Document G6vJz8363R5M18ewJ0q3yY51m

Study Title ORAL (GAVAGE) TWO-GENERATION (ONE LITI'ER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: T-6889.6 Data Requirement U.S. Environmental Protection Agency (1998). Health Effects Test Guidelines; Reproduction and Fertility Effects. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3800, August, 1998. U.S. Environmental Protection Agency (1997). Toxic Substances Control Act (TSCA) Test Guidelines; Final Rule. Reproduction and Fertility Effects, 799.9380 (crossreferenced to OPPTS 870.3800). Federal Register, August 15, 1997. Author Raymond G. York, Ph.D., DABT (Study Director) Study Completed On 26 March, 2002 (Final Report) Performing Laboratory Argus Research 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044-1297 Laboratory_ Project ID Argus Research Protocol Number: 418-020 Page 1 of 1245 ARGUS 418-020 Confidentiality Page This is a blank page to be inserted by the Sponsor. Page 2 ARGUS 418-020 GOOD LABORATORY PRACTICE STATEMENT This study was conducted according to U.S. Environmental Protection Agency (EPA FqFRA/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: , .._________._______..z_O__e_ Date Sponsor: ______.___:___/.____ 3M Corporate Toxicology ....... 2______!.____2 o c' 7.Date Page 3 ARGUS 418-020 Flagging Page This is a blank page to be supplied by the Sponsor P_e4 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 SUBJECT TABLE OF CONTENTS I. SUMMARY AND CONCLUSION A. Methods B. Results C. Conclusion 11. 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 SUBJECT ARGUS 418-020 PAGE IV. RESULTS - F1 GENERATION RATS 55 A. F1 Generation Male Rats 55 B. F1 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 - F1 Generation Male Rats 73 Figure 4. Body Weights - F1 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 B 10. Ratios (%) of Organ Weight to Brain Weight - Summary - P Generation Male Rats 90 P_e6 SUBJECT ARGUS 418-020 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 Table B 17. Table B 18. Mating and Fertility - Individual Data - P Generation Male Rats 116 Necropsy Observations - Individual Data - P Generation Male Rats 121 Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - P Generation Male Rats 127 Table B19. Table B20. Brain Weights and Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - P Generation Male Rats 145 Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Individual Data - P Generation Male Rats 163 Table B21. Cauda Epididymal Sperm Morphology - Individual Data - P Generation Male Rats 169 APPENDIX C - REPORT TABLES - P GENERATION FEMALE RATS 174 Table C 1. 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 SUBJECT ARGUS 418-020 PAGE Table C6. Maternal Body Weights - Lactation - Summary - P Generation Female Rats 182 Table C7, 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 C 10. Maternal Absolute Feed Consumption Values (g/day) - Gestation - Summary - P Generation Female Rats 186 Table C 11. Maternal Relative Feed Consumption Values (g/kg/day) - Gestation - Summary - P Generation Female Rats 187 Table C12. Maternal Absolute Feed Consumption Values (g/day) ' Lactation - Summary - P Generation Female Rats 188 Table C 13. Maternal Relative Feed Consumption Values (g/kg/day) - Lactation - Summary - P Generation Female Rats 189 Table C14. Mating and Fertility, Estrous Cycling and Days in Cohabitation - Summary- P Generation Female Rats 190 Table C15. Necropsy Observations - Summary - P Generation Female Rats 192 Table C 16. Terminal Body Weights and Organ Weights - Summary - P Generation Female Rats 193 Table C 17. Ratios (%) of Organ Weight to Terminal Body Weight - Summary - P Generation Female Rats 194 Table C 18. Ratios (%) of Organ Weight to Brain Weight - Summary - P Generation Female Rats 195 Table C19. Natural Delivery Observations - Summary - P Generation Female Rats 196 Table C20. Litter Observations (Naturally Delivered Pups) - Summary - P Generation Female Rats 197 Page 8 SUBJECT ARGUS 418-020 PAGE Table C21. Clinical Observations from Birth to Day 22 Postpartum - Summary - F1 Generation Pups 200 Table C22. Necropsy Observations from Birth to Day 22 Postpartum - Summary - F1 Generation Pups 201 Table C23. Pup Organ Weights - Summary - F1 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 SUBJECT ARGUS 418-020 PAGE Table C36. Pup Body Weight Litter Averages from Birth to Day 22 Postpartum - Individual Data - F1 Generation Litters 282 Table C37. Pup Body Weights from Birth to Day 22 Postpartum - Individual Data - F1 Generation Pups 287 Table C38. Pup Vital Status and Sex from Birth to Day 22 Postpartum - Individual Data - F1 Generation Pups 312 Table C39. Clinical Observations from Birth to Day 22 Postpartum - Individual Data - F1 Generation Pups 317 Table C40. Necropsy Observations from Birth to Day 22 Postpartum - Individual Data - F1 Generation Pups 320 Table C41. Pup Organ Weights - Individual Data - F1 Generation Pups 330 APPENDIX D - REPORT TABLES - F1 GENERATION MALE RATS 335 Table D1. Clinical Observations - Summary - F1 Generation Male Rats 336 Table D2. Body Weights - Summary - F1 Generation Male Rats 339 Table D3. Body Weight Changes - Summary - F1 Generation Male Rats 341 Table D4. Absolute Feed Consumption Values (g/day) - Summary - F1 Generation Male Rats 343 Table D5. Relative Feed Consumption Values (g/kg/day) - Summary - F1 Generation Male Rats 345 Table D6. Sexual Maturation - Summary - F1 Generation Male Rats 347 Table D7. Mating and Fertility - Summary - F1 Generation Male Rats 348 Table D8. Necropsy Observations - Summary - F1 Generation Male Rats 349 Table D9. Terminal Body Weights and Organ Weights - Summary - F1 Generation Male Rats 351 Table D10. Ratios (%) of Organ Weight to Terminal Body Weight - Summary - F1 Generation Male Rats 353 Table D11. Ratios (%) of Organ Weight to Brain Weight - Summary - F1 Generation Male Rats 355 Page 10 SUBJECT ARGUS 418-020 PAGE Table D12. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Summary - F1 Generation Male Rats 357 Table D13. Cauda Epididymal Sperm Morphology - Summary - F1 Generation Male Rats 359 Table D14. Clinical Observations - Individual Data - F1 Generation Male Rats 360 Table D15. Body Weights - Individual Data - F1 Generation Male Rats 378 Table D16. Feed Consumption Values - Individual Data - F1 Generation Male Rats 398 Table D17. Sexual Maturation - Individual Data - F1 Generation Male Rats 408 Table D18. Table D19. Table D20. Mating And Fertility - Individual Data - F1 Generation Male Rats 410 Necropsy Observations - Individual Data - F1 Generation Male Rats 415 Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - F1 Generation Male Rats 432 Table D21. Brain Weights, Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - F1 Generation Male Rats 447 Table D22. Cauda Epididymal Sperm Motility, Count, Density and Spermatid Count - Individual Data - F1 Generation Male Rats 462 Table D23. Cauda Epididymal Sperm Morphology - Individual Data - F1 Generation Male Rats 468 APPENDIX E - REPORT TABLES - F1 GENERATION FEMALE RATS 473 Table El. Clinical Observations - Summary - F1 Generation Female Rats 474 Table E2. Body Weights - Precohabitation - Summary - F1 Generation Female Rats 479 Table E3. Body Weight Changes - Precohabitation - Summary - F1 Generation Female Rats 481 Table E4. Maternal Body Weights - Gestation - Summary - F1 Generation Female Rats 483 Page 11 SUBJECT ARGUS 418-020 PAGE Table E5. Matemal Body Weight Changes - Gestation - Summary - F 1 Generation Female Rats 484 Table E6. Maternal Body Weights - Lactation - Summary - F1 Generation Female Rats 485 Table E7. Maternal Body Weight Changes - Lactation - Summary - F1 Generation Female Rats 486 Table E8. Absolute Feed Consumption Values (g/day) - Precohabitation .- Summary - F1 Generation Female Rats 487 Table E9. Relative Feed Consumption Values (g/kg/day) - Precohabitation - Summary - F1 Generation Female Rats 488 Table E 10. Maternal Absolute Feed Consumption Values (g/day) - Gestation - Summary - F1 Generation Female Rats 489 Table E 11. Maternal Relative Feed Consumption Values (g/kg/day) - Gestation - Summary - F1 Generation Female Rats 490 Table E 12. Maternal Absolute Feed Consumption Values (g/day) - Lactation - Summary - F1 Generation Female Rats 491 Table E 13. Maternal Relative Feed Consumption Values (g/kg/day) - Lactation - Summary - F1 Generation Female Rats 492 Table El4. Sexual Maturation - Summary - F1 Generation Female Rats 493 Table El5. Mating and Fertility, Estrous Cycling and Days in Cohabitation - Summary - F1 Generation Female Rats 494 Table El6. Necropsy Observations - Summary - F1 Generation Female Rats 496 Table El7. Terminal Body Weights and Organ Weights - Summary - F1 Generation Female Rats 498 Table El8. Ratios (%) of Organ Weight to Terminal Body Weight - Summary - F1 Generation Female Rats 499 Table El9. Ratios (%) of Organ Weight to Brain Weight - Summary - F1 Generation Female Rats 500 Table E20. Natural Delivery Observations - Summary - F 1 Generation Female Rats 501 Page 12 SUBJECT ARGUS 418-020 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 - F1 Generation Female Rats 512 Table E27. Body Weights - Precohabitation - Individual Data - F1 Generation Female Rats 527 Table E28. Maternal Body Weights - Presumed Gestation - Individual Data - F1 Generation Female Rats 537 Table E29. Maternal Body Weights - Lactation - Individual Data - F1 Generation Female Rats 542 Table E30. Feed Consumption Values - Precohabitation - Individual Data - F1 Generation Female Rats 547 Table E31. Maternal Feed Consumption Values - Presumed Gestation - Individual Data - F1 Generation Female Rats 557 Table E32. Maternal Feed Consumption Values - Lactation - Individual Data - F1 Generation Female Rats 562 Table E33, Sexual Maturation - Individual Data - F1 Generation Female Rats 567 Table E34. Mating and Fertility, Estrous Cycling and Days in Cohabitation - Individual Data - F1 Generation Female Rats 569 Table E35. Necropsy Observations - Individual Data - F1 Generation Female Rats 574 Table E36. