments, and Deviation(s) UKAFm/imnmontal I ahnmtnrv 3M Environmental Laboratory Page 111 Paae 19 Page 19 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Protocol FACT-TOX-164 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. Paul, MN 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 LIM S EOO-2738 3M Environmental Laboratory 3M Environmental Laboratory Page 778 Page 1 of io Page 20 3M Medical Department Study: T-6889.6 --r ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOXL-1I6M4S E00-2738 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 Page 2 of it , . /O, U r in i 1/M JnT Page 21 3M Medical Department Study: T-6889.6 Analytical ^ e p o r t ^ 164 Protocol FACT-TOXL-I1M64S EOO-2738 1. S tudy Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats .2 P u r p o se The analytical phase of this study is designed to evaluate levels of PFOA in sera specimens of FO generation 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. R e g u l a t o r y C ompliance This study will be conducted in accordance the United States Environmental Protection Agency Good Laboratory Practice Standards: Final Rule, 40 CFR Part 160/Part 792. 4. Q uality A s s u r a n c e 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. FACT-TOX-164Reference S u bstan ce Fo r Ammonium Perfluorooctanoate (APFO/PFOA), C7F|sCOO'NH4+, CAS 3825-26-1 The target analyte is perfluorooctanoate (PFOA), C7F15COO'. .6 Te s t S u b st a n c e Ammonium Perfluorooctanoate (APFO/PFOA), C7Fi5COO`NEL+, CAS 3825-26-1 7 . Te s t S yste m 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 Environmntal Laboratory 3M Environmental Laboratory Page 780 Page 3 of 0lo^ Page 22 3M Medical Department Study: T-6889.6 T 7 T , ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOXL' 1IM64S E00-2738 Number of Specimens per Dosage group and Dosage Levels Dosage C o n cen tratio n Dosage Group Num ber o f Rats per Sex (m g/kg/day) (m g/m L) 1 30 0 0 II 30 1 0.2 III 30 3 0.6 IV 30 10 2 v 30 30 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. Specimen 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 methylierr-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 cm3 plastic syringe attached to a 0.2 pm nylon filter into glass autovials. 10. Analytical Methods ETS-8-5, "Analysis of Potassium Perfhiorooctanesulfonate or other Fluorochemicals in Serum Extracts using HPLC-Electrospray/Mass Spectrometry" 3M Environmental Laboratory 3M Environmental Laboratory Page 781 Page 4 of010 , , Page 23 3M Medical Department Study: T-6889.6 -- -- ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOXL-I1M64S EOO-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 (C7F15COO ) analysis, is fragmented further 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 of 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 (approxim ately 7 m inutes), by the characteristic primary ion (4 13) and the characteristic product ion (169). Minor modifications to the Data Quality Objectives may be implemented at the discretion of the PAL 12. Sub-Contracted Analysis Pace Analytical Services, Inc. (Tier II 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 o f y Id^ , ( Page 24 3M Medical Department Study: T-6889.6 Analytical 164 Protocol FACT-TOX-L1I6M4 S EOO-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-Ol Use and Maintenance of Ultra-Turrax T25 Homogenizer PSS-OPS-02 Raw Data PSS-OPS-03 Hazardous Waste Pisposal 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-IO 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 Thermometers/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 of 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. Statistical Analysis 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 Environmental Laboratory 3M Environmental Laboratory Page 783 Page 6 of p t o X is r . ,1 - 1 . Page 25 3M Medical Department Study: T-6889.6 -- ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOX-L1I6M4 S E00-2738 14. R e po rt 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. 1 4 .2 Dates upon which the phase was initiated and completed. 1 4 .3 A statement of compliance by the PAI addressing any exceptions to Good Laboratory Practice Standards. 1 4 .4 Objectives and procedures as stated in the approved phase protocol, including any amendments to the original phase protocol. 1 4 .5 Identity, purity, stability and the solubility of the reference standard under the conditions of use. 1 4 .6 A description of the methods used to conduct the test(s). 1 4 .7 A description of the specimens. 1 4 .8 A description of any circumstances that may have affected the quality or the integrity of the data. 1 4 .9 The name of the PAI and the names of other scientists, professionals, and supervisory personnel involved in the phase. 1 4 .1 0 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. 1 4 .1 1 Statistical m ethods used to evaluate the data, if applicable. 1 4 .1 2 The signed and dated reports of each of the individual scientists or other professionals involved in the phase, if applicable. 1 4 .1 3 The location where raw data and the phase report are to be stored. 1 4 .1 4 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. 1 4 .1 5 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 7ofpto^ Page 26 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 Protocol FACT-TOXL-1I6M4S EOO-2738 15. Location of Raw Data, Recordsf 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 Telephone: (651) 778-676 SStf uc 3M Environmental Laboratory 3M Environmental Laboratory Page 785 Page 8 of pio Page 27 3M Medical Department Study: T-6889.6 A nalytical Report: FACT TO X -164 Protocol FACT-TOXL-1I6M4S EOO-2738 17. Protocol Amendments 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. A ttachments 18.1 Attachment A: Material Safety Data Sheets (MSDS) for Reference Standard 3M Environmental Laboratory 3M Environmental Laboratory Page 786 Page 9 o f 0 lo Page 28 3M Medical Department Study: T-6889.6 19. Signatures David Sanders, Ph.D., Sponsor Representative John Butenhqff, Ph.D., Study Director Lisa Clemen., Principal Analytical Investigator ------------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Protocol FACT-TOX-164 Date $ /* ? /* { Date Ouim l oi Date 3M Environmental Laboratory 3M Environmental Laboratory Page 787 Page 10 of 9l^ Page 29 3M Medical Department Study: T-6889.6 ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study Tide 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 M 3M Fnvimnmental Laboratory 3M Environmental Laboratory> Page 788 Paae 1 of 3 Page 30 3M Medical Department Study: T-6889.6 'T , ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Protocol FACT TOX-001 Amendment No. 1 This amendment modifies the following portion(s) of the protocol: 1. P ro to co l r ead s: 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 die 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. 3 M Fnvim nm onta/ / ahnratnrv 3M Environmental Laboratory Page 789 Paae 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 D a vid Sanders, Sponsor Representative 2. John L Butenhoff, Ph.D ., Study Director Date 2 2 . d > iV ( Date 3M Environmental Laboratorv 3M Environmental Laboratory Page 790 Paae 3 of 3 Page 32 3M Medical Department Study: T-6889.6 R ecord o f D eviation /. Identification LIMS EOO-2738 Study/Project No. FACT-TOX-164 Argus 418-020 LIMS EOO-2738 Deviation Type (Check one) 0 SOP X Method 0 Equipment Procedure Q Protocol 0 Other: Document Number(s): ETS-8-4.2, ETS-8-5.2 Date(s) of occurrence: //. Descr0ip6/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 r2 must be > 0.990. Actual Procedure/process: Matrix spikes were prepared (06/14/01) prior to the start of the 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 I Hi. Actions Taken:I were below 1.00 ppb for the target analyte. This serum was then used to prepare the extracted Bmatrix 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 r2 value 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.______________________________________ ____ ; (such as amendment issued, SOP revision, etc.) This deviation was written. Recorded By Lisa A. Clemen 3 ^ 4 ( % ^ IV. impact on Study/ Project No adverse impact on the outcome of this study. Date 08/10/01 , O^jlolc I Authorized By (Study D irecto r / P roject Lead) Date SstuUa D .r e .tiw Tohrt tyor.il.- Re^futnUtvt, Oav.d io u te 3M Environmental Laboratory Form ETS-4-8.0 3M Environmental Laboratory 2 ^ 5 8 0 / __________________________________ ______________ Deviation No. \* (assigned by Study Director or Project Lead at the end of study or project) Page 33 Page 791 3M Medical Department Study: T-6889.6 Record of Deviation /. Identification ARGUS 418-020 Analytical Repon: FACT TOX-164 LIMS EOO-2738 Study/Project No. FACT-TOX-164 Argus 418-020 LIMS EOO-2738 Deviation Type (Check one) Q SOP 0 Method 0 Equipment Procedure X Protocol 0 Other: Document Number(s): FACT-TOX-164 Date(s) of occurrence: II. Descr0i6p/t1io9/n0:1 Required Procedure/process: Section 7 states: An equal number of 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 amendment issued, SOP revision, etc.) This deviation was written. Recorded By Date Lisa A. Clemen ^ fi. 08/10/01 IV. Impact on Study/ Project Dfillojoi These samples' results will add useful information concerning endogenous levels present in the control group. No adverse impact on this study. Authorized By (Study D irecto r / P ro ject Lead) i, Date j 1 ^+ucU Oirertor. Jota uienhoff jptMucr R tp rtA ia ta t D tw .d -Senden 3M Environmental Laboratory Form ETS-4-8.0 s ' ft* * * - __________________1 D eviation No. ck________ (assigned by Study Director or Project Lead at the end o f study or project) 3M Environmental Laboratory Page 34 3M Medical Department Study: T-6889.6 > -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Record o f D eviation /. Identification Study / Project N a FACT-TOX-164 Argus 418-020 LIMS EOO-2738 Deviation Type (Check one) SOP X Method Equipment Procedure Protocol Other: Document Number(s): ETS-4-, ETS-8-5.1 Date(s) of occurrence: ________________________________I_I.__D__e_s_c_r0ip1t/1io7n/0:1,01/23/01___________________ Required Procedure/process: Methods state: A matrix spike and matrix spike duplicate will be extracted and analyzed per forty samples, with a minimum o f 2 per batch. Actual Procedure/process: __ n 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, SOP revisioni, etc.) This deviation was written. Recorded By Date Lisa A. Clemen 10/05/01 IV. Impact on Study/ Project /D W 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 (Study D irector / Project Lead) , Date ___________ Q ift c lw : Tchrv u,W \lio 'S p o r u tr f t t p r e j t A a W - a v i J aLWX 3M Environmental Laboratory Form ETS-4-8.0 /D / / J ./ Deviation No. (assigned by Study Director or Project Lead at the end of study or project) 3M Environmental Laboratory Page 793 Page 35 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 '3" ~--- ARGUS 418-020 Analytical Report: FACT TOX-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 Perfluorooctanesulfonate 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-8-5.1, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (9 pages) ETS-8-5.2, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (11 pages) 3M Environmental Laboratory 3M Environmental Laboratory Page 794 Paae 20 Page 36 3M Medical Department Study: T-6889.6 3M Environmental Laboratory - -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 M ethod E x t r a c t io n o f P o tassiu m P erfluo ro o ctan esu lfo na te o r O th er Fluo r o c h em ic a l co m po unds from Serum fo r A na lysis U sing H P L C - E lectro spray/M ass Spectro m etry Method Number: ETS-8-4.1 Adoption Date: 03/01/99 Author: Lisa Clemen, Glenn Langenburg Revision Date: ^^ Approved By: 0 ' i i i - ______ Laboratory Manager Date Id z---------Group Leader H lu /3 3 Date crft 's* A Technical Reviewer o y /a tM Date t a t CopyofOriginal / W Jm / initial Date 1.0 Sc o p e and Applica tio n 1.1 Scope: This method is for the extraction o f potassium perfluorooctanesulfonate (PFOS) or other fluorochemical compounds from serum. 1.2 Applicable compounds: Fluorochemical surfactants or other fluorinated compounds. 1.3 M atrices: Rabbit, rat, bovine, monkey, and human serum or other fluids as designated in the validation report. Word 6/95 3M Environmental Laboratory ETS-8-4.1 r D1TAC fw w Page 795 Page 1 o f 14 Page 37 3M Medical Department Study: T-6889.6 ------------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 2.0 Su m m a r y o f M eth o d ________________________________________________________ ___ 2.1 1 This method describes the procedure for extracting potassium perfluorooctanesulfonate (PFOS) or other fluorochemical surfactants from serum, or other fluids, using an ion pairing reagent and methyl-terf-butyl ether (MtBE). In this method, seven fluorochemicals were extracted: PFOS, PFOSA, PFOSAA, EtFOSE-OH, PFOSEA, M556, and surrogate standard (see 3.0 D efinitions). An ion pairing reagent is added to the sample and the analyte ion pair is partitioned into MtBE. The MtBE extract is removed and put onto a nitrogen evaporator until dry. Each extract is reconstituted in 1.0 mL o f methanol, then filtered through a 3 cc plastic syringe attached to a 0.2 p.m nylon filter into glass autovials. 2.2 These sample extracts are analyzed following method ETS-8-5.1 or other appropriate methods. 3.0 D e fin it io n s ______________________________________________________ ___________________ 3.1 PFOS: perfluorooctanesulfonate (anion o f potassium salt) C8F,7S 0 3* 3.2 PFOSA: perfluorooctane sulfonylamide C,F17S 0 2NH2 3.3 PFOSAA: perfluorooctane sulfonylamido (ethyl)acetate C8F17S 0 2N(CH2CH3)CH2C 02* 3.4 EtFOSE-OH: 2(N-ethylperfluorooctane sulfonamido)-ethyl alcohol C8FI7S 0 2N(CH2CH3)CH2CH20H 3.5 PFOSEA: perfluorooctane sulfonyl ethylamide C8F,7S 02N(CH2CH3)H 3.6 M556: C8F17S 0 2N(H)(CH2C 00H ) 3.7 Surrogate standard: 1H-1H-2H-2H perfluorooctane sulfonic acid 4.0 W a r n in g s and C a u tio n s_________________________________________________________ _ 4.1 H ea lth an d safety w a rn in g s 4.1.1 Use universal precautions, especially laboratory coats, goggles, and gloves when handling anim al tissue, which may contain pathogens. * 5.0 I n t e r fe r e n c e s ____________ ;________________________________________________ _________ 5.1 There are no interferences known at this time. 6.0 E q u ip 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 6.1.3 Shaker, Eberbach or VWR 3M Environmental Laboratory E TS-8-4.1 ** . f T i P A P ______C Page 796 Page 2 of 14 Page 38 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 6.1.4 Nitrogen evaporator, Organomation 6.1.5 Balance ( 0.100 g) 1 7.0 S u pplies and M aterials 7.1 Gloves 7.2 Eppendorf or disposable pipettes 1 3 Nalgene bottles, capable o f holding 250 mL and 1 L 7.4 Volumetric flasks, glass, type A 7.5 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 o f measuring 5 pL to 50 pL 7.10 Graduated pipettes 7.11 Syringes, disposable plastic, 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 and bottles, rinse 3 times with methanol and 3 times with Milli-QTM water. Rinse syringes a minimum o f 9 times with methanol, 3 rinses from 3 separate vials. 8.0 R e a g e n t s and Standards__________________________________________________________ 8.1 Type I reagent grade watr, Milli-QTM or equivalent; all water used in this method should be Milli-QTM water and may be provided by a Milli-Q TOC PlusTM system 8.2 Sodium hydroxide (NaOH), J.T Baker or equivalent 8.3 Tetrabutylammonium hydrogen sulfate(TBA), Kodak or equivalent 8.4 Sodium carbonate (Na2C03), J.T. Baker or equivalent 8.5 Sodium bicarbonate (NaHCO}), 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 Fluorochemical standards 8.9.1 PFOS (3M Specialty Chemical Division), molecular weight = 538 8.9.2 PFOSA (3M Specialty Chemical Division), molecular weight - 499 3M Environmental Laboratory ETS-8-4.1 F.Ytraetim i n f PFO S frnm Page 3 of 14 Page 39 Page 797 3M Medical Department Study: T-6889.6 -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 8.9.3 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, perfluorooctane sulfonic acid (1-H,1-H, 2-H, 2-H CgFi3S 0 3H) molecular weight = 428 8.9.8 Other fluorochemicals, as appropriate 8.10 Reagent preparation NOTE: When preparing larger volumes than listed in reagent, standard, or surrogate preparation, adjust accordingly. 8.10.1 10N sodium hydroxide (NaOH): Weigh approximately 200 g NaOH. Pour into a 1000 mL beaker containing 500 mL Milli-QTM water, mix until all solids are dissolved. Store in a 1 L Nalgene bottle. 8.10.2 1 N sodium hydroxide (NaOH): Dilute 10 N NaOH 1:10. Measure 10 mL o f 10 N NaOH solution into a 100 mL volumetric flask and dilute to volume using Milli-QTM water. Store in a 125 mL Nalgene bottle. 8.10.3 0.5 M tetrabutylammonium hydrogen sulfate (TBA): Weigh approximately 169 g o f TBA into a 1 L volumetric containing 500 mL Milli-QTM water. Adjust to pH 10 using approximately 44 to 54 mL o f 10 N NaOH (While adding the last mL o f NaOH, add slowly because the pH changes abruptly). Dilute to volume with Milli-QTM water. Store in a 1 L Nalgene bottle. 8.103.1 TBA requires a check prior to each use to ensure pH = 10. Adjust as needed using 1 N NaOH solution. 8.10.4 0.25 M sodium caibonate/sodium bicarbonate buffer (NajCOj/NaHCOj): Weigh approximately 26.5 g o f sodium carbonate (NajCOj) and 21.0 g o f sodium bicarbonate (NaHC03) into a 1 L volumetric flask and bring to volume with M illiQTM water. Store in a 1 L Nalgene 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 1.00 ppm PFOS, 1.02 ppm PFOSA, 0.987 ppm PFOSAA, and 1.10 ppm EtFOSE-OH.) 8.11.3 Weigh approximately 100 mg o f PFOS into a 100 mL volumetric flask and record the actual weight. 8.11.4 Bring to volume with methanol for a stock standard o f approximately 1000 ppm (pg/mL). 8.11.5 Dilute the stock solution with methanol for a working standard 1 solution o f approximately 50 ppm. 8.11.6 Dilute working standard 1 with methanol for a working standard 2 solution o f approx. 5.0 ppm. 3M Environmental Laboratory ETS-8-4.1 o rn c c. . Page 4 o f 14 Page 40 Page 798 3M Medical Department Study: T-6889.6 -- -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 8.11.7 Dilute working standard 1 with methanol for a working standard 3 solution of approx. 0.50 ppm. 8.12 Surrogate stock standard preparation 8.12.1 Weigh approximately 50-60 mg o f surrogate standard 1-H,1-H, 2-H, 2-H, C8FI3S 0 3H into a 50 mL volumetric flask and record the actual weight. 8.12.2 Bring to volume with methanol for a surrogate stock of approximately 1000-1200 ppm. 8.12.3 Prepare a surrogate working standard. Transfer approximately 1 mL o f surrogate stock to a 10 mL volumetric flask and bring to volume with methanol for a working standard o f 100 ppm. Record the actual volume transferred. 9.0 Sa m p l e H andling__________________________________ 9.1 All samples are received frozen and must be kept frozen until the extraction is performed. 9.2 Allow samples to thaw to room temperature prior to extraction. 10.0 Q uality C o n t r o l _________________ ;______ 10.1 Solvent Blanks, Method blanks and matrix blanks 10.1.1 An aliquot of 1.0 mL methanol is used as a solvent blank. 10.1.2 Extract two 1.0 mL aliquots o f Milli-QTM water following this procedure and use as method blanks. 10.1.3 Extract two 1.0 mL aliquots o f the serum following this procedure and use as matrix blanks. See 11.1.4. 10.2 Matrix spikes 10.2.1 Prepare and analyze matrix spike and matrix spike duplicate samples to determine the accuracy o f the extraction. 1 0 .2 .2 Prepare each sp ik e u sin g a sam p le ch osen b y the analyst, u su a lly the control matrix received with each sample set. 10.2.3 Expected concentrations will fall in the mid-range o f the initial calibration curve. Additional spikes may be included and may fall in the low-range o f the initial calib ration curve. 10.2.4 Prepare one matrix spike and matrix spike duplicate per 40 samples, with a minimum o f 2 matrix spikes per batcL 10.3 Continuing calibration checks 10.3.1 Prepare continuing calibration check samples to ensure the accuracy o f the initial calibration curve. 10.3.2 Prepare, at a minimum, one continuing check per group o f 10 samples. For example, if a sample set * 34, four checks are prepared and extracted. 10.33 Prepare each continuing calibration check from the same matrix used to prepare the initial curve. 3M Environmental Laboratory ETS-8-4.1 Page 799 Page 5 o f14 Page 41 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 10.3.4 The expected concentrations will fall within the mid-range o f the initial calibration curve. Additional spikes may be included that fall in the low-range o f the initial calibration curve. This is necessary if the analyst must quantitate using only the low end o f the calibration curve (for example, 5 ppb - 100 ppb, rather than 5 ppb - 1000 ppb). 11.0 C a l ib r a t io n and Sta n d a r d iz a t io n ________________________________________________ 11.1 Prepare matrix calibration standards 11.1.1 Transfer 1 mL o f serum to a 15 mL centrifuge tube. 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 mL o f matrix. Record each sample volume on the extraction sheet. 11.1.3 'While preparing a total o f twenty aliquots in 15 mL centrifuge 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 o f this section, to spike, in duplicate, two standard curves, for a total o f eighteen standards, two matrix blanks, and two method blanks. 11.1.5 Refer to validation report ETS-8-4.0 & ETS-8-5.0-V-1, which lists the working ranges and the Linear Calibration Range (LCR) for calibration curves. 11.1.6 Use Attachment D as an aid in calculating the concentrations o f the working standards. See Section 13.0 to calculate actual concentrations o f PFOS in calibration standards. 11.2 To each standard, blank, or continuing check, add appropriate amount o f surrogate working standard for the concentration to fall within the calibration curve range 5 ppb 1000 ppb. 11.3 Extract spiked matrix standards following 12.6-12.16 o f this method. Use these standards to establish each initial curve on the mass spectrometer. 3M Environmental Laboratory ETS-8-4.1 r tf D l n C frn ft Page 800 Page 6 of 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 pL Approx, final cone, of (approx, cone.) analyte in matrix - - Blank 0.500 ppm 10 0.005 ppm 0.500 ppm 20 0.010 ppm 5.00 ppm 5 0.025 ppm 5.00 ppm 10 0.050 ppm 5.00 ppm 20 0.100 ppm 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 1.00 ppm 12.0 P r o c ed u r e _______ ;_________________________________________________________________ 12.1 Obtain frozen samples and allow to thaw at room temperature or in a lukewarm waterbath. 12.2 Vortex mix for 15 seconds, then transfer 1.0 mL or other appropriate volume to a 15 mL polypropylene centrifuge tube. 12.3 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 11.2. 12.7 Spike each matrix with the appropriate amount o f standard as described in 11.1, or Table 1 in that section, for the calibration curve standards. Also prepare matrix 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. If not, adjust accordingly. 12.10 To each sample, add 1 mL 0.5 M TBA and 2 mL o f 0.25M sodium cafbonate/sodium bicarbonate buffer. 12.11 Using an Oxford Dispenser, add 5 mL methyl-tert-butyl ether. 12.12 Cap each sample and put on the shaker at a setting o f 300 ipm, for 20 minutes. 12.13 Centrifuge for 20 to 25 minutes at a setting o f 3500 rpm, or until layers are well separated. 3M Environmental Laboratory ETS-8-4.1 Page 7 of 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 of the organic layer to this clean 15 mL centrifuge tube. 12.16 Put each sample on the analytical nitrogen evaporator until dry, approximately 1 to 2 hours. 12.17 Add 1.0 mL o f methanol to each centrifuge tube using a graduated pipette. 12.18 Vortex mix for 30 seconds. 12.19 Attach a 0.2 pm nylon mesh filter to a 3 cc syringe and transfer the 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, extraction date, and analyses) performing the extraction. 12.21 Cap and store extracts at room 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 study binder, as appropriate. 13.0 D a t a A nalysis a n d C alculations_______________________________________ 13.1 Calculations 13.1.1 Calculate actual concentrations o f PFOS, or other applicable fluorochemical, in calibration standards using the following equation: mL o f standard x concentration o f standard (up /m D __________________= mL o f standard + mL o f surrogate standard + initial matrix volume (mL) Final Concentration (jig/mL) o f PFOS in matrix 14.0 M e t h o d Pe r f o r m a n c e _______________________________ _______________________ 14.1 The method detection limit (MDL) is analyte and matrix specific. Refer to MDL report for sp e c ific M D L and lim it o f quantitation (L O Q ) v a lu es (se e A tta c h m e n ts B a n d C ). 14.2 The following quality control samples are extracted with each batch o f samples to evaluate the quality o f the extraction and analysis. 14.2.1 Method blanks and matrix blanks. 14.2.2 Matrix spike and matrix spike duplicate samples to determine accuracy and precision o f the extraction. 14.2.3 Continuing calibration check samples to determine the continued accuracy o f the initial calibration curve. 14.3 Refer to section 14 o f ETS-8-5.1 for method performance criteria. 15.0 P o l l u t i o n Prev entio n a n d W aste M a n a g e m e n t _____________________ 15.1 Sample waste is disposed in biohazard containers, 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 c E rToSe-8r t-4e.1a e 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 R e c o r d s ________________________________________________ _ 16.1 Complete the extraction worksheet attached to this method, and tape in the study notebook or include in the 3-ring study binder, as appropriate. 17.0 A t t a c h m e n t s _______________________________________________ _ 17.1 Attachment A, Extraction worksheet 17.2 Attachment B, MDL/LOQ values and summary 17.3 Attachment C, Calibration standard concentration worksheet 18.0 R eferences________ ;______________________________________________________ 18.1 The validation report associated with this method is ETS-8-4.0 & 5.0-V -l. 18.2 FACT-M-3.1, "Analysis o f Serum or Other Fluid Extracts for Fluorochemicals 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-8-5.1, "Analysis o f Serum or Other Fluid Extracts for Fluorochemicals using HPLC-Electrospray Mass Spectrometry" 20.0 R evisions________________ :________________________________________ Revision Number 1 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. Revision Date 04/02/99 3M Environmental Laboratory ETS-8-4.1 Extraction o f PFOS from Seram Page 803 Page 9 of 14 Page 45 3M Medical Department Study: T-6889.6 Extraction Worksheet ETS-8-4.1 -- ARGUS 418-020 Analytical Report: FACT TOX-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-Mix approx. 5 ppm actual ppm # FC-Mix approx. 50 ppm actual ppm # Comments Blank Std# --------- -- ------- amount * - - - - - - - - mL Vortex 15 sec. Pipette Matrix Volume mL Pipette 1 mL of 0.5 M TBA, pH 10. pH * Std. # Pipette 2 mL of 0.25 Na^COVO^SM NaHCO? buffer Std.# Dispense 5 mL of methyl-t-butyl ether TN-A- Shake 20 min. Shaker speed: Centrifuge 20-25 min. Centrifuge speed: Remove a A mL aliquot of organic layer______________________________________________________ Put on Nitrogen Evaporator to dryness ___________________Temperature:_____________________ Vortex 30 sec. ______ _______________________ _________ _Filter using a 3cc B-D syringe with a 0.2um filter into a 1JS mL autosample vial Cont. Cal. Verifications used same matrix as for std curve. -- -- -- -- A __ ___ _ * 3M Environmental Laboratory CTC O A 1 Page 804 Page 46 3M Medical Department Study: T-6889.6 - - -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 MDL/LOQ values for rabbit serum Compound MDL (PPb) LOQ Linear Calibration Range (LCR) (PPb) Approximate concentrations to be used for preparing the Standard Calibration Curve PFOS PFOSA PFOSAA EtFOSE-OH 1.74 1.51 3.46 11.4 5.55 5ppb-1000ppb 4.79 5 ppb - 1000 ppb 20.5 5 ppb - 1000 ppb 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, m onkey, and human serum, and m onkey plasma were n ot statistically determined. Tw o curves in each o f these matrices were extracted and analyzed w ith die rabbit serum curves to determine equivalence. Responses in the rat, bovine, monkey, and human were equivalent to the rabbit responses, therefore, their M DL and LOQ w ill b e the same values as determined in rabbit serum. Please see LOQ Summary and M DL 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 A l 3M Medical Department Study: T-6889.6 - -- -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Compound: P FOS Prepared range Rabbit Serum o f standards (ppb) (ng/mL) Full Range 0.995 - 978 Low Curve 4.94 - 248 High curve 1/X 97.8 - 978 0.995 - 978 Compound: PFOSA 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 24.8-976 0.993 - 976 Compound: PFOSAA Prepared range Rabbit Serum o f standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.991-974 4.92 - 247 49.2 - 974 0.991 - 974 LCR from curve (PPb) (ng/tnL) 24.8 - 978 4.94 - 248 97.8-978 4.94 - 978 % Recovery Range 83-108 85-104 85-106 94-111 LCR from curve (ppb) (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 LCR from curve (ppb) (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 4.67-11.0 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 4.33-12.5 4.11-23.2 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 Report: FACT TOX-164 LIMS EOO-2738 Compound: EtFOSE-OH 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 49.3 - 976 0.993-493 LCR from curve (PPb) (ng/mL) 49.3 - 976 9 .7 6 -9 7 .6 97.6 - 976 9.76 - 976 % Recovery Range 77-110 97-107 90-109 86-111 Compound: PFOSEA Prepared range Rabbit Serum of standards (ppb) (ng/mL) Full Range Low Curve High curve 1/X 0.993 - 976 4.93 - 248 49.3-976 0.993-976 LCR from curve (ppb) (ng/mL) 24.8 - 976 9.76-248 49.3-976 9.76 - 976 % Recovery Range 96-106 91-110 86-106 95-117 Compound: IVI[556 Prepared range Rabbit Serum of 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) 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 11.2-25.5 14.1-213 11.5-19.6 11.1-213 RSD Range 10.1-16.2 11.8-19.5 10.2-18.2 10.1-19.1 RSD Range 4.82-17.9 5.95-183 5.11-9.74 4.77-19.5 Attachment B: MDL/LOQ Summary 3M Environmental Laboratory ETS-8-4.1 Page 807 Page 13 of 14 Page 49 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Ion Pair Standard Curves - Fluids Prep date(s): Standard number: Analyte(s): Equipment number: \ Sample matrix: Final solvent and TN: Blank fluid/identifier: Method/revision: Target analyte(s): FC mix std approx. 0.500 ppm: FC mix std approx. 5.00 ppm: FC mix std approx. 50.0 ppm: Surrogate std approx. 100 ppm: Actual concentrations of standards in the FC mix P F O S P F O S A . P F O S A A E tF O S E P F O S E A 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 0.521 0.500 0.507 0.532 0.501 0.521 5.00 5.07 5.32 5.01 5.21 5.00 5.07 5.32 5.01 5221 5.00 5.07 5.32 5.01 5.21 50.0 50.1 53.2 50.1 52.1 50.0 50.1 53.2 50.1 52.1 50.0 50.1 5322 50.1 52.1 50.0 50.1 53.2 50.1 52.1 M556 Std cone ug/mL 0.501 0.501 5.01 5.01 5.01 50.1 50.1 50.1 50.1 All Ain't spiked mL 0.010 0.020 0.005 0.010 0.020 0.005 0.010 0.015 0.020 All 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 sample matrix PFOS PFOSA PFOSAA EtFOSE PFOSEA M5S6 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 4.93 5.00 5.24 4.94 5.01 5.13 100 9.76 9.89 10.4 9.78 9.93 10.2 24.8 25.1 26.3 24.8 2 5 .2 25.8 Surrogate 49.3 50.0 52.4 49.4 50.1 51.3 Final cone 97.6 98.9 104 97.8 99.3 102 ng/mL 248 251 263 248 252 258 500 493 500 524 494 501 513 735 746 782 737 749 766 976 989 1038 978 993 1017 All Ain't spiked mL 0.005 Validated ranges - approximate concentrations Serum PFOS PFOSA PFOSAA Rabbit 5.00-1000 1 5.00-1000 | 5.00-1000 Bovine Estimates only. Use values for rabbit Rat Estimates only. Use values for rabbit Monkey & Plasma Estimates only. Use values for rabbit Human Estimates only. Use values for rabbit EtFOSE-OH PFOSEA | 5.00-1000 1 5.00-1000 M556 I 5.00-1000 Attachment C: Ion Pair Standard Curves 3M Environmental Laboratory ETS-8-4.1 Page 808 Page 14 of 14 Page 50 3M Medical Department Study: T-6889.6 3 M E n v ir o n m e n t a l L a b o r a t o r y - - -- : ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 M ethod E x tr a c tio n o f F lu o ro ch em ica l com pounds fro m Se r u m fo r A nalysis Using H P L C -E lectrospray/M ass Spectro m etry Method Number: ETS-8-4.2 Adoption Date: 03/01/99 Effective Date: L/oI | 1 Approved By: Laboratory Manager K -l- - fi* -- ~ _ Group Leader 0 3 / c u / c '/ Date O ^ fO iL / C I Date 1.0 Scope and Application 1.1 Scope: This method is for the extraction of fluorochemical compounds from serum. 1.2 Applicable compounds: Fluorochemical surfactants or other fluorinated compounds. 1.3 M atrices: Rabbit, rat, bovine, monkey, and human serum or other flukfrjs jd ^ g ra te d in the validation report. /fe y * L /. , WW Data 7 2.0 Summary of Method 2.1 This performance-based method describes the procedure for extracting perfluorooctanesulfonate (PFOS) or other fluorochemical surfactants from serum, or other fluids, using an ion pairing reagent and methyl-ierr-butyl ether (MtBE). An ion pairing reagent is added to the sample and the analyte-ion pair is partitioned into MtBE. The MtBE extract is removed and put onto a nitrogen evaporator until dry. Each extract is reconstituted in 1.0 mL of methanol, then filtered through a 0.2 pm nylon filter using a 3-mL plastic Word 6/95 3M Environmental Laboratory ETS-8-4.2 Extraction of Fluorocheraicals from Serum Page 809 Page 1 of 15 Page 51 3M Medical Department Study: T-6889.6 Analytical 164 LIMS E00-2738 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 .0 D e fin itio n s }). These sample extracts are analyzed following method ETS-8-5.2 or other appropriate method. 3.0 D efinitions__________________ _______________________________________ 3.1 PFOS: perfluorooctanesulfonate (anion of potassium salt) C8Fi7S 0 3` 3.2 PFOSA: perfluorooctane sulfonylamide CgF|7S0 2NH2 3.3 PFOSAA: perfluorooctane sulfonylamido (ethyl)acetate C8Fi7S0 2N(CH2CH3)CH2C0 2 ` 3.4 EtFOSE-OH: 2(N-ethylperfluorooctane sulfonamido)-ethyl alcohol C8Fl7S 0 2N(CH2CH3)CH2CH20H 3.5 PFOSEA: perfluorooctane sulfonyl ethylamide C8F|7S0 2 N(CH2CH3)H 3.6 M556: C8F17S02N(H)(CH2COOH) 3.7 Surrogate standard THPFOS: 1H-1H-2H-2H perfluorooctane sulfonic acid 4.0 W arnings a n d C autions________________________________________ _ _ _ _ _ 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 In t e r f e r e n c e s _______________________________________________________________ 5.1 There are no interferences known at this time. 6.0 E q u i p m e n t _____________________________________________________________________________________________________ 6.1 T h e fo llo w in g equipm ent is u sed w h ile perform ing this m ethod. E quivalent eq u ip m en t is acceptable. 6.1.1 Vortex mixer, VWR, Vortex Genie 2 6.1.2 Centrifuge, Mistral 1000 or IEC 6.1.3 Shaker, Eberbach or VWR 6.1.4 Nitrogen evaporator, Organomation 6.1.5 Balance (0.100 g) .. 7.0 Su a n d M aterials________________________________ _ _ _ _ _ _ _ 7.1 Gloves 7.2 Eppendorf or disposable pipettes, plastic or glass (or equivalent) 7.3 Polypropylene bottles, capable of holding 250 mL and 1 L (Nalgene or equivalent) 3M Environmental Laboratory ETS-8-4.2 Page 2 of 15 Page 52 Page 810 3M Medical Department Study: T-6889.6 - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 7.4 Volumetric flasks, glass, type A 7.5 40 mL glass 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 pL 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 St a n d a r d s ________________________________________ ____ 8.1 Reagent grade water, Milli-QTM, Nanopure II or equivalent 8.2 Sodium hydroxide (NaOH), J.T Baker or equivalent 8.3 Tetrabutylammonium hydrogen sulfate(TBA), Kodak or equivalent 8.4 Sodium carbonate (Na2C0 3 ), J.T. Baker or equivalent 8.5 Sodium bicarbonate (NaHCOs), 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 Fluorochemical 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, perfluorooctane sulfonic acid ( 1 -H, 1-H, 2-H, 2-H C8F13SO3H, [THPFOS]), molecular weight = 428 8.9.8 Other fluorochemicals, as appropriate 3M Environmental Laboratory ETS-8-4.2 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 1 L polypropylene (or equivalent) bottle. 