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - F1 Generation Female Rats 586 Page 13 SUBJECT ARGUS 418-020 PAGE Table E37. Brain Weights, Organ Weights and Ratios (%) of Organ Weight to Brain Weight - Individual Data - F1 Generation Female Rats 596 Table E38. Natural Delivery, Implantation Sites, and Pup Viability and Sex Individual Data - F1 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 Table E40. Pup Body Weights from Birth to Day 22 Postpartum - Individu'al Data - F2 Generation Pups Table E41. Pup Vital Status and Sex from Birth to Day 22 Postpartum Individual Data - F2 Generation Pups Table E42. Clinical Observations from Birth to Day 22 Postpartum Individual Data - F2 Generation Pups Table E43. Necropsy Observations - Individual Data - F2 Generation Pups Table E44. Pup Organ Weights - Individual Data - F2 Generation Pups Table E45. Anogenital Distance - Individual Data - F2 Generation Pups APPENDIX F - PROTOCOL AND AMENDMENTS APPENDIX G - DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY APPENDIX H - CERTIFICATES OF ANALYSIS APPENDIX I - ANALYTICAL REPORT APPENDIX J - ENVIRONMENTAL AND HUSBANDRY REPORTS APPENDIX K - HISTOPATHOLOGY REPORT APPENDIX L - HISTORICAL CONTROL DATA 611 616 641 646 648 658 663 683 742 755 758 869 924 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. Methods 8 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 F1 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. F1 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 F1 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 F1 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 F1 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 F1 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 F1 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. F1 generation female rats were examined for age of vaginal patency, beginning on day 28 postpartum. F1 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 F1 generation rats to cohabitation, one male rat per female rat. If random assignment to cohabitation resulted in the pairing of F1 generation siblings, an alternate assignment was made. The cohabitation period consisted of a maximum of 14 days. The P and F1 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 F1 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 F1 generation male pups were examined for the presence of nipples. Anogenital distance was measured for all live F2 generation pups on DLs 1 and 22. P and Flgeneration rats were sacrificed necropsied and examined for gross lesions. Gross lesions were examined histologically. Tissue trimming and histopathology was performed under the supervision of or by a Board Certified Veterinary Pathologist. At Page 16 ARGUS 418-020 scheduled sacrifice, after completion of the cohabitation period (male rats) and on DL 22 (female rats), blood samples were collected and centrifuged. The resulting serum was shipped to the Sponsor for analysis. The liver was excised, weighed, and a sample section shipped to the Sponsor for analysis. The following organs were individually weighed and organ-to-body weight and organ-tobrain weight ratios were calculated: brain, kidneys, spleen, ovaries, testes, thymus, liver, adrenal glands, pituitary, uterus with oviducts and cervix, left epididymis (whole and cauda), right epididymis, prostate and seminal vesicles (with coagulating glands and with and without fluid). The following tissues were retained for possible histological evaluation: pituitary, adrenal glands, vagina, uterus with oviducts, cervix and ovaries, right testis, seminal vesicles (with coagulating gland), right epididymis and prostate. Histological examination was performed on tissues from 10 randomly selected rats per sex from the control and high dosage groups. All gross lesions were examined histologically. Reproductive organs of the low and intermediate dosage group rats suspected of reduced fertility were subjected to histological evaluation. Male rats were sacrificed after completion of the cohabitation period. A portion of the left cauda epididymis was used for evaluation of cauda epididymal sperm concentration and motility. The remaining left cauda epididymis was used to manually evaluate sperm morphology and to prepare a homogenate to determine sperm concentration. The left testis was used for evaluation of testicular spermatid concentration. Female rats were sacrificed on day of day 22 of lactation (DL 22). The number and distribution of implantation sites were recorded. Pups that died before examination of the litter for pup viability on DL 1 were evaluated for vital status at birth. Pups found dead on DLs 2 to 22 were examined for gross lesions and for the cause of death. All pups culled on DL 22 were sacrificed. Three pups per sex per litter were examined for gross lesions. Necropsy included a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly. The brain, spleen and thymus from one of the three selected pups per sex per litter were weighed and the brain, spleen and thymus from the three selected pups per sex per litter were retained for possible histological evaluation. All remaining pups were discarded without further examination. All F1 generation rats were weaned on DL 22 based on observed growth and viability of these pups. At weaning, two F1 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. F 1 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.1. 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 F1 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. F1 Generation Male Rats Three, three, three, two and seven F1 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 F1 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 F1 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 F1 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 F1 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 F1 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 F1 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 fight 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 fight 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 F1 generation. A treatment-related microscopic change was observed in the adrenal glands of the F1 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 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 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. F1 Generation Female Rats Two, one, one and six F1 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 F1 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 F1 generation female rats were considered unrelated to the test substance. Terminal body weights of the F1 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 F1 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 C. Conclusion ARGUS 418-020 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 F1 generation paternal no-observable-adverse-effect-level (NOAEL) for _nmonium 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 F1 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 F1 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. //(---Alan M. _oberman Ph.D., DABT Date _]_/-Director/9 _ Research Ras_m_t e GirYOtk, Pt_ _T Date and Study Director Page 24 ARGUS 418-020 H. DESCRIPTION OF TEST PROCEDURES A. Conduct of Study A.1. 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 CrI: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)'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. P_e25 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 19C_A) A.11. Technical Performance John F. Barnett, B.S. (Director of Laboratory Operations) Russell A. Gazzara, Ph.D. (Senior Research Associate) Joseph W. Lech, B.S. (Senior Research Associate) Alaine L. Casey, A.S. (Scheduling Coordinator/Blood Collection Coordinator) Allyson B. Hansell, B.S. (Laboratory Technician) Brian K. Kelsch (Necropsy Team Leader) Christopher K. Ruppert, B.S. (Formulation Laboratory Technician) A.12. Report Preparation Raymond G. York, Ph.D., DABT Valerie A. Sharper, M.S. (Director of Study Management) Jo Ann Fraz_, 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 Gestation a (DG 0) Delivery Period b (Day 1 of lactation) DG 25 Sacrifice (Rats that did not deliver a litter) DLc 22 Sacrifice (P generation dams and F1 generation litters not selected for continued observation) A.15.c. F1 Generation Male Rats Test Substance Dosage Period Male Rats Sacrificed - Interim (Rats not selected for continued observations following observations for sexual maturation) Male Rats Sacrificed - Scheduled ARGUS 418-020 07 NOV 00 13 NOV 00 - 01 MAR 01 26 FEB 01 - 02 MAR 01 07 NOV 00 13 NOV 00 - 18 MAR'01 01 JAN 0l - 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 F1 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. F1 Generation Female Rats Test Substance Dosage Period Precohabitation Estrous Cycle Evaluation Cohabitation Period Female Rats Sacrificed - Interim (Rats not selected for continued observation DG 0 DL 1 following observations maturation) for sexual DG 25 Sacrifice (Rats that did not deliver a litter) DL 22 Sacrifice (F1 generation dams and F2 generation pups) A.16. Records Maintained 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 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.1. Description Ammonium Perfluorooctanoate (APFO) - white powder B.2. Lot Number 332 B.3. Date Received and Storage Conditions The test substance was received on 7 November 2000 and stored at room temperature. B.4. Special Handling Instructions Standard safety precautions (use of protective clothing, gloves, dust-mist/HEPA-filtered mask, safety goggles or safety glasses and a face-shield) were taken when handling the prepared solutions. Tyvek sleeves and a half-face respirator were worn when using the bulk test substance and preparation was conducted under a chemical fume hood. Page 28 ARGUS 418-020 B.5. Analysis of Purity Information to document or certify the identity, composition, method of synthesis, strength and purity of the test substance was provided by the Sponsor to the Testing Facility. A Certificate of Analysis is available in APPENDIX H. C. Vehicle Information C.1. 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.1. Sample Information Sample T_,pe Bulk Test Substance Concentration (all levels) a Stability (all levels) b Bulk Test Substance Reserve Size 1g 2 mL 2 mL 1g Date Retained 15 JUL 01 10 NOV 00 12 JUL 01 l 0 NOV 00 10 NOV 00 Storage/Shipping Conditions Room temperature Refrigerated, protected from light Refrigerated. protected from light Room temperature Shipped To Sponsor Sponsor Sponsor Testing Facility Archives Date Shipped 16 JUL 01 13 NOV 00 12 JUL 01 13 NOV 00 13 DEC O0 Vehicle Reserve 5 mL 10 NOV 00 Room temperature Testin[ Facility Archives 13 DEC 00 a. Duplicate samples were taken on the first and last days of preparation. One sample of each duplicate set was shipped for analysis. The remaining samples were retained at the Testing Facility as backup samples. b. Two sets of duplicate samples were taken on the first day of preparation. One sample of each duplicate set was shipped for analysis on the day of preparation. Samples were analyzed as soon as possible and 10 days after the first analysis. The remaining samples were retained at the Testing Facility as backup samples. D.2. Analytical Results The analytical results are available in APPENDIX I. E. Test System E.I. 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 F1 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 (57). 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 E.7. Method of Randomization Male Rats 165 02 OCT 00 37 days 100 - 143 140 - 164 Female Rats 165 01 OCT 00 38 days 88 - 132 120 - i44 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. F1 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 F1 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 F1 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 F1 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 fh-st 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. F1 Generation Pups/Rats Pups were not individually identified during the postpartum period; all parameters were evaluated in terms of the litter. At weaning, each F1 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.1. 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 Guide for the Care and Use of Laboratory Animals _8). a. See APPENDIX J (ENVIRONMENTAL AND HUSBANDRY REPORTS). Page 32 ARGUS 418-020 F.3.a. P Generation Rats/F1 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. F1 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.IO. Bedding Material Bed-o'cobs bedding (The Anderson's Industrial Products Group, Maumee, Ohio) was used as the nesting material. 