8.10.2 1 N 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. 8.10.3 0.5 M tetrabutylammonium hydrogen sulfate (TBA): Weigh approximately 169 g of TBA into a 1 L 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 of NaOH slowly, as the pH changes abruptly.) Dilute to volume with water. Store in a 1 L polypropylene (or equivalent) bottle. 8.10.3.1 TBA requires a check prior to each use to ensure pH = 10. Adjust as needed using 1 N NaOH solution. 8.10.4 0.25 M sodium carbonate/sodium bicarbonate buffer (Na2C0 3 /NaHC0 3 ): Weigh approximately 26.5 g of sodium carbonate (Na2C 0 3) and 21.0 g of sodium bicarbonate (NaHC03) into a 1 L volumetric flask and bring to volume with water. Store in a 1 L 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). 8.11.3 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. PFOS ( 499 ) molecular wt. KPFOS (538) 0.9275 ( Correction fa c to r ) 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 1 solution of approximately 50 pg/mL. G 000 n g / m L x 5 m L ^ = 50 fig I mL 100 m L 8.11.6 Dilute working standard 1 with methanol for a working standard 2 solution of approx. 5.0 pg/mL. 3M Environmental Laboratory ETS-8-4.2 ____ * _ . . r n _______ i . . . . Page 812 Page 4 of 15 Page 54 3M Medical Department Study: T-6889.6 , - -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 f50 fig / mLxlO mLy = 5.0 fig/mL 100 mL 8.11.7 Dilute working standard 1 with methanol for a working standard 3 solution of approx. 0.50 pg/mL. 8.12 Surrogate THPFOS stock standard preparation 8.12.1 Weigh approximately 50-60 mg of surrogate standard 2-H, 2-H, CgF^SOsH (THPFOS) into a 50 mL volumetric flask and record the actual weight. 8.12.2 Bring to volume with methanol for a surrogate stock of approximately 10001200 pg/mL. 8.12.3 Prepare a surrogate working standard. Transfer approximately 1 mL of surrogate stock to a 10 mL volumetric flask and bring to volume with methanol for a working standard of 100 pg/mL. Record the actual volume transferred. 9.0 Sa m p i.e H a n d lin g ________________________________________________________________ 9.1 All samples are received frozen and must be kept frozen until the extraction is performed. 9.2 Allow samples to thaw at room temperature or in lukewarm water prior to extraction. 10.0 Q u a l it y C o n t r o l _____________________________________________________________ 10.1 Solvent Blanks, M ethod Blanks and M atrix Blanks 10.1.1 Solvent Blanks: An aliquot of 1.0 mL methanol is used as a solvent blank. 10.1.2 Method Blanks: Following this procedure, extract two 1.0 mL aliquots of water and use as method blanks. 10.1.3 M atrix Blanks: M atrix blanks are prepared from one of three sources: 1) a study control matrix from a 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 obtained commercially, but of a different species than the study animal (e.g. if rabbit is used to generate standard curves and CCVs for a monkey or rat sera study). The matrix to use depends on what matrix is used for the curve. 10.1.3.1 Study control matrix curve--If the study control matrix is used for the curve, prepare two (2) matrix blanks using the study control matrix. 10.1.3.2 Commercially obtained (same species) matrix curve--If the curve is prepared using 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 Scrum Page 813 Page 5 of 15 Page 55 3M Medical Department Study: T-6889.6 -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 10.1.3.3 Surrogate matrix curve--If a surrogate 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 matrix blank 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. 10.2 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 matrix is used for the curve and CCV samples (e.g., rabbit sera may be used to generate standard curves for a monkey sera study, due to measurable levels of endogenous analyte in the monkey sera). Prepare and analyze matrix spike and matrix 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 from the 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 minimum of 2 matrix spikes per level per batch. If a batch includes more than 20 samples, additional spikes may be prepared at the same, low, or high range levels. 10.2.6 If more than 25% of the samples are <LOQ, two matrix spikes should be prepared at approximately 2-5 times the expected LOQ. 10.2.7 If the majority of the samples are at or above the high range 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 from the same matrix used to prepare the initial curve (i.e., either the study control matrix, commercial matrix of same species, or surrogate matrix). 3M Environmental Laboratory ETS-8-4.2 Page 814 Page 6 of 15 Page 56 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 10.3.3 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. 10.3.4 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 and four (4) at a mid-range concentration. 10.3.5 Additional continuing calibration verifications may be included at the same, low, mid or high-range concentration. 11.0 Calibration and Standardization__________________________________ _ _ 11.1 P repare m atrix calibration standards 11.1.1 Transfer 1 mL of appropriate serum to a 15 mL centrifuge tube. If commercially available sera is used, prepare two matrix blanks, using the volume of sera available for most study animals. 11.1.1.1 Depending upon study goals or if analyte-free commercial sera is not available, a surrogate matrix may be used for generation of the calibration standard. For example, rabbit sera may be used as a surrogate matrix for rat studies if quantitation of extremely low 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 mL of matrix. Record each sample volume on the extraction sheet. 11.1.3 While preparing a total of thirteen aliquots in 15-mL centrifuge 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 standard concentrations and-spiking amounts listed in Table 1 at the end of this section to spike one standard curve, for a total of nine standards, two matrix blanks, and two method blanks. 11.1.5 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 a constant 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/mL or other concentration as determined by the analyst. 11.3 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 f in .. -- 1- e, Page 815 Page 7 of 15 Page 57 3M Medical Department Study: T-6889.6 418-020 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 (approx, cone.) pL 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 *ppm=(ig/mL 12.0 P ro c ed u re______________________________________________________________________ 12.1 Obtain frozen samples and allow to thaw at room temperature or in lukewarm water. 12.2 Label a 15 mL polypropylene centrifuge tube with the study number, sample ID, date and analyst initials. See attached worksheet (Attachment A or similar worksheet) for documenting the remaining steps. 12.3 Vortex mix for 15 seconds, then transfer 1.0 mL or other appropriate volume to the 15 mL polypropylene 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 and standards, 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 in that section, for the calibration curve standards. Also prepare matrix spikes if necessary 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. If not, adjust accordingly. 12.10 To each sample, add 1 mL 0.5 M TBA and 2 mL of 0.25M sodium carbonate/sodium bicarbonate buffer. 12.11 Using an bottle top dispenser or 5-10 mL graduated glass pipette, add 5 mL methyl-terfbutyl ether. 12.12 Cap each sample and put on the shaker at a setting of 300 rpm for 20 minutes. 3M Environmental Laboratory ETS-8-4.2 Page 8 of 15 Page 58 3M Medical Department Study: T-6889.6 - -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 12.13 Centrifuge for 20 to 25 minutes at a setting of 3500 rpm or until layers are well separated. 12.14 Label a fresh 15 mL centrifuge tube with the same information as in 12.5. 12.15 Remove 4.0 mL of the organic (top) layer to this clean 15 mL centrifuge tube. 12.16 Put each sample on the analytical nitrogen evaporator until dry, approximately 1 to 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 mL glass 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. 12.20 Attach a 25 mm, 0.2 pm nylon mesh filter to a 3 mL syringe and transfer the sample from step 12.18 to this syringe. Filter into the labeled autovial. 12.21 Cap and store extracts at room temperature or at approximately 4 C until analysis. 12.22 Complete the extraction worksheet (Attachment A or similar worksheet) and include in the study binder. 13.0 D ata An a ly sis and C a lc u la tio n s____________________________________________ 13.1 Calculations 13.1.1 Calculate actual concentrations of PFOS, or other applicable fiuorochemical, in calibration standards using the following equation: ------------m--L--o-f--s-t-d--x---c-o--n-c-e--n-t-r-a--to--t-i-o-f--s-t-d--(-f--l g--/-m--L--)--------- -- = . . ... , . F inal concentrauon ( ig / m L ) o f PFO S in m a tn x m L o f std + m L o f surrogate std + m itic i m atrix volum e ( m L ) 14.0 METHOh Pe rf or m an c e 14.1 The method detection limit (MDL) is analyte and matrix specific. Refer to MDL report for specific MDL and limit of quantitation (LOQ) values (see A ttachm ents B and C). At the discretion of the PAI, MDL may not 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. 14.2.3 Continuing calibration check samples to determine the continued accuracy of the initial calibration curve. 14.3 Refer to section 14 o f ETS-8-5.2 for method performance criteria. 3M Environmental Laboratory ETS-8-4.2 F.Tfrartinn o f F hinrnrh^m iralc from Scrum Page 9 of 15 Page 59 3M Medical Department Study: T-6889.6 - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 15.0 P o l l u t io n P r e v e n t io n and W a ste M a n a g em en t_________________________ 15.1 Dispose of sample waste, flammable solvent waste and used 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 At 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 and summary 17.3 Attachment C, Ion Pair Standard Curves worksheet (a similar worksheet may be substituted for Attachment C) 18.0 R e fe r en c es _____________________________________________________________ 18.1 The validation report associated with this method is ETS-8-4.0 & 5.0-V -l. 18.2 FACT-M-3.1, "Analysis of Serum or Other Fluid Extracts for Fluorochemicals using HPLC-Electrospray Mass Spectrometry" 18.3 ETS-8-5.2, "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" 19.0 Af f e c t e d D o c u m en ts__________________________________________________ ;_________ 19.1 ETS-8-5.2, "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" 20.0 R ev isio 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, 14.2.2 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 abort control animal sera, using and not using commercially available tissue In general, make less specific for equipment/supplies. Substitute water for Milli-Q, Nalgene or equivalent bottle may be used. Revision Date 04/02/99 3M Environmental Laboratory ETS-8-4.2 Pvtrarfinn of Plnnrrw-h^mirale frnm Q^mm Page 818 Page 10 of 15 Page 60 3M Medical Department Study: T-6889.6 Analytical Import 164 Extraction Worksheet ETS-8-4.2 LIMS EOO-2738 Studv # Matrix Box # Wk/Dav Surrogate Std actual pg/mL # FC-Mix approx. 0.5 pg/mL # FC-Mix approx. 5 pg/mL # FC-Mix approx. 50 pg/mL # Comments Verified by: Date Spiked/ Analyst: MS MSD -- - --- -- - -- - .-- -- - -- - -- - --- -- - --- -- - .-- -- - --- Blank ID # amount = mL Seram Extraction Method -- ........ i-- .... ..... Pate &. Initials------- -Vortex \5 sec,-- _ _ -- ----------------------------------------------------------------------------------------------------------- Pioette Matrix, strike with appropriate SUtTPSttff OTFCMift---------- ---------------Volume----------------------- mL---- PiDette 2 mL of 0.25 NaiCCh/0.25MNaHCOi buffer DisDense/oipette 5 mL of methvl-t-butvl ether Dispenser ID #: Shake 20 min. Shaker ID#: Std.# TN-A- Shaker speed: Centrifuge 20-25 min. CflttrifattlEifc------------------------------------- CgmrifiiW,,5Bfr---------------------------- Remove a 4 mL aliquot of organic lavei-------------------------------------------------------------- ------------------------- Put on Nitrogen Evaporator to drvness .......-- .......-- -- -- -- ---------------------- Vortex 30 sec. Filter using a 3mL B-D svringe with a 0.2um filter into a 1.5 mL autosamole vial-------------------------- --------------J-------------- Corn. Cal. Verifications used same matrix as for std curve. Appendix A: Extraction Worksheet r . . * _____ * ! - - 3M Environmental Laboratory ETS-8-4.2 ______ * ___ t - r _______r Page 819 Page 11 o f 15 Page 61 3M Medical Department Study: T-6889.6 -----------: ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 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/mLM000 ng/mL M DL/LOQ values in rat, bovine, monkey, and human serum, and monkey plasma were not statistically determined. T w o curves in each o f 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 M DL and LOQ will be the same values as determined in rabbit serum. Please see LOQ Summary and M DL study in ETS-8-4.0 & 5.0-V -l for further information. Appendix B: MDL/LOQ Values and Summary ETS-8-4.2 F.xfrnrtinn o f F hinrnrhw iirsik from Sffnim 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 E00-2738 Compound: P ros Prepared range Rabbit Serum of standards (ng/mL) Full Range 0.995 - 978 Low Curve 4.94 - 248 High curve 97.8 - 978 1/X 0.995 - 978 Compound: PFOSA Prepared range Rabbit Serum o f standards (ng/mL) Full Range 0.993 - 976 Low Curve 4.93 - 97.6 High curve 24.8 - 976 1/X 0.993 - 976 Compound: PFOSAA Prepared range Rabbit Serum o f standards (ng/mL) Full Range 0.991 - 974 Low Curve 4.92 - 247 High curve 49.2 - 974 1/X 0.991 - 974 LCR from 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 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 LCR from curve (ng/mL) 24.7 - 974 9.74 - 247 97.4 - 974 9 .7 4 . 9 7 4 % 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 6.38-21.8 4.33-12.5 4.11-23.2 Appendix B: MDL/LOQ Values and Summary ETS-8-4.2 Extraction of Fluorochemicals from Serum 3M Environmental Laboratory Page 821 Page 13 of 15 Page 63 3M Medical Department Study: T-6889.6 Analytical R e p o ^ W l ^ f S ^ 164 LIMS E00-2738 Compound: EtFOSE-OH Prepared range Rabbit Serum o f standards (ng/mL) Full Range 0.993 - 976 Low Curve 4.93 - 97.6 High curve 49.3 - 976 1/X 0.993 - 493 Compound: P FOSEA Prepared range Rabbit Serum o f standards (ng/mL) Full Range 0.993 - 976 Low Curve 4.93 - 248 High curve 49.3 - 976 1/X 0.993 - 976 Compound: M 556 Prepared range Rabbit Serum o f standards (ng/mL) Full Range 0.993 - 976 L ow Curve 4.93 - 97.6 High curve 97.6 - 976 1/X 0.993 - 976 LCR from curve (ng/mL) 49.3-976 9 .7 6 -9 7 .6 97.6 - 976 9.76-976 LCR from curve (ng/mL) 24.8 - 976 9.76 - 248 49.3 - 976 9.76 - 976 LCR from curve (ng/mL) 24.8 - 976 9.76 - 97.6 97.6 - 976 9.76 - 976 % Recovery Range 77-110 97-107 90-109 86-111 % Recovery Range 96-106 91-110 86-106 95-117 % Recovery Range 88-106 100-105 81-111 97-110 RSD Range 11.2-25.5 14.1-21.3 11.5-19.6 11.1-2 1 .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 5.95-18.2 5.11-9.74 4.77-19.5 Appendix B: MDL/LOQ Values and Summary 3M Environmental Laboratory ETS-8-4.2 Page 822 Page 14 o f 15 Page 64 3M Medical Department Study: T-6889.6 -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Example Ion Pair Standard Curves - Fluids AnaJyst(s) Study number: i Prep date(s): Analyte(s): Study Animal M atrix: Final solvent and TN: Blank fiuid/identlfien (Record matrix used (o prepare curves, <c.g., 'Rabbit.' DD #XXX)| Method/revision: Target analyte(s): FC mix std approx. 0.500 ppm: FC mix std approx. 5.00 ppm: FC mix std approx. 50.0 ppm: Surrogate std approx. 100 ppm: IRecord the standards used to prepare the extracted cunes.} Actual concentrations of standards in die FC mix in methanol PFOS PFOSA PFOSAA EtFOSE PFOSEA M556 Std cone Std cone Std cone Std cone Std cone Std cone Ug/mL ue/mL Ug/mL ug/mL ug/mL ug/mL 0.500 0.507 0.532 0.501 0.521 0.501 0.500 0.507 0.532 0.501 0.521 0.501 5.00 5.07 5.32 5.00 -- W 5.32 5.00 1 ___a o 7 ^ c T" 5Z% ` 5.01 5.01 50.0 i 50.0 J 50.1 r a 1 l1 5.21 5.21 "T I1 5 2 0 5.01 5.01 50.0 50.1 53.2 50.1 1 5 2 .1 " T 50.1 50.0 50.1 53.2 50.1 52.1 1 50.1 AU Ain't spiked mL 0 .0 1 0 0 .0 2 0 0.005 0 .0 1 0 0 .0 2 0 0.005 0 .0 1 0 0.015 0 .0 2 0 All Final voi mL 1.015 1.025 1 .0 1 0 1.015 1.025 1 .0 1 0 1.015 1 .0 2 0 1.025 Calculated concentrations of standards in the sera matrix: Rabbit____________ PFOS PFOSA PFOSAA EtFOSE PFOSEA M556 Surrogate All Final cone Final cone Final cone Final cone Final cone Final cone Std cone Amt spiked ne/mL ne/mL ng/mL ng/mL ne/mL ng/mL ng/mL mL Validated ranges --approximate concentrations Serum PFOS PFOSA PFOSAA Rabbit 5.00-1000 ng/mL 5.00-1000 ng/mL 5.00-1000 ng/mL Bovine Estimates only. Use values for rabbit. Rat Estimates only. Use values for rabbit. Monkey & 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 M556 5.00-1000 ng/mL Attachment C: Ion Pair Standard Curves ETS-8-4.2 Extraction o f Fluorochemicals from Serum SM Environmental Laboratory Page 823 Page 15 of 15 Page 65 3M Medical Department Study: T-6889.6 3 M E n v ir o n m e n t a l L a b o r a t o r y ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 M ethod A n a ly sis o f P o t a ssiu m P er fl u o r o o c t a n e su lfo n a te o r O t h e r F l u o r o c h e m ic a l s in Se r u m E x tr a c ts U sin g H P L C -E lec t r o spr a y /M ass Spe c t r o m e t r y M ethod N um ber: ETS-8-5.1 A doption D ate: 03/01/99 Author: Lisa Clemen, Robert Wynne Revision Date: ^ Approved By: . $ " i ^ ---------- Laboratory Manager Group Leader <1 / z c . , D ate y /w / ? Date fjs*. A Clltwi. Technical Reviewer ohI i l / w D ate Bead Oopyof Original Initial Data 1.0 Scope and Application 1.1 Scope: This method describes the analysis o f serum extracts for fluorochemical surfactants using HPLC-electrospray/mass spectrometry. 1.2 A pplicable Com pounds: Fluorochemical surfactants or other fluorinated compounds, or other ionizable compounds. 1.3 M atrices: Rabbit, rat, bovine, monkey, and human serum, or other fluids as designated in the validation report. Word 6/95 3M Environmental Laboratory ETS-8-5.1 Analysis o f Serum Extract Using ES/MS Page 1 of 9 Page 66 3M Medical Department Study: T-6889.6 ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 2.0 Su m m a ry o f M ethod_______________________________________________ 2.1 This method describes the analysis o f fluorochemical surfactants extracted from serum or other fluids, using HPLC-electrospray/mass spectrometry, or similar system as appropriate. The analysis is performed by 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 tandem mass spectrometer to further verify the identity of a compound by detecting daughter ions o f the parent ion. 3.0 De fin it io n s ____________________________________________________ ____________________ 3.1 A tm ospheric Pressure Ionization (A PI): The Micromass Quattro II triple quadrupole systems allow for various methods o f 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 (i.e., not under a vacuum). 3.2 E lectrospray Ionization (ES, ESI): a method o f ionization performed at atmospheric pressure, whereby ions in solution are transferred to the gas phase via tiny charged droplets. These charged droplets are produced by the application of a strong electrical field. 3.3 Mass Spectrom etry, Mass Spectrom eter (MS), Tandem Mass Spectrom eter (M S/M S): The API Quattro II triple 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 may be 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 o f Micromass Quattro II triple quadrupole systems (post 1998) utilize a "Z-spray" conformation. The spray emitted 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 o f operation, cleaning, and maintenance are the same. However, Z-spray components and conventional 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 M ass Lynx Software: System software designed for the specific operation o f these Quattro II triple quadrupole systems. Currently MassLynx has Windows 95 and WindowsNT 4.0 versions. All versions are similar. For more details see the manual specific to the instrum ent (Micromass Quattro II triple quadrupole MassLynx or MassLynx NT User's Guide). 4.0 W arn ing s and C autions__________________________________________ ________________ _ 4.1 H ealth and Safety W arnings: 4.1.1 Use caution with the voltage cables for the probe. When engaged, the probe employs a voltage o f approximately 5000 Volts. 4.1.2 When handling samples or solvents wear appropriate protective gloves, eyewear, and clothing. 3M Environmental Laboratory ETS-8-5.1 Page 825 Page 2 o f 9 Page 67 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 4.2 Cautions: 4.2.1 Do not operate solvent pumps above capacity o f 400 bar (5800 psi) back pressure. If the back pressure exceeds 400 bar, the HP 1100 will initiate automatic shutdown. 4.2.2 Do not run solvent pumps to dryness. 5.0 I n ter fer en c es_____________________________________ ;__________________ 5.1 To minimize interferences when analyzing samples, teflon should not be used for sample storage or any part of instrumentation that comes in contact with the sample or extract. 6.0 Equipment____________________________________________________ 6.1 Equipment listed below may be modified in order to optimize the system. Document any modifications in the raw data as method deviations. 6.1.1 6.1.2 Micromass Quattro II triple quadrupole Mass Spectrometer equipped with an electrospray ionization source HP 1100 low pulse solvent pumping system, solvent degasser, column compartment, and autosampler 7.0 Su pplies and M aterials__________________;_____________________________________ 7.1 Supplies 7.1.1 High purity grade nitrogen gas regulated to approximately 100 psi (House air system) 7.1.2 HPLC analytical column, specifics to be determined by the analyst and documented in the raw data. 7.13 C apped autovials or capped 15 mL centrifuge tubes 8.0 R e a g en ts and Standards____________________________________ ;_____________________ 8.1 R eag en ts 8.1.1 Methanol,.HPLC grade or equivalent 8.1.2 Milli-QTM water, all water used in this method should be Milli-QTM water or equivalent, and may be provided by a M illi-Q TOC Plus system or other vendor 8.13 Ammonium acetate, reagent grade or equivalent 8.2 Standards 8.2.1 Typically two method blanks, two matrix blanks, and eighteen matrix standards are prepared during the extraction procedure. See ETS-8-4.1. 9.0 Sa m ple H andling___________________________________________________________ _____ 9.1 Fresh matrix standards are prepared with each analysis. Extracted standards and samples are stored in capped autovials or capped 15 mL centrifuge tubes until analysis. 3M E nvironm ental Laboratory.--=_ l-- ETS-8-5.1 Analysis ofSerum Extract Using ES/MS _ --. Page 826 Page 3 o f9 Page 68 3M Medical Department Study: T-6889.6 -- "------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 9.2 If analysis will be delayed, extracted standards and samples can be refrigerated at approximately 4 C, or at room temperature, until analysis can be performed. i 10.0 Q ua lity C o ntrol______________________________________________________________ __ 10.1 Solvent Blanks, Method Blanks and Matrix Blanks 10.1.1 Solvent blanks, method blanks and matrix blanks are prepared and analyzed with each batch to determine contamination or carryover. 10.1.2 Analyze a method blank and a matrix blank prior to each calibration curve. 10.2 M atrix Spikes 10.2.1 Matrix spikes are prepared and analyzed to determine the matrix effect on the recovery efficiency. 10.2.2 Matrix spike duplicates are prepared and analyzed to measure the precision and the recovery for each analyte. 10.2.3 Analyze a matrix spike and matrix spike duplicate per forty samples, with a minimum o f 2 spikes per batch. 10.2.4 Matrix spike and matrix spike duplicate concentrations will fall in the mid-range of the initial calibration curve. Additional spike concentrations may fall in the lowrange o f the initial calibration curve. 10.3 Continuing Calibration Verifications 10.3.1 Continuing calibration verifications are analyzed to verify the continued accuracy o f the calibration curve. 10.3.2 Analyze a mid-range calibration standard after every tenth sample, with a minimum o f one per batch. 11.0 C alibration and Standardization___________________________________________ _ 11.1 Analyze the extracted matrix standards prior to and following each set o f extracts. The average o f two standard curves will be plotted by linear regression (y .my + b), weighted 1/x, not forced through zero, using MassLynx or other suitable software. - 11.2 If the curve does not meet requirements, perform routine maintenance or reextract the standard curve (if necessary) and reanalyze. 11.3 For purposes o f accuracy when quantitating low levels of analyte, it may be necessary to use the low end of the calibration curve rather than the full range o f the standard curve. Example: when attempting to quantitate approximately 10 ppb o f analyte, generate a calibration curve consisting o f tiie standards from 5 ppb to 100 ppb rather than the full range o f the curve (5 ppb to 1000 ppb). This will reduce inaccuracy attributed to linear regression weighting o f high concentration standards. 3MEnvironmental Laboratory-- ETS-8-5.1 Analveis fFSitnim Fvtrsirt TTcino F 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 LIMS E00-2738 12.0 P ro ced u res_____________________________________________________ _____________ ____ 12.1 A cquisition Set up 12.1.1 Click on start button in the Acquisition Control Panel. Set up a sample list. Assign a filename using MO-DAY-last digit o f year-sample number, assign a method (MS) for acquiring, and type in sample descriptions. 12.1.2 To create a method click on scan button in the Acquisition control panel and select SIR (Single Ion Recording) or MRM. Set Ionization Mode as appropriate and mass to 499 or other appropriate masses. A full scan is usually collected along with the SIRs. Save acquisition method. If MS/MS instruments are employed, additional product ion fragmentation information may be collected. See Micromass MassLynx GUIDE TO DATA ACQUISITION for additional information and MRM (Multiple Reaction Monitoring). 12.1.3 Typically the analytical batch run sequence begins with a set o f extracted matrix standards and ends w ith a set o f extracted matrix standards. 12.1.4 Samples are analyzed with a continuing calibration check injected after every tenth sample. Solvent blanks should be analyzed periodically to monitor possible analyte carryover and are not considered samples but may be included as such!. 12.2 Using the A utosam pler 12.2.1 Set up sample tray according to the sample list prepared in Section 12.1.1. 12.2.2 Set-up the HP 1100/autosampler at the 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 12.2.23 Cycle time = 13.5 minutes 12.2.2.4 Solventramp *= Time 0.00 min. 8.50 min. 11.0 min. 12.0 min. MeOH 40% 90% 90% 40% 2.0 mM Ammonium acetate 60% 10% 10% 60% 12.2.2.5 Press the "Start" button. 12.3 Instrum ent Set-up 123.1 Refer to ETS-9-24.0 for more details. 123.2 Check the solvent level in reservoirs and refill if necessary. 3 M E nvironm ental L aboratory-- =- ETS-8-5.1 AnaVveia n f R anim F x tr a r t TTsino F.R/WS -- Page 828 Page 5 of 9 Page 70 3M Medical Department Study: T-6889.6 -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 12.3.3 Check the stainless steel capillary at the end o f the probe. Use an eyepiece to check the tip. The tip should be flat with no jagged edges. If the tip is found to be unsatisfactory, disassemble the probe and replace the stainless steel capillary. i 123.4 Set HPLC pump to "On". Set the flow to 10 - 500 uL/min or as appropriate. Observe droplets coming out o f the tip o f the probe. Allow to equilibrate for approximately 10 minutes. 123.5 Turn on the nitrogen. A fine mist should be expelled with no nitrogen leaving around the tip o f the probe. Readjust the tip o f the probe if no mist is observed. 12.3.6 The instrument uses these parameters at the following settings. These settings may change in order to optimize the response: 123.6.1 Drying gas 250-400 liters/hour 123.6.2 ESI nebulizing gas 10-15 liters/hour 1 2 3 .6 3 HPLC constant flow mode, flow rate 10 - 500 fiL/min 12.3.6.4 Pressure <400 bar (This parameter is not set, it is a guide to ensure the HPLC is 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. 12.3.8 Print the tune page, with its parameters, and store it in the study .binder with a copy taped into the instrument log. 12.3.9 Using the cross-flow counter electrode in the ES/MS source is recommended for the analysis o f biological matrices. 123.10Click on start button in the Acquisition Control Panel (this may vary among MassLynx versions, see appropriate MassLynx USER'S GUIDE). Press the start button. Ensure start and end sample number includes all samples to be analyzed. 13.0 D a ta An a ly sis and C a lcu la tio n s________________________________________________ 13.1 Calculations: 13.1.4 Calculate matrix spike percent recoveries using the following equation: % Recovery = Observed Result - Background Result 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 concentration o f PFOS, or other fluorochemical, in matrix (pg/m L ): fag o f PFOS calc, from std. Curve x Dilution Factor) x 1 ue _ (Initial Volume of matrix (mLl + mL o f Surrogate Standard) 1000 ng Final Volume (mL) ETS-8-5.1 Analysis o f Serum Extract Usinc ES/MS 3M Environm ental 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 E00-2738 14.0 M eth o d P erform ance______________________________________ _ _ _______ ___ 14.1 Method Detection Limit (MDL) and Limit o f Quantitation (LOQ) are method, analyte, and matrix specific. Please see ETS-8-4.1, Attachm ent B, for a listing o f current validated MDL and LOQ values. 14.2 Solvent Blanks, M ethod Blanks, and M atrix Blanks 14.2.1 Solvent blanks, method blanks, and matrix blanks values are must be below the lowest standard in the calibration curve 14.3 C alibration Curves 14.3.1 The r2value for the calibration curve must be 0.980 or better. 14.4 M atrix Spikes 14.4.1 Matrix spike percent recoveries are must be within 30% o f the spiked concentration. 14.5 C ontinuing Calibration Verifications 14.5.1 Continuing calibration verification percent recoveries must be 30% o f the spiked concentration. 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 die 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 of 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 R e c o r d s _________________________________________________________________________ _ 16.1 Each page generated for a study must have the following information included either in the header or hand written on the page: study or project number, acquisition method, integration method, sample name, extraction date, dilution factor (if applicable), and analyst 16.2 Print the tune page, sample list, and acquisition method from MassLynx to include in the appropriate study folder. Copy these pages and tape into the instrument runlog. 16.3 Plot the calibration curve by linear regression, weighted 1/x, then print these graphs and store in the study folder. 16.4 Print data integration summary, integration method, and chromatograms, from MassLynx, and store in the study folder. 3M Environmental Laboratory ETS-8-5.1 Analysis ofScrum Extract Using ES/MS ____ _ Page 830 Page 7 of 9 Page 72 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 16.5 Summarize data using suitable software (Excel 5.0) and store in the study folder, see A ttachm ent A for an example o f a summary spreadsheet 16.6 Back up electronic data to appropriate medium. Record in study notebook the file name and location o f backup electronic data. 17.0 Tables. Diagrams. Flowcharts, and Validation Data______________ 17.1 Attachment A: ETS-8-5.1 Data summary spreadsheet 18.0 References___________________________________________________ _ 18.1 FACT-M-4.1, "Extraction o f Potassium PerfLuorooctanesulfonate 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 Ionization/Mass Spectrometer Quattro n triple quadrupole Systems'* 18.3 The validation report associated with this method is ETS-8-4.0 & 5.0-V-l. 19.0 Affected Documents____________________________________________________ 19.1 ETS-8-4.1, "Extraction o f Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry" 20.0 Revisions__________________________________________________________ ___ R evision Number. 1 Reason For Revision Section 6.1.2 Clarification o f HP1100 system components. Section 11.1 Average o f two curves, not standard values, are used for plotting linear regression and added the 1/x weighting o f the curve. Section 12.2.2.4 Clarification o f solvent ramp. Section 17.1 Changed from attachment B to A. Revision Date 04/02/99 3M Environm ental Laboratory ETS-8-5.1 Analysis of Serum Extract Using ES/MS Page 831 Page 8 of9 Page 73 3M Medical Department Study: T-6889.6 ------------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Laboratory Study # 1 Study: Test Material: Matrix/Final Solvent M ethod/R evision: Analytical Equipment System Number Instrument Software/Versioru Filename: R-Squared Value: Slope: Y Intercept Date o f Extraction/Analyst Date o f Analysis/Analyst Group Dose Sam ple# Concentration ug/mL Initial Voi. m . D ilu tion Factor Final Cone. ug/mL Slope: Taken from linear regression equation. Group/Dose: Taken from the study folder. Sample#: Taken from the study folder. Concentration (ug/mL): Taken from the MassLynx integration summary. Initial Volum e (mL): Taken from the study folder. D ilution Factor: Taken from the study fold . Final Cone. (ug/mL): Calculated by dividing the initial volume from the concentration Attachment A: Summary Spreadsheet ETS-8-5.1 Analysis o f Serum Extract Using ES/MS 3M Environm ental Laborato ry , __ Page 832 Page 9 o f9 Page 74 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Method Modification Methods: Section modified: ETS-8-7.0, ETS-8-5.1, ETS-8-97.0 add section 14.3.2 M ethod reads: NA Modify method to read: 14.3.2 The second (bracketing) calibration curve may be deactivated if instrumental drift affects the data. The first curve and acceptable calibration checks hall bracket usable data. Effective date o f modification ETS-8-7.0: 7/22/99 Effective date o f modification ETS-8-5.1: 4/26/99 Effective date o f modification ETS-8-97.0: 7/28/99 fa -L - lb --- Signature o f PAI and date WlQ`i i G V Exact Copyof Original 3M Environmental Laboratory Page 833 Page 75 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 3 M E n v ir o n m e n t a l L a b o r a t o r y M ethod A n a l y sis o f P o t a ssiu m P er elu o r o o c ta n esu lfo n a te o r O t h e r F l u o r o c h e m ic a l s in Ser u m E x tr a c ts U sin g H P L C -E lec tr o spr a y /M ass Spec tr o m etr y M ethod N um ber: ETS-8-5.2 Adoption D ate: 03/01/99 Author: Lisa Clemen, Kris Hansen Revision Date: ) I 0 1 Approved By: Laboratory Manager -- _________________________________ Q j // 'c- j' s/ /s oL/ s/ Date K a ~ - XA. _ Group Leader n O ^/o l ! Date Technical Reviewer Date Ba/c.tCoJpyofZ(M/izaM/o f 1.0 S c o p e a n d A p p l ic a t io n _______________________________________ _______ _______ ___________ 1.1 Scope: This method describes the analysis of serum extracts for fluorochemical surfactants using HPLC-electrospray/mass spectrometry. 1.2 A pplicable Compounds: Fluorochemical surfactants or other fluorinated compounds, or other ionizable compounds. 1.3 M atrices: Rabbit, rat, bovine, monkey, and human serum, or other fluids as designated in the validation report. Word 6/95 * 3M Environmental Laboratory. . ^ ETS-8-5.2 n f C _ . ~ C ..* . .. T T ,,;.._ C C fW O Page 834 Page 1 of 11. Page 76 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 2.0 Su m m a r y o f M e t h o d _____________________________________ ____________ 2.1 Although supported by a validation for most commonly used matrices, this is a performance-based method. Careful attention should be paid to method QC as there is great variability in sera. This method describes the analysis of fluorochemical surfactants extracted from serum or other fluids, using HPLC-electrospray/mass spectrometry, or similar system as appropriate. The analysis is performed by 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 tandem mass spectrometer to further verify the identity of a compound by detecting daughter ions of the parent ion. 3.0 D efinitions_________________________________________________________ 3.1 A tm ospheric Pressure Ionization (API): The Micromass Quattro Q and Ultima 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., not under a vacuum). 