17.11. 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 G. Methods ARGUS 418-020 G.1. Dosage Administration G.l.a. P Generation Rats Dosage Group I Dosage (mg/kg/day) 0 Concentration' (mg/mL) 0 Dosage Volume (ml.,tk_) 5 Number of Rats per Sex 30 Assigned Rat Numbers Male Rats 13601-13630 Female Rats 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 pm _ose of dosage calculations. G.l.b. F1 Generation Rats Dosage Group I Dosage (mg/kg/day) 0 Concentration a Dosage Volume (mg/mL) (mL/k_) 0 5 Number of Rats per Sex b 60 II 1 0.2 5 60 Assigned Rat Numbers Male Rats I001 - 1017, Female Rats 1301 - 1318, 6553 - 6555 c, 1021 - 1060 19779 a, 19780 a, 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 1319and 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 weight a and given at approximately the same time each day b. Dams in the process of delivering pups were not intubated until completion ofparturition, 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. F1 Generation Rats F 1 generation pups may have been exposed to the test substance during maternal gestation (in utero exposure) or via maternal milk during the postpartum period. F1 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 sacrifice c. Dosages were adjusted at least weekly for body weight changes and given at approximately the same time each day a. 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.S.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 period a. 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 al_out DL 15, feed consumption values were not tabulated after DL 15. During cohabitation, when two rats occupied the same cage with one feed jar, replenishment of the feed jars was documented but individual values were not recorded or tabulated. Estrous cycling was evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuing until spermatozoa were observed in a smear of the vaginal contents and/or a copulatory plug was observed in situ during the cohabitation period b. 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 born 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. F1 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 F1 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 day a. 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. F1 Generation Rats The F1 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 period b. 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 postpartum a. Male rats were evaluated for age of preputial separation, beginning on day 39 postpartum b. 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 F1 generation rats to cohabitation, one male rat per female rat. If random assignment to cohabitation resulted in the pairing of F1 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 F1 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 born 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 l, 5, 8, 15 and 22). Maternal behavior of the F 1 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 F1 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 F1 Generation Rats P and F 1 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 centrifuged a. 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 carcass b. The lungs of the F1 generation male and female rats assigned to scheduled sacrifice were perfused with neutral buffered 10% formalin. The urinary bladder of F1 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), fight 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, fight testis (initially fixed in Bouin's solution for 48 to 96 hours), seminal vesicles (with coagulating gland), fight epididymis and prostate c. 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 evaluation a. 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.1. 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 F1 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 Thorne 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 Thorne 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 Thorne Research and a slide was prepared for analysis by the Hamilton Thorne 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 vetficle 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 F1 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. F1 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. F1 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: Type of Test a I. Parametric 11. Nonparametric b A. Bartlett's Test Sig ificant at p_<0.001 NonpLametric Not Sig ificant Analysis Iof Variance A. Kmskal-Wallis Test (_<75%ties) I Significant at p_<0.05 Not Significant IDunn s Test Sign!ficant at p-<0.05 Not sigLificant B. Fisher's Exact Test (>75% ties) Dunlett'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 orp<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 tg). 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 ) and the Analysis of Variance _ _), when appropriate [i.e., Bartlett's Test was not significant (p>0.001 ]. ff the Analysis of Variance was significant (p<0.05), Dunnett's Test (_2)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(_3)was used, when 75% or fewer ties were present; when more than 75% ties were present; Fisher's Exact Test 4) was used. In cases where the Kruskal-Wallis Test was statistically significant (p<0.05), Dunn's Method of Multiple Comparisons (15)was used to identify the statistical significance of the individual groups. All other natural delivery data involving discrete data were evaluated using the KruskalWallis Test tl3)procedures previously described. Page 45 ARGUS 418-020 HI. RESULTS - P GENERATION RATS A. P Generation Male Rats A.1. Mortality and Clinical Observations - P Generation Male Rats (Summary Table B1; 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 dally 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 (/7_<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_<0.05or 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 mglkg/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_<0.05orp_<0.01) in the 3, 10 and 30 mg/kg/day dosage groups. Within this period, body weight gains were significantly reduced (p_<0.05or p_<0.01) in the 30 mg/kg/day dosage group at almost all tabulated intervals before the cohabitation period, in the l0 mg/kg/day dosage group on DSs 8 to15, 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_<0.05or p_<0.01) in the 30 mg/kg/day dosage group on DS 8 through termination, in the 10 mg/kg/day dosage group on DS 15 through termination and in the 3 mg/kg/day dosage group on DS 50 through termination. Body weight gain was significantly increased (p_<0.05) in the 3 mg/kg/day dosage group on DSs 1 to 8 but this increase was considered unrelated to the test substance because it did not persist. Body weights and body weight gains were unaffected by the 1 mg/kg/day dosage of the test substance. A.3. Absolute (g/day) and Relative (g/kg/day) Feed Consumption - P Generation Male Rats (Summaries - Tables B4 and B5; Individual Data - Table B15) Absolute (g/day) feed consumption values were significantly reduced (p_<0.01) in the 30 mg/kg/day dosage group for the entire dosage period before cohabitation (DSs 1 to 70) and the entire study period (DSs 1 to 106) and at most tabulated intervals within these periods. Relative (g/kg/day) feed consumption values were significantly increased (/7___0.0o5rp_<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 fight 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_<0.5orp<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, fight epididymis and fight 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_g/day dosage groups. The ratios of the liver and left and right kidney weights to the terminal body weight were significantly increased (p<0.01) in the 1, 3, 10 and 30 mg/kg/day dosage groups. The ratio of the left adrenal weight to the terminal body weight was significantly increased (p<0.05) in the 30 mg/kg/day dosage group. Ratios of the organ weight to the brain weight were significantly reduced (p<0.01) in the 30 mg/kg/day dosage group for the left epididymis, left cauda epididymis, fight 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 fight 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 Bll and B12; Individual Data Tables B20 and B21) All sperm parameters evaluated were unaffected by dosages of the test substance as high as 30 mg/kg/day. Values for percent motile sperm, sperm density and spermatid density were comparable among the five dosage groups and did not significantly differ. The significant reduction (p_<0.05) in the number of nonmotile sperm in the 10 mg/kg/day dosage group was considered unrelated to the test substance because it was not dosage dependent. The numbers of sperm with normal morphology and the percentages of sperm with abnormal morphology were comparable among the five dosage groups. Page 49 ARGUS 418-020 B. P Generation Female Rats B.1. Mortality and Clinical Observations - P Generation Female Rats (Summary Table C1; 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<O.05 or p<O.O1) 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 orp<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 liveborn 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 liveborn pups/number of pregnant rats), the numbers of dams with stillborn pups, dams with all pups dying, liveborn 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 (/9<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 - F1 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 - F1 Generation Litters (Summary - Table C23; Individual Data - Table C41) Terminal body weights of the F1 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) LOQ 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 = 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 - F1 GENERATION RATS A. F1 Generation Male Rats A.1. Mortality and Clinical Observations - F1 Generation Male Rats (Summary Table D1; Individual Data - Table D14) A.l.a. Mortality Three, three, three, two and seven F1 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 F1 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 dally 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 dally 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 dally 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 dally 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 dally dosage. There were no adverse clinical observations before death. Body weights and feed consumption were comp.arable 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 ratwas 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, emaciation on DPs 29 to 39, decreased motor activity on DPs 32 to 39, urine-stained abdominal fur on DPs 32 to 39, cold to touch on DPs 33 to 39 and chromodacryorrhea on DP 39. This rat was eating and gaining weight through the first three weeks of dosage administration and then lost body weight over the next two weeks. Feed consumption was reduced on DPs 29 to 36. Necropsy revealed numerous tan areas (pinpoint to 0.1 cm) on the median lobe of the liver and a small (0.04 g) spleen; all other tissues appeared normal. Rat 1277 was found dead on the morning of DP 4. The rat was administered three daily dosages. Clinical observations before death included chromorhinorrhea on DPs 2 and 3 and decreased motor activity, cold to touch, emaciation and urine-stained abdominal fur on DP 3. This rat was one of the smallest in this group at weaning, weighing only 25 g. All tissues examined appeared normal at necropsy. This death was attributed to a failure to thrive postweaning. Rat 1280 was found dead on DP 3 before administration of the 3rd daily dosage. The only adverse clinical observation before death was chromorhinorrhea on DP 2. This rat weighed 34 g at weaning. All tissues examined appeared normal at necropsy. No cause 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 F1 generation rats were increased in the 1, 3, 10 and 30 mg/kg/day dosage groups, reaching statistical significance (p<0.05 orp<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_<0.05or 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 _opecia 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 - F1 Generation Male Rats (Figure 3; Summaries - Tables D2 and D3; Individual Data - Table D15) Body weights and body weight gains were reduced for the F1 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 I, 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 (.o<0.05 or p<0.01) on DPs 8 to 15, 22 to 29, 29 to 36, 43 to 50 and 50 to 57. Body weight gains in the 30 mg/kg/day dosage group were also significantly reduced (p<0.05 or p<0.01) on DPs 1 to 8, 15 to 22, 36 to 43, 57 to 64 and 64 to 70. Body weights were significantly reduced (p<0.05 orp<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 - F1 Generation Male Rats (Summaries - Tables D4 and D5; Individual Data - Table D16) Absolute (g/day) feed consumption values for the F1 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 orp<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 - F1 Generation Male Rats (Summary - Table D6; Individual Data - Table D17) Preputial separation of F1 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 (/7<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 - F1 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 F1 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 - F1 Generation Male Rats (Summary - Table D8 Individual Data - Table D19) The number of F1 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 - F1 Generation Male Rats (Summaries - Tables D9 through Dll; Individual Data - Tables D20 and D21) Terminal body weights of the F1 generation male rats were significantly reduced (p<0.05 orp<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 p<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 orp<0.01) in the 1 and 3 mg/kg/day dosage groups and significantly decreased (p<0.01) in the 30 mg/kg/day dosage group, compared to control group values. The absolute weight of the thymus was also significantly decreased (p<0.01) in the 10 and 30 mg/kg/day dosage groups. The absolute weight of the prostate, brain and left adrenal gland were significantly decreased (p<0.05 orp<0.01) 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 p<0.01) in the 1 mg/kg/day and higher dosage groups, compared to the control group values. The ratios of the weights of the left testis, with and without the tunica albuginea and the right testis to the terminal body weight, were significantly increased (p<0.05 or p<0.01) in the 3 mg/kg/day and higher dosage groups. The ratios of the weights of the left epididymis, left cauda epididymis, right epididymis and brain to the terminal body weight were significantly increased (p<0.05 or p<0.01) in the 10 mg/kg/day and higher dosage groups. * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). Page 60 ARGUS 418-020 The ratios of the weight of the seminal vesicles with fluid to the brain weight were increased in the 1 mg/kg/day and higher dosage groups, compared to the control group values. These ratios were significantly increased (p<0.05) in the 1 and 10 mg/kg/day dosage groups. The ratios of the liver weight to the brain weight were significantly increased (p<0.01) in the 1 mg/kg/day and higher dosage groups, and the ratios of the left and right kidney weights to the brain weight were significantly increased (p<0.05 or p<0.01) in the 1, 3 and 10 mg/kg/day dosage groups. The ratios of the spleen weight to the brain weight were significantly decreased (p<0.05 orp<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 orp<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 F1 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 ceils of the adrenal cortex. Treatment-related microscopic changes also were observed in the liver sections of the F1 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 F1 Generation Male Rats (Summary - Table !)12; Individual Data - Table !)22) 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 - F1 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. F1 Generation Female Rats B.1. Mortality and Clinical Observations - F1 Generation Female Rats (Summary - Table El; Individual Data - Table E26) B.l.a. Mortality Two, one, one and six** F1 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 F1 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 143,2 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 - F1 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_<0.05or 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_<0.05or p_<0.01) on DPs 8, 15, 22, 29, 50, 57 and precohabitation. Body weights and body weight gains during the precohabitation period were unaffected by dosages of the test substance as high as 10 mg/kg/day. Body weight gains in the 1 mg/kg/day dosage group were significantly reduced (p__0.05 or p<_0.01) on DPs 1 to 8 and 8 to 15 and in the 10 mg/kg/day dosage group were significantly reduced (p_<0.01) on DPs 8 to15. Body weights in the 1 mg/kg/day dosage group were also significantly reduced (p_<0.05orp_<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_<0.05or p_<0.01) in the 30 mg/kg/day dosage group on lactation days (DLs) 5, 8, 11 and 15, compared to the control group. Body weights and body weight gains during the lactation period were unaffected by dosages of the test substance as high as 10 mg&g/day. B.3. Absolute (g/day) and Relative (g/kg/day) Feed Consumption - F1 Generation Female Rats (Summaries - Tables E8 through El3; Individual Data - Tables E30 through E32) Absolute (g/day) feed consumption values were significantly reduced (p_<0.05or 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 - F1 Generation Female Rats (Summary - Table El4; Individual Data - Table E33) The 30 mg/kg/day dosage group F1 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 - F1 Generation Female Rats (Summary - Table El5; 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 - F1 Generation Female Rats (Summary - Table El6; Individual Data - Table E35) All necropsy observations for the F1 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 - F1 Generation Female Rats (Summaries - Tables E17 through E19; Individual Data - Tables E36 and E37) Terminal body weights of the F1 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 F1 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 F1 generation selected for histopathologic evaluation that had been given up to 30 mg/kg/day of the test substance. All microscopic chmages 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 - F1 Generation Female Rats (Summaries Tables E20, E21 and E25 ; Individual Data - Tables E38 through E41 and FA5) 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 liveborn pups/number of pregnant rats), the numbers of dams with stillborn pups, dams with all pups dying and liveborn 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 EA2 and EA3) 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.II. 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 Mutagenicit3" 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 CrI: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 Statistics for 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 1 600 .I, 0 MG/KG/DAY 500 ** ** 1 MG/KG/DAY ,_, 400 = (._ -..I I-- "" -r" rT_ _ 300 ** ** ** ** ** ** ** ** ** ** ** ** ,, ** ,, ** k, ** 3 MG/KG/DAY --= 10 MG/KG/DAY X 30 MG/KG/DAY 200 ** [/ * p_<0.05 * p<O.Ol > E3 a. Last value recorded before cohabitation. (_ b. First value recorded after cohabitation, r,_ c. Terminal body weight. .1_ 100 I I I I I I I I I I I 1 I I I I 1 8 15 22 29 36 43 50 57 64 70a 85b 92 99 106 c oo DAY OF STUDY O PROTOCOL 418-020: ORAL(GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) 425 40O 375 -- 35O -- 325 "0 - goo t,_ F- "1- 275 ('_ LU 250 225 - 200 BODY WEIGHTS P GENERATION FEMALE RATS Figure 2 '_ 0 MG/KG/DAY 1 MG/KG/DAY ---C'--3 MG/KG/DAY A 10 MG/KG/DAY X 30 MG/KG/DAY _ > 150 -- a. Last value recorded before cohabitation. 125 I I I "I t'" I I t _ ' -} t I I II I I _ Ii J_ 1 8 15 22 29 36 43 50 57 64 70a 0 7 10 14 18 21 1 5 8 11 15 22 Oo DAYOF STUDY DAY OF GESTATION DAYOF LACTATION PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) BODY WEIGHTS F1 GENERATION MALE RATS Figure 3 600 500 -- 400 -- ....i _" - "I-300 -- (.9 LU _ 200 -- 0 (MG/KG/DAY) =__ 1 (MG/KG/DAY) * 3 (MG/KG/DAY) _-10 (MG/KG/DAY) 30 (MG/KG/DAY) 10o- [ * P<0.05 ** p<O.O1 > . PFirresctowheaebkitlyativoanlubeordeycowrediegdht. _Z_ 0 I I I I I I I I I I I I I I I after cohabitation. r._/3 1 8 15 22 29 36 DA4Y3 POST50WEAN57ING 64 70 a 99b 106 113 -I_ ,5 O ,.,,j PROTOCOL 418-020: 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 5O0 t v 0 (MG/KG/DAY) 400- A 1 (MG/KG/DAY) A 300 -- I- "1- _ [] 200 -- 3 (MG/KG/DAY) I0 (MG/KG/DAY) X 30 (MG/KG/DAY) * p_<O.O1 loo I * p<__O.0]5 a. Precohabitation body weight. > 0 1 I I I I I I I '1 III II I I I I I I I I 1- 1 8 15 22 29 36 43 50 57 64 70 a 0 7 10 14 18 21 1 5 8 11 .15 22 C DAY POSTWEANING DAY OF GESTATION DAY OF LACTATION r_ oo 6 tJ ARGUS 418-020 APPENDIX B REPORT TABLES - P GENERATION MALE RATS Page 75 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER IAPFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B1 (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 10 .................................................................................................................................... MAXIMUM POSSIBLE INCIDENCE 3240/ 30 3240/ 30 3240/ 30 3240/ 30 V 30 3178/ 30 MORIBUND SACRIFICED 0 0 0 0 la CHROMORHINORRHEA 3/ 2 10/ 2 26/ 7 15/ 5 27/ 8 DEHYDRATION 0/ 0 0/ 0 0/ 0 0/ 0 30/ 4**a SOFT OR LIQUID FECES 17/ 7 12/ 8 3/ 2 ii/ 3 4/ 3 LOCALIZED ALOPECIA: TOTAL LIMBS HEAD _(_ URINE-STAINEADBDOMINALFUR 0% UNGROOMED COAT 396/ 8 396/ 8 ol 0 01 0 0/ 0 63/ 2** 58/ i** 51 1 01 0 0/ 0 84/ 3** 84/ 3** 01 0 01 0 0/ 0 38/ i** 38/ i** 01 0 01 0 0/ 0 141/ 3** 141/ 3** 01 0 131 3*'a 21/ 3** EMACIATION 0/ 0 0/ 0 0/ 0 0/ 0 34/ 2a DRIED RED OR RED PERINASAL SUBSTANCE 0/ 0 0/ 0 0/ 0 0/ 0 8/ 2 COLD TO TOUCH INCISORS: TOTAL MISSING/BROKEN MISALIGNED 01 0 16/ 1 16/ 1 0/ 0 01 0 85/ 4 36/ 4 53/ 2 01 0 153/ 3 56/ 2 120/ 2 01 0 35/ 2 16/ 2 19/ 1 61 2a ii/ 1 0/ 0 ii/ I CHROMODACRYORRHEA DECREASED MOTOR ACTIVITY 0/ 0 0/ 0 35/ 2 0/ 0 124/ 2 0/ 0 21/ 1 0/ 0 5/ 1 > i/ la PALE EXTREMITIES 0/ 0 0/ 0 0/ 0 0/ 0 .................................................................................................................................... STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NDMBER N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WERE RESTRICTED OF RATS EXAMINED WITH OBSERVATION. TO THE NUMBER PER GROUP. OF RATS WITH OBSERVATIONS. a. Rat 13732 was moribund sacrificed on day 45 of study. ** Significantly different from the Group I value (p_0.01). 