3.2 Electrospray Ionization (ES, ESI): a method of ionization performed at atmospheric pressure, whereby ions in solution are transferred to the gas phase via tiny charged droplets. These charged droplets are produced by the application of a strong electrical field. 3.3 M ass Spectrom etry, M ass Spectrom eter (MS), Tandem M ass Spectrom eter (M S/M S): The API Quattro II and Ultima triple 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 may be 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 spray emitted 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. However, Z-spray components and conventional 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 M ass Lynx Softw are: System software designed for the specific operation of these Quattro II triple quadrupole systems. Currently MassLynx has Windows 95 and WindowsNT 4.0 versions. All versions are similar. For more details see the manual specific to the instrument (Micromass Quattro II or Ultima triple quadrupole MassLynx or MassLynx NT User's Guide). 4.0 W a r n i n g s a n d C autions......................... ..- .... ........ 4.1 H ealth and Safety W arnings: 4.1.1 Use caution with the voltage cables for the probe. When engaged, the probe employs a voltage o f approximately 5000 Volts. Word 6/95 3M Environmental Laboratory ^ ETS-8-5.2 Analysis of Serum Extract Using ES/MS Page 835 Page 2 o f 1 1 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 HPLC will initiate automatic shutdown. 4.2.2 Do not run solvent pumps to dryness. 5.0 In te r fer e n c e s ______________________________________________ 5.1 To minimize interferences when analyzing samples, Teflon should not be used for sample storage or any part of instrumentation that comes in contact with the sample or extract. 6.0 E q u i p m e n t _________________________________________ 6.1 Equipment listed below may be modified in order to optimize the system. Document any modifications in the raw data as method deviations. 6.1.1 6.1.2 Micromass Quattro II or Ultima triple quadrupole Mass Spectrometer equipped with an electrospray ionization source HP1100 or Agilent low pulse solvent pumping system, solvent degasser, column compartment, and autosampler 7.0 Supplies a n d M aterials____________________________________________________ 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 determined by the analyst and documented in the raw data. 7.1.3 Capped autovials and capped 15 mL centrifuge tubes 8.0 R e a g e n t s a n d St a n d a r d s ___________________________________ _ _ _ 8.1 Reagents 8.1.1 Methanol* HPLC grade or equivalent 8.1.2 Milli-QTM water, all water used in this method should be Milli-QTM water or equivalent, and may be provided by a Milli-Q TOC Plus system or other vendor 8.1.3 Ammonium acetate, reagent grade or equivalent 8.2 Standards 8.2.1 Typically two method blanks, two matrix blanks, and eighteen matrix standards are prepared during the extraction procedure. See ETS-8-4.2. 3M Environmental Laboratory ETS-8-5.2 A n a t r a t e n f S w t m , B v t r a n t TTei n tr Page 836 Page 3 of 11 Page 78 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 9.0 S a m p l e H a n d l in g ________________________________________________ 9.1 Fresh matrix standards are prepared with each analysis. Extracted standards and samples are stored in capped autovials or capped 15 mL centrifuge tubes until analysis. * 9.2 If analysis will be delayed, extracted standards and samples can be refrigerated at approximately 4 C, or at room temperature, until analysis can be performed. 10.0 Q uality C o n t r o l ___________________________________________ _______ 10.1 Solvent Blanks, Method Blanks and Matrix Blanks 10.1.1 Solvent blanks, method blanks and matrix blanks are prepared and analyzed at least once during the course of the study to determine if contamination occurred during sample prep. 10.1.2 Analyze at least one solvent blank prior to 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 and method QC are prepared in a surrogate matrix (e.g. curves in rabbit sera, samples are monkey sera), matrix spikes and matrix spike duplicates are prepared in blank sample matrix (e.g., monkey sera) and analyzed to verify extraction efficiency. 10.2.2 If curves and method QC are prepared in the same matrix as samples, no additional matrix spikes are required. 10.3 Continuing Calibration Verifications (CCVs) 10.3.1 Continuing calibration verifications are analyzed to verify the continued accuracy of the calibration curve. 10.3.2 Analyze two calibration standards (one at each of 2 levels) after every one to ten samples, with a minimum of two per batch and always finishing an injection sequence with at least two calibration standards. 11.0 C a libration and Standardization ____________________ _ 11.1 Analyze the extracted matrix calibration 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. 11.2 If the curve does not meet requirements, perform routine maintenance, reextract samples, or reanalyze the standard curve. 1 1 3 For purposes of accuracy when quantitating levels of analyte at the limits of the curve range, it may be necessary to use either the low end or the high end of the calibration curve rather than the fall range o f the standard curve. Example: when attempting to quantitate approximately 10 ppb of analyte, it may be beneficial to generate a calibration curve consisting of the standards from 5 ppb to 100 ppb rather than the fall range of the curve (5 ppb to 1000 ppb). This will reduce inaccuracy attributed to linear regression weighting of 3M Environmental L aboratory.^ ETS-8-5.2 Analysis of Scrum Extract Usine ES/MS Page 837 Page 4 of 11 Page 79 3M Medical Department Study: T-6889.6 - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 high concentration standards. It is also acceptable to break the linear range into a low curve and a high curve. If this 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 ,2 5 , 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 up 12.1.1 On the MassLynx main page, set up a 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=instmment name (D for "Davey") YY=year o f test (01) MM=month of test (07) DD=day o f 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, and a 3-digit sequential file number that starts with 1 and increases 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 o f test (12) ###=3-digit sequential file number starting with 1 through 999 (001) Also, as part of the sample list, assign a method (MS) for acquiring, an inlet file, a bottle number, an injection volume and sample descriptions. 12.1.3 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 and mass to 499 or other appropriate masses. Also set the acquisition start and stop times. Save acquisition method. If MS/MS instruments are employed, additional product ion fragmentation information may be collected. See Micromass MassLynx GUIDE TO DATA ACQUISITION for additional information and MRM. 12.1.4 Typically the analytical batch run sequence begins with solvent blanks and a set of extracted matrix standards. 12.1.5 Sample extracts are analyzed with 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 l.ahnratary ETS-8-5.2 Analysis nf Swum F.xtract I kino F.S/MS Page 838 Page 5 of 11 Page 80 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 12.2 Using the HPLC 12.2.1 Set up sample tray according to the sample list prepared in Section 12.1.1. 12.2.2 Set-up the HPLC to the 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 12.2.223 Cycle time = 10.0 minutes 12.2.2.4 Flow rate = 300 pL/min 12.2.2.5 Mobile Phase (program) Time 0.00 min. 1.00 min. 5.50 min. 7.50 min. 8.00 min. MeOH 10% 10% 95% 95% 10% 2.0 mM Ammonium acetate (in H2O) 90% 90% 5% 5% 90% 12.3 Instrument Set-up 12.3.1 Refer to ETS-9-24 for more details. 12.3.2 Check the solvent level in reservoirs and refill if necessary. 12.3.3 Check the stainless steel capillary at the end of the probe. Use an eyepiece to check the tip. The tip should be fiat with no jagged edges. If the tip is found to be unsatisfactory, disassemble the probe and replace the stainless steel capillary. The probe should be checked weekly. 12.3.4 Set HPLC pump to "On". Set the flow to 10 - 500 pL/min or as appropriate. Observe droplets coming out of the tip of the probe. 12.3.5 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. 12.3.6 The instrument uses these parameters at the following settings. These settings may change in order to optimize the response: 12.3.6.1 Drying gas 250-400 liters/hour 12.3.6.2 ESI nebulizing gas 10-15 liters/hour 12.3.6.3 HPLC constant flow mode, flow rate 10 - 500 pL/min 12.3.6.4 Pressure <400 bar (This parameter is not set, it is a guide to ensure the HPLC is 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 Environmental Laboratory-- ^ ETS-8-5.2 Analysis of Serum Extract Using ES/MS ------- -- Page 839 Page 6 of 11 Page 81 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 12.3.8 Print the tune page, MS file, HPLC parameters, 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 main page (this may vary among MassLynx versions, see appropriate MassLynx USER'S GUIDE). Ensure start and end sample number includes all samples to be analyzed. 13.0 D a t a A nalysis 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: % Recovery ObservedResult-- MatrixBlankResult x 100 Spiking Level 13.1.2 Calculate percent difference using the following equation: % Difference ExpectedCone. - CalculatedCone. x 100 ExpectedCone. 13.1.4 Calculate actual concentration of PFOS, or other fluorochemical, in matrix (pg/mL): ( Cone, of PFOS Calc, fromStd. Curve(ng/ mL) x DilutionFactor) ( InitialVolumeof Matrix(jnL) + mL of SurrogateStandard) ] | FinalVolume( mL) } 1fJg 1000ng 14.0 M e t h o d Pe r f o r m a n c e ______________________________________________ 14.1 Method Detection Limit (MDL) and Limit of Quantitation (LOQ) are method, analyte, and matrix specific. Please see ETS-8-4.2, A ttachm ent B, for a listing of current validlated MDL and LOQ values. 14.2 Solvent Blanks, M ethod B lanks, and M atrix Blanks 14.2.1 Solvent blanks, method blanks, and matrix blanks values must be below the lowest active standard in the calibration curve. 14.3 C alibration Curves 14.3.1 The coefficient o f determination value for the calibration curve must be 0.990 or better. 3M Environmental Laboratory-- - . - ETS-8-5.2 Annlvsis n f Sw um F.xrrart U sina RS/MS ---- -- Page 840 Page 7 of 11 Page 82 3M Medical Department Study: T-6889.6 -- -- - ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS E00-2738 14.3.2 All active calibration curve points must be within 25% of the theoretical value with the exception of the LOQpoint, which may deviate up to 30%. 14.3.3 Calibration standards withpeak areas less than two times the curve matrixblank t must be deactivated to disqualify a datarange that maybe affected by background levels of the analyte. 14.3.4 Low or high curve points may be deactivated to optimize a linear range appropriate to the data. 14.3.5 Not including low or high points dropped to optimize the linearrange, curve points may be deactivated if they deviate more than 25%fromthe theoretical value when the curve is evaluated over alinear range appropriate to the data. 14.3.6 Onepoint below the LOQmay remainactive even if it deviates more than30% or has apeak arealess thantwo times the matrix blank; however, the LOQwill be defined at the lowest point with acceptable deviation. 14.3.7 A valid calibration curve must contain at least 5 active points above andincluding 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 shouldbe discussed in the report. 14.5 Continuing Calibration Verifications (CCVs) 14.5.1 Continuing calibration samples within the linearrange of the runmust show a percent recovery within25%of the spiked concentration. If a CCV is outside of this recovery, subsequent data should not be accepted. Acceptable data must be bracketed bythe curve andpassing CCVs. 14.6 If criteria listed inthis methodperformance section isn't met, maintenance may be performed on the systemand 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 criteriahave not been met, the data must be footnoted ontables anddiscussed in the text of the report. 15.0 P o llu tion P revention and W aste M anagement 15.1 Sample extract waste andflammable solvent is disposed inhighBTU containers, andglass pipette waste is disposed in broken glass containers located inthe laboratory. 16.0 R ecords________________________ ____________________________ 16.1 The first page of each datapacket generated for astudy must have the following informationincluded either in the header, in the footer or handwritten on the page: study or project number, instrument, sample matrix andtime point, date, and analyst. 16.2 A data packet includes the following: data review summaryform, MassLynx quantify compound summaryreport for each target analyte, quantify calibration report for each target analyte (curve), method report, Word document listing set-up parameters, tune 3M Environmental Laboratory^. ETS-8-5.2 Analysis of Serum Extract Using ES/MS =----.. . Page 841 Page 8 o il 1 Page 83 3M lyledical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 method report, MassLynx scanning method report, HPLCmethod report, sample list, and quantity sample report (chromatogram). 16.3 For each analysis, after printing the tune method report, Word document listing, set-up parameters, MassLynx scanning method report, andsample list, copy and tape into the instrument runlog. The original is maintained in the data packet. 16.4 On each page of the quantifycompoundreport, quantify calibration report (curve), and quantify sample report (chromatogram), the following information must be included either in the header, the footer, or handwrittenon the page: study or project number, instrument, method, calibration (the method andcalibration are usually assigned the same name), analyst, and date. 16.5 The analyst must date and initial the first page in a packet as long as their initials and date are electronically included on each page. If initials and date are not electronically included, they must dateand initial each page. 16.6 Summarize data using suitable software (e.g., Excel) for inclusion in the final report. See Attachment A for anexample of a summaryspreadsheet. 16.7 Back up electronic datato appropriate medium. Record the file name and location of backup electronic datain instrument log book. 17.0 Tables. Diagrams. Flowcharts, and Validation Data______________________ 17.1 Attachment A: Data summaryspreadsheet. 18.0 References 18.1 FACT-M-4.1, "Extraction of PotassiumPerfluorooctanesulfonate or Other Fluorochemical compounds fromSerumfor Analysis Using HPLC-Electrospray/Mass Spectrometry 18.2 ETS-9-24.0, "Operation andMaintenance of the Micromass Atmospheric Pressure Ionization/Mass Spectrometer Quattro II triple quadrupole Systems" 18.3 The validation report associated with this method is E T S-8-4.0 & 5 .0 -V -l. 19.0 Af fe c t e d Documents _____________ _ _ _ _ _ 19.1 ETS-8-4.2, "Extraction of PotassiumPerfluorooctanesulfonate or Other Fluorochemical Compounds fromSerumfor Analysis Using HPLC-Electrospray/Mass Spectrometry" 3M Environmental Laboratory^^ ETS-8-5.2 Analysis of Serum Extract Usina ES/MS Page 842 Page 9 of 11 Page 84 3M Medical Department Study: T-6889.6 ? -- ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS EOO-2738 20.0 R e v is io n s ______________________________________________________________________ _________ _ Revision ; Number. Reason For Revision * 1 Section 6.1.2 Clarification ofHP1100 systemcomponents. Section 11.1 Average of two curves, not standard values, are used for plotting linearregression and addedthe 1/x weighting of the curve. Section Section 1172..12.C2.h4aCnglaerdiffircoatmionattoafcshomlveennttBratmopA.. Revision Date 04/02/99 2 10.1 Clarified when blanks are ran. 10.2 Added instructions for when surrogate matrix is used. 10.3 Specify requirements for CCVs. 11.1 Requires only a calibration curve before the samples. 11.2 Clarify what to do if curve does not meet requirements. 11.3 Allow to truncate the curve. 12.1.1 Clarify sample list ID. 12.1.3 Clarify typical run. 12.2 Changes to mobile phase gradient and specify flow rate. 14.3 Change acceptable limits. Add specifics for acceptance of calibration curve. 14.3.3 When to deactivate calibration standards based on blank response. 14.3.5 When to deactivate calibration standards within the linear range. 14.4 Modifies evaluation and use of matrix spikes. 14.5 Describes evaluation and use of CCVs. 14.5.1 Evaluation of CCVs. 16.0 Add requirements for records and documentation. Attachment A: Summary Spreadsheet ETS-8-5.2 Analysis of Serum Extract Using ES/MS 3M Environmental Laboratory^. -1 ---------- Page 843 Page 10 of U Page 85 3M Medical Department Study: T-6889.6 -- ------= ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Laboratory Study # * Study: Test Material: MatrixyFinai Solvent: Method/Revision: Analytical Equipment System Number Instrument Software/Version: Filename: R-Squared Value: Slope: Y Intercept' Date of Extraction/Analyst: Date of Analvsis/Analvst: Group Dose Sample# Concentration ue/mL Initial VoL m l. Dilution Factor Final Cone. ue/mL Slope: Taken from linear regression eauation. Group/Dose: Taken from the study folder. Sample#: Taken from the study folder. Concentration (ue/mL): Taken from the MassLvnx integration summary. Initial Volume (mL): Taken from the study folder. Dilution Factor: Taken from the study folder. Final Cone. (ug/mL): Calculated by dividing the initial volume from the concentration Attachment A: Summary Spreadsheet ETS-8-5.2 3M Environmental Laboratory . _ Analysis of Serum Extract Using ES/MS Page 844 Page 11 of 11 Page 86 3M Medical Department Study: T-6889.6 3M Medical Department Study. T-6889.6 -- -- -- ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS E00-2738 Analytical Report: LFIAMCSTET0O0X-2-176384 Appendix D: Dose Confirmation Analyses and Data Summary Tables Table 12. Dose Confirmation Analyses - Extracted 11/17/00, Analyzed 11/27/00 Group Dose Sam ple# Concentration o f PFOA Expected Cone of PFOA ug/mL or % Ree PFOA ug/mL* % Recovery Mean Method Blk 111700-W B Ik-1 111700-W BIk-2 111700-W BIk-3 QC B-418-020-A-C-100ppb-MS B -418-020-A -C -100oO b-M S D S tability Day 0 11/10/00 B-418-020-A-C-0.5 mL B-418-020-A-A-0.5 mL B-418-020-A-D10-0.5 mL B-418-020-A-A-1 B -4 18-020-A -A -2 B-418-020-B-A-1 B-41 B-020-B-A-2 Stability Day 0 11/10/00 B-41 B-020-C-A-1 B -4 18-020-C -A -2 B-41B-020-D-A-1 B -4 18 -0 2 0 -D -A -2 < LO Q (10 ng/mL) <LOQ (10 nfymL) <LOQ(10ng/m 0.0822 0.0855 < LO Q (10 ng/mL) < LO Q (10 ng/mL) < LO Q (10 no/m < LO Q (10 ng/mL) < LO Q (10 ng/mL) 191 189 485 438 1809 1893 NA NA NA 0.0979 0.0979 NA NA NA NA NA 200 200 600 600 2000 2000 NA 64% 87% NA NA 95% 95% 81% 73% 90% 95% NA 86% NA NA 95% 77% 93% Stability Day 10 11/10/00 B-418-020-E-A-1 B -4 18 -0 2 0 -E -A -2 B -418-0 2 0 -A -D 1 0 -1 B-418-020-A-D10-2 B-418-020-B-D10-1 B -418-020-B -D 10 -2 B -418 -0 2 0 -C -D 1 0 -1 B-418-020-C-D10*2 B -4 18 -0 2 0 -D -D 1 0-1 B -4 18 -0 2 0 -D -D 1 0 -2 B -4 18 -0 2 0 -E -D 1 0-1 5579 6350 < LO Q (10 ng/mL) < LO Q (10 ng/mL) 177 175 461 451 1732 1695 5825 6000 6000 NA NA 200 200 600 600 2000 2000 6000 B -4 18 -0 2 0 -E -D 1 0 -2 B-418-020-A-C-1 C o n c e n tra tio n 11/10/00 B -418-020-B -C -1 B -4 18-020-B -C -2 B -4 18 -0 2 0 -C -C -1 B -4 18 -0 2 0 -C -C -2 B -418-0 2 0 -D -C -1 B -4 18 -0 2 0 -D -C -2 B -4 18 -0 2 0 -E -C -1 5614 <LOQ (10 ng/mL) < LO Q (10 no/m 179 170 494 478 1820 1800 6140 6000 NA NA 200 200 600 600 2000 2000 6000 B -418 -0 2 0 -E -C -2 6026 6000 * information was obtained from chain of custody forms accompanying samples. 93% 106% NA 88% 88% 77% 75% 87% 85% 97% 94% NA 90% 85% 82% 80% 91% 90% 102% 100% 99% NA 86% 76% 86% 95% NA 87% 81% 90% 101% PFOA RPD NA 4% NA NA 1% 10% 5% 13% NA 1% 2% 2% 4% NA 5% 3% 1% 2% P n v im n m a n ta l I a h n ra tn rv 3M Environmental Laboratory Page 845 Paae 21 Page 87 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ^ ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS EOO-2738 Analytical Report: FACT TOX-164 LIMS EOO-2738 Table 13. Dose Confirmation Analyses - Extracted 11/27/00, Analyzed 11/28/00 Group Dose Sam ple# Concentration o f PFOA uq/m Lor% R ec Method Bik 1 12700-WBIk-1 112700-WBIk-2 < LO Q (10 ng/mL) <LOQ(10 rtg/m L) 112700-WBIk-3 < LO Q H O no/m Q C B-418-020-A-C-100ppb-MS B-418-020-A-C-1 OODDb-MSD 0.0864 0.0856 Stab11il/i1ty0/D00ay 0 B-418-020-A-C-0.5 mL B-418-020-A-A-0.5 mL < L O Q (10 ng/mL) < L O Q (10 ng/mL) B-418-020-A-D10-0.5 mL B-418-020-A-A-1 < LO Q (10 no/mLI (10< LO Q ng/mL) B-418-020-A-A-2 < LO Q (10 no/m B-418-020-B-A-1 155 B-418-020-B-A-2 147 Stability Day 0 11/10/00 B-418-020-C-A-1 B-418-020-C-A-2 489 468 B-418-020-D-A-1 1788 B-418-020-D-A-2 1793 B-418-020-E-A-1 * 11183 B-418-020-E-A-2* 11256 B-418-020-A-D10-1 < LO Q (10 ng/mL) 1 0 1 V B-418-020-A-D10-2 B-418-O20-B-D10-1 138 B-418-020-B-D10-2 157 Stability Day 10 B-418-020-C-D10-1 11/10/00 -------- B-418-020-C-D10-2 B-418-020-D-D10-1 ,n1 464 496 1560 B-418-020-D-D10-2 1758 B-418-020-E-D10-1 5553 B-418-020-E-D10-2 5957 Concentration 11/10/00 B-418-020-A-C-1 B-418-020-A-C-2 B-418-020-B-C-1 B -4 1 8-020-B -C -2 B-418-020-C-C-1 B-418-020-C-C-2 B-418-020-D-C-1 B-418-020-D-C-2 B-418-020-E-C-1 < LO Q (10 ng/mL) < LO Q (10 no/m 158 165 452 443 1741 1883 5376 B-418-020-E-C-2 5441 Expected Cone of PFOA ug/mL* % Recovery NA NA NA NA 0.0979 86% 0.0979 87% NA NA NA NA NA NA 200 200 600 600 2000 2000 6000 NA 78% 73% 82% 78% 89% 90% 186%* 6000 NA NA 188%* NA 200 200 600 600 2000 2000 6000 69% 78% 77% 83% 78% 88% 93% 6000 99% NA NA 200 200 600 600 2000 2000 6000 NA 79% 82% 75% 74% 87% 94% 90% 6000 91% PFOA Mean NA 88% NA NA 76% 60% 90% 187%* NA 74% 80% 83% 96% NA 81% 75% 91% 90% *oAuI=ntlfiSoearrm.maptlieonrew-eaxstroabcttaeidneodnf0ro1m/23c/h0a1intoocfocnufsirtmodyrefcoormvesrya.ccRoemcpoavenryyinwgassanmoptlceosn. firmed, considered an PFOA RPD NA 1% NA NA 6% 4% 0% 1% NA 13% 7% 12% 7% NA 4% 2% 8% 1% 3M Fnvirnnmanta/ Laboratory 3M EnvironmentalLaboratot^u^. ,, Page 846 Paae22 Page 88 3M Medical Department Study: T-6889.6 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS EOO-2738 Analytical Report: LFIAMCSTETOOOX--2176348 Table 14. Dose Confirmation Analyses - Extracted 01/17/01, Analyzed 01/23/01 Group Dose Sam ple# Concentration o f PFOA Expected Cone of ug/mL o r % Ree PFOA ug/mL* % Recovery Method Blk 0 1170 1-W B Ik-1-1 011701-WBIk-1-2 < LO Q (10 ng/mL) < LO Q (10 no/mL) NA NA Stability Day 0 B-418-020-E-A-1 5466 6000 11/10/00 B-418-020-E-A-2 5014 6000 * Information was obtained from chain ofcustody forms accompanying samples. NA 91% 84% PFOA Mean NA 87% PFOA RPD NA 9% Table 15. T O X 164 Data Summary of PFOA Concentration--Rat Serum (pg/mL) TGlmeenpdoeirn/ t PFOA Cone. Average* SO Group 1 0.0 mg/kg/day Group# 10 mg/kg/day Group 5 30 mg/kg/day LactaFteiomnaDleay 22 End of cMoahlaebitation LactaFteiomnaDleay 22 End of cMoahleabitation LactaFteiomnaDleay 22 End of cMoahleabitation <LOQ (0.0rt0=5328 ug/mL) 0.0344n=*03.0148 0.370n=* 100.0805 51.n1=*190.30 1.02n*=100.425 45.n3=*1102.6 3M Environmental Laboratorv F .n v irn n m e n tn l T s ih n rn ta ry - - - -------- _ Page 847 Pace 23 Page 89 3MMedical Department Study: T-6889.6 3M Medical Department Study. T-6889.6 -- Appendix E: Data Spreadsheets -- ARGUS 418-020 Analytical Report: FACTTOX-164 LIMS EOO-2738 Analytical Report FACT TOX-164 LIMS EOO-2738 3M Environmental Laboratorv 3M Environmental Laboratory._____ __. Page 848 Pace 24 Page 90 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus# 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Study: Preduct N um befT Subitanee): M an: Mcthodttcwion: Analytical Eqwpnam Syitcm Number. iH m m tt Soflnre/Vanai: Filename: R-Sqaand Value: Slope inFACT-TOX-164, Aigul 411-020, t e l (Cavage) Twodjcncnnon Reproduction Study of AFFO Rati FFOA Caeccuaaaeu Sanpki ETS-6-4.1 A ETS-8-5.1 Devey 070799 Maaalyw3.4 See Below See A ttadnenti Set A ttadaran Duel of Etmenoa/Aoelyat Datei of Asafym/Ajulyic Dm* of Data ReduetmVAnalyst Sample Data DOSE VERIFICATION SAMPLES Croup Sample a Date Method Blk 111700-WBlk-t IU700-WBIk-2 111700-WBik-J QC B-4l-020-A-C-100ppb-MS B-d 184120-A-C- 100ppb-MSD Stability Day 0 11/10/2000 B-41W20-A-C-0.5 mL B4I8-020-A-A-0.5 mL B-t ie-020-A-D 10-0.J mL Stability Day 0 11/10/2000 B-418-020-A-A-1 B-418-020-A-A-2 B-418-O20-B-A-I B-418-02D-B-A-2 B-4I8-020-C-A-I B-418-020-C-A-2 B-4II-020-D-A-1 B-4H-020-D-A-: B-4 IM 20-E -A -I B-41S-020-E-A-2 StawbixliotynoDaaoy 10 B-4I8-020-A-DKM B-U8-020-A-DI0-2 B-418-020-B-DI-1 B-4U-020.B-D10-2 B-4II-02OC-DIO-I B-411-020-C-D10-2 B-41S-020-D-DI0-I B-4I8-020-D-D10-2 B-41S-020-E-D10-1 B-4I8-020-E-DIO-2 Canecatradon B-418-020-A-C-I 11/10/2000 B-4II-020-A-C-2 B-418-020-B-C-l B-4I8-020-D-C-2 B-4I8-020-C-C-1 B-418-020-C-C-2 B-418-020-D-C-I B-4I8-020-D-C-2 B -4 IM 20-E -C -I B-4I84120-E-C-2 FFOA/FOAA * Periluoroocu noaic Date Entertd/By: 01/15/01 LAC Date Verified/ By: 0I/I& 0I kjh 11/17/00 RWW 11/27/00 MMH 11/21/00 MMH Eitracaaa VaL mL 1 1 I 1 1 1 1 1 l 1 1 1 1 l I 1 ( I 1 1 1 1 1 1 1 1 1 1 1 1 1 \ 1 1 l Surrogate Vertflad 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 Center Letter AwOmg/mL B 0.2 nig/mL C-0.6m g/siL D 2 trgrmL Letraensu DUaPaa Factar 1.23 1.23 1.23 1.23 1.23 1.25 1.23 1.23 1.25 1-25 1.23 1.25 1.23 1.23 1.23 1.25 1.23 1.23 1-23 1.25 U5 1.23 103 1.25 105 1.23 IOS 1.25 1.23 IOS 103 1.25 103 IOS tas 103 105 105 FFOA Dtlauua Factor 1 1 1 1 1 2 2 2 2001 2001 2001 2001 3001 5001 20001 20001 30001 50001 2001 2001 2001 2001 5001 3001 20001 20001 30001 50001 2001 2001 2001 2001 5001 5001 20001 20001 50001 50001 FFOA C iac. af/aiL 0.00 0.00 0.00 65.7 61.40 0.00 0.00 0.00 0.00 0.00 76.24 73.72 77.34 70.01 72.35 75.73 89.27 101.60 0.00 0.00 70.76 69.91 73.80 72.13 69.27 67.79 95.20 I9.S3 0.00 0.00 71.72 67.94 79.10 76.41 72.10 71.98 91.24 96 42 Fiioamc DOOI1270IS D001127016 D001127017 DODI 127065 D001127066 DOOI127018 D001127019 D001127022 DOOI 127025 DOOI127026 DOOI127033 DOOI127036 DOOI 127043 DOOI127044 DOOI127051 DOOI127052 DOOI 127039 DOOI 127060 DOOI 127029 DOOI 127030 DOOI127037 DOOI127038 DOOI 127045 DOOI 127046 DOOI 127053 DOOI 127034 DOOI127061 DOOI 127064 DOOI 127023 DOOI127024 DOOI 127031 DOOI127032 DOOI127039 DOOI127040 0001127047 DOOI127050 DOGI127057 DOOI 127058 Coaccotratioa of FFOA B|/mL or % Ree <LOQ(10ng/mt) <LOQ(IOntpmL) <LOQ (10 na/niL) 0.0822 0.0135 <LOQ(10ngfmL) <LOQ ( IOng/mL) <LOO HO n(f,-niU LOQnOag/niLI <LOQ (IO Rg/ml) IVI 189 485 438 1809 1893 5379 6350 <LOQilOng/mL) <LOQ ftOng/ml.) [77 175 461 451 1732 1695 3823 5614 <LOQ (IO ng/rnL) <LOO(IOn/niU 179 70 494 478 1820 1800 6140 6026 Target Cane or FFOA tL NA NA NA 0.0979 00979 NA NA NA NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 % Recovery or V. T irfc t Cooc. FFOA FFOA M eta RPD NA NA NA 84% 87% 16% 4% NA NA 95% 95% 81% 73% 90% 95% 93% 106% NA 88% 81% 77% 75% 87% 83% 97% 94% NA 90% 15% 82% 80% 91% 90% 102% 100% NA NA 95% 77% 93% 99% NA 88% 76% 16% 95% NA 17% 81% 90% 101% NA NA 1% 10% 5% 13% NA 1% 2% 2% 4% NA 5% 3% 1% 2% 3M Environmental Laboratozju^ Page 849 Page 91 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus# 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Study: Product NumbofTcst Subitanee): Mairi*: Method-Revision Aaalybcal Equipment System Nianfacr Immanent Software/Vctston: Filename: R-Squamd Value: Slope: Y-lnicroept: atm o fExnctiooMaalyst Dates o f Analysis/Analyse Date o f Data RcducoorvAnalyst Sample Data DOSE VERIFICATION SAMPLES Groap Saaqtiae Dose Method Blk QC 111700-WBik-l lII70O-WBIk-2 1II7O0-WB01-3 B-4l(-020-A-C-IOOppb-MS B-418-020-A-C-IOOppb-MSD Stability Day 0 11/10/00 B-41(-O2O-A-C-0.SmL B-41(-020-A-A-0.5 mL B-418-020-A-DI0-0.S mL Stability Day 0 11/10/00 B-418-02O-A-A-1 B-4IM20-A-A-2 B-4I8420-B-A-1 B-418-020-B-A-2 B-4IM 20CA-1 B-4I84220-C-A-2 B-4I-020-D-A-I Stability Day 10 11/10/00 B-4K-020-D-A-2 B-4II-020-E-A-1 B -4 IM 2 0 -E.A -2 B-41I-020-A-DI0-1 B-4 IS-020-A-D10-2 B-4II-02W-D10-I B-4IS-020-B-D10-2 B-4M-02O-C-DIO-I B-4IS-020-C-D10-2 B-4I-020-D-D10-1 B-4II-020-D-OIO-2 B-41MB0-E-DI0-I B-411-020-E-D10-2 Coaceatrattoa 11/10/00 B-41S-020-A-C-I B-4IM20-A-C-2 B-4M-020-B-C-I B-4IS-020-8-C-2 B-411-02OC-C-1 B-4IS-020C-C-2 B-4II-020-D-C-1 B-418-020-D-C-2 B-4I1-020-E-C-1 B-411-020-B-C-2 PFOA/POAA =Peifluoroocunoate Date EucKd'By: Date Verified/By: 01/15/01 LAC 01/16/01 kjh FACT-TOX-164, A rp a 4 11-020, Ond (Cavai) Two-Gentranon Reproduction Study of APPO in Ran PFOA C oacom aa Saaaki E 75-M .I A ETS-I-.I Dsvcy 070799 Maaslyw3.d Set Attachments II/17A RWW 11/27/00 MMH 1I/24A MMH PFOA Caes. 8/aiL 0.00 000 0.00 65.8 68.4 aoo aoo 0.00 0.00 aoo 76.2 75.7 77.5 7ft0 72.4 75.7 ISU 102 0.00 0.00 7as 70.0 73.1 72.1 69.3 67.8 95.2 (9.1 aoo 0.00 71.7 67.9 79.1 76.4 72.1 72.0 91.2 96.4 C e a caatra b e n afPFOA at/aiL or % Rac <LOQ(IOa|/aiL) <LOQ(IOag/mL) <LOO(IOa/M.) 0.0122 0.0(55 <U3Q(10ag/mL> <LOQ(IOng/tnL) <LOQ(IOag/mL) <LOQ(10a|/mL) <LOOflOoa/ritL) 190.6953 119.3947 414.72)9 437.6500 1808.8404 1893.3447 5579.4(7 6350.127 <lO Q (lQ n*/m U <LOQ(10ng/mL) 176.9U5 175.0375 461.3423 450.9027 1731.8366 1694.8347 5(25.1165 5614.4173 < L O Q (IO n |/m U <LOQ(IOn*/mU 179.3(97 169.9349 494.4739 477.6580 1(20.0910 1799.5900 6140.1228 6026J7Q5 Center Letter A Orng/mL B - 0.2 mgrtnL C 0.6 m|/mL D - 2 wlg/mL E - 6 ittphnL Terfel Coac. afFFOA f/mL NA NA NA a0979 0.0979 NA NA NA NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 Recovery or % Target Cone. ! PFOA Mean PFOA RPD NA NA NA 84% 87% 86% 4% NA NA 95% 95% 81% 73% 90% 95% 9J% 106% NA 88% 81% 77% 75% (7% 85% 97% 94% NA 90% 85% (2% 80% 91% 90% 102'/. 100% NA NA 95% 77% 93% 99% NA 88% 76% 86% 95% NA 87% o% 90% 101% NA NA 1% 10% 5% 13% NA 1% 2% 2% 4% NA 5% 3% 1% 2% 3M Environmental Laboratory Page 850 Page 92 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus# 418-020 sPtmuddya:aNimnbcfTe Subauace): FPAFCOTA-TOX-164, A lfa 416-020,0*1 (Gavafe)TwG-- Rrpraducxian StudycfAFFO in Ra Analytical Report: FACT TOX-164 LIMS E00-2738 Mctfcod/Rcviaiaa: Analytical Eqtdpa-- t System Nm bcr. hat-- Softwan/Vcniea: Filettane: R-Squarad Value: Siene: ETS-8-4.1A ETS-8-5.1 Darcy 070799 M-- Iyax 3.4 Sac Below See Alteri-- nu Ses AttctoNm i De-- ofExmcbon/Aiialyac 11/21/00 RWW Da-- o f Analyi/Analyn: 11/21/00 MUH Date of Data Reduction/Analyst: 11/29/00 MMH Sample Dati DOSE VERIFICATION SAMPLES C ta u p Dace Sample# Extra---- VnL Serrsgaac Veriflad K1.--1BfiftTT Dlla-- a mL Feeler Method Blit. 112700-WBHc-l l NA U S I12700-WBIL-2 1 NA U 5 QC I12700-WBII-5 B-4IS-O2O-A-C-IO0ppb-MS 1 NA 1.25 i NA 1.25 B-418-020-A-C-100ppb-MSD NA 1.25 Stability Day 0 11/1*2000 B-4IM20-A-C-05mL B-418-020-A-A-0.5 mL 1 NA 1-25 1 NA 125 Stability Day 0 11/102000 B-418-020-A-010-0.5 mL B-41I-020-A-A-I B-418-020-A-A-2 i NA 1.25 1 NA 1-25 1 NA 1.25 B-4IS-020-B*A-l 1 NA 125 B-4IS-020-B-A-2 1 NA 125 BMI6-020C-A-I ! NA 125 B-418-02OC-A-2 1 NA 1.25 B-418-020-D-A-I 1 NA 125 B-418-020-D-A-2 1 NA 1.25 B-418-020-E-A-1 1 NA 125 B-4I8-020-E-A-2 1 NA 1.25 Stability Day 10 B-4I8-02O-A-DIO-1 1 NA 125 11/10/2000 B-4I8-020-A-DIO-2 1 NA 125 B-4I84I20-B-DIO-I 1 NA 125 B-4I8-020-B-D10-2 1 NA 1.25 B-4I8-020-C-D10-I NA 125 B-4I84I20C-DIO-2 1 NA 1.25 B-4I8-020-D-DI0-1 1 NA 125 B-418-020-D-DI0-2 1 NA 1.25 B-4I8-020-E4D10-1 1 NA 125 B-4I8-020-E-DI0-2 1 NA 125 Concent-- n/ioaooo B-4I84120-A-C-1 B-418-020-A-C-2 1 NA 125 1 NA 125 B-418-020-B-C-J l NA 125 B-418-020-B-C-2 1 NA 1.25 B-418-0204:4:-1 B-4I8-020-C-C-2 1 NA 125 1 NA 1.25 B-4I8-020-D-C-1 B-4I8-020-D-C-2 1 NA 1.25 1 NA 125 B-4I8-020-E-C-I 1 NA 125 B-4IB-020-E-C-2 1 NA 25 PFOA/POAA Fcrfluoraoctanoate A -Sam plern-- ae d o 01/17/01 to coafiim high tncovety. Recevez w -- eoofinnad,e-- idend an outlier FFOA Factor 1 1 1 1 1 2 2 2 2001 2001 2001 2001 5001 5001 20001 20001 soni 50001 2001 2001 2001 2001 5001 5001 20001 20001 50001 50001 2001 2001 2001 2001 5001 SCOI 20001 20001 50001 50001 Date Entend/By: 01/15/01 LAC Date Verified/ By: 01/16/01 kjh FFOA Fim o k Cene af/m L 0.00 D00I128015 0.00 0001128016 0.00 D001128017 69.15 D001128065 68.44 D001128066 ao o D001128018 0.00 D001128019 0.00 D001128022 ao o D001128025 0.00 DOOIJ2SOZ6 62.10 0001128055 58.75 DOOI128056 7828 0001128045 74.90 DODI 128044 7122 DOOI 128051 71.75 DOOI 1280S2 178.92 DOOI 128059 180.10 DOOI 128060 a o o DOOI 128029 0.00 DOOI 128050 55.05 DOOI128057 62.61 DOOI128058 74.25 DOOI128043 79.57 DOOI 128046 62.41 DOOI 128055 7052 DOOI128054 88.85 DOOI 128061 95.51 DOOI 128064 0.00 DOOI 128025 ao o DOOI 128024 65.25 DOOI128051 65.86 DOOI 128052 7225 DOOI128059 70.46 DOOI 128040 69.62 DOOI 128047 75.51 DOOI I2IOSO 16.01 DOOI128057 17.05 DOOI128058 Center Letter A -Omg/mL B - 0.2 mg/mL C - 0.6 mg/mL 0 - 2 mg/mL B-6m^mL CottcefitraiHMt f PFOA iig/mL or % Ree <LOQ(IOng/mL| <LOQ(10ng/mL) <LOQ (IO RK/mL 0.0864 0.0856 <LQQ ( 10 iig/ntL) <LOQ<IOng/niL) <LOO(iO ng/mLi <LOQ ( IO itg/mL) <LOO(Ons/niL) 155 147 489 468 1718 1793 11183 11256 <LOQ(IOng/mL) LOOdOng/mU 138 157 464 496 1560 1758 5555 5957 <LOQ(IOng/mL) <LOQ(IOn*/mL) 158 165 452 443 1741 1883 5576 5441 Target Cene or PFOA vg/mL NA NA NA 00979 00979 NA NA NA NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 % Recovery ar % Tam et Cene. FFOA PFOA Mean RPD NA NA NA 88% 87% 88% 1% NA NA 78% 75% 82% 78% 89% 90% 186% 188% NA 69% 78% 77% 85% . 78% 88% 93% 99% NA 79% 82% 75% 74% 87% 94% 90% 91% NA NA 76% 80% 90% A A 187% NA 74% 80% 85% 96% NA 81% 75% 91% 90% NA NA 6% 4% 0% 1% NA 13% 7% 12% 7% NA 4% 2% 8% 1% 3M Environmental Laboratory _____ __v- _ Page 851 Page 93 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study: Product NymberfTeet Sufaaaacc): Matrix: Mcthod/Reruion: Analytical Equipment Syaaon Number laatrumem SoAarare/Vcnion: Filename: R-Squarod Value: Slope Y-lucncpt: FACT-TOX-164. A ||b 418-020, O nl (Gange) Tm-Cenentioo Reproducen Study o f AFFO in Raa PFOA ETS-4-4.1 A ETS-8-.I Duvcy 0707*9 M ealyn3.4 SdA Sacfenm Sec A sa d n o s See ABaduneoi See Anackmcnn Datca o f Exmaxxk'AaaJytt: D ata of Auiyiu/Anaiyst Date of Data Reducnan/Auaiyat: I1I/12/2S7/0/000 MRWMWH 11/29/00 MMH Sample Data DOSE VERIFICATION SAMPLES Group Dom Sample * rro A Came. C n m n S ii a f PFOA Target Coac. f PFOA R tcvvtry or PFOA Mean Method 81k QC 112700-WBIk-l 112700-WBtk-2 H2700-WBDt-3 B-416-020-A-C-J00ppb-MS B - 4 18-020-A-C-100ppb-MSD Bf/mL aoo aoo 0.00 69.1 61.4 B |/M LarK R ae <LOQ (10 u| / biL) <L 0 Q (1 0 b |fio L ) <LOO(IOaanaL) 00864 00856 uy/biL NA NA NA 0.0979 0.0979 V T i r i * Cone. NA 88% 87% NA 88% Stability Day 0 I1/KV00 Stablbty Day 0 U/ltVOO Stability Day 10 U/1CV00 CtMiceut r a d oa ll/UVOO B-4l-020-A-C-05iL B-418-02Q-A-A-0.5 mL B-418-020-A-D104.5 mL B-418-020-A-A-1 IM 18-O20-A--2 B-4I8-020-B-A-1 B-418-020-B-A-2 B-4I8-020-C-A-1 B-41S-020-C-A-2 B-4I8-020-D-A-I B-4I8-020-D-A-2 B-418-02O-E-A-l B-4I8420-E-A-2 B-4IS-020-A-DIO-I B-413420-A-D1O2 B-418-02O-B-DIO-I B-4I842O-B-DI0-2 B-4I8-020-C-OKM B-418-020-C-D10-2 B-4II-02(M)-DIO-I B-4I8-O20-D-DIO-2 B-418-020-E-D10-1 B-418-020-E-D10-2 B-4I8-020-A-C-1 B-418-QQO-A-C-2 B-4I8-020-B-C-1 B4I8-020-8-C-2 B-418-02O-C-C-l B-4I8-OQO-C-C-2 B-418420-D-C-1 B-418-02O-D-C-2 B-418-020-E-C-I B-4I8-020-E-C-2 0.00 <LXX}(IOb|/BiL) aoo <LOQ(IOna/mL) 0.00 <LOO(10n/mL) 0.00 <LOQ(10a|/BiL) 0.00 <LOO(10na/mL) 62.1 155 38.7 147 78.3 489 74.9 461 71.5 1788 71.7 1793 179 11183 ISO 11256 0.00 <LOQ(IOb|/niL) 0.00 <LOO(IOaa/mL) 55.1 138 62.6 157 74.3 464 79.4 496 62.4 1560 7 0 J 1758 88.9 5553 9 J J 3937 0.00 <LOQ(IObf/mL) aoo <LOO(10n/mL) 63.2 158 65.9 165 TZZ 452 709 443 69.6 1741 75.3 1883 86.0 537 87.1 5441 NA NA NA NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 2000 2000 6000 6000 NA NA 71% 73% 82% 78% 89% 90% 186% 181% NA 69% 78% 77% 83% 78% 88% 93% 99% NA 79% 82% 75% 74% 87% 94% 9Q% 91% NA NA 76% 80% 90% A A 187% NA 74% 80% 83% 96% NA 81% 75% 91% 90% PFOA/POAA - PertluorooctaooHe A Sample roextracted on 01/17/01 cconfirm tagS tucovery. Racovn y w m not afirolad. eoneidiroti aitoutliet. Center Letter A 'O m m L B " Q.2 mg/mL Date Eniered/By: Date Verified/ By: 0I/IS/0I LAC 01/16/01 kjb C " 0.6 mg/niL D - 2 mg/mL E 6 mg/mL PFOA RFO NA 1% NA na 6% 4% 0% 1% NA 13% 7% 12% 7% NA 4% 2% 8% 1% 3M Environmental Laboratory.