6/ 1 OO _ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO} IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION TABLE B1 (PAGE 2): CLINICAL OBSERVATIONS - SUMMARY - P GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... MAXIMUM POSSIBLE INCIDENCE 3240/ 30 3240/ 30 MORIBUND SACRIFICED 0 0 DRIED, RED SUBSTANCE ON FUR b ol o Ol o NO FECES SCANT FECES RALES 01 0 ol o 01 0 01 0 ol o 01 0 III 3 3240/ 30 0 ol o 01 0 ol o 01 0 IV 10 3240/ 30 0 ol o 01 0 ol o 01 0 V 30 3178/ 30 la 61 i 21 1 21 I 11 1 RIGHT OR BOTH EARS: SWOLLEN 15/ 1 38/ 2 0/ 0 11/ 1 0/ 0 SCAB c 0/ 0 46/ 4** 8/ 2* 0/ 0 01 0 RIGHT FORELIMB: ABRASION 0/ 0 4/ 1 0/ 0 0/ 0 0/ 0 PENIS: RED SUBSTANCE 0/ 0 i/ 1 0/ 0 0/ 0 0/ 0 VOCALIZATION I/ 1 0/ 0 .................................................................................................................................... STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13732 was moribund sacrificed on day 45 of study. b. Located on both forepaws. c. Located on the nose, mouth, head, right forelimb or back. * Significantly different from the Group I value (p_0.05). ** Significantly different from the Group I value (p_0.01). 0/ 0 0/ 0 OF RATS WITH OBSERVATIONS. 0/ 0 O _n oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE B2 (PAGE 1): BODY WEIGHTS - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 BODY WEIGHT (G) DAY 1 MEANS.D. 180.9 + 7.3 180.7 + 7.6 DAY 8 MEANfS.D. 242.8 + 12.4 243.6 + 10.4 DAY 15 MEAN+S.D. 296.7 + 15.9 297.1 + 12.2 DAY 22 MEAN+S.D. 338.2 + 16.2 340,9 + 16.8 REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE III 3 30 179.9 + 6.7 245.7 + 8.4 295.1 + 10.7 334.8 + 16.0 IV V i0 30 30 30 178.4 + 7.2 238.1 + 10.4 282.4 + 14.7"* 316.8 + 22.6** 178.6 + 7.2 211.3 + 17 0"* 259.4 + 16 0"* 284.9 + 26 3** DAY 29 DAY 36 OO DAY 43 MEAN+S.D. MEAN+S.D. MEAN+S.D. 370.9 397.6 + 19.0 + 21.8 424.0 + 25.2 376.6 402.5 + 21.6 + 26.4 427.0 + 28.4 363.3 384.3 + 23.9 27.0 407.0 + 32.6 345.2 363.4 + 27.4** + 31.9"* 384.2 + 37.5** 300.9 312.3 + 29 9** + 35 2** 326.3 + 45 8** DAY 50 MEAN+S.D. 448.7 + 26.7 449.7 + 30.5 425.7 + 34.2* DAY 57 MEAN+S.D. 469.9 + 28.9 468.0 + 33.8 444.8 + 36.9* DAY 64 MEANfS.D. 487.9 32.4 486.1 + 37.8 459.9 38.3* .................................................................................................................................... DAY [] a. * = DAY OF STUDY = NUMBER Excludes OF VALUES AVERAGED values for rat 13732, which was Significantly different from the Group I moribund sacrificed value (p<_0.05). on day 45 of study. ** Significantly different from the Group I value (p<_0.01). 404.2 + 39.0** 421.5 + 42.9** 434.1 + 44.9** 341.7 + 39.1"* [ 29]a 359.3 + 44.0** [ 29] a 367.6 + 49.3** [ 29]a C 4_ 00 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE ABLE B2 (PAGE 2): BODY WEIGHTS - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 30 30 30 30 30 INCLUDED IN ANALYSES N 30 30 30 30 29a BODY WEIGHT (G) DAY 70b MEAN+S.D. 501.1 + 33.8 498.0 + 38.8 470.4 43.2* 444.2 + 46.2** 375.0 54.0** DAY 85c MEANS.D. 528.3 + 34.7 528.8 43.2 495.8 42.3* 468.3 49.2** 389.9 + 64.4** DAY 92 MEANS.D. 543.8 + 37.1 541.6 43.1 506.7 44.7** 479.9 52.0** 400.9 69.2** DAY 99 MEANS.D. 561.1 37.8 555.1 44.2 521.6 47.5** 495.8 53.0** 414.6 64.3** DAY 106 MEANS.D. 575.5 + 39.7 568.3 45.2 533.8 + 46.2** TERMINAL BODY WEIGHT d MEANfS.D. 580.7 40.0 575.3 47.6 .................................................................................................................................... 541.7 i 47.2** DAY = DAY OF STUDY a. Excludes values for rat 13732, which was moribund b. Last value recorded before cohabitation. c. First value recorded after cohabitation. sacrificed on day 45 of study. d. Terminal body weights were recorded when the rats were day 106 to 109 of study. Significantly different from the Group I value (p<_0.05). * Significantly different from the Group I value (p<0.01). 504.9 54.4** 513.0 53.9** 424.3 62.9** 431.8 64.1"* > o0 C_ PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION CONE LITTER PER GENERATION) (APFO} IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION TABLE B3 (PAGE I): BODY WEIGHT CHANGES - SUMMARY - p GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... 3 10 30 RATS TESTED N 30 30 30 30 30 BODY WEIGHT CHANGE (G) DAYS 1 - 8 MEAN,S.D. +61.9 + 7 3 +63.0 4.7 +65 8 f 4.9* +59.7 6.2 +32.7 + 17 0"* DAYS 8 - 15 MEAN+S.D. +53.9 + 12 5 +53.5 + 8.0 +49 4 + 7.8 +44.3 + 10.0"* +48.1 i0 8* DAYS 15 - 22 MEAN_S.D. +41.5 + 6 1 +43.8 7.9 +39 8 + 9.5 +34.4 + 12.6 +25.5 + 17 8** DAYS 22 - 29 MEAN+S.D. +32.7 + 7 9 +35.6 + 7.8 +28 5 10.7 +28.3 + 8.7 +16.0 + 16 5** DAYS 29 - 56 MEAN+S.D. +26.7 + 7 0 +26.0 8.3 + +21 0 6.6** + 6.0** +18.3 +11.4 + 10 5** (% DAYS 36 - 43 MEANfS.D. +26.4 + 6 6 +24.5 + 5 8 O DAYS 43 - 50 MEAN+S.D. +24.7 + 5 8 +22.7 + 5.0 DAYS 50 - 57 MEANfS.D. +21.3 f 6.4 +18.3 + 8.3 DAYS 57 - 64 MEAN_S.D. +17.9 7.1 +18.1 + 6.6 .................................................................................................................................... DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED +22 7 + 9.7 +18 7 5.2** +19 1 8.3 +15 1 + 7.0 +20.7 f 9.2 +20.0 9.8* +17.4 + 7.8 +12.6 + 6.0* +14 0 + 26 7** +10.7 + 16 5** [ 29] a +17.6 + 14 7 [ 29]a +8.2 9 6** [ 29] a a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. * Significantly different from the Group I value (p<_0.05). ** Significantly different from the Group I value (p_<0.01). > C 4= O_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B3 (PAGE 2): BODY WEIGHT CHANGES - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 30 30 30 30 30 INCLUDED IN ANALYSES N 30 30 30 30 29a BODY WEIGHT CHANGE (G) DAYS 64 - 70b MEANS.D. +13.2 7.4 +11.9 10.8 +10.5 f 10.7 +10.1 7.0 +7.4 9.8 DAYS 1 - 70b MEANS.D. +320.2 30.8 +317.3 37.3 +290.5f 43.1" +265.8 44.5** +196.6 53.2** DAYS 85c- 92 MEANS.D. +15.5 7.4 +12.8 5.4 +10.9 6.8* +11.6 7.7 +11.0 18.4 DAYS 92 - 99 MEANiS.D. +17.3 5.8 +13.6 5.5 +14.9 _ 7.6 +15.9 6.7 +13.7 16.5 DAYS 99 -106 MEANS.D. +14.4 7.1 +13.2 6.1 +12.3 f 10.0 OO _._ DAYS 1 -106 MEANiS.D. +394.6 36.8 +387.7 43.4 +353.9_ 46.6** DAY 1- TERMINATION d MEANS.D. +399.8 37.0 +394.7 45.7 .................................................................................................................................... +361.8 DAY(S) = DAY(S) OF STUDY a. Excludes values for rat 13732, which was moribund sacrificed b. Last value recorded before cohabitation. c. First value recorded after cohabitation. d. Terminal body weights were recorded when the rats were day * Significantly different from the Group I value (p_0.05). ** Significantly different from the Group I value (p_0.01). on day 45 of study. 106 to 109 of study. 47.7** +9.1 9.2 +326.5 53.1.* +334.5 52.6** +9.7 11.3 +246.0 61.5"* +253.4 62.9** > CD C %n & PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B4 (PAGE 1}: ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - P GENERATION STUDY OF AMMONIUM MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 10 .................................................................................................................................... RATS TESTED N 30 30 30 30 FEED CONSUMPTION (G/DAY) PERFLUOROOCTANOATE V 30 30 DAYS 1- 8 DAYS 8 - 15 DAYS 15 - 22 MEAN+S.D. MEANS.D. MEAN+S.D. 23.8 + 1.6 26.6 + 3.2 28.7 + 1.6 23.9 1.3 26.4 + 1.8 28.8 2.3 23.9 + 1.2 26.1 + 2.2 [ 28]a 28.6 + 2.0 23.0 _ 1.6 25.7 2.2 28.9 3.1 19.5 [ 25.1 29]a + 3 3** 24 26.7 46 DAYS 22 - 29 MEANS.D. 28.0 19 28.6 + 2.2 28.2 + 2.6 28.5 f 3.2 [ 29] a 26.0 + 2 7** _I_ DAYS 29 - 36 MEAN+S.D. 27.8 19 28.2 + 2.1 28.1 + 2.6 28.4 + 3.4 25.4 2 6** [ 29] a [ 28] a (O%0 DAYS 36 - 43 MEAN+S.D. 28.3 21 28.3 + 2.3 28.4 i 2.7 28.5 3.4 25.2 + 5 0"* _O DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 64 - 70c DAYS 1 - 70C DAYS 85d- 92 DAYS 92 - 99 MEAN+S.D. MEANS.D. MEAN+S.D. MEANS.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. 28.7 [ 29]a 29.4 [ 29]a 29.8 + 19 18 22 28.2 [ 29]a 27.9 + [ 29]a 29.9 [ 29]a 29.0 21 15 24 24 28.6 + 2.4 29.6 + 3.0 29.9 + 2.5 29.3 + 2.8 [ 29]a 28.1 + 1.8 [ 29]a 29.8 + 3.1 29.2 + 2.8 28.4 + 2.7 [ 29]a 29.4 + 2.9 29.4 + 3.5 29.3 4.0 [ 26]a 28.1 + 2.0 [ 26]a 29.7 + 3.0 29.1 + 3.2 28.7 + 3.4 [ 28]a 29.2 _ 3.4 29.5 + 3.5 28.5 [ 27.9 [ 29.5 29]a + 29]a i 35 27 39 28.9 38 26.2 2 5** [ 28]a,b 26.8 + 2 9** [ 29]b 27.1 + 3 5** [ 29]b 25.8 + 3 2** [ 29]b 25.6 2 2** [ 29]b 26.3 + 5 3** [ 29]b 26.6 + 3 0-* DAYS 99 -106 [ 29]b > MEANS.D. 28.9 + 21 29.3 + "2.4 28.7 + 2.7 28.2 + 38 25.8 3 2** [ 29]a [ 27]a [ 29]a [ 29]h DAYS 1 -106 MEANS.D. 28.3 1.6 28.3 + 1.8 28.1 + 2.2' 28.1 28 25.7 + 2 2** [ 29]a [ 27]a [ 29]a [ 29]b [2_ -_ .................................................................................................................................. DAYS - DAYS OF STUDY [ ] I _ER OF VALUESAUERAGED a. Excludes values that were associated with spillage, _-OO l_) b. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. O c. Last value recorded before cohabitation. d. First value recorded after cohabitation. ** significantly different from the Group I value (p<_0.01) . PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE B5 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 10 .................................................................................................................................... RATS TESTED N 30 30 30 30 FEED CONSUMPTION (G/KG/DAY) PERFLUOROOCTANOATE V 30 30 DAYS 1- 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 MEANS.D. MEANfS.D. MEANS.D. MEAN+S.D. MEANS.D. MEANfS.D. 112,2 5.7 98.8 10.9 90,6 + 4.6 78,8 + 3.8 72.4 3.1 69,0 3.6 112.8 5.0 97.8 6.5 90.2 5.7 79.6 4.5 71.9 3.4 [ 29]a 68.2 5.1 112.2 4.4 96.7 + 7.8 [ 28] a 90.7 5.4 80.8 5.4 75.4 [ 28]a 71.7 4.6* 5.3 110.6 + 5.6 98.6 6.4 96.2 + 7.4** 85,7 [ 293a 80.0 5.6** 6.4** 76,3 6.2** 99.8 + 14.8"* [ 29] a 107.1 10.9"* 97.9 15.3"* 89.0 8.5** 83.2 + 6.2** 79.0 14.8"* O0 DAYS 43 - 50 MEANS.D, 66.0 3.7 65 3 47 68.5 5.2 73.4 7.7** 78.7 7.6** [ 29]a [ 29]a [ 28]a 28]a,b DAYS 50 - 57 MEANS.D. 64.0 2.9 64.6 + 6.1 67.6 5.5* 70,7 + 5.6** 76.7 7.4** [ 29]a 29]b DAYS 57 - 64 MEANS.D. 62,2 3.1 62.7 4.0 65.2 7.1" 69,1 5.8** 74.8 7.0** 29]b DAYS 64 - 70c MEANS.D. 57.1 2.4 59.8 5.6 63.4 9.1"* 65,0 7.2** 70.0 6.9** [ 29]a [ 29]a [ 26]a [ 29]a 29]b DAYS 1 - 70c MEANS.D. 73.7 2.2 [ 29]a 74.3 3.7 [ 29]a 77.1 [ 26]a 4.7* 80.5 [ 29]a 4.7** 84.8 29]b 6.6** DAYS 85d- 92 MEANS.D. 55.7 3.5 ( 29]a 55.9 5.2 59.4 4.7** 62,4 6.3** 66.6 12.4"* 29]b DAYS 92 - 99 MEANS.D. 52.6 2.7 53.3 4.4 56.7 4.8** 59.3 5.5** 66.5 10.5"* 29]b DAYS 99 -106 MEANS.D. 50.9 2.8 52.6 3.4 [ 29]a 54.7 [ 27]a 4.0** 56,6 [ 29]a 4.9** 62.5 11.8"* [ 29]b DAYS 1 -106 MEANS.D. 65.8 2.4 66.4 [ 29]a .................................................................................................................................... 3.6 69.2 [ 27]a 4.3** 72,6 . [ 29]a 4.4** 77.6 [ 29]b 6.3** DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED Oo a. Excludes values that were associated with spillage. b. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. I_ c. Last value recorded before cohabitation. CD d. First value recorded after cohabitation. * significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B6 (PAGE i) : MATING AND FERTILITY - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS IN COHABITATION N 29 29 III 3 30 STUDY OF AMMONIUM PERFLUOROOCTANOATE IV V 10 30 30 29 DAYS IN COHABITATION a RATS THAT MATED FERTILITY INDEX b RATS WITH CONFIRMED MATING DATES MEAN+S.D. N(%) N/N (%) N 3.3 + 2.6 29(100.0) 28/ 29 (96.6) 29 1.9 + 1.2" 29(100.0) 27/ 29 (93.1) 29 2.4 + 1.7 [ 29] 30(100.0) 30/ 30 (i00.0) 29 3.1 + 2.4 [ 28] 29(96.7) 29/ 29 (100.0) 27 2.6 + 1.4 [ 28] 29(100.0) 28/ 29 (96.6) 28 RATS MATING c f_ DAYS 1-7 O0 4_ DAYS 8-14 N(%) N(%) 27(93.1) 2( 6.9) 29(100.0) 0( 0.0) 28(96.6) i( 3.4) RATS PREGNANT/RATS IN COHABITATION N/N 28/ 29 27/ 29 (%) (96.6) (93.1) .................................................................................................................................... [ ] = NUMBER OF VALUES AVERAGED a. Restricted to rats with a confirmed mating date and rats that did b. Number of pregnancies/number of rats that mated. c. Restricted to rats with a confirmed mating date, * Significantly different from the Group I value (p_<0.05). not mate. 30/ 30 (i00.0) 27(i00.0) 0( 0.0) 29/ 30 (96.7) 28(100,0) 0( 0.0) 28/ 29 (96.6) > Cb _n 4_ OO bO O (_ OO t21 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIL_ PERFLUOROOCTANOATE TABLE B7 (PAGE i): NECROPSY OBSERVATIONS - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS EXAMINED a N 30 30 30 30 30 MORIBUND SACRIFICED N 0 0 0 0 ib APPEARED NORMAL N 29 28 28 28 25 TESTES : RIGHT OR BILATERAL, SMALL AND FLACCID N 0 1 0 1 1 LEFT, LARGE N 0 0 0 0 1 BILATERAL, RED N 0 0 0 0 lb EPIDIDYMIDES : RIGHT, LEFT OR BILATERAL, SMALL AND FLACCID N 0 1 0 1 2 KIDNEYS : RIGHT, PELVIS, SLIGHT OR MODERATE DILATION N 0 1 2 1 2 LUNGS : ALL LOBES, NUMEROUS DARK RED AREAS N 1 0 0 0 0 LIVER : ALL LOBES, TAN AND PALE N 0 0 0 0 lb .................................................................................................................................... a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. b. Rat 13732 was moribund sacrificed on day 45 of study. 4_ O0 cb O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B8 (PAGE I): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 10 RATS TESTED N 30 30 30 30 V 30 29a TERMINAL BODY WEIGHT MEANS.D. 580,7 t 40.0 575.3 47,6 541.7 47.2** 513,0 _ 53.9** 431.8 64.1"* EPIDIDYMIS LEFT MEANfS,D. 0.7210 0.0599 0.6991 I0.0468 0.6901 0.0477 0,7039 0,0476 0.6322 0.0722** CAUDA EPIDIDYMIS LEFT MEAN_S.D. 0.3320 0.0398 0.3172 0.0256 0.3148 0.0280 0.3215 _0.0307 0.2898 0.0374** TESTIS LEFT MEANS,D. 1.7953 0.1369 1.8103 0.1477 1.7868 0.1312 1.8194 f0,0995 1.7878 _0.2930 LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D. 1.6613 0.1410 1.6822 _0.1356 1.6598 0.1268 1,6955 f0.0943 1.6361 0.3290 SEMINAL VESICLES WITH FLUID O00% SEMINAL VESICLES WITHOUT FLUID MEANS.D. MEANfS.D. 2.2662 0.3478 [ 29]b 1.2686 f0.1554 2.3326 0.3472 1.2539 0.1685 2.3550 0.3246 1.2789 0.1608 2.3052 f0.3281 [ 28]b 1.2664 _0.1670" 2.0652 0.2934* 1.1329 0.1545.* EPIDIDYMIS RIGHT MEANS.D. 0.7187 _0.0573 0.6891 0.0791 0.6930 0.0521 0.6771 _0.0958 0.6366 0.0663** TESTIS RIGHT MEANiS.D. 1.8173 f0.1687 1.8398 0.3036 1.7915 0.1293 1.7660 f0.2117 1.7475 0.2063 PROSTATE MEANS.D. 1.1378 _0.1852 1.1426 0.2030 .................................................................................................................................... 1.1181 0.1672 1.0368 f0.2031 0.8619 0.1841-* ALL WEIGHTS WERE RECORDED IN GRAMS (G). [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Excludes values for rats that had fluid loss prior to weighing or organs damaged (weight affected). * Significantly different from the Group I value (p50.05). O ** Significantly different from the Group I value (p_0.01). O0 4_ O_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B8 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 10 RATS TESTED N 30 30 30 30 V 30 29a PITUITARY MEAN+S.D. 0.014 0.004 0,014 f 0,003 0.012 0.003* 0.014 + 0.003 0.010 + 0.003** BRAIN MEANS.D. 2.26 0.17 2.28 0.10 2.26 + 0.12 2.24 + 0.12 2.20 0.14 LIVER MEANtS.D. 20.30 2.46 24.27 3.22** 27.71 2.74** 28.74 3.88** 27.49 3.68** KIDNEY LEFT MEANiS.D. 2.19 0.20 2.51 0.28** 2.51 0.21"* 2.34 0.24* 1.99 + 0.19"* KIDNEY RIGHT MEANS.D. 2.19 0.18 2.54 0.30** 2.50 i 0.18"* 2.36 0.25** 2.06 0.20* ADRENAL LEFT MEANiS.D. 0.032 0.005 0.032 0,004 0.030 0.006 0.030 + 0.006 0.028 + 0,006** t_ ADRENAL RIGHT O0 ,J SPLEEN MEAN+S.D. MEANfS.D. 0.032 0.005 0,94 0.16 0.031 + 0.005 0.87 0.12 0,030 0.008 0.86 0.11 0.031 0.007 0.87 0.14 0.026 0,007** 0.74 0.17"* THYMUS MEAN+S.D. 0.44 0.10 0.38 .................................................................................................................................... 0.08 ALL WEIGHTS a. Excludes WERE RECORDED IN GRAMS values for rat 13732, (G). which was moribund sacrificed on day * Significantly ** Significantly different different from from the Group the Group I value I value (p_<0.05) . (p<_0.01) . 45 of 0.38 study. 0.i0 0.40 0.14 0.30 f 0.09** > O C C_ tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B9 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - P GENERATION .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 III 3 30 MALE RATS IV i0 30 V 30 29a TERMINAL BODY WEIGHT MEANS.D. 580.7 40.0 575.3 47.6 541.7 47.2** 513.0 53.9** 431.8 64.1"* EPIDIDYMIS LEFT MEANS.D. 0.123 0.013 0.123 t 0.010 0.127 0.011 0.138 0.015"* 0.150 0.023** CAUDA EPIDIDYMIS LEFT MEANiS.D. 0.058 0.007 0.055 0.007 0.057 0.006 0.062 0.008 0.067 0.012"* TESTIS LEFT MEANS.D. 0.311 0.025 0.316 t 0.031 0.332 0.036 0.358 0.042** 0.419 0.080** LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D. 0.287 0.026 0.294 0.030 0.307 0.034 0.333 0.040** 0.386 0.089** SEMINAL VESICLES WITH FLUID O0 O0 SEMINAL VESICLES WITHOUT FLUID MEANS.D. MEANS.D. 0.397 0.062 [ 29]b 0.219 0.026 0.407 0.068 0.219 0.031 0.436 0.064* 0.237 0.034 0.465 0.062** [ 28]b 0.249 0.034** 0.484 0.076** 0.266 0.044** EPIDIDYMIS RIGHT MEANS.D. 0.123 0.012 0.120 0.017 0.128 0.012 0.133 0.022** 0.149 0.022** TESTIS RIGHT MEANS.D. 0.313 0.028 0.321 0.056 0.334 0.036 0.347 0.055** 0.410 0.064** PROSTATE MEANS.D. 0.195 0.033 0.200 0.045 .................................................................................................................................... 0.207 0.033 0.202 0.038 0.199 0.035 ALL WEIGHTS WERE RECORDED IN GRAMS (G). RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, which was moribund sacrificed on day 45 of study. b. Excludes values for rats that had fluid loss prior to weighing or organs damaged (weight affected). * Significantly different from the Group I value (p_0.05). ** Significantly different from the Group I value (p_0.01). O 4_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B9 (PAGE 2): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT ...... - ............................................................................................................................. DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 - SUMMARY - P GENERATION III 3 30 MALE RATS IV 10 30 V 30 29a TERMINAL BODY NEIGHT MEANS.D. 580.7 40.0 575.3 i 47.6 541.7 47.2** 513.0 53.9** 431.8 64.1"* PITUITARY b MEANS.D. 2.409 0.607 2.435 0.533 2.248 0.543 2.752 0.748 2.476 0.749 BRAIN MEANS.D. 0.390 0.034 0.399 0.035 0.418 0.038* 0.442 0.056** 0.518 0.066** LIVER MEANS.D. 3.490 0.286 4.223 0.500** 5.131 0.472** 5.606 0.514"* 6.420 0.729** KIDNEY LEFT MEANS.D. 0.378 0.036 0.437 0.047** 0.465 0.043** 0.457 0.040** 0.466 0.054** KIDNEY RIGHT MEANS.D. 0.379 0.030 0.443 0.048** 0.463 0.039** 0.462 0.034** 0.481 0.051"* ADRENAL LEFT b O0 ADRENAL RIGHT b MEANS.D. MEANS.D. 5.562 0.786 5.439 0.852 5.575 0.749 5.361 1.016 5.594 1.125 5.513 1.361 5.879 1.094 6.157 1.646 6.593 1.776" 6.177 1.589 SPLEEN MEANS.D. 0.161 0.027 0.152 0.020 0.160 0.024 0.169 0.025 0.171 0.035 THYMUS MEANS.D. 0.075 f 0.017 0.066 0.012 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes values for rat 13732, which was moribund sacrificed b. Value was multiplied by 1000. * Significantly different from the Group I value (p_0.05). ** Significantly different from the Group I value (p_0.01). on day 0.071 0.017 RATIOS (%) = (ORGAN 45 of study. 0.079 0.027 WEIGHT/TERMINAL 0.071 0.022 BODY WEIGHT) X 100. > O C 4_ oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE BI0 (PAGE I) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS TESTED N 30 30 REPRODUCTION STUDY OF AMMONIUM - P GENERATION MALE RATS III IV 3 i0 30 30 PERFLUOROOCTANOATE V 30 29a BRAIN WEIGHT MEAN+S.D. 2.26 + 0.17 2.28 + 0.10 2.26 + 0.12 2.24 + 0.12 2.20 0.14 EPIDIDYMIS LEFT MEAN+S.D. 32.08 3.12 30.68 2.33 30.68 2.74 31.47 + 2.72 28.82 3.71.* CAUDA EPIDIDYMIS LEFT MEANS.D. 14.75 1.80 13.92 1.32 13.99 1.38 14.37 1.58 13.21 1.88"* TESTIS LEFT MEANS.D. 79.85 7.02 79.38 6.31 79.43 7.22 81.27 5.21 81.63 15.65 LEFT TESTIS MINUS TUNICA ALBUGINEA MEANS.D. 73.91 7.27 73.76 5.75 73.79 + 6.84 75.74 5.08 74.85 17.14 SEMINAL VESICLES WITH FLUID %0_ SEMINAL VESICLES WITHOUT FLUID MEANfS.D. MEANS.D. 101.29 19.24 [ 29]b 56.50 8.07 102.13 f 14.14 54.94 7.05 104.58 14.68 56.82 7.49 105.25 + 13.91 ( 28]b 56.65 + 8.37 94.09 14.20 51.62 7.45 EPIDIDYMIS RIGHT MEANS.D. 31.96 2.81 30.21 3.52 30.81 + 2.85 30.29 + 4.62 29.00 3.36** TESTIS RIGHT MEANS.D. 80.89 9.04 80.67 13.57 79.66 7.30 78.95 9.84 79.61 10.36 PROSTATE MEANS.D. 50.58 8.22 50.09 .................................................................................................................................... 8.73 49.67 7.57 46.29 ALL WEIGHTS WERE RECORDED IN GRAMS [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13732, b. Excludes values for rats that (G). RATIOS (%) which was moribund sacrificed on day 45 of study. had fluid loss prior to weighing or organs damaged = (ORGAN WEIGHT/BRAIN (weight affected). ** Significantly different from the Group I value (p_<0.01). 9.04 WEIGHT) 39.12 8.06** X 100. C OO |,J PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE B10 (PAGE 2) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 REPRODUCTION STUDY OF AMMONIUM - P GENERATION MALE RATS III IV 3 10 30 30 PERFLUOROOCTANOATE V 30 29a BRAIN WEIGHT PITUITARY LIVER KIDNEY LEFT MEAN+S.D. MEAN+S.D. MEAN+S.D. MEANS.D. 2.26 f 0.17 0.62 + 0.18 903.14 +118.64 97,52 + 10.67 2.28 + 0.10 0.61 + 0.12 1066.18 +153.82"* 110.12 + 12.60"* 2.26 + 0.12 0.54 + 0.14" 1230.29 +119.75"* 111.70 + 10.49"* 2.24 + 0.12 0.62 + 0.14 1284.45 182.50"* 104.60 + 11.72" 2.20 + 0.14 0.48 + 0.14"* 1248.34 +144.28,* 90.41 + 8 68* KIDNEY RIGHT ADRENAL LEFT MEAN+S.D. MEAN+S.D. 97,52 + 9.94 1.43 + 0.20 111.62 13.45"* 1.40 + 0.19 110.97 + 9.45** 1.34 + 0.26 105.62 _ 12.37"* 1.34 + 0.26 93.51 8 68 1.28 + 0 30 ADRENAL SPLEEN RIGHT MEANS.D. MEANS.D. 1,40 + 0.23 41.51 + 6.97 1.35 + 0.25 38.41 5.84 1.32 + 0.35 38.55 + 6.02 1.40 + 0.35 38.86 + 6.15 1.20 f 33.40 + 0 29 7 37** THYMUS MEAN+S.D. 19.38 + 4.57 16.89 + .................................................................................................................................... 3.73 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes values for rat 13732, which was moribund sacrificed * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). on day 17.11 + 4.59 RATIOS (%) = (ORGAN 45 of study. 18.08 + WEIGHT/BRAIN 6.17 WEIGHT) 13.73 4 01"* X 100. > C OO _O PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE Bll (PAGE 1) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP I II III IV V . .DO.SAG E JM.G__KG./.DA.Y._ ........................... 0........................... _......................... 3 .......................... _O ........................ _O .......... RATS TESTED N 30 30 30 30 29a NUMBER MOTILE MEANS.D. 354.0 98.9 346.5 118.4 373.3 102.5 338.2 89.0 327.4 130.2 MOTILE PERCENT STATIC COUNT (NONMOTILE) MEANS.D. MEANfS.D. 82.6 f II.I 73.3 f 44.0 84.7 7.0 63.0 33.9 86.8 6.7 56.7 f 32.4 87.4 4.0 48.4 20.3* 83.9 8.8 58.4 , 31.0 TOTAL COUNT b MEANIS.D. 427.2 105.5 409.6 i 135.6 430.0 112.6 386.6 100.6 385.8 138.3 SPERM COUNT c MEANfS.D. II0.6 f 33.8 119.5 f 38.3 111.2 37.6 117.7 42.9 98.1 36.9 SPERM DENSITY d MEANIS.D. 962.65 279.89 1086.87 323.61 1016.78 i 322.39 1047.73 318.51 952.81 i 307.64 tO a. Excludes values for rat 13732 which was moribund sacrificed on day 45 of study. b. Sum of number motile and static count. 20 fields were evaluated. Groups of five fields were evaluated until a sperm count of at least 200 was achieved or c. Sperm count used in the calculation of sperm density. Ten fields were evaluated. d. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10 .6 mL), multiplying by 2 (dilution factor) and multiplying by 10 -6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table B17 for the weight of the left cauda epididymis) to obtain the sperm density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 plxels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. * Significantly different from the Group I value (p _ 0.05). > C O0 4_ O0 tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE Bll (PAGE 2): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - P GENERATION MALE RATS DOSAGE GROUP I II III IV V .oDOSAGoE JMoG_KG_DAY _.........................0..........................._.........................._.........................._.. ......................_.O. .......... RATS TESTED N 30 30 30 30 29a SPERMATID COUNT b MEAN,S.D. 50.7 , 16.6 45.9 _ 13.0 47.3 15.6 46.4 14.8 42.6 _ 16.2 a. b. c. _I_ %O Uo Excludes values for rat 13732 which was moribund sacrificed on day 45 of study. Spermatld count used in the calculation of spermatid density. Ten fields were evaluated. The spermatld density was calculated by dividing the spermatld count by the volume in the image area (34.3 x 10 "6mL), multiplylng by 2 (dilutlon factor) and multiplying by 10-6 to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to 1 decimal place) was multlplled by 50 (volume) and divided by the weight of the left testis minus tunlca albuginea (see Table B18 for the weight of the left testis minus tunica albuglnea) 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 overestimate of the concentration. of the actual volume and an > C U9 4= OO _I_ 4= PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889,6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI2 (PAGE i): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - SUMMARY - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 I0 30 .................................................................................................................................... RATS TESTED N 30 30 30 30 30 INCLUDED IN ANALYSES N 30 30 30 30 29a NORMAL MEAN+S.D. 187.1 + 24.4 191.4 + 7.0 191.2 + 5.3 190.9 + 3.5 178.6 + 48.7 PERCENT ABNORMAL MEAN%+S.D. 6.4 12.2 4.3 + 3.5 4.4 + 2.6 4,6 + 1.8 9.7 + 21.0 DETACHED HEAD MEAN+S.D. 7.5 + 11.2 4,4 + 3.8 4.5 + 2.8 5.9 + 2.9 7.4 + 14.9 NO HEAD MEAN+S.D. 5.2 + 13.3 3.5 + 3.5 3.7 i 2.9 2.9 + 2.3 6.1 + 17.0 BROKEN FLAGELLt_ MEAN+S.D. 0.2 + 0.4 0.6 + 1.0 0.4 + 0.6 0.2 + 0.4 1.1 + 3.1 NO HOOK MEAN+S.D. 0.0 + 0,2 0.0 0.0 0.0 + 0.2 0.1 + 0.2 0.i + 0,3 EXCESSIVE HOOK MEAN+S.D. 0.0 + 0.0 0.1 + 0.2 0.0 + 0.2 0.0 + 0.2 0,1 + 0.2 COILED FLAGELLUM MEANfS.D. 0.0 + 0.0 0.0 0.0 0.0 + 0.2 0.0 0.2 0.0 + 0.2 BENT FLAGELLUM MEAN+S.D. 0.0 + 0.0 0.0 + 0.0 0.0 + 0.0 0.0 + 0.2 0.0 + 0.0 SHORT SPERM HEAD MEAN+S.D. 0.0 + 0.0 0.0 + .................................................................................................................................... 0.0 a. Excludes values for rat 13732, which was moribund sacrificed on day 0.0 45 of study. 0.0 0.0 + 0.0 0.i 0.2 > O 4= oo O PRoToCoL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION B13 (PAGE I): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13601 13602 13603 13604 13605 13606 13607 13608 DS( 60 ) DS( 67 ) DS( 58- 59) DS( 10 ) DS( 30- 36) DS( 18- 20) DS( 88 ) DS( 10- 49) DS( 72- 85) DS(93-i0_) DS( 22- 75) SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS SOFT OR LIQUID FECES SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZEDALOPECIA: LIMBS a LOCALIZED ALOPECIA: LIMBS DDSS(( 94-44 96)) SLOOFCTALIZOERD LIQAULIODPECIFAE:CES LIMBS 13609 NO ADVERSE FINDINGS 13610 NO ADVERSE FINDINGS 13611 13612 DS( 44- 84) LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS 13613 NO ADVERSE FINDINGS 13614 DS( 17 } CHROMORHINORRBEA DS( 17- 35) LOCALIZED ALOPECIA: LIMBS 13615 DS(25-108) LOCALIZED ALOPECIA: LIMBS a 13616 DS( 15- 17) SOFT OR LIQUID FECES DS(94-108) BOTH EARS: SWOLLEN a 13617 DS( 22 ) VOCALIZATION .................................................................................................................................... DAY OF STUDY Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE g 4_ I,J PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI3 (PAGE 2): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13618 13619 13620 13621 13622 13623 13625 13626 13627 13628 13629 DS( 69- 84) DS(29-109) DS( 23- 60) DS ( 39 ) INCISORS: NO ADVERSE MISSING/BROKEN FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS SOFT OR LIQUID FECES DS( 86- 87) DS( 108 ) SOFT OR LIQUID FECES SOFT OR LIQUID FECES _D 0% 13630 DS ( 8 - 9 ) CHROMORHINORRHEA .................................................................................................................................... DS = DAY OF STUDY > C GO 4_ OC PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI3 (PAGE 3}: CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 DS( 2- 3) DS( 96- 97) DS( 9) DS( 24- 27) DS( 24- 28) DS(94-107) DS( 59 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA SOFT OR LIQUID FECES SOFT OR LIQUID FECES INCISORS: MISSING/BROKEN INCISORS: MISALIGNED NO ADVERSE FINDINGS BOTH EARS: SWOLLEN a SOFT OR LIQUID FECES NO ADVERSE FINDINGS 13641 NO ADVERSE FINDINGS 13G42 DS( 7) SOFT OR LIQUID FECES _D DS( 18- 21) CHROMORHINORRHEA DS( 22- 79) LOCALIZED ALOPECIA: LIMBS DS( 72- 75) CHROMORHINORRHEA DS( 86- 87) SOFT OR LIQUID FECES 13643 NO ADVERSE FINDINGS 13644 DS 36- 60) INCISORS: MISSING/BROKEN DS 36- 62) CHROMODACRYORRHEA DS 61-108) INCISORS: MISALIGNED a DS 88- 92) CHROMODACRYORRHEA DS 94 ) CHROMODACRYORRHEA DS 108 ) SOFT OR LIQUID FECES .................................................................................................................................... DS = DAY OF STUDY a. Observation confirmed at necropsy. > O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION BI3 (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13645 DS(101-106) NOSE: SCAB (0.2 UM X 0.2 CM) 13646 NO ADVERSE FINDINGS 13647 NO ADVERSE FINDINGS 13648 13649 DS( 46 ) SOFT OR LIQUID FECES NO ADVERSE FINDINGS 13650 DS_ 33- 36) RIGHT FORELIMB: ABRASION (2.0 CM X 1.0 13651 DSI 37- 39) RIGHT FORELIMB: SCAB NO ADVERSE FINDINGS (1.0 CM X 0.5 CM) 13652 DS' 19- 43) BACK: SCAB (1.0 CM X 1.0 CM) 13653 DS 10 ) SOFT OR LIQUID FECES DS, 31 ) SOFT OR LIQUID FECES DS 86-109) RIGHT EAR: SWOLLEN a 13654 DS 83- 94) HEAD: SCAB (0.5 CM X 0.2 UM) DS 95- 99) LOCALIZED ALOPECIA: HEAD DS 102 ) INCISORS: MISSING/BROKEN 13655 DS 59 ) PENIS: RED SUBSTANCE, SLIGHT 13656 NO ADVERSE FINDINGS 13657 13658 DS( 72- 73) CHROMODACRYORR/4EA NO ADVERSE FINDINGS 13659 DS (105-110) INCISORS: MISSING/BROKEN a 13660 DS( 48 ) SOFT OR LIQUID FECES .................................................................................................................................... DAY OF STUDY Observation confirmed at necropsy. CM) STUDY OF AMMONIUM PERFLUOROOCTANOATE > OO 4_ O0 CD PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION BI3 (PAGE 5): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13661 NO ADVERSE FINDINGS 13662 DSq 74-106) INCISORS: MISSING/BROKEN a 13663 13664 DS, 61 ) DS 31- 32) SOFT OR LIQUID CHROMORHINORP/4EA FECES DS 31- 53} DS 31-106) DS 31-106) DS I01-i06) INCISORS: MISSING/BROKEN CHROMODACRYORRHEA a INCISORS: MISALIGNED a LOCALIZED ALOPECIA: L_MBS a 13665 13666 DS 9- 10) DS 90- 94) SOFT OR LIQUID FECES MOUTH: SCAB (0.2 CM X 0.2 CM) NO ADVERSE FINDINGS 13667 13668 DS( 57- 69) DS(57-100) DS( 72- 75) DS(77-107) CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA a NO ADVERSE FINDINGS 13669 NO ADVERSE FINDINGS 13670 NO ADVERSE FINDINGS 13671 NO ADVERSE FINDINGS 13672 NO ADVERSE FINDINGS 13673 NO ADVERSE FINDINGS 13674 NO ADVERSE FINDINGS 13675 NO ADVERSE FINDINGS .................................................................................................................................... DAY OF STUDY Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE > O C OO d:, I0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION BI3 (PAGE 6): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 DS( 16- 17) DS(39-109) DS( 25- 27) DS( 51- 52) DS( 20 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA LOCALIZED ALOPECIA: CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA NO ADVERSE FINDINGS LIMBS a 13686 13687 DS( 95- 97} NOSE: SCAB (0.2 CM X 0.2 CM) NO ADVERSE FINDINGS 13688 NO ADVERSE FINDINGS 13689 DS( I0- 23) CHROMORHINORRHEA 13690 DS( 59 ) DS( 16- 22) CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS DS( 18 } CHROMORHINORRHEA .................................................................................................................................... DAY OF STUDY Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE > C 4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION BI3 (PAGE 7): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 DS( 71 ) DS( 82- 84) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORBINORRHEA SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS 13701 DS 64- 65) DS 64- 78) CHROMORHINORRHEA INCISORS: MISSING/BROKEN DS 65- 70) DS 73- 76) CHROMODACRYORRHEA CHROMODACRYORRHEA DS 79- 97) INCISORS: MISALIGNED DS 95- 96) DS 99-107) CNROMODACRYORRHEA CHROMODACRYORRHEA a 13702 DS 2) CHROMORHINORRHEA 13703 DS 23- 28) CHROMORHINORRHEA NO ADVERSE FINDINGS 13704 DS( 15- 18) SOFT OR LIQUID FECES 13705 DS( 36 ) SOFT OR LIQUID FECES NO ADVERSE FINDINGS .................................................................................................................................... DAY OF STUDY Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE > C U_ O0 0 _D _._ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B13 (PAGE 8): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 DS ( 108 ) DS( 15- 16) DS(99-109) DS(72-I09) NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN a CHROMORHINORRHEA BOTH OR RIGHT EARS: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a NO ADVERSE FINDINGS 13716 13717 NO ADVERSE FINDINGS NO ADVERSE FINDINGS 