^, _____,, Page 852 Page 94 ARGUS 418-020 3M Medical Department Study: T-6889.6 Analytical Report: FACT TOX-164 Argus 418-020 LIMS E00-2738 Study: Produci N im ta fT s t Suteunce): M ar Mctted/Rcvitian: Antlyucel Equipment Syrian K a n te r (nttnanent Softwat/Vaiion: Filatene: R-Squired Velue: Slope Y-lniaccpc D a a ofExncdon/Amlyit Duet o f Amelyiu/Anelyit: D o t o f Dom ReducnaWAmly: Sample Data DOSE VERIFICATION SAMPLES Greup Do m S taple* M ated Blk POAA011701-WBlk-l-l POAA01 l701-WBlk-I-2 B-4IS-020--A-i B-4I8-020-E-A-2 PFOA/POAA - Pcrfluorooctinouc D ae Enletrd'By: Dae Verified/ By: IO/OS/01 LAC FACT-TOX-164. A l l 41S-020, Orni (Gevtfie) TwoO rnm oon Reproduction Study of AFFO in Ran PFOA ConccBBanon Smula E T S -M .I4 ETS-t-5.1 Dwey 070799 MaolyanSA See Below 0I/I7/DI RWW 01/25/01 MMH 01/24/01 MMH E ltruedon VoL ibL 1 1 i 1 Serratile Verified NA NA NA NA C otta Letta A -Oini/mL B - 0.2 m*/mL C > 0.6 af/m L D- 2n pni E-mfdnL Cxtncdm DthtOan Factor 1.25 125 1.25 1.25 PFOA PUndeu Factor 1 1 50001 50001 FFOA Cone of/mL 0.00 0.00 17.45 10.22 FUaame SOIOI230I5 SOIO1230I6 SOIOI250I7 S010I230IS C u o m traiian of PFOA pud. or % Rk <LOQ(10nK/mU <LOO ( 10 iwmLl 5466 5014 Tirjet Cone, of PFOA af/mL NA NA 6000 6000 % Recovery or % Target Cose NA 91% 84% PFOA PFOA Mean RTD NA NA 87% 9% 3M Environmental Laboratory. Page 853 Page 95 ARGUS 418-020 3M Medical Department Study: T-6889.6 F A C T - T O X - l 64 Argus# 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study: Product NtoribeifTcst Sahcianr r ): Manx: Method/Revision: Analytical Eqiupmoit System Number Immanent Software/Venion: Filename: R-Squaied Value: Slope: Y-hueraepc Dates of Exoacoon/Analyat: Dates of Analysts/Analyst: Date of Dau Reduction/Analyst: Sample Data DOSE VERIFICATION SAMPLES C m ip Sample f Dote Method Blk P O A A 0ll70l-W B Ik -M POAAOI |70l*WBHt-l -2 B-*lt-020-E-A-l B-4II-020-B-A-2 PFOA/POAA PeifluanxKlanaaie Date Entered/By: Date Verified/ By- ItVGS/OI LAC 0 FACT-TOX-164, A jgm 4ll^)20. Oral (Garage) Tao-Gcnmtjoa Rtpcnduetioa Study of AFFO at Rasi PPOA CmemoMkm Sa ^ I r ETS4-4.I A ETS--S.I Durey 07079 Maaalyn3.4 Sec Anacttmena See Attafhnaeu Sec An a d i a n Set Anertenmn 0I/I7/0I RWW 01/23/01 MMH 01/24/01 MMH PFOA Cone */tL 0.00 aoo 17 (0 C an ee ntn M o a of PFOA etyotL a r % Ree <LOQ(IOag/mL) <LOO(IOna/mU 5446 5014 Target Cone, of PFOA u*/mL NA NA 6000 6000 Center Letter A " 0 m^mL B 0.2 mg/m L C -0.6it/inL D 2 mg/mL E --6 m g/mL /. Recovery or V# Tarcct Cone. NA 91% 84% PFOA PFOA M a n RPD NA NA 87% 9% 3MEnvironmental Laboratory,. ^ ^ - - - - > . . _ . Page 854 Page 96 3M Medical Department Study: T-6889.6 FACT-TOX-l64 Argus# 418-010 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study: Product NumberfTest Substance): Matrix: Method^Revision : Analytical Equipment System Number Instrument Software/Venion: FACT-TOX-164, Argus 418-020, Oral (Gavage) Two-Generation Reproduction Study of APFO in Rats PFOA Comparison o f Concentration Sanarles ETS-8-4.1 & ETS-8-5.1 Davey 070799 Masslynx 3.4 Sam ple D a ta D O S E V E R IFIC A T IO N S A M P LES Group Dose Sample # Method Blk QC Stability Day 0 11/10/00 Stability Day 0 11/10/00 WBIk-1 WBlk-2 WBlk-3 B-418-020-A-C-1 OOpph-MS B-418-020-A-C- 100ppb-MSD B-418-020-A-C-Q.S mL B-418-020-A-A-0.S mL B-418-020-A-D10-0.5 mL B-418-020-A-A-1 B-418-020-A-A-2 B-418-020-B-A-1 B-418-020-B-A-2 B-4)8-020^:-A-l B-418-020-C-A-2 B - 4 18 -020-D -A-1 B-418-020-D-A-2 Extracted 11/17/00, Analyzed 11/27/00 % PFOA PFOA Recovery or % Target Cone. Mean RPD NA NA NA 84% 87% 86% 4% n a NA NA NA NA NA 95% 93% 95% 1% 81% 73% 77% 10% 90% 95% 93% 5% Extracted 1 1/27/00. Analyzed 11/28/00 % Recovery or % Target Cone. PFOA Mean PFOA RPD NA NA NA 88% 87% 88% 1% NA NA NA NA NA NA 78% 73% 76% 6% 82% 78% 80% 4% 89% 90% 90% 0% Stability Day 10 11/10/00 Concentration 11/10/00 B-418-020-E-A-1 B-418-020-E-A-2 B-418-020-A-D10-1 B-418-020-A-D10-2 B-418-020-B-DI0-I B-418-020-B-D10-2 B-418-020-C-D10-1 B-418-020-C-D10-2 B-418-020-D-D10-1 B-418-020-D-D10-2 B-4I8-020-E-D10-1 B-418-020-E-D10-2 B-418-020-A-C-1 B-418-020-A-C-2 B-418-020-B-C-1 B - 4 18-020-B-C-2 B-418-020-C-C-l B-418-020-C-C-2 B-418-020-D-C-1 B-418-020-D-C-2 B-418-020-E-C-1 B-418-020-E-C-2 93% 106% NA 88% 88% 77% 75% 87% 85% 97% 94% NA 90% 85% 82% 80% 91% 90% 102% 100% 99% NA 88% 76% 86% 95% NA 87% 81% 90% 101% 13% NA 1% 2% 2% 4% NA 5% 3% 1% 2% 186%a 188%a NA 69% 78% 77% 83% 78% 88% 93% 99% NA 79% 82% 75% 74% 87% 94% 90% 91% 187%A 1% NA NA 74% 13% 80% 7% 83% 12% 96% 7% NA NA 81% 4% 75% 2% 91% 8% 90% 1% A- Sample re-extracted on 01/17/01 to confirm high recovery. Recovery was not confirmed considered an outlier. Extracted 01/17/0). Analyzed 01/23/0) % Recovery or % Target Cone. PFOA Mean PFOA RPD 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 NA NA NA NA NA 87% 9% NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 3M Environmental Laboratory. Page 855 Page 97 _ ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus# 418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Study: FACT-TOX-164, EOO-2738 Product NumbeifTest Subitancej: Mitm: Method/Revision: Analytical Equipment System Number: lastrament Software/Veisioo: Filename: R-Squated Value: Slope: Y-Interecpt: Dates of Extraction/Analyst: Dates of Analysis/Analyst: Date of Data Reduction/Analyst: Sample Data Oral (Gavage) Two-Generaooo (One Litter per Generation) Reproduction Study of PFOA in Rats T-6889.6 RatSenan ETS-8-4.2 & ETS-8-5.2 venui an extracted tat serum curve AmeU062498 Masslyax3.4 See Below See Attacianents Sec Attachments See Attachments 06/19/01 RWW 06/21/01,06/27/01,07/17/01 MMH 06/22/01,06/28/01,07/18/01 MMH Box: 01-029 R A T SERUM Group Dose Sample * Method Blk Matrix Blit RTS062101-H20 Blk-1 RTS062101-H2O Blk-2 RTS062IOI-Sera Blk-I Group 1 RTS062I01-Sera Blk-2 P13801F.Gip 1.OMKDXD22 0.0 mg/kg/day P 13802F.Gtpl.0MKD.LD22 P !3806F,Grp 1.0MKD.LD22 P1360lM.Gtpl.0MKD. PDI06 Groupe PI3607M.Grpl.0MKD. PDI07 PI3613M.Gtpl.0MKD. PD108 P13891F.Gip4,10MKD.LD22 10 mg/kg/day P13892F.Gtp4.10MKD.LD22 P l3893F.Gtp4.10MKD.LD22 P13894F.Grp4.10MKD.LD22 P 1389SF.Gtp4.10MKDXD22 P13896F.Grp4,10MKDXD22 P 13897F.Gtp4.10MKDXD22 P 13898F.Gtp4.10MKDXD22 P 13899F.Gtp4.10MKDXD22 P13901F.Gtp4.l0MKD.LD22 P13691M.Gtp4,10MKD. PD106 PI3692M.Gip4.10MKD. PD106 P I3697M.Gtp4,10MKD. PD107 P 13698M,Grp4.10MKD, PDI07 Pl3703M.Gtp4,10MKD. PD108 P13704M.Gip4.!0MKD, PD108 ' P 13709M,Grp4,10MKD. PD109 P137|0M.Grp4.10MKD, PD109 PI37l5M,Gtp4,10MKD, PDU0 P137l6M.Grp4,!0MKD. PD110 Group 5 30 mg/kg/day P13921F.Grp5.30MKD.LD22 P13922F.GtpS30MKD.LD22 P13923F.Gtp5.30MKDXD22 P 13924F.GipS.30MKD.LD22 P13925F.Gtp530MKD.LD22 P 13926F.Grp5.30MKD.LD22 P13927F.Grp530MKDXD22 P 13928F.GtpS.30MKD.LD22 P 13930F.Gtp5.30MKDXD22 P 13931 F.Gtp530MKD.LD22 P13721 M,GrpS,30MKD, PDI06 P13722M.GrpJ0MKD. PDI06 P13727M,GtpS.30MKD. PD107 P13728M.Gtp530MKD. PD107 PI3733M.Gtp5.30MKD. PDI08 P13734M.Grp5,30MKD. PD108 P13739M.Gtp5.30MKD. PDI09 P13740M.Gip5.30MKD, PD109 P 13746M.Grp530MKD, PD110 P13747M.GrpS30MKD. PD110 PFOA - Petfluorooctanoate Date Entercd/By: 07/10/01.08/06/01 LAC Date Verified/ By: 08/13/01 nunh Initial Voi. mL 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l 1 l 1 1 1 1 1 I 1 1 1 1 l 1 1 1 1 1 1 1 1 I 1 1 1 1 1 Surrogate Verified 2nd Analysis OK 2nd Analysis OK NA 2nd Analysis OK NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Confirmed Low Confirmed Low NA Confirmed Low Confirmed Low Coofinned Low NA Confirmed Low NA NA NA Confirmed Low NA NA NA NA NA NA Confirmed low Confirmed Low Confirmed Low NA Confirmed Low Confumed Low NA Coofinned Low Confirmed Low NA Confirmed Low PFOA Dlution Factor l \ 1 1 1 I I 1 1 1 5 5 5 5 5 25 5 5 25 5 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 50 so 50 so 50 10 10 10 10 JO 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 PFOA Conc. ng/mL 1.63 1.29 1.77 1.48 2.66 1.81 3 24 SO. 14 20.81 32.17 65.14 79.13 48.13 8S.4S 90.13 16.73 50.11 77.67 18.94 66.15 36.82 56.73 68.41 50.18 54.44 39.46 59.00 51.78 48.04 46.29 22.08 16.96 27.60 37.63 18.21 57.45 90.11 92.70 39.07 26.43 50.92 29.94 39.57 61.12 33.44 42.17 56.43 27.42 50.07 61.55 Filename A0106270I6 AO10627017 A010627018 AOI0627019 A010627020 A0I0627021 A010627022 A010627023 A010627024 A010627025 A010627029 A010627030 A010627031 A010627032 A010627033 M0I07I7023 A010627035 A010627036 M0I07I7024 A010627038 M010717031 M010717032 M010717036 MO10717037 MO10717038 MOI07I7039 MO10717040 MO10717041 MO10717042 MO10717043 MO10717025 MO10717026 M01Q717Q27 MO10717028 M0IQ717029 AO10627060 AOI0627061 AO10627062 AO10627063 M0107I7030 M010717044 M010717045 MO10717049 M0I07I7050 M0I07I705I M0I0717052 M010717053 M0I07I7054 M0107I7055 MO10717056 Concentration of PFOA ug/mL or % Ree <LOQ <0.00528 ug/mL) <LOQ (0.00528 ub/iuL) <LOQ (0.00528 ug/mL) <LOQ (0.00528 ug/inL) <LOQ (0.00528 ug/mL) <LOQ (0.00528 ug/mL) <LOQ (0.00528 uiv'mL) 0.0501 0.0208 0.0322 0.326 0.396 0.241 0.427 0.451 0.418 0.251 0.388 0.474 0.331 36.8 56.7 68.4 50.2 54.4 39.5 59.0 51.8 48.0 46.3 1.10 0.848 1.38 1.88 0.910 0.574 0.901 0.927 0.391 1.32 50.9 29.9 39.6 61.1 33.4 42.2 56.4 27.4 50.1 61.6 Mean PFOA ug/mL <LOQ <LOQ < 1 .0 0 0.0344 0.370 51.1 1.02 45.3 RSD Std. Dev. MS/MSD RPD NA NA NA NA 43.0 0.0148 21.7 0.0805 18.2 9.30 41.5 0.425 27.9 12.6 3M Environmental Laboratory Page 856 Page 98 3M Medical Department Study: T-6889.6 Study: FACT-TOX-164.EOQ-Z738 . Product Numbci(Tcst Substance): Matrix: Method/Revision: Analytical Equipment System Number Instrument Software/Version: Filename: R-Squared Value: Slope: Y-Intercept: Oates of Extraction/Analyst: Dates of Analysis/Analyst: Date of Data Reduction/Analyst: Sample Data FAArgCuTs#-T4O18X-0-l2604 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Oral (Gavage) Two-Oenetadoo (One Liner per Generation) Reproduction Study of PFOA in Rats T-6889.6 Rat Seram ETS-8-4.2 & ETS-S-J.2 versus an extracted rat senun curve Araelia062498 Masalyiix 3.4 See Attacbmeats Sec Attacfanests See Attacbmeats See Attacbmeats 06/19/01 RWW 06/21AI1.06/27/01,07/17/01 MMH 06/22/01,06/28/01,07/18/01 MMH R A T SERUM Group Dose Sample # Method Blk Matrix Blk Group 1 0.0 mg/kg/day Group 4 10 mg/kg/day Croup 5 30 ntg/kg/day PFOA " Perfiuorooctanoate RTS062101-H20 Blk-1 RTS062101-H20 Blk-2 RTS062101-Sera BUc-l RTS062101-Sera Blk-2 P1380IF.Grpl.0MKD.LD22 PI3802F.GtpL0MKD.LD22 PI3806F.Grpl.0MKD.LD22 P1360IM.Gtpl.0MKD. PDI06 PI3607M.Gtpl.0MKD, PDI07 PI3613M.GrpI.0MKD, PD108 P 13891F.Gip4.10MKDXD22 P I3892F.Grp4.10MKD.LD22 P 13893F.Gip4,10MKDXD22 P13894F,Gip4.10MKDXD22 P13893F.Gtp4.10MKDXD22 P13896F.Grp4.IOMKD.LD22 PI3897F.Grp4.IOMKD.LD22 P13898F.Gfp4.10MKD.LD22 P13899F,Gip4.10MKDXD22 P1390IF.Grp4.10MKD.LD22 P1369IM,Gip4,l0MKD, PD106 P13692M,Gtp4.10MKD, PD106 P13697M,Gip4.IOMKD. PD107 P13698M.Gip4.I0MKD. PD107 P 13703M,Grp4,10MKD, PDI08 Pl3704M.Grp4.10.MKD. PD108 Pl3709M.Gtp4,I0MKD, PD109 PI3710M.Grp4,10MKD. PD109 P13715M,Grp4,10MKD. PD110 PI3716M,Grp4.10MKD. PD110 PI3921 F.GrpJ0MKD4-D22 P13922F.Grp5.30MKD.LD22 P 13923F.Gtp .0MKDXD22 P 13924F.Grp5J0MKD.LD22 P 1392SF,Grp5J0MKDXD22 P 13926F.Grp5.30MKD.LD22 P l3927F.Grp5J0MKDXD22 P 13928F.Grp3J0MKD.LD22 P13930F.Grp5.30MKD.LD22 P 1393 lF.Grp5.30MKD.LD22 P13721M.Gip5JOMKD. PD106 Pl3722M,Grp5.30MKD, PD106 P1372.7M,Gtp5.30MKD. PD107 P13728M.Grp530MKD. PD107 P13733M,Gip5JOMKD. PDI08 P13734M,Gtp530MKD, PD108 PI 3739M,GrpSJ0MKD, PD109 P13740M,Grp5J0MKD, PD109 P 13746M.Gip5J0MKD, PDI10 P13747M,Grp5.30MKD, PDI 10 PFOA Caac ag/niL 1.63 1.29 1.77 1.48 2.66 1.81 3.24 50.1 20.8 32 65.1 79.1 48.1 85.4 90.1 16.7 50.1 77.7 18.9 66.2 36.8 56.7 68.4 50.2 54.4 39.5 59.0 51.8 48.0 46.3 22.1 17.0 27.6 37.6 18.2 57.4 90.1 92.7 39.1 26.4 50.9 29.9 39.6 61.1 33.4 42.2 56.4 27.4 50.1 61.6 Concentration of PFOA ug/mL or % Ree <LOQ (0.00528 ug/mL) <LOQ (0.00528 ug/mL) <LOQ (0.00528 ug/mL) <LOQ (O.OOS28 ug/mL) <LOQ (O.OOS28 ug/mL) <LOQ (0.00528 ug/mL) <LOQ (0.00528 ug/mL) 0.0501 0.0208 0.0322 0.326 0.396 0.241 0.427 0.451 0.418 0.251 0.388 0.474 0.331 36.8 56.7 68.4 50.2 54.4 39.5 59.0 51.8 48.0 46.3 1.10 0.848 1.38 1.88 0.910 0.574 0.901 0.927 0.391 1.32 50.9 29.9 39.6 61.1 33.4 42.2 56.4 27.4 50.1 61.6 Mean PFOA ug/mL NA NA <LOQ 0.0344 0.370 51.1 1.02 45.3 RSD Sid. Dev. MS/MSD RPD NA NA NA NA 43.0 0.0148 21.7 0.0805 18.2 9.30 41.5 0.425 27.9 12.6 Date Entered/By: Date Verified/By: 07/10/01.08/06/01 LAC 08/13/01 modi 3M Environmental Laboratory^ Page 857 Page 99 ARGUS 418-020 3M Medical Department Study: T-6889.6 FACT-TOX-164 Argus 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study: FACT-TOX-164. EOO-2738 Product NumbetfTett Substance): M ura: Method/Kevision: Analytical Equipment System Number: instrument Software/Version: Filename: R-Squared Value: Slope: Y-Intereept: Dates of Extraction/Analyst: Dates of Anaiysis/AnaJyst: Date of Data Reduction/Analyst: Sample Data Oral (Gavage) Two-Geneiation (One Litter per Generation) Reproduction Study of PFOA in Rats T-6889.6 Rat Serum ETS-8-4_2 A ETS-8-5.2 venue an unextraded curve Soup020199 Mualynx 3.4 See Below See Attachments See Attachments See Attachments 06/14/01 RWW 06/15/01 MMH 06/18/01 MMH Box: 01-028 RAT SERUM Croup Dose Sample * Method Blank RTS061401-H2O Blk-1 RTS061401-H20 Blk-2 Matrix Blank RTS0614Ol-Sera Blk-1 RTS061401-Sera Blk-2 QC RTS061401-MS-25 ppb RTS061401-MSD-25 ppb RTS061401-MS-500 ppb RTS061401-MSD-500 ppb PFOA - Perfluorooctanoate Initial VoL mL 1 1 1 1 1 1 1 Extraction Dilution Factor 1.25 1.25 1.25 125 125 125 1.25 1.25 Surrogate Verified Out High Out High Out High Out High Out High Out High NA NA PFOA Dilution Factor 1 1 1 1 1 1 1 1 PFOA Cone. ng/mL 0.00 0.00 0.00 0.00 12.67 14.36 287.30 276.16 Filena me S0I06130I8 S0I06150I9 SO10615020 S0106IS02I SO10615022 S0106IS023 SO10615024 S010615025 Concentration of PFOA ug/mL or % Ree <LOQ (0.00107 ug/rnL) <LOQ (0.00107 ug'niL) <LOQ (0.00107 ug/niL) <LOQ (0.00107 ug/mL) 60% 68% 68% 65"/. Mean PFOA ug/mL <LOQ <LOQ 64% 67% RSD Std. Dev. MS/MSD RPD NA NA 13% 4% Date Entered/By: 06/22/01 LAC Date Verified/ By: 08/13/01 mmh 3M Environmental Laboratory. ---------- Page 858 Page 100 3M Medical Department Study: T-6889.6 Study: FACT-TOX-164, EOO-2738 Product NumberfTest Substance!: Matrix: Method/Revision: Analytical Equipment System Number: Instrument Software/Venioo: Filename: R-Squared Value: Slope: Y-Intercept: Dates of Extraction/Analyst: Daces of Analysis/Analyse Date o f Data Reduction/Analyst Sample D ata FACT-TOX-164 Argus 418-020 ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Oral (Gavage) Two-Generation (One Liner per Generation) Reproduction Study of PFOA in Rats T-68W.6 Rat Serum ETS-8-4.2 A ETS-8-5.2 versus an unextracted curve Soup020199 Masalynx 3.4 See Attacbments See Attachments See Attachments See Attacbments 06/14/01 RWW 06/13/01 MMH 06/18/01 MMH RATSERUM Group Dose Method Blank Matrix Blank QC PFOA - Perfluorooctanoate Sample* RTS06I40I-H2O Blk-1 RTS061401-H2O Blk-2 RTS06I401-Saa Blk-1 RTS06I401-Sera Blk-2 RTS061401-MS-25 ppb RTS061401-MSD-25 ppb RTS06I40I-MS-S00 ppb RTS061401-MSD-S00 ppb PFOA Conc ng/mL 0.00 0.00 0.00 0.00 1X7 14.4 287 276 Concentration of PFOA ug/mL or % Ree <LOQ (0.00107 ug/mL) <LOQ (0.00107 ug/niL) <LOQ (0.00107 ug/mL) <LOO (0.00107 ug/mL) 60% 68% 68% 65% Mean PFOA ug/mL <LOQ <LOO 64% 67% KSD Std. Dcv. MS/MSD RPD NA NA 13% 4% Date Eatered/By Date Verified/ By: 06/22/01 LAC 08/13/01 mmh SM 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 E00-2738 Study: FACT-TOX-164. E00-Z738 Product Numfaet(Test Substance): Matrix: Method/Revision: Analytical Equipment System Number: Instrument Software/Version: Filename: R-Squared Value: Slope: Y-Intercept: Oates of Extraction/Analyst: Dates of Analysis/Analyst: Date of Data Reduction/Analyst: Simple Data Oral (Cavate) Two-Generation (One Utter per Generation) Reproduction Study of PFOA in Rats T-6889.6 Rat Scrum ETS-8-4.2 & ETS-8-5JZ verna an extracted rat serum curve Soup020l99 Masslyna3.4 See Below See Attachments Sec Attachment See Attachments 08/13/01 RWW 08/15/01 MMH 08/20/01 MMH Box#: 01-031 RATSERUM Group Dose Sample # Method Blank RTS08130I-H20 Blk-1 R T S 0 8 I3 0 I-H 2 0 Blk-2 M atrix Blank RTS081301-Sera Blk-I RTS081301-Sera Blk-2 QC RTS0BI30I-MS-50 ppb RTS081301-MSD-50 ppb RTS08I30I-MS-I500 ppb RTS08I301-MSD-I500 ppb RTS081301-MS-50000 ppb RTS08I30I-MSD-50000 ppb PFOA " Periluorooctanoate A - Peak was not integrated, not above die threshhold limit Initial VoL mL l I 1 1 1 1 1 ! 1 I Surrogate Verified NA NA NA Confirmed High NA NA NA NA NA NA PFOA Dilution Factor 1 1 1 1 1 1 50 so 1000 1000 PFOA Filename Concentration Mean Cone. of PFOA PFOA ng/mL ug/mL or % Ree ug/mL 0.00 MOI08I5030 <LOQ (0.00536 ug/mL) 0.00 M 01081503I <LO Q (O.OOS36 us/m L ) <LOQ 0.00 MOI0815032 <LOQ (0.00536 ug/m L) A 0.00 M010815033 <LOQ (0.00536 ug/mL) <LOQ 55.81 M0I08I5034 106% 58.24 M0I08ISO35 110% 108% 28.44 M010815Q36 92% 24.88 M0I08I5037 80% 86% 46.89 M0I08IS038 92% 43.40 MO10815039 86% 89% Date Entered/By: 08/29/01 LAC Dale Verified/ By: 9/4/01 mmh RSD Std. Dev. MS/MSD RPD NA NA 4% 13% 8% 3M Environmental Laboratory. Page 860 Page 102 3M Medical Department Study: T-6889.6 Study: FACT-TOX-164. EOO-2738 Product NumberfTest Substance): Matrix: Melhod/Revision: Analytical Equipment System Number: Instrument Software/Verston: Filename: R-Squared Value: Slope: Y-intercept: Oates of Extraction/Analyst: Dates of Analysis/Analyst: Date of Data Reduction/Analyst: Sample Data - ..... ARGUS418-020 Analytical Report: FACT TOX-164 LIMS EOO-2738 Oral (Gavage) Two-Generation (One Litter per Generation! Reproduction Study of PFOA in Rats T-6889.6 Rat Serum ETS-8-4.2 & ETS-8-5.2 versus an extracted rat serum curve Soup020l99 Masslynx 3.4 See Attachments See Attachments See Attachments See Attachments 08/13/01 RWW 08/15/01 MMH 08/20/01 MMH RAT SERUM Group Dose Sample 4 Method Blank RTS081301-H2O Blk-l RTS08130I-H2O Blk-2 Matrix Blank RTS081301-Sera Blk-l RTS081301-Sera Blk-2 QC. RTS081301-MS-50 ppb RTS081301-MSD-50 ppb RTS081301-MS-1500 ppb RTS081301-MSD-1500 ppb RTS081301-MS-50000 ppb RTS081301-MSD-50000 ppb PFOA Perfluorooaanoate A - Peak was not integrated, not above the threshbold limit. Date Entered/'By: Date Verified/ By: 08/29/01 LAC 9/4/01 mmh PFOA Cone. ng/mL 0.00 0.00 0.00 0.00 55.8 58.2 28.4 24.9 46.9 43.4 Concentration Mean of PFOA PFOA ug/mL or % Ree ug/ml. <LOQ (0.00536 ug'mL) <LOO (0.00536 ug'mL) <LOQ <LOQ (0.00536 ug'mL) A <LOQ (0.00536 ug'mL! :LOQ 106% 110% 108% 92% 80% 86% 92% 86% 89% RSD Sid. Dev. MS/MSD RPD NA NA 4% 13% 8% 3M Environmental Laboratory-- =. Page 861 Page 103 3M Medical Department Study: T-6889.6 FAArgCuTs-T41O8X-0-2l604 ARGUS 418-020 Analytical Report: FACT TQX-164 LIMS E00-2738 Study: FACT-TOX-164, EOO-2738 Product NumberfTest Substance): Matrix: Method/Revision: Analyticai Equipment System Number: Instrument Software/Version: Filename: R-Squared Value: Slope: Y-Intercept: Dates of Exmctioo/Analyst: Dates of Analysis/Analyst: Date o f Data Reduction''Analyst: Sample Data Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of PFOA in Kau T-6889.6 Rat Serum ETS-8-4-21 ETS-8-5J versus an nnextracted curve Madeline 1098 Masalyax3.4 See Below See Attacbments See Attachments See Attacbments 08/13/01 RWW 08/27/01 MMH 08/29/01 MMH Box*: 01-031 RATSERUM G ronp. Dose Sample * Method Blank Matrix Blank RTS08130I-H2O Blk-1 RTS081301-H20 Blk-2 RTS081301-Sera Blk-1 RTS08I301-Sera Blk-2 QC RTS081301-MS-50 ppb RTS08130l-MSD-50 ppb RTS081301-MS-1500 ppb RTS081301-MSD-1500 ppb RTS081301-MS-50000 ppb RTS08130I-MSD-S0000 ppb PFOA - Perfluorooctanoate Initial VoL mL 1 1 1 1 1 1 1 1 1 1 Extraction Dilution Factor 1.25 1.25 1.25 1.25 1-25 1.25 1.25 1.25 105 105 Surrogate Verified Confirmed High Confirmed High Confirmed High Confirmed High Confirmed High Confirmed High NA NA NA NA PFOA Dilution Factor 1 1 1 1 1 1 50 50 1000 1000 PFOA Cone. ng/inL 0.00 0.00 0.00 0.00 4IJI 3947 20.83 22.47 32.71 28.46 Filename MU10827017 MOI08270I8 M0I0827019 M010827020 M01082702) M010827022 M010827023 M010827024 M010827025 M010827026 Concentration of PFOA ug/mL or % Ree <LOQ (0.00268 ug/mL) <LOQ (0.00268 ug/mL) <LOQ (0.00268 ug/mL) <LOQ 0.00268 ug/tnL) 98% 93% 84% 90% 81% 70% Mean PFOA ug/mL LOO <LOQ 96% 87% 75% RSD Std. Dev. MS/MSD RPD NA NA 5% 8% 14% Date Entered/By: 09/04/01 LAC Date Verified/ By: 9/4/01 mmh 3M Environmental Laboratory Page 862 Page 104 3M Medical Department Study: T-6889.6 Study: F A C T -T O X -164. EOO-2738 Product N u m b c rfT c si Substance): Matrix: Method/Revision: Analytical Equipment System Number: Instrument SoAware/Version: Filename: R-Squared Value: Slope: Y-Intercept: Dates of Extraction/Analyst: Dates of Analysis/Analyst: Date of Data Reduction/Analyst: Sample Data : > -- - ARGUS 418-020 FAArCguTs-T4O18X--012604 Analytical Report: FACT TOX-164 LIMS E00-2738 Oral (Gavagc) Tw o-G eneration (O ne Litter per G eneration) Reproduction Study Of PFOA in Rats T-6889.6 Rat Serum ETS-8-4.2 Sl ETS-8-5.2 versus an unextracted curve Madelme04l098 Maasiynz 3.4 See Attachments See Attachments Sec Attachments See Attachments 08/13/0! RWW 08/27/01 MMH 08/29/01 MMH RATSERUM Croup Dose Sample# Method Blank Matrix Blank QC PFOA = Perfluorooctanoate RTS081301-H2O Blk-1 RTS08I301-H2O Blk-2 RTS081301-Sera Blk-1 RTS081301-Sera Blk-2 RTS081301-MS-50 ppb RTS081301-MSD-50 ppb RTS081301-MS-1500 ppb RTS08I301-MSD-1500 ppb RTS08I301-MS-50000 ppb RTS081301-MSD-50000 ppb PFOA Cone. ug/mL 0.00 0.00 0.00 0.00 41.3 39.S 20.8 22.5 32.7 28.5 Concentration of PFOA ug/mL or */ Ree <LOQ (0.00268 ug/mL) <LO0 (0.00268 ug/mL) <LOQ (0.00268 ug/mL) <LOQ (0.00268 ug/mL) 98% 93% 84% 90% 81% 70% Mean PFOA ug/mL <LOQ <LOQ 96% 87% 75% RSU Sid. Dev. MS/MSD RPD NA NA 5% 8% 14% Date Entered/By: Date Verified/ By: 09/04/01 LAC 9/4/01 nunli 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-I64 LIMS E00-2738 Analytical Report FACTTOX-164 LIMS E00-2738 Appendix F: Example Calculations Formula Used for Sera Analyses in Study FACT TOX-164 AR (ng/mL) XDF XFV (mL) x 1.0 pg = Reported Concentration (pg/mL) EV (mL) lOOng Calculation Used fo r Group 4, LD22, Animal ID P13891F 65.14 ng/mL x 5 x 1 mL x 1.0 pg = 0.326 pg/mL 1 mL 1000 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 "3AX P n u irn n m o n ta l I a h n ra tn n t 3M Environmental Laboratory.^ Page 864 PariA 25 Page 106 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: LFIAMCSTET0O0X-2-713684 Appendix G: Interim Certificate(s) of Analysis Pnuirnnm anta! I ahnrsttnrv 3M Environmental L a b o r a to r ^ ^ Page 865 Pan 26 Page 107 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 -- LiMS fcoo-2738 SSfeOAk Centre Analytical Laboratories. Inc. 3048 Research Drive State College, PA 16801 www.centreiab.com (B14) 231,6032 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% _____________ Test Name Specifications P u rity 1 Result 95.0% Appearance Identification NMR M etals (ICP/MS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium S. N ickel 6 . Iron 7. Manganese Total % Impurity (NMR) Total % Impurity (LC/M S) 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 A nalysis4: 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine Ammonium A nalysis4 Ion 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 P o sitiv e 1. 0 .0 0 1 wt./wt.% 2 . <0 .0 0 1 wtVwt.% 3. 0.001 w t/wt.% 4. <0.001 wt./wt% 5. <0.001 wt./wt.% 6 . <0 .0 0 1 wt/wt.% 7. <0.001 wt/wt.% 0.36 w t/w t% 4.68w t/w t% None Quantified.% None Detected 99.8% 1. <0.015 wt/wt.% 2. <0.005 w t/w t.% 3. <0.040 w t/w t.% 4. <0.009 w t/w t% 5. <0.006 w t/w t% 6 . <0.006 w t/w t% 7. <0.040 wt/wt.% 1. <0 .1 w t/w t.% 2 . <0 .1 w t/w t.% 3. 0 .1 w t./w t% 4. <0.25 wtJwt% I. 18.9w t/w t% 2. 1.27 w t/w t.% 3. 3.76 w t/w t% 4. 4.38 w t/w t.% 5. 62.1 w t/w t.% 2.94 w t/w t. % COA023034 REVISION 2.doc 3M Environmental Laboratory. Page 866 Page 1 o f2 Page 108 3M Medical Department Study: T-6889.6 ARGUS 418-020 Analytical Report: FACT TOX-164 L1MS LUO-z / js aSSSSfik Centre Analytical Laboratories, Inc. 3048 Research Drive State College, PA 16801 www.centrelab.com ^ ^ # V O S k Phone: (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 INTERIM CERTIFICATE OF ANALYSIS 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: 10/33/06 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 acid Nonafluoropentanoic acid Pentafluoropropanoic acid 'Theoretical value calculations based on the empirical formula, CgFi5 0 2 (')NH4i+) (MW=431.1) T h is w ork w as conducted under EPA G ood Laboratory Practice Standards (4 0 CFR 160). LC /M S Purity Profile: Peak# 1 2 3 Total Retention Time (min) 12.144 13.533 14.238 - Mass(s) 269.0 331,319 369 - Identity C6 F|j/C7 PfOA - Area 205859 903329 22630600 23739788 % Area 0.87 3.81 - 4.68 Prepared By Charles ns Scientist,-Cent ical Laboratories Dafe Reviewed By: /X L M f j J6hn Flaherty Date Laboratory Manager, Centre Analytical Laboratories COA023034 REVISION 2.doc 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: UFAMCSTET0O0X-2-176348 John Butenhoff, Ph.D., Study D irector Date David SanHers, Ph.D., Sponsor Representative t-l-0 7 ^ Date Ui syal CkleamenC, bP u lb il rincipa l A n a ly tic a l Inve stigator 0) onto*. Date William Reagen, Ph.D., Laboratory Management Date Fm/irrmrrmntal I ahnratnrv 3M Environmental Laboratory____ ^ Page 868 Paoe27 Page 110 ARGUS 418-020 APPENDIX J ENVIRONMENTAL AND HUSBANDRY REPORTS Page 869 ARGUS ARGUS 418-020 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 TSapregceiet sR:aRnagte: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DDHaaotyuasrs:P:oints: T6e4mFpteora7t9urFe 1137389.5 Rel3a0ti%vetoH7u0m%idity 1137389.5 Mean ( SD): MMMeaindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss iLHnoigRwha(n(%%g)e):: (%): 68.5 ( 1.4) 51.9 (4.0) 71.1 68.0 66.6 465430...189 139 0 0 (1((0000..00.0)) ) 139 0 0 (1((000.0.00.)0) ) Report Generated: 18-Jul-2001 at 11:07 COMMENTS: REVIEWED BY: C -O ' n DATE: 7 7 a Page 870 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 TSapregceiet sR:aRnagte: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DHDaaotyuasrs:P:oints: T6e4mFpteora7t9urFe 3031802079.875 Rel3a0ti%vetoHu70m%idity 3031802079.875 Mean ( SD): MMMeiandximiiamnuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss iHLnoigRwha(n(%%g)e):: (%): 67.4 ( 0.6) 45.8 ( 6.2) 667075...139 463620...748 3078 0 0 (1((0000..00.0)) ) 3078 0 0 (1((0000..00.)0) ) Report Generated: 18-Jul-2001 at 14:06 COMMENTS: REVIEWED BY: ___ C DATE: 7 2 ^ - j Page 871 ARGUS ARGUS 418-020 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 TSapregceiet sR:aRnagte: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DDHaaotyuasrs:P:oints: T6e4mFpteora7t9urFe 5052202.125 Rel3a0ti%vetoH7u0m%idity 5052202.125 Mean ( SD): MMMeaindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss HLinoigRwha(n(%%g)e):: (%): 70.3 ( 0.8) 46.5 ( 5.6) 776208...132 462357...187 501 0 0 (1((0000..00.0)) ) 498 03 (((9009...064))) Report Generated: 18-Jul-2001 at 14:11 COMMENTS: REVIEWED BY: ^ Q J in ^ V L DATE: 7 71^ 0 1 ARGUS ARGUS 418-020 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 222555---FFFDeeeabbb---t222e000000111 T000786im:::000000e R222978.H...075. LLL 30% to 70% Date Time R.H. H = Value out of Rra.Hn.g=e R- Heliagthive HLu=mVidaitluye(%ou) t of range - Low Report Generated: 18-Jul-2001 at 14:16 hese 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 TSapregceiet sR:aRnagte: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DDHaaotyuasrs:P:oints: T6e4mFpteora7t9urFe 3831997.025 Rel3a0ti%vetoHu70m%idity 3831997.025 Mean ( SD): MMMaeindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss LHinoigRwha(n(%%g)e):: (%): 70.0 ( 0.5) 55.2 ( 2.0) 776070...119 653359...233 390 0 0 (1((0000..00.))0) 390 0 0 (1((000.0.00.))0) Report Generated: 18-Jul-2001 at 11:13 COMMENTS: REVIEWED BY: C- 'P im -vt-* DATE: 1 H - l Page 874 ARGUS ARGUS 418-020 Temperature and Relative Humidity Report Location: Room 40 Protocol Number: 418-020 Range of Dates: 21-Mar-2001 16:00 to 24-Mar-2001 08:59 TSapregceiet sR:aRnagte: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DHDaaotyuasrs:P:oints: T6e4mFpteora7t9urFe 6464.575 Rel3a0ti%vetoH7u0m%idity 6464.575 Mean ( SD): MMMeaindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss LiHnoigRwha(n(%%g)e):: (%): 70.5 ( 3.3) 51.4 (6.7) 767442...126 446387...099 65 0 0 (1((0000..00.)0) ) 65 0 0 (1((0000..00.)0) ) Report Generated: 18-Jul-2001 at 14:01 COMMENTS: REVIEWED BY: C o ) tz DATE: 7 2 <+-cJ Page 875 ARGUS ARGUS 418-020 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 TSapregceiet sR:aRnagte: TTToootttaaalll NNNuuummmbbbeeerrr ooofff HDDaaotyuasrs:P:oints: T6e4mFpteora7t9urFe 6464.575 Rel3a0ti%vetoH7u0m%idity 6464.575 Mean ( SD): MMMeaindximiiamnuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss HLinoigRwha(n(%%g)e):: (%): 72.0 (1-7) 57.8 ( 2.8) 7724..62 68.6 655307...548 65 0 0 (1((0000..00.))0) 65 0 0 (1((000..000.))0) Report Generated: 18-Jul-2001 at 11:32 COMMENTS: REVIEWED BY: ( ' DATE: 7 J Q! Page 876 ARGUS ARGUS 418-020 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: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DDHaaotyuasrs:P:oints: Temperature 64F to 79F 2 31.25 32 Relative Humidity 30% to 70% 2 31.25 32 Mean ( SD): MMMeaindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss iHLnoigRwha(n(%%g)e):: (%): +i 70.7 71.2 70.8 69.9 32 0 0 (100.0) (0.0) (0.0) 52.0 55.8 51.7 48.8 32 0 0 (1.7) (100.0) (0.0) (0.0) Report Generated: 18-Jul-2001 at 14:08 COMMENTS: REVIEWED BY: / * .Q fa i D A TE: 1-2V 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: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DHDaaotyuasrs:P:oints: Temperature 64F to 79F 2 31.25 32 Relative Humidity 30% to 70% 2 31.25 32 Mean ( SD): MMMeaindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss LHinoigRwha((n%%g)e):: (%): 69.7 70.5 69.6 68.8 32 0 0 (0.5) (100.0) (0.0) (0.0) 42.1 45.3 41.7 39.2 32 0 0 (1.6) (100.0) (0.0) (0.0) Report Generated: 18-Jul-2001 at 14:09 COMMENTS: REVIEWED BY: f 1 f -Tw DATE: 7 2Y-/ 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: TToottaall NNuummbbeerr ooff DHaoyusrs: : Total Num ber of Data Points: Temperature 64F to 79F 22 504.0 504 Relative Humidity 30% to 70% 22 504.0 504 Mean ( SD): MMMeaindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss LHinoigRwha((n%%g)e):: (%): 72.6 75.4 72.7 70.1 504 0 0 (1.0) (100.0) (0.0) (0.0) 50.5 71.5 50.5 33.3 503 1 0 ( 5.0) (99.8) (0.2) (0.0) Report Generated: 15-Aug-2001 at 09:30 COMMENTS: REVIEWED BY: . DATE: g - /S ' >/ Page 879 ARGUS ARGUS 418-020 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 Species: RTaatrget Range: 30% to 70% Date 06-Apr-2001 Time 06:00 R.H. 71.5 H Date Time R.H. H = Value out of Rra.Hn.g=e R- Heliagthive HLu=mVidailtuye(%o)ut of range - Low 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 ARGUS 418-020 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: TTToootttaaalll NNNuuummmbbbeeerrr ooofff DDHaaoytuasrs:P:oints: Temperature 64F to 79F 22 504.01 504 Relative Humidity 30% to 70% 22 504.01 504 Mean ( SD): MMMaeindximiimanuu:mm:: NNNuuummmbbbeeerrr ooofff PPPoooiiinnntttsss iHLnoigRwha(n(%%g)e):: (%): 73.2 75.8 73.3 70.4 504 0 0 ( 0.9) (100.0) (0.0) (0.0) 59.3 76.0 59.1 43.0 495 9 0 (4.8) (98.2) (1.8) (0.0) Report Generated: 18-Jul-2001 at 11:15 COMMENTS: REVIEWED BY: I! 0 r i iy n DATE: "7 l^Q j Page 881 ARGUS ARGUS 418-020 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 Species: RTaatrget Range: 30% to 70% 000111111799223322---------AAAAAAAAADppppppppparrrrrrrrr---------t222222222e000000000000000000111111111 T0066im::0000e 00017891::::00000000 0106::0000 11:00 R777777777610120222.H.........068627833. HHHHHHHHH Date H = Value out of Rra.Hn.g=e R- Heliagthive HLu=mVidaitluye(%ou) t of range - Low 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 PMI NUTRITION INTERNATIONAL Page 1 o f 2 Sample No.: L0022289-3 Received: 08/03/00 Reported: 08/16/00 Site: RHl Locator: 5002 Project: CERT. CERTIFIED RODENT DIET MEAL LOT NUMBER AUG 01 00 2C Assay / Analvte Protein, Kjeldahi (N x 6.25) Protein Fat Fat Fiber, crude Fiber, Crude Arsenic Arsenic Cadmium Cadmium Calcium Calcium Lead Lead M ercury 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 0.362 Units % % % ppm ppm % ppm ppm % ppm 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 of quantitation ofthe procedure under the conditions employed. The use of the term "Less Than" does not implythat traces ofAnalyte were present. Samples submitted to Ralston Analytical Laboratories for routine analysis will be retained for a minimumofthirty (30) days after the report of analysis is issued. Extended storage requirements must be brought to the attention of Ralston Analytical Laboratories prior to or at the time of sample submission. PPPL, I--------------------- Q k tk i------- REVIEWED BY: DATE 1401 S. Hanley Road St. Louis, M O 63144 Phone: 314-768-4100 Fax: 314-768-4765  ARGUS 418-020 PMI NUTRITION: 5002 .................... " ... .....................Piujeu . CERT INTERNATIONAL CERTIFIED RODENT DIET MEAL LOT NUMBER AUGOl 00 2C Assay / Analvte Result Organophosphate pesticides Diazinon Disulfoton Ethion Malathion Methyl Parathion Parathion Thimet Thiodan Trithion O rganochlorine pest& PC B '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 of quantitation ofthe procedure under the conditions employed. The use of the term "Less Than" does not imply that traces ofAnalyte were present. Samples submitted to Ralston Analytical Laboratories for routine analysis will be retained for a minimum of thirty (30) days after the report of analysis is issued. Extended storage requirements musts be brought to the attention of Ralston Analytical Laboratories prior to or at the time of sample submission. ia n n Jp A A O i\ ____________ REVIEWED BY: DATE 1401 S. Hanley Road St. Louis, M O 63144 Phone: 314-768-4100 Fax: 314-768-4765 Page 884 ' exact cop"? Certified Papers Retrieval ARGUS 418-020 Return to Certified Analysis Retrieval 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 LESS THAN 0.02 ORGANOPHOSPHATES PPM Disulfoton LESS THAN 0.02 Malathion LESS THAN 0.02 Parathion LESS THAN 0.02 Thiodan LESS THAN 0.02 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.labdiet.com/certified/pwa_spc002.asp exact cop ,Page 885 ` J POjP ^ . tifiA M lA ________ 19^1/fiP REVIEWED BY: DATE 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. Ptw ilA A REVIEWED BY: i 3-(at/6ft DATE Page 886 j EXACT \ iL 2 COr ln h l m ARGUS 418-020 Pag* l o f 2 Sample No.s L0Q28475-2 Received: 11/30/00 Reported: 12/14/00 Site: RHI Locator: 3002 Project CERT. CERTIFIED RODENT DIET MEAL LOT NUMBER DEC 01 00 IB Assav / Analvte Protein, Kjeldahl (N x 6J25) Protein Fat Fat Fiber, erode Fiber, Crude Arsenic Arsenic Cadmium rym iiim Calcium Calcium Lead Lead Mercury Mercury Phosphorus Phosphorus Selenium Selenium PHKR FTEE/FTAH FIBR ASF CDF CAF PB HGSP PF SE Result 20.8 5.92 3.99 <0.200 0.033 0.977 0.139 <0.025 0.639 0.159 Unita % % % ppm ppm % ppm ppm % ppm For additional information, please contact: (1) For assay methodology Customer Services, 314*982*1310 (2) ForNutritional Interpretation Dr. Dorrance Haught, 314*768-4362 (3) AD other questions - Richmond, IN Manufacturing Plant, 765-962-9561. The tens "Lest Than" is used to signiiy the lowerUmtt of quanttMtoa ofthe procedute under the eoodfttau employed. Theuso of the tm n <`Lms Then" does net imply that tmoc* o fAnalyte werepresent Semples submitted toJUirtoaAnalytic! U taato rtes lbr routine m alyia will br w tan id for i minimum oftfafaty (30) diyi after tin iiport o f ii tuned. Extended tenge requiitBMots must be brought to ths ettmtion of Rsjihm Analytical laboratories prior to or i t the time of sample submission. REVIEWED BY: B-Vs\o\ DATE EXACT CC J L M is M . Page 887 *7 CERTIFIED RODENT DIET MEAL LOTNUMBER DEC 01 00 IB Orfanopfaoaphate pesticides DisuUton Bthlon Malatfaion Methyl Parathioo Pantfhion Thimet Thiodan Trhhion OrganoehloriM pestlkFCB'i Heptachlor Epoxide Heptachlor DDE T Eadrin Mirsx Alpha-BHC DeltapBHC Aldrin Dieldrin DDT Chlardsne Methoxychlor Beta*BHC HCB PCB Aflatoxin aereen Aflatoxins ORGP RSPB AFTC Locator 5002 Proda*: CERT. ARGUS 418-020 RpfUlt <0.0200 <0.0200 <0.0200 <0.0200 <0.0200 <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 .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 .0 2 0 0 0 .0 2 0 0 0 .1 5 0 <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 asmy methodology* CustomerServices, 314-982*1310 (2) For Nutritional Interpretation - Dr. Dorrance Haugbt, 314-768-4362 (3) All otherquestions - Richmond, IN Maaufocturing Plant, 765-962-9561. The tam *X H i Then" to used to tip tfy the kar limit o f qaentitstioncftheprooedui* under 1h conditions employed. The use of the to n n in e Then" dess not imply fla t tu e ofAnalyte-aere ptts ent Sample* submitted to Ralston ntlytioel Laboratori fbr routine eodytto will be retained f tr imim nnun o fthirty (30) day afterthe report o f nelyi* is iuood. Extended Stonge requimiMats muMSbe brought to Hu Motion o fRalston Analytical Laboratories prior to or at the time o f sample submission. REVIEWED BY: j EXACTCC: " L & Sl / l Page 888 a s s is t DATE ARGUS 418-020 Lancaster Laboratories Where quality is ascience. Lancaster Laboratories Sample No. WW 3634413 Collected:06/20/2001 10:40 by EA Account Number: 02423 Submitted: 06/20/2001 16:30 Primedica Argus Reported: 06/28/2001 at 14:28 57 Union Street Discard: 07/29/2001 Worcester MA 01608 Point #2 Formulation Lab 905 Sheehy Dr Bldg F Grab Water Sample Page 1o f2 CAT No. 00224 00226 00228 00368 01504 C1506 01505 Analysis Name Chloride Ortho-Phosphate as P Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Bromide 00178 Pesticides/PCB1s in Water 00453 00454 00455 00469 00477 00478 00638 01902 01903 01904 01905 01906 01907 01908 01909 01910 01911 01912 01913 01914 01915 01916 01917 01918 01919 Gamma BHC - Lindane Heptachlor Aldrin Dieldrin Endrin DDT Endrin Aldehyde Alpha BHC Beta BHC Delta BHC Heptachlor Epoxide DDE DDD Chlordane Toxaphene Endosulfan I Endosulfan II Endosulfan Sulfate PCB-1016 PCB-1221 PCB-123Z PCB-1242 PC5-124S FCB-1254 PCE-1260 01356 Herbicides m Water CAS Number 16887-00-6 14265-44-2 14808-79-8 14797-55-8 16984-48-8 14797-65-0 n .a . As Received Result < 2.0 < 0.020 < 5.0 < 0.50 < 0.50 < 0.50 < 2.5 As Received Limit of Quantitation 2.0 0.020 5.0 0.50 C .50 0.50 2.5 Units mg/1 m g /I mg/1 mg/1 mg/1 mg/1 mg/1 Dilution Factor 5 1 5 5 5 5 5 58-89-9 . 76-44-8 309-00-2 60-57-1 72-20-8 50-29-3 7421-93-4 319-84-6 319-85-7 319-86-8 1024-57-3 72-55-9 72-54-8 57-74-9 8001-35-2 959-98-8 33213-65-9 1031-07-8 . 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 11096-82-5 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < 0.0094 < 0.094 < 0.0094 < 0.0094 < 0 ;0094 < 0.0094 < 0.0094 < 0.0094 < 0.23 < 3.8 < 0.0094 < 0.0094 < 0.028 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 0.0094 0.0094 0.0094 0.0094 0.0094 0.0094 0.094 0.0094 0.0094 0.0094 0.0094 0.0094 0.0094 0.28 3.8 0.0094 0.0094 0.028 0.94 0.94 0.94 0.94 0.94 0.94 0.94 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 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 IVI E M b e r Lancaster Laboratories. Inc. 2^25 New Holland Pine SH I 717..5-2300 Fax: 717-05-25S1 ^ km - lfnh\ Page 889 V s/"' 2216 Rev. 9/11/00 ARGUS 418-020 T # Lancaster Laboratories r Where quality is a science. Lancaster Laboratories Sample No. ww 3 6 3 4 4 1 3 Collected:06/20/2001 10:40 by EA Account Number: 02423 Submitted: 06/20/2001 16:30 Primedica Argus Reported: 06/28/2001 at 14:28 57 Union Street Discard: 07/29/2001 Worcester MA 01603 Point #2 Formulation Lab 905 Sheehy Dr Bldg F Grab Water Sample Page 2 of2 CAT No. Analysis Name 01857 01858 05286 05287 05288 05289 05290 05291 05292 05293 08103 2,4-D 2,4,5-TP 2,4,5-T Dalapon Dinoseb Dicamba MCPP MCPA 2,4-DP (Dichlorprop) 2,4-DB Pentachlorophenol CAS Number 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 As Received Result < 0.49 < 0.049 < 0.049 < 1.2 < 0.25 < 0.30 < 200. < 200. < 0.49 < 0.49 < 0.05 Commonwealth of Pennsylvania Lab Certification No. 36-037 As Received Limit of Quanti tation 0.49 0.04S 0.049 1.2 0.25 0.30 200. 200. 0.49 0.49 0.05 Units ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/1 ug/'l ug/1 ug/1 Dilution Factor 1 I 1 4 4 1 1 4 4 1 1 CAT No. 00224 00226 00228 00363 01504 01506 01505 00178 01856 00816 00817 Analysis Name Chloride Ortho-Phosphate as P Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Bromide Pesticides/PCB's in Water Herbicides in Water Water Sample Herbicide Extract Water Sample Pest. Extraction LaborJ-a--t-oryj Chronicle Analysis Method Trial# Date and Time EPA 300.0 EPA 365.3 1 06/21/2001 14:25 1 06/21/2001 21:00 EPA 300.0 1 06/21/2001 14:25 EPA 300.0 EPA 300.0 1 06/21/2001 14:25 1 06/21/2001 14:25 EPA 300.0 1 06/21/2001 14:25 EPA 300.0 EPA 608 1 06/21/2001 14:25 1 06/21/2001 19:45 SW-84 8151A SW-846 8151A 1 06/25/2001 16:12 1 06/22/2001 09:00 EPA 608 1 06/21/2001 09:45 Dilution Analyst Factor Mark A. Buckwalter 5 Daniel S . Smith 1 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Anita M. Dale 1 Tiffany A. Leyda Deborah M. Zimmerman 1 1 Amanda E:. Wade 1 M EM BER Lancaster Laboratories. Inc. 2425 New Holland Pike PO Box 12425 Lancaster, PA 17605-2425 717-656-2300 Fax:717-656-2681 o' A ; EXACT C O - JU M M Page 890 ARGUS 418-020 Analysis Report Lancaster Laboratories Where quality is a science. Lancaster Laboratories Sample No. WW 3634414 Collected:06/20/2001 10:30 by EA Account Number: 02423 Submitted: 06/20/2001 16:30 Reported: 06/28/2001 at 14:28 Discard: 07/29/2001 Point #3 Analytical Lab 905 Sheehy Dr Bldg B Grab Water Sample Primedica Argus 57 Onion Street Worcester MA 01608 Page 1o f2 CAT No. 00224 00226 00223 00368 01504 01506 01505 Analysis Name Chloride Ortho-Phosphate as P Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Bromide 00178 Pesticides/PCB's in Water 00453 00454 00455 00469 00477 00478 00638 01902 01903 01904 01905 01906 01907 01908 01909 01910 01911 01912 01913 01914 01915 01916 C1917 01918 01919 Gamma BHC - Lindane Heptachlor Aldrin Dieldrin Endrm DDT Endrin Aldehyde Alpha EHC Beta BHC Delta BHC Heptachlor Epoxide DDE DDD Chlordane Toxaphene Endosulfan I Endosulfan II Endosulfan Sulfate PCB-1016 PCB-1221 PCB-1232 PCB-1242 PCB-1248 FCB-1254 PCB-1260 0185 6 Herbicides in Water CAS Number 16887-00-6 14265-44-2 14808-79-8 14797-55-8 16984-48-8 14797-65-0 n.a. As Received Result < 2.0 < 0.020 < 5.0 < 0.50 < 0.50 < C .50 < 2.5 As Received Limit of Quantitation 2.0 0.020 5.0 0.50 0.50 0.50 2.5 Units mg/1 mg/1 mg/1 mg/1 mg/1 mg/1 mg/1 Dilution Factor 5 1 5 5 5 5 5 58-89-9 76-44-8 309-00-2 60-57-1 72-20-8 50-29-3 7421-93-4 319-84-6 319-85-7 319-86-8 1024-57-3 72-55-9 72-54-8 57-74-9 8001-35-2 959-98-8 33213-65-9 1031-07-8 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 11096-82-5 < 0.0095 < 0.0095 < 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 0.0095 0.0095 0.29 3.8 0.0095 0.0095 0.029 1.0 1.0 1.0 1.0 1.0 1.0 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 ug/1 M EM BER Lancaster Laboratories, Inc. 2425 New Holland Pike PO Sox 12425 Lancaster. PA 17505-2425 717-656-2300 Fax:717-656-2681 exact c c : 2216 Rev. 9/11/00 Page 891 ARGUS 418-020 Lancaster Laboratories Where quality is a science. Lancaster Laboratories Sample No. WW 3634414 Collected:06/20/2001 10:30 by EA Account Number: 02423 Submitted: 06/20/2001 16:30 Reported: 06/28/2001 at 14:28 Discard: 07/29/2001 Point #3 Analytical Lab 905 Sheehy Dr Bldg B Grab Water Sample Primeaica Argus 57 Union Street Worcester MA 01608 Paee 2 of 2 CAT NO. Analysis Name 01857 01858 05286 05287 05288 05289 05290 05291 05292 05293 08103 2,4-D 2 . 4 , 5-TP 2 , 4 , 5-T Dalapon Dinoseb Dicamba MCPP MCPA 2,4-DP Dichlorprop) 2,4-DB Pentachlorophenol CAS Number 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 S7-86-5 As Received Result < 0.48 < 0.048 < 0.048 < 1.2 < 0.24 < 0.29 < 190. < 190. < 0.48 < 0.48 < 0.05 Commonwealth of Pennsylvania Lab Certification No. 36-037 As Received Limit of Quantitation 0.48 0.048 0.048 1.2 0.24 0.29 190. 190. 0.48 0.48 0.05 Units ug /1 ug/1 ug/1 ug/i 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 CAT No. 00224 00226 00229 00368 01504 01506 01505 00178 01856 00816 00817 Analysis Name Chloride Ortho-Phosphate as P Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Bromide Pesticides/PCB's in water Herbicides in Water Water Sample Herbicide Extract Water Sample Pest. Extraction Laboratory Chronicle Analysis Method Trial* Date and Time EPA 300.0 1 06/21/2001 14:39 EPA 365.3 1 06/21/2001 21:00 EPA 300.0 1 06/21/2001 14 :39 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 608 SW-846 S151A 1 06/21/2001 14:39 1 06/21/2001 14:39 1 06/21/2001 14:39 1 06/21/2001 14:39 1 06/21/2001 20:05 1 06/25/2001 16:49 SW-346 8151A 1 06/22/2001 09:00 EPA 608 1 06/21/2001 09:45 Dilution Analyst Factor Mark A. Buckwalter 5 Daniel !S. Smith 1 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Mark A. Buckwalter 5 Anita M . Dale 1 Tiffany A. Leyda 1 Deborah M. Zimmerman 1 Amanda :E. Wade 1 MEMBER Lancaster Laboratories, ine. 2425 New Hctiand Pike Lancaster. 17805-2425 r / -- 2 - * - 7A A EXACT COPY ! IJ O J Page 892 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. Dena 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 Sample source: Formalation U.*borcbcnj r <Sta*hy'brive- 00' = * i 7 / 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 ), L ^ - r - 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 EXACT (X 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. Dena 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 Sample source Rm. 39 v^htcKi Vive. 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. SajcamefcgE m l Re su l t Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.1 > .L * A r / j / c j 7 / > > All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks {**). Symbol ke y : < - less than TNTC - too numerous to count mg/1 - milligram/liter (> 200) PA DEP # 0 9 - 3 3 2 Maryaim E. Fedock/ President Page 894 IexcTcT-v . 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. Dena 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 &hc.c.hij b n v 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 7/ o All results which are outside the "Maximum Contaminant Level" (MCL) establishec under the "Safe Drinking Water Act" are marked by asterisks (**) . Symbol k e y : < - less than 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. Dena 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 sour(cSe>: An7a0lSyti6cal l-- *bdbrnhv>cr. y kc -u / lM 7 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 <1 <1 < 0.1 2) 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 than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP #09-332 Maryann E. Fedock/ President EXACT ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Attn: FAX # Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Dena Lebo 215-443-8710 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 1- 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 ML Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 "U *- * * /< * / S 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 mg/1 - milligram/liter (> 200) PA DEP #09-332 Maryan; Fedock/ President Page 897 ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number Date sampled Time sampled Date received Sampled by 8331-00B 12/18/00 1315 12/18/00 EM Sample source: Chem. Lato 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 -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 Maryani^E. Fedock/ President Page 898 ARGUS 418-020 ANALYTICAL LABORATORIES( INC. >.0. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLB ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8331-00C 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 jviij Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <l <l <l < 0.1 "V Jo/ 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 mg/1 - milligram/liter (> 200) PA DEP #09-332 Maryann^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., Building A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8331-OOD 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, water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. MCL Rg.SUlt 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 #09-332 Maryann^E. Fedock/ President Page 900 camcT CC ARGUS 418-020 Analysis Report # r LancasterLaboratories W here quality is a 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 Water Sample Semi-Annual Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page 1of2 90 SAP CAT NO. 00224 00228 00368 01504 01506 07322 01S05 Analysis Name Chloride Sulfate Nitrate Nitrogen Fluoride Nitrite Nitrogen Ortho-phosphate Bromide 00178 Pesticides/PCB's in water 00453 00454 00455 00469 00477 00473 00638 01902 01903 01904 01905 01906 01907 01908 01909 01910 01911 01912 01913 01914 01915 01916 01917 01919 01919 Gamma BHC - Lindane Heptachlor Aldrin Dieldrln Endrin DDT Endrin Aldehyde Alpha BHC Beta BHC Delta BHC Heptachlor Epoxide DDE DDD Chlordane Toxaphene Endosulfan I Endosulfan II Endosulfan Sulfate PCB-1016 PC8-1221 PCB-1232 PCS-1242 PC3-1248 PCS-1254 PCB-1260 CAS Number 16887-00-6 14808-79-8 14797-55-8 16984-48-8 14797-65-0 14265-44-2 n.a. Aai Received Result < 2.0 < 5.0 < 0.50 < 0.50 < 0.50 << 5.0 2.5 As Received Limit of Quantitation 2.0 5.0 0.50 0 .SO 0.50 5.0 2.5 Units 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 76-44-8 309-00-2 60-57-1 72-20-8 50-29-3 7421-93-4 319-84-6 319-85-7 319-95-8 1024-57-3 72-55-9 72-54-8 57-74-9 8001-35-2 959-98-8 33213-65-9 1031-07-3 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 11095-52-5 < 0.0098 < 0.0098 < 0.0098 C 0.0098 c 0.0098 < 0.0098 < C .098 c 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 < 1.3 < 1.0 < i .: < 2.3 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/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 l\rt g g g ---------- A C IL L24a2n5caNsteewr LHaoblolarnadtorPieikse. ine PO Boa 12425 L7a1n7c-6a5s6te-2r.3P0A0 17F6a0x5: -721472-5656-2681 EXACT COPY ^ rr/zr/o i Page 90 f ~2>. 2216 Rev. 9/11/00 ARGUS 418-020 LancasterLaboratories r W here quality is a science. Lanastar Laboratories Sample No. WW 3S42350 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 Water Sample Semi-Annual Account Number: 02423 Primedica Argus 57 Onion Street Worcester MA 01608 Page 2 o f 2 905AP CAT No. 018S6 Analysis Naas Herbicides in water 0X857 01858 05286 05287 05288 05289 05290 0S291 05292 05293 08103 2,4-D 2.4.S-TP 2,4,5-T Dalapon Dinoseb Dicamba MCPP MCPA 2,4-DP (Dichlorprop) 2,4-DB Pentachlorophenol CAS Number As Received Result 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 < 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 As Received Limit of Quantitation Units 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 Dilution Factor 1 l 1 1 1 1 1 1 1 1 1 ~~2) . a- ^ A u / o i Lancaster Laboratories. Inc. A C ILM E M BER 2425 New Holland Pike PLOanBcaosxte1r2, 4P2517605*2425 717-656-2300 Fax: 717-656-2681 Page 902 2216 Rev. 9/11/00 ARGUS 418-020 ^ LancasterLaboratories ^ | r W here quality is a science. Lancaster Laboratories Sampla No. WW 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 Hater Sample Semi-Annual Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page 1of 905-2 CAT No. 00224 00228 00368 01504 01S06 07322 01S0S Analysis Name Chloride Sulface Nitrace Nitrogen Fluoride Nitrite Nitrogen Crtho-phosphate Bromide 00178 Pesticides/PCB's in water 004S3 00454 00455 00459 00477 00478 00638 01902 01903 01904 01905 01905 01937 01908 01909 01910 01911 01912 01913 01914 C1915 01915 01917 01913 01919 Gamma BKC - Lindane Heptachlor Aldrin Cieldnn Endrin EDT Endrin Aldehyde Alpha BHC Beta BHC Eelta 3HC Heptachlor Epoxide DOE COD Chlordane Coxaphene Endosulfan I Endosulfan II Endosulfan Sulfate PCB-1016 PCS-1221 PCS-1232 P03-1242 PC3-1248 F23-12S4 PCS-1253 CAS Nuobsr 16887-00-6 14808-79-8 14797-55-8 16984-48-8 14797-65-0 14265-44-2 n.a. Axi Received Result < 2.0 < 5.0 < 0.50 < 0.50 < 0.50 < 5.0 < 2.5 As Received Liait of Quantitation 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 Dilution Pactor 5 5 5 5 5 5 5 58-89-9 76-44-8 309-00-2 60-57-1 72-20-8 SO-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 8001-35-2 959-98 -8 33213-65-9 1031-07-8 12674-11-2 11104-29-2 11141-16-5 53469-21-9 12672-29-5 11097-69-1 11096-32-5 < 0.0096 < C .0096 < 0.0096 < C .3096 < 0.0096 < 0.3096 < 0.096 < < 0.0096 < 0.0096 < 0.0096 < 0.0096 < 0.0096 < 0.29 < 3.8 < 0.0096 < 3.0096 < 0.029 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.0 < 1.3 o U*oo\0 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 3.8 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 MEMBER Lancaster Laboratories, inc. 2425 New Holland Pike PO Box 12425 Lancaster. PA 17605*2425 717-656-2300 Fax: 717-656-2681 E`TXnArCzT/isC-OJPoYj Page 903 *~2) 2216 Pew. 9/ 11/00 ARGUS 418-020 LancasterLaboratories : W here quality is a science. Lancaster Laboratories Sample No. WW 35423S1 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 2 o f 2 905-2 CAT No. 01856 Analysis Nana Herbicides in water 01857 01858 05286 05287 05288 05289 05290 05291 05292 05293 08103 2,4-D 2,4,5-TP 2,4,5-T Dalapon Dinoseb Dicamba MCPP MCPA 2,4-DP (Dichlorprop) 2,4-DB Per.tachlorophenol CAS Nuaber As Received Result 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-B2-6 87-86-5 < 0.48 < 0.048 < 0.048 < 1.2 c 0.24 c 0.29 < 190. < 190 . 0.48 < 0.48 e 0.05 Commonwealth of Pennsylvania Lab Certification No. 36-037 As Recsived Liait of Quantitation Onits 0.48 0.048 0.048 1.2 0.24 0.29 190. 190 . 0.48 0.48 0.05 u g/1 u g/1 u g /1 u g /1 u g /1 u g /1 u g /1 u g /1 u g /1 u g /1 u g /1 Dilution Factor 1 1 1 1 1 1 l 1 1 1 l EXACT COPY A C IL 2L4a2nScaNsteewr LHaoDlolarnatdonPeik*e. Inc. PU7O1n7cB-6ao5sx6te-12r2.34P02A05 17605-2425 Fax: 717-656-2681 Page 904 " ) . - J s - r - . 2216 Rev. 9/11/00 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 '/pA i f<5 F 'S.Ae.cJy i/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 Rss.ult Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 > /r/o 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 Maryaim E. Fedock/ President Page 905 0 7I EXACT C ? * 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.f Bldg. A Horsham, PA 19044 Attn. Dena 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 ' r/o 1 90s s j i 7u v <l . 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 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 # 0 9 - 3 3 2 Maryajin E^ Fedock/ President Page 906 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: 2018-01C Date sampled : 01/03/01 Time sampled : 1430 Date received: 01/03/01 Sampled by : EM Sample source: Analytical L.aLoroi'ortf 906.fi ShM Jwbriv. ! / b A>i 7 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 L -jj s -z r `/ r / e ! 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 ARGUS 418-020 ANALYTICAL LABORATORIES P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS JRBPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena 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 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 ML Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <l <1 0.6 ~0L-jjL--3-- / -r - o 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/1iter PA DEP #09-332 Marnn E. Fedock/ President Page 908 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFQNT, PA 18914 (215) 723-6466 SAMPLE.ASALYSIS-REB ^RI Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena 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 F Sh^hy o/* t 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) --2-- 02/L ? 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/1iter PA DEP # 0 9 - 3 3 2 Maryann E. Fedock/ President Page 909 I EXACT C G C 7 LA&H' 7/fg/fti 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. Dena 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 ) ^ 70S c.e.hy 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 ML Bfifiult Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <l <1 <1 0.5 ~~2) / --d i'-- c= ^ /= ^ / / 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 iCVAPT /-<' Z v 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. Dena 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 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> '^ L'/ c J . o / a 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 Maryann 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. 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 /Ai C.C.Ay i 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 Rssu.l.t Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 < 0.1 2) A --*JL/~~pr~ 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 2 /b \ 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: 4135-01A Date sampled : 03/07/01 Time sampled : 1430 Date received: 03/08/01 Sampled by : FO 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 Hesni.t Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.6 ~2) L jA s -&- 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 Page 913 JE X A C fcO P Y t L & i z s & i ARGUS 418-020 ANALYTICAL LABORATORIES P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 INC. 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: 4135-01B Date sampled : 03/07/01 Time sampled : 1430 Date received: 03/08/01 Sampled by : FO Sample source: Chem. Lab F ji irive- 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 #09-332 Maryai E. Fedock/ President Page 914 ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. Box 319 CHALFONT, PA 18914 (215) 723-6466 SAMPLE._A8&LYSXS.-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 I 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 E. Fedock/ President Page 915 j \ E X Mt A C1-- - , ,, h T'cop ?tn/b yI r 1 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: 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 EPA and DEP drinking water standards for this parameter. Parameter Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 /r> - sfo-luc- F o r r >Otr-t )-r> Ula-S >.2 PPm . ~i> ML <1 Res u l t <1 <1 1.5 9 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/1iter PA DEP # 0 9 - 3 3 2 Marynn E. Fedock/ President Page 916 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: 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 Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 ML> <1 Result <1 <1 < 0.1 / - 9-oj 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 T CO. i M ? 'ft? /? ' 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. Dena 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 <1 <1 <1 0.6 9-9 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 Page 918 IIEfmXA-C7! lCnOfor\': 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: 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 Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.3 * -9-0} All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/1 - milligram/liter PA DEP #09-332 Maryann E. Fedock/ President Page 919 I EXACT 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: 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 <1 < 0.1 2)-L^ y - 9 - v 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 EXACT Page 920 ARGUS 418-020 #Lancaster Laboratories Where quality is a science. Lancaster Laboratories Sample No. G5 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 3542353 Account Number: 02423 Primedica Argus 57 Union Street Worcester MA 01608 Page 1of2 CAT So. 00159 01646 01649 01651 01655 01666 06935 06936 Analysis Name Mercury Barium Cadmium Chromium Lead Silver Arsenic TR Selenium TR 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 As Rseeived Result < 0.096 < 9.9 < 2.0 < 4.0 < 9.9 < 2.0 <0.99 1.2 0 As Received Limit of Quantitation 0.096 9.9 2.0 4.0 9.9 2.0 0.99 0.99 Units mg /kg mg/kg mg/kg mg/kg mg/kg mg/kg rng/ng mg/kg Dilution Factor 1 1 1 1 1 1 1 1 01224 Pesticides/PCBs in solids 01218 01219 01220 01221 01222 01223 01859 01981 01982 01983 01984 01985 01986 01987 01988 01989 01990 01991 01992 01993 01994 01995 01996 01997 01998 Gamma BHC - Lindane Heptachlor Aldrin DDT Dieldrin Endrin Methoxychlor Alpha BHC Beta BHC Delta BHC Heptachlor Epoxide DDE DDD Chlordane Toxaphene Endosuifan I Endosuifan XX Endosuifan Sulfate Endrin Aldehyde PCS-1016 PCB-1221 PCS-1232 PCB-1242 PCB-1248 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 72-54-8 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. < 17- 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 . (L)C^nTCun, 'i-ji- i . r i \ i u C/7f />< fn u E. -n C /t u > .fh .>_ /n io jr'nu'7' m y ' OJ vLO ^ cL/r>I n tin f /e-ve.i o r- d 4. Lancaster LjDon tones, :nc. -1 H M 3 H 3 2425 New Holland Pike x.i'e.r j-^ndu rd&, ^ / n , / 5, PO Sox 12425 Lancaster. PA 7505-2425 717-555-2300 fax: 717-555-2S1 *EhXr)APC?ThCxO\oPYi 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 1 1 1 1 1 1 1 1 1 1 1 1 1 1 -i Ptr h u .riA/i d r . ~ O .U b n - 2215 .lev. 0/11/00 Page 921 ARGUS 418-020 nalysis Report # LancasterLaboratories : Where quality is a science. Lancaster Laboratories Sample Mo. G5 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 of2 CAT NO. 01999 Analysis Naas PCB-1260 CAS Number 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 Result < 17. < 17. < 1.7 As Received Limit of Quantitation 17. Units ug/kg 17. ug/kg 1.7 ug/kg Dilution Factor 1 1 1 ~2>. -V /6 A / EXACT COPY MEMBER ACIL Lancaster Laboratories. Inc. 2425 New Holland Pike PO Box 12425 Lancaster, PA 17605-2425 717-656-2300 Fax:717-656-2681 Page 922 2216 Rev. 9/11/00 ARGUS 418-020 Explanation of Symbols and Abbreviations The following defines common symbols and abbreviations used in reporting technical data: N .D . TNTC IU n h o s /c m C Cal m eq 9 ug ml m3 none detected Too Num erous To Count International Units m icrom hos/cm degrees Celsius (diet) calories m illieq u ivalen ts gram (s) microgram (s) m illiliter(s) cubic m eter(s) BMQL MPN CP U nits NTU Flb . kg mg 1 ul fib >5 um /m l Below Minimum Quantitation Level Most Probable Num ber cobalt-chloroplatinate units nephelom etric turbidity units degrees Fahrenheit pound(s) kilogram (s) m illigram (s) liter(s) m icroliter(s) fibers greater than 5 microns in length per ml < less than - The num ber followinq the siqn is the limit of quantitation, the sm allest am ount of analyte which can be reliably determ ined using this specific test, > greater than ppm parts per million - O ne ppm is equivalent to one milligram per kilogram (m g/kg). or one gram per million gram s. For aqueous liquids, ppm is usually taken to be equivalent to milligrams per liter (m g/l), because one liter of w ater 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. ppb parts per billion D ry w e ig h t Results printed under this heading have been adjusted for moisture content. This increases the analyte basis w eight concentration to approxim ate the value present in a sim ilar sam ple without moisture. U.S. EPA data qualifiers: O rganic Q u a lifie rs In o rg an ic Q u alifiers A B C D E J N P U X ,Y Z T IC is a possible aldol-condensation product Analyte w as also detected in the blank Pesticide result confirmed by G C /M S Compound quantitated on a diluted sam ple Concentration exceeds the calibration range of the instrument Estim ated value Presum ptive evidence of a compound (T IC s only) Concentration difference between primary confirm ation columns >25% Compound was not detected Defined in case narrative B Value is <CRDL, but >IDL E Estim ated due to interference M Duplicate injection precision not m et N Spike sam ple not within control limits S Method of standard additions (M SA ) used for calculation U Compound w as not detected W Post digestion spike out of control limits * Duplicate analysis not within control limits Correlation coefficient for M SA <0.995 Tests results relate only to the sam ple tested. Clients should be aw are that a critical step in a chem ical or microbiological analysis is the collection of the sam ple. Unless the sam ple analyzed is truly representative of the bulk of m aterial involved, the test results will be m eaningless. If you have questions regarding the proper techniques of collecting sam ples, please contact us. W e cannot be held responsible for sam ple integrity, however, unless sampling has been perform ed by a m em ber of our staff. This report shall not be reproduced except in full, without the written approval of the laboratory. WsOTELtNahuA"HXcFoeAbcBEMPRmpFeSTORupCIPRtiETRtaErttUOaAcNDenSAhnRNdSdESTacT.aRSTSOesEOrYETISedDBRo.HNoATIrFIDLOEETreoNOIAdS)RTrrDFeRmMdYOOBrIeAMsFLPoOErRGIaArPsMLFELnoEuRLAIGIdStbTISATNhEmOUSBCIeCDCFCILrioNtOOA.UtEoHneGSRFLWrdddFTADiLtELeEOEbiRAoIOrXyARRnMDfPPSocBsILAIRlUSSriNIeoALGwECRDnOfIBTESoPLLtIFO.RrYSASaOkRE.IPnSMWscACRWEhIanATTAOaseAOR.NalFtleNSacRRYbIrTccDPeIALEecOEONaWeapSTCRbcptTiHAnAcIotYAGegERrnNaLpIoRORDSa.ttoenAOlCeWrE(daiNBODgeXlAbya)sTWNCtyRlWYiacSLrIRLneLaHUOEadLsAlQESFnwpNwRTIcUooVMTeEaHnErEIskEGEsEhNt,iRAeSebARTwrrNi.CRleIieULAtEDHDbyaLwNXyALbf.IoPaSECNooOrrRSrbATrGRataEhjSAeStInoeVSIcBTNtOrtESiIptEeLChFtNEuosIReITrD(DpawAIYaNUEon)Oh.csyNBTLciRceIuITcHONhEsroIAEaMURfiNnnLocAPfNcOryOliDlcLTEwuFoAtEIOdiGEhfnMVAetiDRgLceEsLAIh,IsGtLNEGaetItNEnrThSOrEmeyNCeSTSsHsCLccHuHAIUolcENlEitAeSnosDCRLnd(nIEfBLLNitottWaIiEUuorGTLinsEADntHAheeANsRINEesNdtRRWChIGtsNihnAaAaA,SeFNmtSaRBOOvtTnTpeURaLRyIElsEerETAMyRtSNarNOEf.esrTOoDRsYmuTOltsF. 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 SUBMITTED TO: Raymond G. York, Ph.D., D.A.B.T. Argus Research 905 Sheehy Drive Horsham, PA 19044 SUBMITTED BY: W. Rfay Brown, D.V.M., Ph.D. Veterinary Pathologist March 25, 2002 Page 925 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONHSIOSTRO'SPSATTUHDOYLONGUYMBREERP:OTR-T6889.6 TABLE OF CONTENTS Page REPORT Method............................................................................................................................1 Results........................................................................................................................... 3 Summary........................................................................................................................ 6 Quality Assurance Unit Statement................................................................................8 TABLES 1. Incidence and Degree of Severity of Histomorphologic Observations 2. InPciGdeennceeraatniodnD..e..g..r..e..e...o..f..S...e..v.e..r..it..y...o..f..H..i.s..t.o..m...o..r..p..h..o..l.o..g..ic....O..b..s..e..r..v.a..t.i.o..n..s...-...............9 3. 4. IInnPFcc1iiGddGeeennenccneeerearaatainnotddinonDDR.ee.e.gg.d.rr.u.ee.c.ee.e..ood..ff.F.SS..eee..r.vvt.iee.l.itrr.y.iitt.yy.A..o.on..ffi.m.HH..aii.ss.l.tst.oo....mm......oo....rr...pp....hh....oo....ll.o.o....gg....ii.cc......OO......bb....ss....ee....rr..vv....aa....tt..ii..oo....nn....ss......-.........................1163 F1 Generation Reduced Fertility Animals........................................................22 APPENDICES I. Histomorphologic Observations - P Generation....................................... 1-1 to 1-18 Key to Histomorphologic Observations.................................................................1-1 Tables 1-1. Histomorphologic Observations - Group I Male Rats.................................I-2 I-2. Histomorphologic Observations - Group II Male Rats................................I-4 I-3. Histomorphologic Observations - Group III Male Rats...............................I-6 I-4. Histomorphologic Observations - Group IV Male Rats...............................I-8 I-5. Histomorphologic Observations - Group V Male Rats..............................1-10 I-6. Histomorphologic Observations - Group I Female Rats.......................... 1-12 I-7. Histomorphologic Observations - Group II Female Rats......................... 1-14 I-8. Histomorphologic Observations - Group III Female Rats........................ 1-15 I-9. Histomorphologic Observations - Group IV Female Rats....................... 1-16 1-10. Histomorphologic Observations - Group V Female Rats........................ 1-17 Page 926 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 HISTOPATHOLOGY REPORT TABLE OF CONTENTS (Continued) Page II. Histomorphologic Observations-F1 Generation......................................11-1 to II-20 Key to Histomorphologic Observations............................................................... 11-1 Tables II1II1---321... HHHiiissstttooommmooorrrppphhhooolllooogggiiiccc OOObbbssseeerrrvvvaaatttiiiooonnnsss --- GGGrrrooouuuppp IIIIIIMMMaalaeleleRRRaaattsts.s.........................................................................................IIIIII---642 II-4. Histomorphologic Observations - Group IV Male Rats.............................II-8 II-5. Histomorphologic Observations - Group V Male Rats........................... 11-11 II-6. Histomorphologic Observations - Group I Female Rats........................ 11-14 II-7. Histomorphologic Observations - Group II Female Rats....................... 11-16 II1II1--89-1..0. HHHiiissstttooommmooorrrppphhhooolllooogggiiiccc OOObbbssseeerrrvvvaaatttiiiooonnnsss --- GGGrrrooouuuppp IIVIVI FFFeeemmmaaallleee RRRaaatttsss.................................................................111111---111897 III. Individual Animal Gross and Histomorphology Data P Generation.................................................................................. 111-1 to 111-106 IV. Individual Animal Gross and Histomorphology Data F1 Generation................................................................................. IV-1 to IV-130 V. Individual Animal Gross and Histomorphology Data Gross Lesions - F1and F2 Pups..................................... ...............................V-1 Page 927 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONHSIOSTRO'SPSATTUHDOYLONGUYMBREERP:OTR-T6889.6 METHOD: Microscopic examination was made of the specified tissues from male and female Crl:CD(SD)IGS BR 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 same dosage levels of the test substances as their respective P generation sires and dams (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 gross 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 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 HISTOPATHOLOGY REPORT 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, eopviidduidcytsm,isu, teprruoss,tatcee,rvsiexmainnadl vveasgiicnleas(afenmdacloeagrautlsa)t.ingInglaandddit(imona,lethraetsr)eoprroodvuacriteivse, tissues were examined from male and female rats of the P generation and male rats of the F1 generation suspected of reduced fertility. Gross 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 Argus Re search for archiving. Research Pathology Services, Inc. Page 929 -2 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION STUDY O(OFNAEMLMITOTNEIRUMPEPREGRFELNUEORRAOTIOOCNT)ARNEOPARTOED(UACFTPIOO)NIN RATS PROTOCOL 418-020 SPONHSIOSTRO'SPSATTUHDOYLONGUYMBREERP:OTR-T6889.6 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. apmPunInnareidecdalcisrrnvoeomiddcsnpoiuctscFeraoyrr1dolpesioscgimcnpbeocsoitncpheaneriarbdocrvnuiasangcltotagieiooobrspnnsf,mioescwpr,rimcvahframireonetinnisidnoccitrannAaoopsgplpspspicaclpeoidcfrnpuarefoidilbcnctmiledcerfediai,nnsettagsdhsrs,IieneargTeniisnnPasd,cbpltuIleaaeIh,dcnneetdrdie1vd-tse1aiFspilny1sec.auAconetpgridMvsrpeeeenallaTwynect.adrriitooabihcAsntlieecosgoknorepf1IoyI1iIcast-1htdsa.oeolnuybdltTthgshoereIVroebravsisnftassoegdtrrriivaovoatehnnisrdddeess changes for the F1 and F2 pups are listed in Appendix V. P Generation Adult Rats (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 was observed in the adrenal glands of 2/10 and 7/10 male rats of Groups IV and V, respectively, designated for tehxicakmniensastioannd(Tparbolmein1e).ncTehoef cthheanzgoenaingltohme eardurloesnaaldguleantodscyctoonpslaisstmedicohfyipnecrrteraospehdy and vacuolation of the cells of this zone of the adrenal cortex. A similar adrenal effect was not observed in the male rats of Groups II and III or in any of the Group V female rats. Male and female rats described as 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 as "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 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONHSIOSTRO'SPSATTUHDOYLONGUYMBREERP:OTR-T6889.6 Afsaceoprpreomtpinlseipttunyoamd"unirnemxadotaIs-urra,siezslblyeau"dtSitentSdihnm.ReTasFale"eb. claeThnha2den.fgetTyemphsaeeo,lreceicnrwuacreitdsrreeeodnfacstehpfeioaswrnaadcdghiedcaeaanglnlgrydeeaessntoordabf iassnreee(rvTveoeanfdbttyhleineo2ftt)hythepaesenesdteh"warfeietndrodeucinccneguodsrt 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 ttfrheeesqtsueseusnbpcsoietnastnaacneme.oounsgInlythogececncueorrnraitnlr,goltchahenasdnegcecoshmawpnaogsuensndo-ottrciencafulturmreeendcnetadgtrbosyuinpagsdl.em, iTnlohiswetrs,aetoiocrnhsaoinmfgtihleaesr 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. tehfifcekcntMessiicmsroialasnrcdotoppirtcohmaetxinaseemneicnneaitnoioftnhtheoefPztohgneeanaegdrlaoretminoeanrlumglolaaslneadrdsautsere, tvcoeoacnlyestidosptianlagstrmeoafictamhneyinpntec-rrrteerlaoaspteehddy 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 was not observed in the F1 generation male rats of Groups II, III and IV or in any of the F1 generation Group V female rats. Treatment-related microscopic changes also were observed in the liver of male rats of Groups III, IV and V. These livers were grossly observed to be enlarged or to have tan areas in the liver lobes. Microscopically, these gross 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 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 HISTOPATHOLOGY REPORT eosinophilic cytoplasm. A very low incidence of single-cell or focal/multifocal necrosis of hepatocytes also was observed in a few rats of these groups. Hepatic tissue was available for microscopic examination only from rats with gross observations in the liver. There were no compound-related microscopic changes observed in any of the male rats identified as having "reduced fertility" (Table 4). The few changes in the tdmNyepoagenler,eeierneocptfoirdtohehdenaucvcecethivoarerenssgtiueselvssteeudretihtsyianwtwreawerspeerrnoetoydptuoiaccbftasfievleecrovtfeeindtdhsoubisyfnfeicatitdhehmenascitneyoi.scmtcrTaauhtlrieeossnpreaootnrfsattathwsneeeatroereeusstoildsyfeusanbuntsifdftfiaiecntdhiceeenini.rt the individual tables of microscopic findings as "SSRF". 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 APFO administration. These changes are listed and summarized in the attached histomorphology tables. Research Pathology Services, Inc. Page 932 -5 ARGUS 418-020 (ONE LIOTRTEARL (PGEARVAGGEEN)ETRWATOI-OGNE)NREERPARTOIODNUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT SUMMARY: Microscopic examination was made of the specified tissues from selected parental male and female rats of the P and F1 generations and F1 and F2 greepnreordauticotnionpusptusdyofofanamomraolni(ugmavapgeerf)luotwrooo-gcteanneoraatteion(AP(oFnOe).littTehr epecor ngceennetrraattiioonns) 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 dosage levels of APFO. 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 APFO-treatment groups and eaocFhdi1fthartehreganerecangtlloeeecwrrnioazeertertrioeaddnxtio.bosynmAa.hagysleepimegrirraltoartsour ppeehsffxyepocaortnsiindendfvtehamtecouaaol3del0aretrianmotansgl/oogkffglac/tndhedaellsys3wo0ofaftmshAegPn/ozkFtogOn/od.abasygeTlrodhvmoiessdearcguihnelaomnsggaaroeleoufwprtahaotessf 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 as 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 as "reduced fertility" animals showed no consistent microscopic changes and the changes that were seen were not considered to be treatment-related. Research Pathology Services, Inc. Page 933 -6 ARGUS 418-020 (ONE LIOTRTEARL (PGEARVAGGEEN)ETRWATOI-OGNE)NREERPARTOIODNUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT All other microscopic changes 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 APFO. Research Pathology Services, Inc. Page 934 ARGUS 418-020 STUDY O(OFNAEMLMIOTORTNEAIRLUM(PGEAPRVEAGRGEFELNU)EOTRWRAOTOIO-OGCNET)NARENEROPAARTTOIOEDN(UACFTPIOO)NIN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT QUALITY ASSURANCE UNIT STATEMENT 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 QA inspections was submitted to the Study Director on March 25,2002. Dates of Inspection 10/25/01,01/15/02 11/07/01,01/18/02 11/17/01,12/27/01,01/22/02 11/19/01,12/28/01,01/23/02 01/02/02 01/03/02 01/24/02 01/24/02 01/28/02 01/31/02 02/01/02 03/25/02 Study Phase Trimming Embedding M icro to m y Staining 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 Page 935 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 Dose Group: Sex: TABLE 1 Incidence and Degree of Severity of Histomorphologic Observations P Generation I II III IV V MMMMM 13 15 13 13 15 I II III IV FFFF 13 4 3 4 V F 13 ADRENAL GLANDS: NO. EXAMINED NO. NORMAL -degeneration, cystic, cortex minimal -hypertrophy/vacuolati on, zona glomerulosa minimal mild moderate -vacuolation, cortex minimal mild moderate PITUITARY: NO. EXAMINED NO. NORMAL -cyst(s), pars intermedia 10 10 10 10 10 78672 [0] [0] [0] [0] [0] 00000 [0] [0] [0] [2] [7] 00021 00002 00004 [3] [2] [4] [1] [3] 122 13 20100 00100 10 0 0 0 10 10 0 0 0 10 00000 10 0 0 0 10 8 0 009 Cl] [0] [0] [0] Cl] 10001 [1] 1 [0] 0 [0] 0 [0] 0 [0] 0 00000 00000 [0] [0] [0] [0] [0] 00000 00000 00000 10 0 0 0 10 9 0 0 0 10 10000 TESTIS: NO. EXAMINED NO. NORMAL -atrophy/degenerati on, multi focal moderate marked -dilatation, rete testis -hypoplasia, diffuse marked FPTDIDYMIS: NO. EXAMINED NO. NORMAL -atrophy minimal mild moderate -exfoliated spermatogenic cells minimal mild moderate 13 4 2 2 15 12 3 2 1 13 [1] [0] [0] [0] [2] 100U1 00001 0 10 1 1 [0] [1] [0] [1] [0] 0 10 1U 13 4 2 2 14 10 0 1 1 10 [0] [1] [0] [1] [1] 0 10 0 0 000 10 00001 [0] [1] [1] [0] [2] 00001 01000 0010 1 [ ] = Total incidence of specified lesion, a ll grades. Page 936 -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 TABLE 1 (Continued) 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 FFFF 13 4 3 4 EPIDIDYMIS (Continued): -hypospermi a mild marked C0] Cl] [1 ] [1 ] C2] 001 00 01 01 2 -infiltration, mononuclear-cell, focal [3 ] [3 ] [0] [1 ] C2] minimal 3 2 01 2 mild 01 000 PROSTATE: NO. EXAMINED NO. NORMAL 13 3 2 1 14 4 1 2 06 -atrophy, focal minimal mild C3] [0] [0] [0] C2] 2 0001 10001 -dilatation, glandular, focal minimal mild moderate C2] [0] [0] [0] C2] 00001 1 0001 1 0000 -inflammation, chronic minimal mild C5] [2 ] [0] Cl] C4] 3 1 002 2 1 01 2 -inflammation, suppurative, focal minimal mild [2 ] [0] [0] [0] Cl] 1 0001 1 0000 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 -cyst(s), intraovarian 2000 -cystic bursa(e) 10 0 0 OVIDUCT fS): 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 specified 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 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 UTERUS (Continued): -distention, lumen minimal mild moderate m arked [1] [1] [0] [0] [3 ] 00001 10 0 0 1 00001 0 1000 -gland(s), endometrial, cystic 00001 -macrophages, pigmented minimal mild moderate marked [10] [0] [0] [0] [10] 2 0001 10002 7 0006 00001 CERVIX: NO. EXAMINED NO. NORMAL 11 2 11 2 1 0 10 109 -dilatation moderate VAGINA: NO. EXAMINED NO. NORMAL [0] [0] [0] [0] [1] 00001 10 2 82 10 10 10 10 -mucification mild moderate [2 ] [0] [0] [0] [0] 10000 10000 OVARIAN FOLLICLES/CORPORA LUTEA: -absence of corpora lutea 00001 -presence of corpora lutea 11 2 1 0 10 -presence of growing/antral follicles 11 2 10 11 EAR(S): NO. EXAMINED NO. NORMAL 02 010 00000 2 1 13 2 00000 -chondropathy, auricular mild moderate marked [0] [2 ] 00 02 00 [0] [1] [0] 000 0 10 000 [2 ] [1] [1] [3 ] [2 ] 000 10 10011 11111 EXTREMITIES: NO. EXAMINED NO. NORMAL -fracture 00000 00000 00000 0 1000 0 0 0 00 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 NUMBER: T-6889.6 TABLE 1 (Continued) 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 FFFF 13 4 3 4 EYES: NO. EXAMINED NO. NORMAL 00000 00000 0 0 10 0000 -cataract 00000 00 10 -keratitis, chronic moderate [0] [0] [0] [0] [0] 00000 [03 [0] [13 [0] 0 0 10 KIDNEYS: NO. EXAMINED NO. NORMAL 0 12 12 00001 0000 0000 -dilatation, pelvis minimal mild moderate CO] [1] [2] [1] [1] 01110 00001 00100 [0] [0] [0] [0] 0000 0000 0000 -hyperplasia, pelvic/papillary epithelium, focal mild [0] [0] [0] [1] [0] 00010 [0] [0] [03 [03 0000 LUNG: NO. EXAMINED NO. NORMAL 10000 00000 0000 0000 -hemorrhage, multifocal moderate [13 [0] [0] [0] [03 i 0000 [03 [03 [03 [03 0000 -inflammation, interstitial, multifocal [i] [0] [0] [0] [03 moderate i 0000 [03 [03 [0] [0] 0000 PALATE: NO. EXAMINED NO. NORMAL -fracture 00000 00000 00000 1000 0000 1000 -hemorrhage marked [0] [0] [0] [0] [03 00000 [13 [03 [03 [03 1000 V F 13 0 0 0 [0] 0 0 0 [0] 0 0 0 [03 0 0 0 [03 0 [0] 0 0 0 0 [03 0 [ ] = Total incidence of specified lesion, all grades. Page 939 -12 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 TABLE 2 Incidence and Degree of Severity of Histomorphologic Observations - Reduced Fertility Animals P Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 332 14 I II III IV V FFFFF 12 1 11 ADRENAL GLANDS: NO. EXAMINED NO. NORMAL 00100 0 0 10 0 00000 00000 TESTIS: NO. EXAMINED NO. NORMAL 33 2 14 232 13 -atrophy/degenerati on, multifocal moderate [1] [0] [0] [0] [1] 100 0 1 -dilatation, rete testis 0000 1 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 33 2 14 30112 -atrophy moderate [0] [0] [0] [0] [1] 00001 -exfoliated spermatogenic cells minimal mild moderate [0] [1] [1] [0] [2] 00001 01000 00101 -hypospermia mild marked [0] [0] [1] [0] [2] 00100 00002 -infiltration, mononuclear-cell, focal [0] [2] [0] [0] [0] minimal 01000 mild 01000 PROSTATE: NO. EXAMINED NO. NORMAL 3 3 2 14 0 1203 -atrophy, focal minimal mild [3] [0] [0] [0] [1] 20001 10000 -inflammation, chronic minimal mild [1] [2] [0] [1] [0] 11000 0 10 10 SEMINAL VESICLES: NO. EXAMINED NO. NORMAL 33214 3 3 2 14 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 3 3 2 14 332 14 [ ] = Total incidence of specified lesion, all grades. -13 Page 940 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 (Continued) Incidence and Degree of Severity of Histomorphologic Observations - Reduced Fertility Animals P Generation Dose Group: Sex: Number of Animals/Grouo: I II III IV V MMMMM 332 14 I II III IV V FFFFF 12111 OVARIES: NO. EXAMINED NO. NORMAL 12 101 02 100 -cyst(s), intraovarian OVIDUCT!Si: NO. EXAMINED NO. NORMAL UTERUS: NO. EXAMINED NO. NORMAL -distention, lumen moderate marked CERVIX: NO. EXAMINED NO. NORMAL VAGINA: NO. EXAMINED NO. NORMAL -muci fication mild 10001 12 10 1 12 10 1 12 10 1 11100 [0] [1] [0] [0] [1] 00001 01000 12 10 1 12 10 1 12 101 02 101 [1] [0] [0] [0] [0] 10000 OVARIAN FOLLICLES/CORPORA LUTEA: -absence of corpora lutea 00001 -presence of corpora lutea 12 100 -presence of growing/antral follicles 12 10 1 EAR(S): NO. EXAMINED NO. NORMAL 01000 00000 00100 00000 -chondropathy, auricular moderate marked CO] Cl] [0] [0] [0] 01000 00000 [0] [0] [1] [0] [0] 00000 00100 KIDNEYS: NO. EXAMINED NO. NORMAL 01002 00001 00000 00000 [ ] = Total incidence of specified lesion, all grades. Page 941 -14 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 (Continued) Incidence and Degree of Severity of Histomorphologic Observations - Reduced Fertility Animals P Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 332 14 I II III IV V FFFFF 12111 KIDNEYS (Continuedl: dilatation, pelvis minimal mild [0] [1] [0] [0] [1] 0 10 0 0 00001 [0] [0] [0] [0] [0] 00000 00000 [ ] = Total incidence of specified 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 of Severity of Histomorphologic Observations FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 17 13 19 26 25 I II III IV FFFF 12 5 1 1 ADRENAL GLANDS: NO. EXAMINED NO. NORMAL 10 10 10 10 9 66982 10 0 0 0 10 0 0 0 -hyperplasia, cortical, focal minimal [0] [0] [0] [0] [0] 00000 [03 [0] [03 [0] 0000 -hypertrophy/vacuolation, zona glomerulosa minimal mild [0] [0] [0] [0] [7] 00003 00004 [0] [0] [03 [03 0000 0000 -vacuolation, cortex minimal [4] [4] [1] [23 [2] 44 122 [03 [0] [03 [0] 0000 LIVER: NO. EXAMINED NO. NORMAL 0 0 6 9 10 00000 0100 0000 -hematopoiesis, extramedullary, multifocal minimal [0] [0] [1] [13 [13 0011i [03 [03 [03 [0] 0000 -hypertrophy, hepatocellular, diffuse [0] [0] [6] [9] [103 mild 00233 moderate 00466 marked 00001 [0] [03 [03 [03 0000 0000 0000 -infarct, liver lobe 00000 0100 -inflammation, chronic, focal/multifocal [0] [0] [2] [2] [13 minimal 00111 mi Id 00 110 [03 [0] [03 [03 0000 0000 -necrosis, focal/multifocal minimal mild [0] [0] [1] [3] [23 00010 00 122 [03 [03 [0] [03 0000 0000 -necrosis, single-cell minimal [0] [0] [0] [1] [0] 00010 [03 [03 [03 [03 0000 TESTIS: NO. EXAMINED NO. NORMAL 12 3 2 2 10 11 3 2 2 10 -atrophy/degenerati on, multi focal minimal [1] [0] [0] [0] [03 10000 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 12 3 2 2 10 10 3 2 2 7 V F 11 10 9 [13 1 [0] 0 0 [03 0 0 0 [0] 0 [03 0 0 0 0 [0] 0 0 [03 0 0 [03 0 [ ] = Total incidence of specified lesion, all 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 of Severity of Histomorphologic Observations FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 17 13 19 26 25 I II III IV FFFF 12 5 1 1 EPIDIDYMIS (Continued!: -infiltration, mononuclear-cell, focal [2] [0] [0] [0] [3] minimal 20003 PROSTATE: NO. EXAMINED NO. NORMAL 12 3 2 2 10 10 2 1 1 7 -atrophy, focal minimal mild [0] [0] [0] [1] [1] 000 10 00001 -dilatation, glandular, focal mild [1] [0] [0] [0] [0] 10 0 0 0 -inflammation, chronic minimal mild [2] [13 [1] [0] [1] 1 i0 0 1 10 10 0 -inflammation, suppurative minimal [0] [0] [0] [0] [1] 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 0 0 0 -cyst(s), intraovari an 0000 UTERUS: NO. EXAMINED NO. NORMAL 10 0 0 0 2000 -distention, lumen minimal mi Id moderate [2] [0] [0] [0] 1000 1000 0000 V F 11 10 9 1 10 0 [2] 0 0 2 [ ] = Total incidence of specified lesion, all grades. Page 944 -17 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 3 (Continued) Incidence and Degree of Severity of Histomorphologic Observations FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 17 13 19 26 25 I II III IV V FFFFF 12 5 1 1 11 UTERUS (Continued!: -macrophages, pigmented minimal mild moderate marked [7] [0] [0] [0] [10] 00001 10001 40007 20001 CERVIX: NO. EXAMINED NO. NORMAL 10 0 0 0 10 10 0 0 0 10 VAGINA: NO. EXAMINED NO. NORMAL 10 0 0 0 10 60007 -inflammation, chronic, focal minimal [1] [0] [0] [0] [0] 10000 -mucification minimal mild moderate [4] [0] [0] [0] [3] 20000 10 00 1 10002 OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles 10 0 0 0 10 10 0 0 0 10 PITUITARY: NO. EXAMINED NO. NORMAL -cyst(s), pars distal is -cyst(s), pars intermedia 10 0 0 0 8 10 0 0 0 6 00001 00001 10 0 0 0 10 10 0 0 0 9 00001 00000 CECUM: NO. EXAMINED NO. NORMAL -distention marked -edema/inflammation, submucosa mild 000 10 00000 [0] [0] [0] [1] [0] 000 10 [0] [0] [0] [1] [0] 00010 00000 00000 [0] [0] [0] [0] [0] 00000 [0] [0] [0] [0] [0] 00000 COLON: NO. EXAMINED NO. NORMAL 00010 00000 00000 00000 [ ] = Total incidence of specified lesion, all 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 of Severity of Histomorphologic Observations FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 17 13 19 26 25 I II III IV FFFF 12 5 1 1 V F 11 COLON (Continued): -distention marked [0] [0] [0] [1] [0] 000 10 [0] [0] [0] [0] [0] 00000 EARS1: NO. EXAMINED NO. NORMAL -chondropathy, auricular moderate marked 00010 00000 [0] [0] [0] [1] [0] 00000 00010 30uuX 00000 [3] [0] [0] [0] [1] 10000 20001 EYES: NO. EXAMINED NO. NORMAL -abscess, periocular -atrophy, iris/ciliary body marked -atrophy, retinal, focal mild -inflammation, chronic, iris moderate -neuropathy, optic nerve(s) moderate 40002 10002 00000 [1] [0] [0] [0] [0] 10000 [1] [0] [0] [0] [0] 10000 [2] [0] [0] [0] [0] 20000 [2] [0] [0] [0] [0] 20000 000 10 00000 0 0 0 10 [0] [0] [03 [0] [0] 00000 [0] [0] [0] [0] [0] 00000 [0] [0] [0] [0] [0] 00000 [0] [0] [0] [0] [0] 00000 ILEUM: NO. EXAMINED 000 10 NO. NORMAL 00000 -Advanced autolysis precludes evaluatiori 0 0 0 1 0 -distention marked [0] [0] [0] [0] [0] 00000 0 100 0000 0000 [0] Cl] [0] [ 0 ] 0100 0 0 0 [0] 0 KIDNEYS: NO. EXAMINED NO. NORMAL -dilatation, pelvis mild moderate 00030 00000 [0] [0] [0] [3] [0] 00020 00 0 10 0 0. .1 .. U 1 00000 [0] [0] [1] [0] [1] 00 100 00001 -hyperplasia, pelvic/papillary urotheli urn minimal [0] [0] [0] [1] [0] 00010 [0] [0] [0] [0] [0] 00000 [ ] = Total incidence of specified lesion, all 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 of Severity of Histomorphologic Observations FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 17 13 19 26 25 I II III IV FFFF 12 5 1 1 KIDNEYS (Continued): -mineralization, pelvis minimal -pyelonephritis moderate [0] [0] [0] [1] [0] 00010 [0] [0] [0] [0] [0] 00000 [0] [0] [0] [0] 0000 [0] [0] [0] [0] 0000 SKIN (GROSS LESION): NO. EXAMINED NO. NORMAL -dermatits, chronic moderate -dermatitis, ulcerative moderate 10 100 00000 [0] [0] [1] [0] [0] 00100 [1] [0] [1] [0] [0] 10100 0000 0000 [0] [0] [0] [0] 0000 [0] [0] [0] [0] 0000 SPLEEN: NO. EXAMINED NO. NORMAL -atrophy marked -necrosis marked 00011 00000 [0] [0] [0] [0] [1] 00001 [0] [0] [0] [1] [0] 000 10 1000 0000 [1] [0] [0] [0] 1000 [0] [0] [0] [0] 0000 STOMACH: NO. EXAMINED NO. NORMAL -erosion(s), glandular mucosa minimal mild -peritonitis, focal minimal -ulcer(s), glandular area moderate 00010 00000 [0] [0] [0] [1] [0] 0 00 10 00000 [0] [0] [0] [1] [0] 00010 [0] [0] [0] [1] [0] 00010 0 10 0 0000 [0] [13 [0] [0] 0000 0 10 0 [0] [0] [0] [0] 0000 [0] [0] [0] [0] 0000 TAIL: NO. EXAMINED NO. NORMAL -abscess -constriction, focal 000 13 00002 000 10 00001 0300 0 100 0000 0000 V F 11 [0] 0 [1] 1 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 [ ] = Total incidence of specified lesion, all 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 of Severity of Histomorphologic Observations FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 17 13 19 26 25 I II III IV V FFFFF 12 5 1 1 11 TAIL (Continued): -hyperplasi a/hyperkeratosi s moderate [0] [03 [0] [13 [0] 000l 0 [0] [0] [0] [03 [03 00000 -inflammation, chronic minimal mild [0] [03 [03 [03 [03 00000 00000 [03 [13 [03 [03 [13 0i 000 0000l -necrosis, focal mild [0] [03 [0] [03 [03 00000 [0] [13 [03 [03 [13 0l 00l THYMUS: NO. EXAMINED NO. NORMAL 000i 0 00000 00000 00000 -atrophy marked [0] [03 [0] [13 [0] 000i 0 [03 [0] [0] [03 [0] 00000 URETER: NO. EXAMINED NO. NORMAL 00000 00000 00001 00000 -distention marked Co) [0] [0] [0] [0] 00000 [0] [0] [03 [0] [1] 00001 -hyperplasia, mucosa moderate to] [03 [03 [03 [03 00000 [03 [0] [03 [03 [1] 00001 -inflammation, chronic mild [03 [03 [03 [03 [03 00000 [03 [03 [03 [03 [13 0000i URINARY BLADDER: NO. EXAMINED NO. NORMAL 000Q0 00000 0000i 00000 -c y stitis, hyperplastic marked [03 [03 [03 [03 [03 00000 [03 [03 [03 [03 [13 0000l [ ] = Total incidence of specified lesion, all grades. Page 948 -21 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 4 Incidence and Degree of Severity of Histomorphologic Observations - Reduced Fertility Animals FI Generation Dose Group: Sex: Number of Animals/GrouD: I II III IV V MMMMM 23 2 2 1 ADRENAL GLANDS: NO. EXAMINED NO. NORMAL TESTIS: NO. EXAMINED NO. NORMAL EPIDIDYMIS: NO. EXAMINED NO. NORMAL 000 10 000 10 23221 23221 23221 23 220 -infiltration, mononuclear-cell, focal minimal PROSTATE: NO. EXAMINED NO. NORMAL -atrophy, focal minimal -inflammation, chronic minimal mild SEMINAL VESICLES: NO. EXAMINED NO. NORMAL [0] [0] [0] [0] Cl] 00001 23221 22111 [0] CO] [0] [1] [0] 0 00 10 [0] [1] Cl] CO] [0] 0 10 0 0 00 100 23221 23221 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 23221 23 2 2 1 [ ] = Total incidence of specified lesion, all grades. Page 949 -22 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 I HISTOMORPHOLOGIC OBSERVATIONS P GENERATION Page 950 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) 1-1 Page 951 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 1-1 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/degeneraiion, multi focal -3 ----- EPIDIDYMIS: -infiltration, mononuclear-cell, focal 1------ PROSTATE: -atrophy, focal -dilatation, glandular, focal -inflammation, chronic -inflammation, suppurative, focal - 211- - - -- - - -3 1--1-2- ------1 SEMINAL VESICLES: COAGULATING GLAND: ------------- LUNG: -hemorrhage, multifocal -inflammation, interstitial, multifocal <3> <3> Page 952 1-2 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-B889.6 TABLE I-I (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 _ _ 12 PITUITARY: TESTIS: EPIDIDYMIS: -infiltration, mononuclear-cell, focal PROSTATE: -dilatation, glandular, focal -inflammation, chronic -inflammation, suppurative, focal SEMINAL VESICLES: ----------- _ - _ 1_ 1 2 - - 2 1- _ ----2- __ COAGULATING GLAND: ------ EAR(S): <*> Page 953 1-3 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 1-2 Histomorphologic 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: -vacuolation, cortex 1 TESTIS: -dilatation, rete testis -hypoplasia, diffuse <p> <4> EPIDIDYMIS: -atrophy -exfoliated spermatogenic cells -hypospermi a -infiltration, mononuclear-cell, focal <1> 2 <4> <1> - 1 PROSTATE: -inflammation, chronic 2 SEMINAL VESICLES: COAGULATING GLAND: EAR(S): -chondropathy, auricular <3> KIDNEYS: -dilatation, pelvis <1> Page 954 1-4 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 TABLE 1-2 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: 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 ADRENAL GLANDS: -vacuolation, cortex 1 TESTIS: EPIDIDYMIS: -infiltration, mononuclear-cell, focal 2 PROSTATE: -inflammation, chronic 1 SEMINAL VESICLES: 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 TvDe: III 13661 M SS III 13662 M SSRF III 13668 M SS III 13670 M SS III 13671 M SS III 13672 M SS III 13673 M SS ADRENAL GLANDS: -vacuolat ion, 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) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death TvDe: ADRENAL GLANDS: -vacuolation, cortex III 13674 M SSRF III 13675 M SS III 13676 M SS Ill 13682 M SS III 13683 M SS III 13684 M SS 2- 13 - TESTIS: EPIDIDYMIS: -exfoliated spermatogenic cells -hypospermia 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 PERFLUQROQCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 TABLE 1-4 Histomorphologic 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 -hypospermi a -infiltration, mononuclear-cell, focal - <2> - <4> - <1> PROSTATE: -inflammation, 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/vacuo!ati on, zona glomerulosa - 11 EAR(S): -chondropathy, auricular KIDNEYS: -dilatation, pelvis -hyperplasia, pelvic/papillary epithelium, focal <3> <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 STUDY NUMBER: T-6889.6 TABLE 1-5 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death TvDe: V 13721 M SS V 13722 M SS V 13728 M SS V 13729 M SSRF V 13731 M SS V 13732 M SM V 13733 M SSRF V 13734 M SS ADRENAL GLANDS: -hypertrophy/vacuolation, zona glomerulosa -vacuolation, cortex 13 3 --1 2 - 1 PITUITARY: TESTIS: -atrophy/degenerati on, multi focal --- --- - - <4> - - - EPIDIDYMIS: -atrophy -exfoliated spermatogenic cells -hypospermi a -infiltration, mononuclear-cell, focal ----- ----- 11--- <3> <1> - 4-- PROSTATE: -dilatation, glandular, focal -inflammation, chronic -inflammation, suppurative, focal 21 2- - - 2 ----- -- -1 SEMINAL VESICLES: ----- -- COAGULATING GLAND: ----- -_ KIDNEYS: -dilatation, pelvis <-> <2> 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 STUDY 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 glomerulosa -vacuolation, cortex -3 -- 23 1-- PITUITARY: -- --- TESTIS: -atrophy/degenerati on , multi focal -dilatation, rete testis - - <3> - - - <-> - - <P> - - - <-> EPIDIDYMIS: -exfoliated spermatogenic cells -hypospermi a - - <3> - - - - - <4> - - - - PROSTATE: -atrophy, focal -inflammation, chronic 2-----1 - 1- - 1- - SEMINAL VESICLES: ------- COAGULATING GLAND: ------- Page 961 1-11 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 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: -cyst(s), pars intermedia OVARIES: -cyst(s), intraovarian OVIDUCTiS): UTERUS: -distention, lumen -macrophages, pigmented CERVIX: VAGINA: -mucification P- - _ P- _ -_ - -- - 2 3 3-3 3 - --- - 3 - 2_ _ OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles P PPP P P PPP P EAR(S): -chondropathy, auricular <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) Histomorphologlc 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, cystic, cortex -hypertrophy/vacuolation, zona glomerulosa 1-- - - -1---- PITUITARY: ------ OVARIES: -cyst(s), intraovarian -cystic bursa(e) P- - - - -----P OVIDUCTfSl: ------ UTERUS: -macrophages, pigmented 1233 3 1 CERVIX: VAGINA: ----------* OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPPPPP PPPPPP EARS): -chondropathy, auricular <4> 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 STUDY NUMBER: T-6889.6 TABLE 1-7 Hi stomorphologic Observtions 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: -distention, lumen CERVIX: -4 -- VAGINA: -- OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PP PP EARfSl: -chondropathy, auricular <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 Histomorphologic Observations P Generation Dose Group: Aniniai Number: Sex: Death Type: OVARIES: III III III 13862 13869 13885 FF F SSRF SS SS OVIDUCTfS): UTERUS: CERVIX VAGINA OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles P P EAR(S): -chondropathy, auricular <4> EYES: -cataract -keratitis, 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 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: OVARIES: OVIDUCTfSl: 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, auricular <4> <3> <2> Page 966 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 TABLE 1-10 Histomorpholog1c Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: 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, cystic, cortex -- - 1- PITUITARY: -- - -- OVARIES: -cyst(s), intraovari an -- - P-- OVIDUCT fS): -- ---- UTERUS: -distention, lumen -gland(s), endometrial, cystic -macrophages, pigmented CERVIX: VAGINA; -- -33 -- -- 23 -- - P2 - 23 * - -- * - -- OVARIAN FOLLICLES/CORPORA LUTEA: -absence of corpora lutea -presence of corpora lutea -presence of growing/antral follicles -- PP PP -P-P-PP PPPP EAR(S): -chondropathy, auricular <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: OVIDUCT(S): UTERUS: -distention, lumen -macrophages, pigmented 1 14 3 3 3 CERVIX: -dilatation 3--- VAGINA: OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPPPP PPPPP EARfS): -chondropathy, auricular <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= 1= = = = Indicated change or lesion present. Minimal degree or amount of indicated change or lesion. Mild degree or amount of indicated change or lesion. Moderate degree or amount of indicated change or lesion. Marked degree or amount of indicated change or lesion. SS = Sacrifice-Scheduled SD = Spontaneous Death SM = Sacrifice-Moribund SSRF = Scheduled (Reduced Fertility) CM CO 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 II-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 ADRENAL GLANDS: -vacuolation, cortex _1 TESTIS: --- EPIDIDYMIS: -infiltration, mononuclear-cell, focal 1 - - PROSTATE: --- SEMINAL VESICLES: - -- COAGULATING GLAND: --- PITUITARY: -- EYES: -atrophy, iris/ciliary body -atrophy, retinal, focal -inflammation, chronic, iris -neuropathy, optic nerve(s) <-> - - <-> <3> <3> <-> <3> <3> <-> SKIN (GROSS LESION): -dermatitis, ulcerative <3> I 1024 M SD I 1026 M SS 1 - - - <4> <2> - - Page 971 11--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 II-l (Continued) HIstomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: I 1034 M SS I 1035 M SS I 1040 M SSRF I 1047 M SS I 1048 M SS I 1051 M SS I 1052 M SS I 1054 M SS ADRENAL GLANDS: -vacuolation, cortex -- --11- TESTIS: -atrophy/degenerati on, multi focal -----1-- EPIDIDYMIS: -Infiltration, mononuclear-cell, focal - - - 1 - - - - PROSTATE: -dilatation, glandular, focal -inflammation, chronic 2- - - ---- ---2 -- - 1 SEMINAL VESICLES: -------- COAGULATING GLAND: -------- PITUITARY: -- ---_ _ 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 Histomorphologlc Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: II 1063 M SS II 1066 M SSRF II 1077 M SSRF II 1078 M SS II 1082 M SSRF TESTIS: -- <-> EPIDIDYMIS: -- <-> PROSTATE: -inflammation, chronic _1 _ SEMINAL VESICLES: -- - COAGULATING GLAND: -- - ADRENAL GLANDS: -vacuo!ation, cortex 1 II 1096 M SS 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 II-2 (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: II 1100 M SS II 1106 M SS II 1107 M SS II 1116 M SS II 1118 M SS ADRENAL GLANDS; -vacuo!at1on, cortex 1- 1- - II 1120 M SS 1 Page 974 11-5 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 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 TESTIS: EPIDIDYMIS: PROSTATE: -inflammation, chronic 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> - <2> <1> <2> - - SKIN (GROSS LESIONI: -dermatitis, chronic -dermatitis, ulcerative <3> <3> III 1142 M SSRF 2 III 1149 M SS Page 975 11-6 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 TABLE I1-3 (Continued) Histomorphologi c Observtions FI Generation Dose Group: Animal Number: Sex: Death TvDe: 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, di ffuse <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 Histomorphologic 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 -inflanmation, chronic, focal/multifocal -necrosis, single-cell <3> <1> < 1> <3> <3> TAIL: -abscess -hyperplasi a/hyperkeratosi s <P> <3> IV 1198 M SS Page 977 11-8 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) Hlstomorphologlc Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: IV 1200 M SM IV 1205 M SS IV 1206 M SS IV 1207 M SSRF IV 1211 M SS IV 1212 M SS IV 1217 M SS IV 1218 M SS IV 1223 M SS TESTIS: EPIDIDYMIS: PROSTATE: SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: -vacuolation, cortex CECUM: -distention -edema/inflamnation, submucosa <4> <2> COLON: -distention <4> ILEUM: <A> LIVER: -hematopoiesis, extramedullary, multifocal -hypertrophy, hepatocellular, diffuse -necrosis, focal/multifocal <3> < 2> <2> <1 > < 2> <1 > < 2> STOMACH: -erosion(s), glandular mucosa -peritonitis, focal -ulcer(s), glandular area <1> <1> <3> THYMUS: -atrophy <4> Page 978 11-9 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-6889.6 TABLE I1-4 (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: IV 1224 M SS IV 1225 M 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 ADRENAL GLANDS: -vacuolation, cortex 1 EARiSl: -chondropathy, auricular <4> KIDNEYS: -dilatation, pelvis <3> -hyperplasia, pelvic/papillary urothelium - -mineralization, pelvis < 2> < 2> <1> <1> LIVER: -hypertrophy, hepatocellular, diffuse -inflammation, chronic, focal/multifocal -necrosis, focal/multifocal <3> <3> < 2> < 2> SPLEEN: -necrosis <4> Page 979 11-10 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-6889.6 TABLE I1-5 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: V 1241 M SS V 1243 M 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: -inflammation, chronic -- 1 SEMINAL VESICLES: _- - COAGULATING GLAND: -- - ADRENAL GLANDS: -hypertrophy/vacuolation, zona glomerulosa 21 -vacuolation, cortex -1 2 - PITUITARY: -cyst(s), pars distal is -P - EYES: <-> 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 I1-5 (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: V 1264 M SD V 1266 M SS V 1268 M SS V 1269 M SS V 1270 M SS V 1271 M SS V 1273 M SS V 1275 M SM V 1276 M SS TESTIS: - - -- EPIDIDYMIS: -infiltration, mononuclear-cell, focal - - 1- PROSTATE: -atrophy, focal -inflammation, suppurative 2 1 - -- SEMINAL VESICLES: - - -- COAGULATING GLAND: - - -- ADRENAL GLANDS: -hypertrophy/vacuolation, zona glomenti osa -vacuo!ation, cortex 2 - -1 - - -1 PITUITARY: -cyst(s), pars intermedia P - -* EYES: <-> LIVER: -hypertrophy, hepatocellular, diffuse -inflammation, chronic, focal/multifocal -necrosis, focal/multifocal <4> - <2> <2> <3> - <1> <2> - SPLEEN: -atrophy <4> TAIL: <-> 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) Hi stomorphologi c Observati ons FI Generation Dose Group: Animal Number: Sex: Death TvDe: 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 12 PITUITARY: -- LIVER: -hematopoiesis, extramedullary, multifocal -hypertrophy, hepatocellular, diffuse - <1> <3> <2> -- <3> <3> Page 982 11-13 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-6889.6 TABLE II-6 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Tvoe: 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 -3333 CERVIX: ----- VAGINA: -mucification -- 2- 3 OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles ADRENAL GLANDS: PPPPP PPPPP ----- PITUITARY: ----- EARfSl: -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 I1-6 (Continued) Histomorphologic Observations 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 OVARIES: - --- UTERUS: -distention, lumen -macrophages, pigmented 2 --44 CERVIX: ---- VAGINA: -inflammation, chronic, focal -mucification 1 -1-- OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPPP PPPP ADRENAL GLANDS: ---- PITUITARY: ---- EAR(S): -chondropathy, auricular <4> SPLEEN: -atrophy I 1359 F SS - I 19780 F SS 2 - 1 P P - - <4> Page 984 11-15 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 I1-7 Hlstomorphologic 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: -inflammation, chronic -necrosis, focal <P> <2> <-> <1> <2> < - > - Page 985 11-16 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-6889.6 TABLE II-8 Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death Type:____________ 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: Animal Number: Sex: Death TvDe: EYES: -abscess, periocular IV 1495 F SS <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 OVARIES: -- - UTERUS: -distention, lumen -macrophages, pigmented 3 343 CERVIX: --- VAGINA: -mucification -- - OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles PPP PPP ADRENAL GLANDS: -hyperplasia, cortical, focal 1-- PITUITARY: -cyst(s) , pars distal is P- - EAR(SI; -chondropathy, auricular <4> TAIL: -inflammation, chronic -necrosis, focal <2> <2> V 1552 F SS - 3 3 - _ P P - - V 1557 F SS - 2 - 3 P P - - Page 988 11-19 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 TABLE II-10 (Continued) Histomorphologic Observations FI Generation Dose Group: Animal Number: Sex: Death TvDe: 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 CERVIX: VAGINA: -mucification OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence of growing/antral follicles 3 1333 ----- _32. _ PPPPP PPPPP ADRENAL GLANDS: PITUITARY: KIDNEYS: -dilatation, pelvis -pyelonephritis --------- <3> <3> URETER: -distention -hyperplasia, mucosa -inflammation, chronic <4> <3> <2> URINARY BLADDER: -cystitis, hyperplastic <4> Page 989 11-20 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS HISTPORPOATTOHCOOLOL G41Y8R-0E2P0ORT APPENDIX III INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA P Generation KEY TO CORRELATION OF HISTOMORPHOLOGIC OBSERVATIONS 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 OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) inflammation, 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) 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: 13609 SEX: M DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) GROSS OBSERVATION!SI: GENERAL: No aross chanaes. 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 End of Record- 13609 SEMINAL VESICLES Page 992 I I I -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 Appendi x III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13610 SEX: M DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfST: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: atrophy, focal (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13610 TESTIS Page 993 I I I -3 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: 13611 SEX: M DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) GROSS OBSERVATIONS: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS!: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflamnation, chronic (minimal) atrophy, focal (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13611 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 Histomorphology 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 TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13612 PITUITARY Page 995 I I I -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 OBSERVATION(Si : LUNG: All lobes- dark red areas too numerous to count ranging in size from pinpoint to 0.2cm in diameter. HISTOMORPHOLOGIC OBSERVATION^! : hemorrhage, multifocal inflammation, interstitial, multifocal HISTOMORPHOLOGIC OBSERVATIONS: LUNG: PROSTATE: hemorrhage, multifocal (moderate) inflammation, interstitial, multifocal (moderate) inflammation, chronic (mild) THE FOLLOWING TISSUElSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13614 PITUITARY Page 996 I I I -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 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13615 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHQLOGIC OBSERVATION!Si : Not applicable HISTOMORPHQLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolati on, cortex (mild) inflammation, 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 (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: 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 TISSUEiS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY TISSUEiS) NOT AVAILABLE FOR EVALUATION: EAR(S) End of Record- 13616 Page 998 111-8 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 Appendi x 111 Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13621 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND 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 OBSERVATIONfS): 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-1 0 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 GROSS OBSERVATIONS) : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) inflammation, chronic (minimal) dilatation, glandular, focal (mild) THE FOLLOWING TISSUEfSl 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) 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 Histaoirphology Data P Generation ANIMAL NUMBER: 13625 SEX: M DOSE .ROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: HIST')MORPHOLOGIC OBSERVATION(S) : Not applicable vacuolati on, cortex (minimal) inflammation, suppurative, focal (mild) THE FOLLOWING TISSUEiS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13625 SEMINAL VESICLES Page 1002 111-12 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: 13626 SEX: M DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION!Si : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfSi : 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(S): 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 I I I -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 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: EPIDIDYMIS: TESTIS: End of Record- 13636 atrophy (minimal) hypospermia (marked) infiltration, mononuclear-cell, focal (minimal) hypoplasia, diffuse (marked) dilatation, rete testis Page 1005 I I 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 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13638 SEX: M DOSE GROUP: DEATH TYPE: II Scheduled (Reduced Fertility) GROSS OBSERVATION(S): EAR(S): Swollen, riaht. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): EPIDIDYMIS: chondropathy, auricular (moderate) exfoliated spermatogenic cells (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 13638 TESTIS Page 1006 II1-16 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUOY 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^!: dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) dilatation, pelvis (minimal) inflammation, chronic (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES TESTIS End of Record- 13639 Page 1007 I I 1-17 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: 13642 SEX M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13642 Page 1008 111-18 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 Sacrifice-Scheduled GROSS OBSERVATIONS) : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS): Not applicable THE FOLLOWING TISSUES) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13644 Page 1009 I I I -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!S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13645 Page 1010 I I I --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 STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13646 SEX M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13646 vacuolation, cortex (minimal) Page 1011 111-21 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 OBSERVATIONIS1: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (mild) inflammation, chronic (minimal) THE FOLLOWING TISSUEfS) 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: 13651 SEX M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION!S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION'S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13651 vacuolation, 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 OBSERVATION(Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13652 Page 1014 I I I -24 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: 13653 SEX M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION!S): EARfST: Swollen, right. HISTOMORPHOLOGIC OBSERVATION IS): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13653 chondropathy, auricular (moderate) Page 1015 I 11-25 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 Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13654 SEX M DOSE GROUP: DEATH TYPE: II 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- 13654 Page 1016 I I 1-26 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 Histomorphology Data P Generation ANIMAL NUMBER: 13655 SEX M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATIONiSI: GENERAL : No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13655 Page 1017 I I 1-27 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 Histomorphology Data P Generation ANIMAL NUMBER: 13656 SEX M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS! : Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13656 Page 1018 I I 1-28 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: 13661 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- 13661 vacuolation, cortex (minimal) Page 1019 111-29 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: 13662 SEX M DOSE GROUP: DEATH TYPE: III Scheduled (Reduced Fertility) GROSS OBSERVATION(SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(Si: Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13662 PROSTATE Page 1020 I I 1-30 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-5889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13668 SEX M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(SI : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13668 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 OBSERVATION(S): KIDNEYS: Right- pelvis, moderate dilation. HISTOMORPHOLOGIC OBSERVATION(Si : dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 13670 dilatation, pelvis (moderate) Page 1022 111-32 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 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- 13671 Page 1023 111-33 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 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13672 SEX M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION!Si: KIDNEYS: Right- pelvis, slight dilation. HISTOMORPHOLOGIC OBSERVATION(S): dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 13672 dilatation, pelvis (minimal) Page 1024 I I 1-34 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 Histomorphology Data P Generation ANIMAL NUMBER: 13673 SEX M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION^) : Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13673 Page 1025 III-35 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: 13674 SEX: M DOSE GROUP: DEATH TYPE: III Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: hypospermia (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 II1-36 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 OBSERVATION!Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13675 vacuolati on, 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 OBSERVATIONfSl: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13676 Page 1028 111-38 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: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13682 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 PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13683 SEX M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONS! : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13683 vacuolati on, cortex (moderate) Page 1030 III-40 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: 13684 SEX M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATIONfS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUEiSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13684 Page 1031 III--41 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: 13693 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION!Si: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION^!: Not applicable THE FOLLOWING TISSUES! WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13693 Page 1032 I I 1-42 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 OBSERVATION!SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13695 Page 1033 111-43 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 Sacrifice-Scheduled GROSS OBSERVATIONfSi: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(Si : Not applicable THE FOLLOWING TISSUEfSl 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 Gross 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: inflammation, chronic (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 13700 TESTIS Page 1035 II1-45 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 DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONfS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUE!Si WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13703 Page 1036 111-46 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: 13704 SEX M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMQRPHQLQGIC OBSERVATIQN(S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13704 Page 1037 I I 1-47 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 OBSERVATIONS): EPIDIDYMIDES: Right- small and flaccid. TESTES: Right- small and flaccid. HISTOMORPHOLOGIC OBSERVATION(S): atrophy, EPIDIDYMIS hypospermia, EPIDIDYMIS infi1trati on, mononuclear-cel 1, 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, focal (minimal) hypoplasia, diffuse (marked) dilatation, rete testis Page 1038 I I 1-48 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: 13708 SEX M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONfS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBS E R V A T I O N S : Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Rcord- 13708 Page 1039 111-49 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: 13710 SEX M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION!SI: EARfS): Swollen, right. HISTOMORPHOLOGIC OBSERVATIONS! : chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13710 chondropathy, auricular (moderate) Page 1040 111-50 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 Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13711 SEX M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION!Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13711 hypertrophy/vacuolation, zona glomerulosa (minimal) Page 1041 I I I -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 SEX M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATIONfSl: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 13716 hypertrophy/vacuolation, zona glomerulosa (minimal) Page 1042 I I I -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 Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13717 SEX: M DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): KIDNEYS: Right- pelvis, slight dilation. HISTOMORPHOLOGIC OBSERVATION(S): 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 OBSERVATION(S): GENERAL: No gross changes. HISTQMQRPHOLQGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13719 Page 1044 III-54 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: 13721 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!Si : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (minimal) infiltration, mononuclear-cell, focal (minimal) inflammation, chronic (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PITUITARY SEMINAL VESICLES End of Record- 13721 TESTIS Page 1045 II1--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 OBSERVATION!Si: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!Si: 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 111-56 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-8889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13728 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!Si : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBS E R V A T I O N S : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (moderate) vacuolation, cortex (minimal) THE FOLLOWING TISSUEfS) 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 TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS KIDNEYS End of Record- 13729 PROSTATE Page 1048 111-58 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 OBSERVATIONS!: GENERAL: No gross changes. HIST0M0RPH0LQ6IC OBSERVATION(Si : Not applicable HIST0M0RPH0L06IC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (mi 1d) inflammation, chronic (mild) dilatation, glandular, focal (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13731 SEMINAL VESICLES Page 1049 11 1-59 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 H1stomorphology Data P Generation ANIMAL NUMBER: 13732 SEX M DOSE GROUP: DEATH TYPE: V Sacrifice-Moribund GROSS OBSERVATION(S): LIVER: All lobes pale, tan in color. TESTES: Bilateral- red. HISTOMORPHOLOGIC OBSERVATION(S): necrosis, centri lobular atrophy/degeneration, multifocal, TESTIS HISTOMORPHOLOGIC OBSERVATIONS: LIVER: TESTIS: End of Record- 13732 necrosis, centri lobular (moderate) atrophy/degeneration, multifocal (marked) Page 1050 II1-60 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: 13733 SEX: M DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATION(Si: 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 I I 1--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 GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!Si : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolation, cortex (minimal) inflammation, suppurative, focal (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13734 PITUITARY SEMINAL VESICLES Page 1052 I I 1-62 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 Appendi x 111 Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13735 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled 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 1 11-63 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: 13736 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONiSl: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (moderate) inflamnation, 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) 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: 13741 SEX: M DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATION(S): EPIDIDYMIDES: Bilateral- soft and flaccid. TESTES: Bilateral- soft and flaccid. HIST0M0RPH0LQ6IC OBSERVATION(S): 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 TISSUEiS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 13741 Page 1055 I I I -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: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (mild) vacuolation, cortex (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 13742 PROSTATE Page 1056 I I I -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 Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13743 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONiS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (moderate) inflammation, chronic (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 13743 PITUITARY SEMINAL VESICLES Page 1057 I I 1-67 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: 13744 SEX M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13744 PITUITARY Page 1058 I I 1-68 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 SEX: M DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATIONiSl: TESTES: Left- larae. HISTOMORPHOLOGIC OBSERVATIONiSl: 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 (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: 13802 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS!: 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 TISSUEfS) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS CERVIX End of Record- 13802 OVARIES OVIDUCT(S) Page 1060 I I 1-70 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 OBSERVATIONfS): HEAD: Broken palate. HISTOMORPHOLOGIC OBSERVATIONfS): fracture, PALATE hemorrhage, PALATE HISTOMORPHOLOGIC OBSERVATIONS: PALATE: End of Record- 13804 fracture hemorrhage (marked) Page 1061 111-71 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 H1stomorphology Data P Generation ANIMAL NUMBER: 13809 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfS): 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 End of Record- 13809 OVARIES OVIDUCT(S ) Page 1062 I I I -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 DOSE GROUP: DEATH TYPE: I Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!SI: 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 TISSUE(S) WERE WITHIN NORMAL LIMITS: CERVIX OVIDUCT(S) UTERUS End of Record- 13811 Page 1063 II1-73 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: 13812 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONS! : GENERAL: No aross chanaes. 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 TISSUEiSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA CERVIX OVARIES PITUITARY TISSUEfSl NOT AVAILABLE FOR EVALUATION: OVIDUCTS) 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 STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13814 SEX F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION!S): EAR(S): Swollen, right. HISTOMORPHOLOGIC OBSERVATIONS) : chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13814 chondropathy, auricular (moderate) Page 1065 II1-75 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 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONfSl: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfSl: 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 End of Record- 13815 OVARIES OVIDUCT(S) Page 1066 II1-76 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: 13816 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled 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 growing/antral follicles macrophages, pigmented (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13816 PITUITARY Page 1067 II1-77 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 H1stomorphology Data P Generation ANIMAL NUMBER: 13821 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): 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 TISSUEfSl WERE WITHIN NORMAL LIMITS: CERVIX OVIDUCT(S) PITUITARY End of Record- 13821 VAGINA Page 1068 I I I -78 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-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 OBSERVATIONiSi : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION!S): Not appli cable 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- 13822 OVARIES OVIDUCT(S) Page 1069 I I 1-79 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: 13824 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION!Si : GENERAL: No aross chanaes. 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 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 OBSERVATIONfS): EAR(S): Swollen, both. HISTOMORPHOLOGIC OBSERVATIONfS): 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 I I I --81 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: 13826 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATIONiSi: GENERAL: No aross chanaes. 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 TISSUEfS) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS CERVIX OVIDUCT(S) PITUITARY TISSUEiSl 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 STUDY 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 OBSERVATION(S): EXTREMITIES: Swollen limbs, left front leg, left front paw. HISTOMORPHOLOGIC OBSERVATION!S): fracture HISTOMORPHOLOGIC OBSERVATIONS: EXTREMITIES: End of Record- 13836 fracture Page 1073 111-83 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: 13840 SEX: F DOSE GROUP: DEATH TYPE: II Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: presence of corpora lutea presence of growing/antral follicles THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS CERVIX VAGINA OVARIES End of Record- 13840 OVIDUCT(S) UTERUS Page 1074 111-84 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 H1stomorphology Data P Generation ANIMAL NUMBER: 13851 SEX: F DOSE GROUP: DEATH TYPE: II Scheduled (Reduced Fertility) GROSS OBSERVATION!Si : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not appli cable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles distention, lumen (marked) THE FOLLOWING TISSUEiSl WERE WITHIN NORMAL LIMITS: CERVIX OVARIES OVIDUCT(S) End of Record- 13851 VAGINA Page 1075 II1-85 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix III Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13856 SEX F DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION!S): EAR(S): Swollen, right. HISTOMORPHOLOGIC OBSERVATION!Si : 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 Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13862 SEX: F DOSE GROUP: DEATH TYPE: III Scheduled (Reduced Fertility) GROSS OBSERVATION(S): EARfS1: Swollen, both. HISTOMORPHOLOGIC OBSERVATION!S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): OVARIAN FOLLICLES/CORPORA LUTEA: chondropathy, auricular (marked) presence of corpora lutea presence of growing/antral follicles THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13862 UTERUS Page 1077 111-87 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 OBSERVATIONfSI: EYES: Traumatized cornea. HISTOMORPHOLOGIC OBSERVATION IS): keratitis, chronic cataract HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 13869 keratitis, chronic (moderate) cataract Page 1078 I I 1-88 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: 13885 SEX F DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS OBSERVATION!S): KIDNEYS: Left- pelvis, marked dilation. HISTOMORPHOLOGIC OBSERVATIONfST: Tissue not available TISSUEfSl NOT AVAILABLE FOR EVALUATION: KIDNEYS End of Record- 13885 Page 1079 111-89 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 SEX: F DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen, right. 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 DOSE GROUP: DEATH TYPE: IV Scheduled (Reduced Fertility) GROSS OBSERVATIONfSl: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable TISSUE fS1 NOT AVAILABLE FOR EVALUATION: CERVIX OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT(S) UTERUS VAGINA End of Record- 13900 Page 1081 I I I --91 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTICf STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendi x 111 Individual Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13901 SEX F DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen, right. HISTO'ORPHOLOGIC OBSERVATIONS) : chond opathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13901 chondropathy, auricular (moderate) Page 1082 I I I -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 OBSERVATIONS): EAR(S): Swollen, right HISTOMORPHOLOGIC OBSERVATIONISi : chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13908 chondropathy, auricular (mild) Page 1083 111-93 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: 13921 SEX: F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!SI: 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 TISSUEfSl WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX VAGINA End of Record- 13921 OVARIES OVIDUCT(S) Page 1084 I I I -94 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: 13922 SEX: F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATIONS): 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 TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13922 OVIDUCT(S) Page 1085 III-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 GROSS OBSERVATION(S): EAR(S): Swollen, right. HISTOMORPHOLOGIC OBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13927 chondropathy, auricular (marked) Page 1086 II1-96 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 Histomorphology Data P Generation ANIMAL NUMBER: 13928 SEX: F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATIONS) : 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 I I -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 SEX: F DOSE GROUP: DEATH TYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATIONS!: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: UTERUS: absence of corpora lutea presence of growing/antral follicles cyst(s)r intraovarian distention, lumen (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: CERVIX OVIDUCT(S) VAGINA End of Record- 13929 Page 1088 111-98 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: 13933 SEX: F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled 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 growing/antral follicles gland(s), endometrial, cyst ic macrophages, pigmented (mild) THE FOLLOWING TISSUE!Si WERE WITHIN NORMAL LIMITS CERVIX VAGINA OVARIES End of Record- 13933 OVIDUCT(S) PITUITARY Page 1089 111-99 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 Trft: V Sacrifice-Scheduled GROSS OBSERVATIONfS): 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 TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13934 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 DOSE DEATH V Sacri fice-Scheduled GROSS OBSERVATIONS: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (minimal) THE FOLLOWING T I S S U E S WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13935 OVIDUCT(S) Page 1091 III-101 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 DOSE GROUP: DEATH rf%: V Sacrifice-Scheduled GROSS OBSERVATIONS): GENERAL: No aross chanaes. 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 TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA OVARIES OVIDUCT(S) End of Record- 13936 PITUITARY Page 1092 I I 1-102 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: 13942 SEX: F DOSE GROUP: DEATH THE: 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 TISSUE(S) 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: V DEATH TYfiE: Sacrifice-Scheduled GROSS OBSERVATION!Si : 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 TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13943 OVIDUCT(S) Page 1094 I I 1-104 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 T1E: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATION(S): 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 TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13944 OVIDUCT(S) Page 1095 111-105 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 V Sacri fice-Scheduled GROSS OBSERVATIONS) : EAR(S): Swollen. HISTOMORPHOLOGIC OBSERVATION!Si : chondropathy, auricular HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): End of Record- 13946 chondropathy, auricular (moderate) Page 1096 111-106 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 HISTOPATHOLOGY REPORT <0 APPENDIX IV INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA F1 Generation KEY TO CORRELATION OF HISTOMORPHOLOGIC OBSERVATIONS 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 TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: infiltration, mononuclear-cell, focal (minimal) THE FOLLOWING TISSUEfSl 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 GROSS OBSERVATIONfSl: GENERAL: No gross changes. HISTOMQRPHOLOGIC OBSERVATIONfSl: Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: 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 GROSS OBSERVATIONfSi : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: vacuolation, cortex (minimal) THE FOLLOWING TISSUEfSl WERE 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 GROSS OBSERVATIONS): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATION(S): inflammation, chronic, iris neuropathy, optic nerve(s) HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 1018 inflammation, 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 STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1019 SEX M GROSS OBSERVATIONfS): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATIONS) : inflammation, chronic, iris neuropathy, optic nerve(s) HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 1019 inflammation, 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 GROSS OBSERVATION^!: EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATION!SI : 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- 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 T W : Sacri fice-Schedul ed GROSS OBSERVATION(S): HEAD: Lesion, left side, 1.0cm in diameter. HISTOMORPHOLOGIC OBS ERVATION(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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1024 SEX M 1DOSE GROUP: DEATH TTTE: I Spontaneous Death GROSS OBSERVATION(S): LUNG: Mottled dark red, all lobes. HISTOMORPHOLOGIC OBSERVATION(S): hemorrhage, multifocal HISTOMORPHOLOGIC OBSERVATIONS: LUNG: End of Record- 1024 hemorrhage, multifocal (mild) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1026 SEX: M DOSE GROUP: DEATH TTFE: I Sacrifice-Scheduled GROSS OBSERVATIONfSl: EYES: Right eye enlarged. HISTOMORPHOLOGIC OBSERVATIONfSl: atrophy, retinal, focal atrophy, iris/ciliary body HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: EYES: vacuolation, cortex (minimal) atrophy, retinal, focal (mild) atrophy, iris/ciliary body (marked) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 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-6889.6 ANIMAL NUMBER: 1034 SEX M Appendix IV Individual Animal Gross and Histomorphology Data FI Generation WDOSE GROUP: DEATH T#t: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1035 SEX M GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 1035 PITUITARY Page 1108 IV-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 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1040 SEX M GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1047 SEX: M DOSE GROUP: DEATH TYft: I Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) inflammation, chronic (mild) dilatation, glandular, focal (mild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1048 SEX M Sacri fice-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 1048 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1051 SEX M GROSS OBSERVATION(SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION( Si: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: TESTIS: vacuolation, cortex (minimal) atrophy/dgnrtion, multifocal (minimal) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS PITUITARY End of Record- 1051 PROSTATE Page 1112 IV-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 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1052 SEX M GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: vacuolation, cortex (minimal) THE FOLLOWING TISSUEIS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1054 SEX: M DOSE GROUP: DEATH TWE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflanmation, chronic (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 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 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1063 SEX M GROSS OBSERVATIONfSl: GENERAL: No gross changes. DOSE GROUP: DEATH' j f k : II Sacri fice-Schedul ed HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1063 Page 1115 IV-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 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1066 SEX M GROSS QBSERVATIONfS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 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 DOSE GROUP: DEATH T M : II Scheduled (Reduced Fertility) GROSS OBSERVATIONfSl: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONfSl: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflammation, chronic (minimal) THE FOLLOWING TISSUEfSl 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 SEX M WEDOSE GROUP: DEATH Tf k : II Sacri fi ce-Scheduled GROSS O B S E R V A T I O N S : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1078 vacuolation, cortex (minimal) Page 1118 IV-21 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: 1082 SEX M GROSS OBSERVATION(S): EPIDIDYMIDES: Left- small. TESTES: Left- small, flaccid. HISTOMORPHOLOGIC OBSERVATION(S): 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1096 SEX M II Sacri fi ce-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HIST0M0RPH0L06IC 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 Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1098 SEX M DOSE GROUP: DEATH T # t : II Sacrifice-Scheduled GROSS OBSERVATIONS!: 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1100 SEX M DOSE GROUP: DEATH T#fe: II Sacri fi ce-Scheduled GROSS OBSERVATIONfSI : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!SI : 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 STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1106 SEX M DOSE GROUP: DEATH TrPt: II Sacri fi ce-Schedul ed 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- 1106 Page 1123 IV-26 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: 1107 SEX M DOSE GR DEATH T II Sacri fi ce-Scheduled GROSS OBSERVATION!S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1116 SEX M DOSE GROUP: DEATH TYPE: II Sacri fi ce-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- 1116 Page 1125 IV-28 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: 1118 SEX M DOSE GROUP: DEATH TYPE: 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- 1118 Page 1126 IV-29 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: 1120 SEX M DOSE GROUP: DEATH T1$E: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLQGIC OBSERVATION(S): Not applicable HISTOMORPHOLQGIC 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 Tifi: III Sacri fi ce-Scheduled GROSS OBSERVATION(S): HEAD: Swollen snout. HISTOMORPHOLOGIC OBSERVATION(S): 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 (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: 1124 SEX M DOSE GROUP: DEATH T W E : III Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Left lateral lobe- tan areas too numerous to count, ranging from pinpoint to 0.3cm. HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal hematopoiesis, extramedullary, multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1124 hypertrophy, hepatocellular, diffuse (moderate) necrosis, focal/multifocal (mild) hematopoiesis, extramedullary, multifocal (minimal) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1125 SEX M DOSE GROUP: DEATH T # E : III Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Left lateral lobe- tan areas (4) ranged in size from pinpoint to 0.1cm. HISTOMORPHOLOGIC OBSERVATION(Si : hypertrophy, hepatocellular, diffuse inflammation, chronic, focal/multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1125 inflammation, chronic, focal/multifocal (mild) hypertrophy, hepatocellular, diffuse (moderate) Page 1130 IV-33 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: 1126 SEX: M DOSE GROUP: DEATH TYPE: III Sacrifice-Scheduled GROSS O B SE RV AT IO NS : HEAD: Lesion, neck, right side, 2.0 x 0.5cm; lesion, head, top, 0.2cm in diameter; lesion, head, right side, 0.2cm in diameter; lesion, head, left side, 0.2cm in diameter. LIVER: Left lateral lobe- tan areas ranging from a pinpoint to 0.2cm in size, too numerous to count. HIST0M0RPH0L0GIC OBSERVATION!S): dermatitis, chronic, SKIN (GROSS LESION) dermatitis, ulcerative, SKIN (GROSS LESION) hypertrophy, hepatocellular, diffuse inflammation, chronic, focal/multifocal HIST0M0RPH0L0GIC OBSERVATIONS: LIVER: SKIN (GROSS LESION): End of Record- 1126 inflammation, chronic, focal/multifocal (minimal) hypertrophy, hepatocellular, diffuse (mild) dermatitis, chronic (moderate) dermatitis, ulcerative (moderate) Page 1131 IV-34 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANATE (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: 1128 SEX M GROSS OBSERVATIONfSi: LIVER: Left lateral lobe- tan area, 0.4 x 0.2cm. HISTOMORPHOLOGIC OBSERVATIONfSl: hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1128 hypertrophy, hepatocellular, diffuse (moderate) 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-6889.6 Appendix IV Individual Animal Gross and HIstomorphology Data FI Generation ANIMAL NUMBER: 1129 SEX M DOSE GROUP: DEATH TYPE: III Sacri fi ce-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1129 HISTOMORPHOLOGIC OBSERVATION!S): Not applicable Page 1133 IV-36 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: 1134 SEX M GROSS OBSERVATION(SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(SI: Not applicable THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1134 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1136 SEX M III Sacri fi ce-Schedul ed GROSS OBSERVATION(S): HEAD: Swollen snout. HIST0M0RPH0L06IC OBSERVATION(S) : fracture with callus formation necrosis, tooth rhinitis, suppurative HISTOMORPHOLOGIC OBSERVATIONS: HEAD: fracture with callus formation necrosis, tooth rhinitis, suppurative (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1136 Page 1135 IV-38 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: 1142 SEX: M DOSE GROUP: DEATH TY5E: III Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: inflammation, chronic (mild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS COAGULATING GLAND EPIDIDYMIS End of Record- 1142 SEMINAL VESICLES 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 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1149 SEX M 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- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1154 SEX M DOSE GR DEATH T III Sacri fi ce-Scheduled GROSS OBSERVATIONS): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!S): Not applicable THE FOLLOWING TISSUES) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1156 SEX M GROSS OBSERVATIONfS): LIVER: Left lateral lobe- 6 tan areas, pinpoint to 0.3cm. HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1156 hypertrophy, hepatocellular, diffuse (mild) Page 1139 IV-42 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: 1159 SEX M III Sacri fi ce-Scheduled GROSS OBSERVATION(Si : GENERAL: No gross changes. THE FOLLOWING TISSUEfSl MERE UITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1159 HISTOMORPHOLOGIC OBSERVATION(S): Not applicable Page 1140 IV-43 ARGUS 418-020 ORAL (GAVASE) 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: 1164 SEX M DOSE GROUP: DEATH TrPE: III Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1164 HISTOMORPHOLOGIC OBSERVATION(S): Not applicable 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1165 SEX M DOSE GROUP: DEATH T ^ E: III Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Left lateral lobe- tan areas too numerous to count, ranging in size from pinpoint to 0.2cm. HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1165 hypertrophy, hepatocellular, diffuse (moderate) Page 1142 IV-45 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: 1167 SEX M DOSE GROUP DEATH T*fc III Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATI0N(S): Not applicable THE FOLLOWING TISSUEfSl 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 GROSS OBSERVATIONS! : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfSl: 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 Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1177 SEX M GROSS OBSERVATION!Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!Si : 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 Sacri fi ce-Schedul ed GROSS OBSERVATION(S): GENERAL: No gross changes. THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1180 HISTOMORPHOLOGIC OBSERVATIONS): Not applicable Page 1146 IV-49 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: 1182 SEX M GROSS OBSERVATIONfS): GENERAL: No gross changes. THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1182 HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable 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 Histomorphology Data Fl Generation ANIMAL NUMBER: 1189 SEX M DOSE GROUP: DEATH T# t : 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- 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1190 SEX M DOSE GROUP: DEATH Tl^E: IV Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Left lateral lobe, median lobe- tan areas ranging from a pinpoint to 0.2cm in size, too numerous to count. HISTOMORPHOLOGIC OBSERVATION!S): hypertrophy, hepatocellular, diffuse inflammation, chronic, focal/multifocal necrosis, single-cell HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1190 inflammation, chronic, focal/multifocal (minimal) necrosis, single-cell (minimal) hypertrophy, hepatocellular, diffuse (moderate) Page 1149 IV-52 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: 1191 SEX: M DOSE GROUP: DEATH TWfe: IV Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Lateral lobe- tan areas too numerous to count ranging in size from pinpoint to 0.1cm. HISTOMORPHOLOGIC OBSERVATIQNfS): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1191 hypertrophy, hepatocellular, diffuse (moderate) Page 1150 IV - 53 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: 1192 SEX M DOSE DEATH IV Scheduled (Reduced Fertility) GROSS OBSERVATION!SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS! : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE: atrophy, focal (minimal) THE FOLLOWING TISSUEfSl 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) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 ANIMAL NUMBER: 1193 SEX M Appendix IV Individual Animal Gross and Histomorphology Data FI Generation 1DOSE GROUP: DEATH TrrE: IV Sacrifice-Scheduled GROSS OBSERVATION^!: LIVER: Left lateral lobe- four tan areas, pinpoint to 0.2cm. HISTOMORPHOLOGIC OBSERVATION!Si : hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1193 hypertrophy, hepatocellular, diffuse (moderate) Page 1152 IV-55 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: 1194 SEX M GROSS OBSERVATION!Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1194 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 GROUP: DEATH T#E: IV Sacrifice-Scheduled GROSS OBSERVATION(S): TAIL: Tip missing 5.0cm from base. HISTOMORPHOLOGIC OBSERVATION(S): hyperplasi a/hyperkeratosis abscess HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End of Record- 1197 hyperplasia/hyperkeratosi s (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 Histomorphology Data FI Generation ANIMAL NUMBER: 1198 SEX M DOSE GROUP: DEATH T#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- 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 Individual Animal Gross and H1stomorphology Data FI Generation ANIMAL NUMBER: 1200 SEX: M DOSE GROUP: DEATH TYTC: IV Sacrifice-Moribund GROSS OBSERVATIONS! : 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 di ameter. THYMUS: Small. HISTOMORPHOLOGIC OBSERVATION(Si : ulcer(s), glandular area, STOMACH erosion(s), glandular mucosa, STOMACH peritonitis, focal, STOMACH Advanced autolysis precludes evaluation, ILEUM distention, COLON distention, CECUM edema/inflammation, submucosa, CECUM atrophy HISTOMORPHOLOGIC OBSERVATIONS: CECUM: COLON: ILEUM: STOMACH: THYMUS: distention (marked) edema/inflammation, submucosa (mild) distention (marked) Advanced autolysis precludes evaluation ulcer(s), glandular area (moderate) erosion(s), glandular mucosa (minimal) peritonitis, focal (minimal) atrophy (marked) AUTOLYSIS PRECLUDES EVALUATION: ILEUM End of Record- 1200 Page 1156 IV-59 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: 1205 SEX M DOSE GR DEATH T IV Sacri fice-Schedul ed GROSS OBSERVATION^!: LIVER: Left lateral lobe- tan areas ranging in size from pinpoint to 0.5cm, too numerous to count. HISTOMORPHOLOGIC OBSERVATIONS): hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal HISTOMORPHOLOGIC 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 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: 1206 SEX M GROSS OBSERVATIONS): LIVER: Left lateral lobe- tan ares, too numerous to count, ranging in size from pinpoint to 0.5 x 0.1cm. HISTOMORPHOLOGIC OBSERVATION!S): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC 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 T^E: IV Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable THE FOLLOWING TISSUEfSl 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 T#E: IV Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1211 HISTOMORPHOLOGIC OBSERVATION(Si : Not applicable 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 DOSE GROUP: DEATH T^E: IV Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTQMQRPHQLQ6IC OBSERVATION(S): Not applicable THE FOLLOWING TISSUE(S) 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1217 SEX: M DOSE GROUP: IV DEATH T#E: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1218 SEX M IV Sacri fice-Scheduled GROSS OBSERVATION(SI: LIVER: Left lateral lobe- one tan and black area, 0.2 x 0.2cm; caudate lobe- one tan area, 0.4cm. HISTOMORPHOLOGIC OBSERVATION(S): 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 (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: 1223 SEX M DOSE GROUP: DEATH TYPE: IV Sacri fice-Scheduled GROSS OBSERVATION(Si: LIVER: Left lateral lobe- tan area, too numerous to count, ranging in size from pinpoint to 0.2cm in diameter. HISTOMORPHOLOGIC OBSERVATION!Si : hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1224 SEX M GROSS OBSERVATION(S): KIDNEYS: Right- pelvic dilation, slight. HISTOMORPHOLOGIC OBSERVATIONfSI : dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 1224 dilatation, pelvis (moderate) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1225 SEX M IV Sacri fi ce-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS! : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: End of Record- 1225 vacuolation, cortex (minimal) Page 1166 IV-69 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: 1229 SEX M DOSE GROUP: DEATH TW t : IV Sacri fi ce-Scheduled GROSS OBSERVATION(Si: EAR(S): Swollen, both. SPLEEN: Tan area, 2.0 x 1.5cm, extends into the parenchyma. HISTOMORPHOLOGIC OBSERVATION(Si : chondropathy, auricular necrosis HISTOMORPHOLOGIC OBSERVATIONS: EAR(S): SPLEEN: End of Record- 1229 chondropathy, auricular (marked) necrosis (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 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1232 SEX M DOSE GROUP: DEATH TYff : IV Sacri fi ce-Scheduled GROSS OBSERVATION(S): KIDNEYS: Right- pelvic dilation, slight. HISTOMORPHOLOGIC OBSERVATIONS! : dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 1232 dilatation, pelvis (mild) Page 1168 IV-71 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-3889.6 Appendix IV Individual Animal Gross and Histow>rphology Data FI Generation ANIMAL NUMBER: 1234 SEX: M DOSE 'iROUP: DEATH T\i|: IV Sacri fi ce-Scheduled GROSS OBSERVATION(S): LIVER: Tan areas, median lobe oie tan area 0.2cm, left lateral lobe too numerous to count, ranging from pinpoint to 0.7cm. HISTOMORPHOLOGIC OBSERVATION(Si : hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal inflammation, chronic, focal/multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1234 necrosis, focal/multifocal (mild) inflammation, chronic, focal/multifocal (mild) hypertrophy, hepatocellular, diffuse (moderate) Page 1169 IV--72 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: 1235 SEX: M DOSE GROUP: DEATH TWfc: IV Sacrifice-Scheduled GROSS OBSERVATION!S): LIVER: Tan areas, median lobe too numerous to count ranging in size from pinpoint to 0.3cm, left lateral lobe 4-5 tarn areas ranging from pinpoint to 0.1cm. HISTOMORPHOLOGIC OBSERVATIONS!: hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1235 hypertrophy, hepatocellular, diffuse (moderate) Page 1170 IV-73 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: 1236 SEX M DOSE GROUP: DEATH TYW: IV Sacri fi ce-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- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1240 SEX M DOSE GROUP: DEATH TYPfe: IV Sacri fi ce-Scheduled GROSS OBSERVATION(S): KIDNEYS: Right- pelvic dilation, slight. HISTOMORPHOLOGIC OBSERVATION!S): dilatation, pelvis mineralization, pelvis hyperplasia, pelvic/papillary urothelium HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 1240 dilatation, pelvis (mild) mineralization, pelvis (minimal) hyperplasia, pelvic/papillary urothelium (minimal) Page 1172 IV--75 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: 1241 SEX M GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (mild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 1241 PROSTATE Page 1173 IV-76 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: 1243 SEX M DOSE GROUP: DEATH TY^E: V Sacrifice-Scheduled GROSS OBSERVATION(S): HEAD: Lesion, 0.2cm in diameter. HISTOMORPHOLOGIC OBSERVATIONfS): dermatitis, chronic HISTOMORPHOLOGIC OBSERVATIONS: HEAD: End of Record- 1243 dermatitis, chronic (moderate) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1244 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION!SI: GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONiS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PITUITARY: hypertrophy/vacuolation, zona glomerulosa (minimal) vacuolation, cortex (minimal) cyst(s), pars distal is THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1250 SEX: M DOSE GROUP: DEATH TYrfe: V Sacrifice-Scheduled GROSS OBSERVATION!SI: TAIL: Annular constriction. HISTOMORPHOLOGIC OBSERVATION!S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: TAIL: No microscopic change to correlate THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: TAIL End of Record- 1250 Page 1176 IV-79 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 ANIMAL NUMBER: 1251 SEX M Appendix IV Individual Animal Gross and Histomorphology Data FI Generation mDDOESAETHGRTOYmUPPE:: V Sacrifice-Scheduled 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. HISTOMORPHOLOGIC OBSERVATIONfS): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1251 hypertrophy, hepatocellular, diffuse (moderate) Page 1177 IV-80 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: 1254 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATIONfS): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (mild) inflammation, chronic (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS COAGULATING GLAND TESTIS EPIDIDYMIS End of Record- 1254 PITUITARY SEMINAL VESICLES Page 1178 IV-81 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: 1256 SEX: M DOSE GROUP: DEATH TYPC: V Sacrifice-Scheduled GROSS OBSERVATIQN(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 T#E: V Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Tan areas, median lobe five tan areas pinpoint to 0.3cm; left lateral lobe tan six tan areas pinpoint to 0.1cm. TAIL: A nnular c o n s t r ic t io n s o f t a i l . HIST0M0RPH0L06IC OBSERVATION(S): hypertrophy, hepatocellular, diffuse co n strictio n , 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 Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1263 SEX: M DOSE GROUP: DEATH TVfE: V Spontaneous Death GROSS OBSERVATION(S): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGIC OBSERVATION!Si: No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: EYES: No microscopic change to correlate THE FOLLOWING TISSUEfS) 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 STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1264 SEX: M DOSE GROUP: DEATH TYPE: V Spontaneous Death 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 TISSUEfSl 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1266 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATIONfSi : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S1: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: PITUITARY: PROSTATE: hypertrophy/vacuolation, zona glomerulosa (mild) cyst(s), pars intermedia inflammation, suppurative (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 1266 TESTIS Page 1183 IV-86 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: 1268 SEX M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(Si: LIVER: Tan area, median lobe too numerous to count ranging in size from pinpoint to 0.4 x 0.2cm. HISTOMORPHOLOGIC OBSERVATIONfSl: 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 OBSERVATIONS) : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable THE FOLLOWING TISSUEfSl 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 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: 1270 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): TAIL: Annular constriction. HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: TAIL: No microscopic change to correlate THE FOLLOWING TISSUEfSl 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 DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION^!: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration, mononuclear-cell, focal (minimal) atrophy, focal (mild) THE FOLLOWING TISSUEfS) 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 Histomorphology Data FI Generation ANIMAL NUMBER: 1273 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HIST0M0RPH0L06IC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (minimal) vacuolation, cortex (minimal) THE FOLLOWING TISSUEfSl 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. TISSUE(S) NOT AVAILABLE FOR EVALUATION: PITUITARY End of Record- 1273 Page 1188 IV-91 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: 1275 SEX M DOSE GROUP: DEATH TYPE: V Sacrifice-Moribund GROSS OBSERVATION!Si: LIVER: Median lobe- tan areas too numerous to count ranging in size from pinpoint to O.lcm. SPLEEN: Small. HISTOMORPHOLOGIC OBSERVATION!S): hypertrophy, hepatocellular, diffuse necrosis, focal/multifocal atrophy HISTOMORPHOLOGIC OBSERVATIONS: LIVER: SPLEEN: End of Record- 1275 necrosis, focal/multifocal (mild) hypertrophy, hepatocellular, diffuse (mild) atrophy (marked) Page 1189 IV-92 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: 1276 SEX M mDOSE GR[OQUUPP: DEATH TYFt: V Sacri fice-Scheduled GROSS OBSERVATIONfSl: LIVER: Large. HISTOMORPHOLOGIC OBSERVATIONfSl: hypertrophy, hepatocellular, diffuse inflammation, chronic, focal/multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1276 inflammation, chronic, focal/multifocal (minimal) hypertrophy, hepatocellular, diffuse (moderate) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1278 SEX M DOSE GR DEATH T V Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLQGIC OBSERVATI0N(S): Not applicable HISTOMORPHOLQGIC OBSERVATIONS: EPIDIDYMIS: infiltration, mononuclear-cell, focal (minimal) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND PROSTATE SEMINAL VESICLES End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1279 SEX M DOSE GROUP: DEATH TYW: V Sacri fice-Scheduled GROSS OBSERVATION!S): LIVER: Left lateral lobe- tan areas too numerous to count. HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1279 hypertrophy, hepatocellular, diffuse (moderate) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1283 SEX: M DOSE GROUP: DEATH TY: V Sacri fice-Scheduled GROSS OBSERVATION!S): LIVER: Left lateral and median lobes- tan areas too numerous to count ranging in size from pinpoint to 0.3 x 0.1cm. HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse hematopoiesis, extramedullary, multifocal HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1283 hematopoiesis, extramedullary, multifocal (minimal) hypertrophy, hepatocellular, diffuse (mild) Page 1193 IV--96 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: 1287 SEX M V Sacri fice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMQRPHOLQGIC OBSERVATION(SI: Not applicable HISTOMQRPHOLQGIC OBSERVATIONS: ADRENAL GLANDS: EPIDIDYMIS: hypertrophy/vacuolation, zona glomerulosa (minimal) infiltration, mononuclear-cell, focal (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS PITUITARY PROSTATE End of Record- 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 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1288 SEX: M DOSE GRQUP: DEATH TYft: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolation, zona glomerulosa (mild) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1293 SEX M DOSE GRQUP: DEATH TYfE: V Sacri fice-Scheduled GROSS OBSERVATIONfS): LIVER: Left lateral lobe too numerous to count tan areas ranging in size from pinpoint to 0.5cm. HISTOMORPHOLOGIC OBSERVATIONfS): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1293 hypertrophy, hepatocellular, diffuse (moderate) Page 1196 IV-99 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: 1295 SEX M DOSE GR DEATH T V Sacri fice-Scheduled GROSS OBSERVATIONS!: LIVER: Left lateral lobe four tan and white areas ranging in size from pinpoint to 0.3cm. HISTOMORPHOLOGIC OBSERVATION(S): hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1295 hypertrophy, hepatocellular, diffuse (moderate) Page 1197 IV-100 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: 1312 SEX F DOSE G IP: I DEATH E: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATI0N(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: presence of corpora lutea presence of growing/antral follicles THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX UTERUS OVARIES VAGINA End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1321 SEX F 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 TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 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 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 Appendix IV Individual Animal Gross and H1stomorphology Oata FI Generation ANIMAL NUMBER: 1328 SEX: F DOSE GROUP: DEATH TwE: I Sacrifice-Scheduled GROSS OBSERVATIONS) : GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) mucification (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS ADRENAL GLANDS PITUITARY CERVIX End of Record- 1328 OVARIES OVIDUCT(S) Page 1200 IV--103 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: 1335 SEX F GROSS OBSERVATION!Si: EAR(S): 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 macrophages, pigmented (moderate) THE FOLLOWING TISSUEfSl 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 Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1340 SEX F DOSE G DEATH Sacri fi ce-Scheduled GROSS OBSERVATION!SI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: HISTOMORPHOLOGIC 0BSERVATI0NS): Not applicable presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) distention, lumen (minimal) mucification (moderate) THE FOLLOWING TISSUEfS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1340 OVIDUCT(S) Page 1202 IV--105 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: 1341 SEX F DOSE 6I1P: DEATH T # E: Sacri fi ce-Scheduled GROSS OBSERVATION(S): 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 GRAUP: DEATH TTPE: I Sacrifice-Scheduled GROSS OBSERVATION!Si: EAR(S): Swollen, both. HISTOMORPHOLOGIC OBSERVATION^ 1: 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 TISSUEfSl 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 SEX F GROSS OBSERVATION(S): 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 inflammation, chronic, focal (minimal) mucification (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX UTERUS OVARIES End of Record- 1345 OVIDUCT(S) Page 1205 IV-108 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: 1353 SEX F GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS): Not applicable 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) 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 Generati on ANIMAL NUMBER: 1355 SEX F GROSS OBSERVATION!Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION!Si : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (marked) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1355 OVIDUCT(S) Page 1207 IV-110 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: 1359 SEX: F DOSE GRftUP: DEATH T # E : I Sacrifice-Scheduled GROSS OBSERVATION!S): GENERAL: No aross chanaes. HISTOMORPHOLOGIC OBSERVATIONS): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (mild) mucification (minimal) THE FOLLOWING TISSUEiSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1359 OVIDUCT(S) Page 1208 IV-111 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: 19780 SEX F GROSS OBSERVATION(S): SPLEEN: Small. HISTOMORPHOLOGIC OBSERVATION(S ): 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 GROSS OBSERVATION(S): TAIL: Tip missing. 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 Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1373 SEX F GROSS OBSERVATION(S): GASTROINTESTINAL TRACT: Stomach and intestinesdistention. LUNG: Dorsal surface, right apical lobe, depressed white area, 0.3cm in diameter. HISTOMORPHOLOGIC OBSERVATIONS) : 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) 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: 1374 SEX F II Sacri fice-Scheduled GROSS OBSERVATION(Si: TAIL: Annular constrictions of the tail. HISTOMORPHOLOGIC OBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGIC OBSERVATIONS: TAIL: No microscopic change to correlate THE FOLLOWING TISSUEfSl 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1407 SEX F DOSE GROUP: DEATH i m : II Sacri fice-Scheduled GROSS OBSERVATIONIS1: TAIL: Tip missing. HISTOMORPHOLOGIC OBSERVATION(Si : inflammation, chronic HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End of Record- 1407 inflammation, chronic (minimal) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1415 SEX F WDOSE GRgUP: DEATH TfFE: II Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Left lateral lobe- mass adhered to left lateral lobe, 2.0 x 1.2 x 0.4cm, firm. HISTOMORPHOLOGIC OBSERVATION(S): infarct, liver lobe HISTOMORPHOLOGIC OBSERVATIONS: LIVER: End of Record- 1415 infarct, liver lobe Page 1214 IV-117 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: 1428 SEX F DOSE GRQllP: DEATH T#E: III Sacri fice-Scheduled GROSS OBSERVATIONS: KIDNEYS: Pelvic dilation, slight, bilateral. HISTOMORPHOLOGIC OBSERVATION^) : dilatation, pelvis HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: End of Record- 1428 dilatation, pelvis (mild) Page 1215 IV-118 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: 1495 SEX F GROSS OBSERVATION(S): EYES: Soft tissue surrounding eye swollen. HISTOMORPHOLOGIC OBSERVATION(S): abscess, periocular HISTOMORPHOLOGIC OBSERVATIONS: EYES: End of Record- 1495 abscess, periocular Page 1216 IV-119 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: 1544 SEX F GROSS OBSERVATION!Si : GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S): Not applicable HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: OVARIAN FOLLICLES/CORPORA LUTEA: PITUITARY: UTERUS: hyperplasia, cortical, focal (minimal) presence of corpora lutea presence of growing/antral follicles cyst(s), pars distal is macrophages, pigmented (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: CERVIX OVARIES OVIDUCT(S) End of Record- 1544 VAGINA Page 1217 IV-120 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: 1546 SEX F V Sacri fice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONfS: Not applicable 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- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1548 SEX F GROSS OBSERVATION(SI: EARfS): Swollen, right. HISTQMQRPHQLQ6IC OBSERVATION(Si : 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) distention, lumen (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1548 OVIDUCT(S) Page 1219 IV--122 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: 1551 SEX F DOSE GROUP: DEATH TTFE: V Sacrifice-Scheduled GROSS OBSERVATION(S): TAIL: Tip missing 11 cm from the base. HISTOMORPHOLOGIC OBSERVATION!Si : inflanmation, chronic necrosis, focal HISTOMORPHOLOGIC OBSERVATIONS: TAIL: End of Record- 1551 inflammation, chronic (mild) necrosis, focal (mild) 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1552 SEX F 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) distention, lumen (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1557 SEX F GROSS OBSERVATIQN(S): GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATIONS) : Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (mild) mucification (moderate) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1557 OVIDUCT(S) Page 1222 IV-125 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: 1573 SEX: F DOSE GROUP: DEATH TwE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTQMORPHOLOGIC OBSERVATIONfS): Not applicable HISTQMORPHOLOGIC 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- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1579 SEX F GROSS OBSERVATION ISI: GENERAL: No gross changes. HISTOMORPHOLOGIC OBSERVATION(S1: Not applicable HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: UTERUS: VAGINA: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (minimal) mucification (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1579 OVIDUCT(S) Page 1224 IV-127 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: 1589 SEX F 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) mucification (mild) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1593 SEX: F DOSE GRQUP: V DEATH T#E: Sacrifice-Scheduled GROSS OBSERVATION^!: KIDNEYS: Right- pelvis moderate dilation. URETER: Calculi, 1.0 x 0.5xm, one located at the caudal end of each ureter. URINARY BLADDER: Walls thickened. HISTOMORPHOLOGIC OBSERVATIONfSl: dilatation, pelvis pyelonephritis distention hyperplasia, mucosa inflammation, chronic cystitis, hyperplastic HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: OVARIAN FOLLICLES/CORPORA LUTEA: OVARIES: URETER: URINARY BLADDER: UTERUS: dilatation, pelvis (moderate) pyelonephritis (moderate) presence of corpora lutea presence of growing/antral follicles cyst(s), intraovarian distention (marked) hyperplasia, mucosa (moderate) inflammation, chronic (mild) cystitis, hyperplastic (marked) macrophages, pigmented (moderate) THE FOLLOWING TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA CERVIX OVIDUCT(S) End of Record- 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-6889.6 Appendix IV Individual Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1598 SEX F 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 TISSUEfSl WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1598 OVIDUCT(S) Page 1227 IV-130 ARGUS 418-020 (ONE LIOTRTEARL (PGEARVAGGEEN)ETRWATOI-OGNE)NREERPARTOIODNUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (AFPO) IN RATS PROTOCOL 418-020 SPONHSIOSTRO'SPSATTUHDOYLONGUYMBREERP:OTR-T6889.6 APPENDIX V INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA GROSS LESIONS - F1 and F2 Pups Page 1228 ARGUS 418-020 REOPRRAOLD(UGCATVIOAGNES)TTUWDOY-GOEFPNAREMORMTAOIOTNCNIOROIUNALMT(4SO1PN8E-E0R2LF0ILTUTOERROPOECRTGAENNOEARTAET(IAOPNF)O) SPONSOR'S STUDY NUMBER: T-6889.6 APPENDIX V IndividualGArnoismsaLleGsrioonsss -anFd1 HanisdtoFm2oPrpuhposlogy Data Dam #. Group #. Pud # Gross Observations) HistomorDholoaic Observations 13921, Group V, Pup#1 Mouth- mass #3, 0.2 x 0.3 x 0.1cm Tissue not available 13946, Group I, Pup #10 Kidney- right, pelvis, dilated, moderate Tissue not available 1304, Group I, Pup #1 Kidney- pelvis, dilated, slight Dilatation, pelvis, moderate 1383, Group II, Pup #6 Kidney- right, dilation, pelvis, moderate Dilatation, pelvis, moderate 1469, Group III, Pup #14 Kidney- bilateral, dilation, pelvis, moderate Dilatation, pelvis, mild 1476, Group III, Pup #3 Kidney- right, pelvis, dilated, slight Dilatation, pelvis, mild 1523, Group IV, Pup #11 Tail- bent Tissue not available 1523, Group IV, Pup #3 Domed head; braindilated 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 DELIVERED LITTERS # STUDIES INCL. AVERAGE MINIMUM MAXIMUM IN ANALYSIS 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% 0.0% 2.7% 72 DAYS 1-4 N N % 2.2% DAYS 15-21 N N % 0.3% 97.8%VIABILITY INDEX (Day 4) % 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% 9.0% 0.0% 3.8% 91.0% 100.0% 91.5% 100.0% 94.4% 100.0% 12.0 16.1 Page 1231 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 DELIVERED LITTERS Day 4 (Preculling) Day 4 (Postculfing) Day 21 AVERAGE MINIMUM N4 MEAN 13.9 11.4 MEAN 8.7 7.6 MEAN 11.8 6.0 MAXIMUM 33 15.8 10.0 15.5 # STUDIES INCL. IN ANALYSIS 93 89 27 67 PUP WEIGHT/LITTER (GRAMS) Day 7 MEAN 13.0 10.6 17.6 Day 14 MEAN 26.0 21.2 34.8 Day 21 MEAN 40.9 31.1 60.4 62 48 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 SUMMARY 1428 TOTAL LITTERS # STUDIES INCL. IN AVERAGE MINIMUM MAXIMUM ANALYSIS DELIVERED LITTERS N 8 33 DURATION OF GESTATION IN DAYS MEAN 22.6 21.7 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 N Preputial Separation (Avg. day postpartum obs.) MEAN FEMALE RATS N Vagina Patent (Avg. day postpartum obs.) MEAN AVERAGE MINIMUM MAXIMUM 46.1 43.9 47.7 32.1 30.1 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. Il/lll 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 N 25 25 25 25 25 25 25 Preputial Separation (Avg. day postpartum obs.) MEAN 46.7 46.7 44.7 46.1 45.9 44.5 47.6 FEMALE RATS N 24 25 25 25 25 25 25 Vagina Patent (Avg. day postpartum obs.) MEAN 32.4 32.1 31.9 32.2 31.6 31.8 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. 222 228 234 01/14/97 01/23/97 03/05/97 Seg. Il/Ill Pre and Seg. Il/Ill Postnatal Dev. SE X U A L MATURATION MALE RATS N 66 25 24 25 Preputial Separation (Avg. day postpartum obs.) MEAN 45.3 45.9 45.8 46.2 FEMALE RATS N 80 25 25 24 Vagina Patent (Avg. day postpartum obs.) MEAN 32.9 31.7 31.7 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: 242 251 255 04/09/97 06/02/97 06/11/97 Seg. Il/lll Pre and Post Seg. Il/lll Natal 258 07/18/97 Seg. Il/lll 266 282 290 09/30/97 02/03/98 03/10/98 Seg. Il/lll Pre and Post Dev. Natal Neurotox. SEXUAL MATURATION MALE RATS N 25 136 25 25 25 24 20 Preputial Separation (Avg. day postpartum obs.) MEAN 46.6 45.3 45.7 43.9 46.8 45.7 44.2 FEMALE RATS N 25 34 25 25 25 24 20 Vagina Patent (Avg. day postpartum obs.) MEAN 32.0 33.7 30.1 30.3 32.0 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 REPORTMAIL 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 N 60 25 14 60 30 57 Preputial Separation (Avg. day postpartum obs.) MEAN 45.2 46.7 45.1 45.4 46.1 47.2 FEMALE RATS N 60 Vagina Patent (Avg. day postpartum obs.) MEAN 31.6 25 32.1 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 1 9 9 2 -2 0 0 2 SUMMARY 3343 TOTAL RATS A VE R A G E M INIM UM M AXIM UM # STUDIES IN C L U D E D ESTRO US CYC LING O BSERVATIO NS RATS EVALUATED N 8 48 131 PR E D O SA G E ESTROUS CYC LING ESTROUS STAGES/7 DAYS EEESSSTTTRRROOOUUUSSS SSSTTTAAAGGGEEESSS///111645 DDDAAAYYYSSS MEAN MMMEEEAAANNN 2.0 3.4 3.6 3.9 2.0 2.4 3.6 3.9 2.0 3.9 3.6 3.9 2 79 1 1 MEAN NUMBER OF COMPLETE ESTROUS CYCLES/GROUP MEAN 3.7 3.5 3.8 3 RATSWITH 6 OR MORE CONSEC. DAYS OF DIESTRUS N 0 2 85 RADTASYSWOITFHE6SOTRRUMSORE CONSEC. N 0 0 85 MEAN ESTROUS CYCLE LENGTH/GROUP MEAN 4.1 4.1 4.1 3 PRECO HABITATIO N ESTROUS C Y C L IN G 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 # STUDIES AVERAGE MINIMUM MAXIMUM INCLUDED RECOVERY PER. ESTROUS CYCLING ESTROUS STAGES/28 DAYS MEAN 5.0 5.0 5.0 RATSWITH 6 OR MORE CONSEC. DAYS OF DIESTRUS N 00 RATSWITH 6 OR MORE CONSEC. DAYS OF ESTRUS N 00 1 1 1 Page 1240 ARGUS 418-020 FEMALE FERTILITY HISTORICAL CONTROL DATA Crl:CDBR VAF/Plus [Cr!:CD(SD)IGS BR VAF/Plus] RATS 1992 - 2002 SUMMARY 3343 TOTAL RATS AVERAGE MINIMUM MAXIMUM #INSCTLUUDDIEEDS RATS IN COHABITATION N 7 40 DAYS IN COHABITATION MEAN 2.8 1.6 5.2 RATS THAT MATED %N 99.3% 87.5% 100.0% RAMTASTWINIGTHDACTOENSFIRMED N 7 39 RATS MATING DAYS 1-4 DAYS 5-7 %%NN 96.0% 4.0% 96.0% 4.0% 96.0% 4.0% RADTASYSMA1-T7ED BY FIRST MALE DAYS8-14 DAYS 15-21 %%%NNN 97.0% 2.1% 2.0% 84.0% 0.0% 0.0% 100.0% 16.0% 4.0% RATS MATED BY SECOND MALE DAYS8-14 %N 2.6% 0.0% 12.5% DAYS 15-21 N % 2.0% 0.0% 8.0% FERTILITY INDEX %NN 93.8% 64.0% 100.0% COPULATION INDEX N %N 98.5% 93.3% 100.0% PREGNANCY RATE %NN 96.7% 92.0% 100.0% RACTOSHPARBEITGANTIAONNT/RATS IN NN % 93.1% 64.0% 100.0% 117 116 111 115 1 1 113 97 2 13 54 111 7 4 107 Page 1241 ARGUS 418-020 APPENDIX M QUALITY ASSURANCE STATEMENT Page 1242 ARGUS 418-020 905 Sheehy Drive, Bldg. A Horsham, PA 19044 Telephone: (215) 443-8710 Telefax: (215)443-8587 ARGUS RESEARCH Charles RiverLaboratories 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. Organisation for Economic Co-operation and Development (1998). The Revised OECD Principles of Good Laboratory Practices [C(97)186/Final]. 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: Date(s) Findings Date(s) Findings Submitted to Study Submitted to Inspection Phase______ Inspection Patels)_____ Director_____ Management Protocol TS Preparation TS Administration Natural Delivery/ Litter Observations Blood Collection Male Sacrifice/ Sperm Evaluations Dam/Litter Sacrifice Vaginal Patency Preputial Separation FI Natural Delivery/ Litter Observations FI Blood Collection FI Male Sacrifice/ Sperm Evaluations FI Dam/Litter Sacrifice In-Life Data Formulations Data Necropsy Data 06-07 NOV 00 16 NOV 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 08 MAR 01 13 MAR 01 23 MAR 01 12 MAR 01 12 MAR 01 13 MAR 01 30 MAR 01 21 JUN 01 03 JUL 01 27 JUN 01 03 JUL 01 03 JUL 01 13 JUL 01 16-24 MAY 01 19-20 JUL 01 and 23-26 JUL 01 19-21 NOV 01, 26-30 NOV 01 and 01,03-04 DEC 01 10-17 DEC 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 04 DEC 01 17 DEC 01 06 AUG 01 17 DEC 01 07 DEC 01 18 DEC 01 07 NOV 00 20 NOV 00 20 NOV 00 26 FEB 01 12 MAR 01 12 MAR 01 12 MAR 01 13 MAR 01 30 MAR 01 27 JUN 01 03 JUL01 05 JUL01 23 JUL 01 24 MAY 01 27 JUL 01 04 DEC 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 Date(s) Findings Submitted to Study Submitted to Inspection Datefs)_____ Director_____ Management 30 JUL01 and 03 AUG 01 03 AUG 01 30 JUL 01 to 05 AUG 01 06 AUG 01 17-21 DEC 01 21 DEC 01 06-09 AUG 01 09 AUG 01 13-14 AUG 01 14 AUG 01 17,20,21,26 DEC 01 26 DEC 01 26-27 DEC 01 27 DEC 01 27 DEC 01 27 DEC 01 25 MAR 02 25 MAR 02 03 AUG 01 06 AUG 01 21 DEC 01 09 AUG 01 14 AUG 01 26 DEC 01 27 DEC 01 27 DEC 01 25 MAR 02 Matthew J. Vaneman, B.S. Date Manager of Regulatory Compliance & J*- Cynthia M. Kelsch Date Quality Assurance Associate/Team Leader and Principal Auditor Page 1245