13718 13719 13720 DS( 16- 18) DS( 16- 17) DS ( 23 ) SOFT OR LIQUID FECES CHROMORHINORRHEA CHROMORHINORRBEA NO ADVERSE FINDINGS .................................................................................................................................... DS = DAY OF STUDY a. Observation confirmed at necropsy. > C o0 to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI3 (PAGE 9): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS -_ .................................................................................................................................. DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13721 NO ADVERSE FINDINGS 13722 13723 13724 13725 DS 87 ) DS 22 ) DS 85 ) DS 85 ) DS 87- 92) DS 87- 99) DS 94- 95) SOFT OR LIQUID FECES PALES DEHYDRATION UNGROOMED COAT UNGROOMED COAT DEHYDRATION DRIED RED PERINASAL NO ADVERSE FINDINGS NO ADVERSE FINDINGS SUBSTANCE _I_ _-_ t_ 13726 DS( 24- 26) DS( 52- 53} CHROMORHINORRHEA SOFT OR LIQUID FECES 13727 DS( 73- 84) LOCALIZED ALOPECIA: LIMBS DS( 93- 99) LOCALIZED ALOPECIA: LIMBS 13728 NO ADVERSE FINDINGS 13729 NO ADVERSE FINDINGS 13730 DS 8} CHROMORHINORRHEA DS 16- 21) CHROMORHINORRHEA 13731 DS 3) CHROMORHINORRHEA DS 58- 68) INCISORS: MISALIGNED 13732 DS 8- 9) DEHYDRATION DS 18- 34) EMACIATION DS 41- 45) EMACIATION a DS 44- 45) COLD TO TOUCH DSI 44- 45) URINE-STAINED ABDOMINAL FUR DSI 45 ) DECREASED MOTOR ACTIVITY DSI 45 ) MORIBUND SACRIFICED .................................................................................................................................... DS = DAY OF STUDY > a. Observation confirmed at necropsy. C _n oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE BI3 (PAGE i0) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13733 13734 13735 13736 13737 13738 13739 DS( 14- 17) DS ( 23- 24) DS( 85- 90) DS ( 85- 92) DS { 92 ) DS( 20- 23) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORP.HEA DEHYDRATION UNGROOMED COAT DEHYDRATION CHROMORHINORRHEA NO ADVERSE FINDINGS 13740 13741 DS(36-100) DS(I07-I09} DS 85- 94) DS 86- 91} LOCALIZED LOCALIZED ALOPECIA: ALOPECIA: LIMBS LIMBS a URINE-STAINED ABDOMINAL FUR DRIED, RED OR RED PERINASAL SUBSTANCE DS 86- 91) DS 86- 91) UNGROOMED COAT BOTH FOREPAWS: DRIED, RED SUBSTANCE DS 86- 92) DEHYDRATION DS 88- 91) COLD TO TOUCH DS 88- 93) PALE EXTREMITIES DS 88- 99) EMACIATION DS 90- 91} NO FECES DS 92- 93) SCANT FECES 13742 DS 2 - 3) CHROMORHINORRHEA .................................................................................................................................... DS = DAY OF STUDY a. Observation confirmed at necropsy. ON FUR STUDY OF AMMONIUM PERFLUOROOCTANOATE > O C O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI3 (PAGE ii} : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13743 13744 13745 13746 13747 13748 13749 13750 DS( 16 ) DS ( 100 ) DS( 31- 60) DS( 78- 84) DS(94-110) DS( 17- 21) DS ( 3 - 5 ) NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINORRHEA LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a CHROMODACRYORRHEA NO ADVERSE FINDINGS CHROMORHINORRHEA DS( . 72 ) URINE-STAINED ABDOMINAL FUR (_ DS = DAY OF STUDY a. Observation confirmed at necropsy. O Ca 4= O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE BI4 (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 57 64 70a 77 85b 92 99 106 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 166. 216. 275 191. 252. 315 187. 253. 312 189. 251. 313 166. 225. 279 196. 267. 326 178. 232. 288 182. 243. 295 172. 233. 286 184. 244. 304 177. 247. 314 177. 239. 286 171. 226. 270 181. 229. 279 182 238. 294 190. 272. 270 178. 236. 292 191. 253. 303 176. 237. 292 178. 243. 290 174. 234. 27( 182. 238. 290 181. 233. 296 185. 246. 293 180. 247. 311 186. 245. 308 176. 244. 304 188. 256. 312 310. 340. 369 362. 394. 418 351. 382. 409 365. 401. 434 327. 353. 380 363. 399. 432 329. 353. 373 336. 363. 400 335. 374. 409 341. 365. 392 363. 402. 425 332. 366. 397 314. 343. 359 313. 344. 368 339. 379. 410 317. 368. 404 332. 361. 378 335. 366. 386 334. 366. 392 339. 375. 406 323. 358. 381 330. 354. 378 336. 374. 402 327. 356. 375 341. 361. 385 353. 408. 434 348. 374. 386 356. 377. 423 398. 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. 431. 462. 455. 490. 425. 489. 416. 428. 464. 456. 489. 445. 408. 422. 457. 465. 429. 433. 438. 462. 423. 424. 458 420 432 492 423 489 455 487 460 516 440 520 438 448 486 471 509 470 432 446 471. 498 440 444 455 482 440 454 486 440. 461. 513. 444. 516. 480. 500 511. 520 484. 511 537. 556 458. 472 546. 555 455. 463 478. 479 502. 515 484. 477 533. 542 482. 492 450. 470 460. 462 493. 511 514. 537 441. 462 462. 472 471. 485 495. 511 453. 472 460. 472 496. 514 458. 467 481. 487 545. 566 449. 466 535. 555 507. 529 538. 553 508. 517 565. 586 487. 494 566. 598 481. 497 502. 505 523. 548 500. 518 554. 578 504. 509 479. 489 473. 493 511. 527 557. 570 471. 478 482. 499 501. 509 517. 536 486. 496 483. 504 525. 531 482. 490 504. 532 564. 570 486. 510 570. 583 555. 567 592 576. 592 610 538. 552 570 604. 631 633 514. 530 533 610. 630 653 514. 529 545 522. 542 562 565. 580 604 534. 554 567 597. 616 632 527. 543 554 514. 528 549 500. 525 527 542. 562 582 590. 614 637 489. 494 507 510. 525 540 526. 543 564 543. 565 570 492. 513 523 520. 544 554 534. 555 580 502. 512. 524 544. 563. 567 606. 616. 636 523. 551. 564 599. 604. 617 13629 13630 176. 187. 241. 263. 297 331. 326. 368. 362. 408. ...................................................................................................... = DAY OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 388 434 409. 437 469. 498 454. 476. 485 522. 547. 556 504. 579. 515 529. 540. 586 596. 614. r ............................. 547 622 [2_ 4_ First value recorded after cohabitation. O to O PROTOCOL 418-020: ORAL _GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI4 (PAGE 2): BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 13641 163. 194 180 182 167 193 183 181 175 190 179 225. 256. 241. 245. 221. 265. 251. 250. 244. 259. 237. 285. 317. 292. 301. 279 313 322 296 302 317 300 319. 359. 328. 358. 318. 360. 372. 335. 360. 362. 340. 348. 394. 362. 405. 348. 386. 408. 370. 404. 398. 372. 375. 417. 376. 433. 362. 414. 440 398 441 429 394 396 440 398 462 392 429 459. 432. 466. 465. 411. 415. 459. 418. 484. 410. 438. 481. 460. 483. 485. 434. 57 433. 465. 431. 509. 427 468 506 482 493 501 456 64 453. 476. 444. 522. 441. 485. 524. 517. 510. 531. 464. 70a 77 472. 486. 456. 499. 454. 514. 544 532 499 545 477 481. 494. 472. 478. 470. 524. 556. 548. 521. 558. 488. 85b 92 99 502. 512. 485. 541. 485. 540. 584. 574. 536. 577 502 512. 523. 498. 564. 503. 551. 604. 592. 553. 585. 516. 532. 546. 498. 585 513 571 622 605 564 600 523 106 548. 558. 502. 607. 526. 587. 640. 611. 562 614 536 13642 13643 13644 13645 13646 13647 13648 13649 13650 176 242. 308 184 250. 305 186. 249. 307 348. 385. 403 350. 389. 422 352. 387. 403 420. 443. 449 451. 482. 496 428. 449. 467 471. 460 517. 517 488. 504 472. 512 542. 562 515. 538 180. 244 285. 335. 374. 400 427. 455 455 471. 486 498. 512 184. 248 294. 335. 370. 392 422. 439 460. 479. 490 497. 516 173. 231 288. 339. 381. 415 431. 453 476. 491. 507 515. 527 188. 247 298. 343. 387. 419. 452. 478 505. 523 542. 539. 562 180. 244 294. 334. 353. 372. 396. 416 431. 442 461. 476. 488 187. 247 290. 345. 376. 402. 430. 455 470. 483 501. 502. 520 530. 571. 542. 527. 527. 537. 566. 496 544 547 586. 560. 541. 533. 550. 588. 510. 563. 561 593 583 560 548 564 606. 515. 568. 13651 166. 227 287. 337. 369. 418. 442. 467 500. 519 537. 545. 559. 570 575. 592. 13652 181. 243 292. 335 370 405. 429. 458 469. 490 502. 526. 538. 553 562. 572. 13653 176. 233 275. 313 350 370. 391. 414 429. 439 454. 468. 482. 488 499. 517. 13654 188. 253 307. 353 388 407. 434. 460. 476. 491 501. 522. 546. 558 569. 578. 13655 178. 244 296. 344 395 422. 454. 483. 515. 540 565. 577 604. 611 627. 635. 13656 188. 246. 282. 316 343 367. 381. 400. 420. 437 445. 458 470. 488 496. 514. 13657 174. 232. 277. 305 322 332. 355. 377. 385. 393 411. 416 433. 440 455. 462. 13658 182. 241. 300. 328 363 394. 412. 431. 460. 485 494. 508 516. 527. 543. 566. 13659 175. 234. 294. 336 385 404. 427. 451. 464. 484 490. 484 497. 517. 529. 545. _> 13660 187. 260. 311. 369. 415 450. 478. 512. 541. 573 594. 618 643. 654. 662. 680. ...... _................................................................................................ _ ............................. = DAY OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). O_ Last value recorded before cohabitation. 4_ First value recorded after cohabitation, o0 6bO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER {APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B14 (PAGE 3): BODY WEIGHTS - INDIVID[_L DATA - P GEWERATIONMALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 57 64 70a 77 85b 92 99 106 .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13661 13662 13663 13664 13665 13666 13667 13668 13669 13670 13671 171. 231. 287 195. 260. 305 181. 250. 306 180 245. 298 171 235. 290 191 257. 292 182 250. 307 182 242. 292 170 227. 279 187 247. 304 174 243. 291 336. 368. 394. 432 333. 361. 387. 411 347. 378. 398. 426 337. 378. 384. 403 338. 360. 376. 398 312. 320. 343. 359 356. 391. 415. 441 321. 323. 338. 355 303. 318. 336. 369 341. 365. 386. 412 339. 366. 375. 391 450. 461 421. 445 448. 472 422. 430 412. 433 373. 390 468. 460 371. 378 392. 400 432. 450 405. 431 474. 48E 464. 479 476. 494 441. 444 454. 466 406. 418 451. 476 385. 402 419. 385 468. 484 446. 460 509. 532 447. 488 505. 523 442. 470 472. 480 422. 432 492. 516 408. 414 441. 452 498. 520 472. 483 551. 569 502. 515 547. 567 475. 485 499. 507 436. 459 519. 513 417. 425 462. 480 534. 549 488. 501 585. 539 567 511 511 481 542 449 502 555 526 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 13685 13686 13687 13688 184 240. 284 326. 361. 385. 378 398. 420 440. 454 448. 466 475. 490 497 168 232. 282 320. 352. 374. 399 421. 447 463. 477 483. 499 516. 538 551 185 244. 292 319. 332. 346. 360 378. 401 414. 426 447. 460 468. 484 496 175 246. 301 339. 363 385. 410 428. 445 475. 473 492. 518 524. 540 556 184 258. 289 318. 339. 354. 363 386. 398 410. 418 431. 447 455. 458 46, 175 244. 293 327. 363. 381. 404 418. 438 450. 460 479. 488 492. 514 52_ 182 251. 311 356. 404. 434. 468 485. 511 532. 55( 562. 574 589. 610 617 178 248. 284 329. 362. 386. 415 430. 452 472. 47 502. 510. 520. 540 546 182 253. 308 359. 394. 417. 434 445. 469 490. 493 481. 506 523. 540 521 172 240. 288 337. 361. 393. 412 425. 439 452. 460 466. 469 481. 490 507 177 253. 312 357. 400. 424. 453 483. 501 520. 538 544. 504 533. 569 584 180 249. 287 333. 374. 406. 426 444. 471 483. 495 519. 532 554. 563 572 185 248. 288 330. 359. 384. 398 420. 446 458. 469 477. 497 499. 515 525 172 232. 275 308. 342. 362. 382 400. 418 431. 447 461. 472 479. 483 487 188 252. 300 325. 337. 346. 364 389. 409 427. 433 450. 461 470. 482 499 175 240. 288 329. 355. 374. 394 408. 428 445. 450 456. 472 478. 496 507 187 254. 316 358. 386. 402. 433 450. 466 488. 497 513. 531 542. 558 561 13689 178 244. 293 344. 380. 13690 186 255. 310 368. 408. ...................................................................................................... = DAY OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before First value recorded after cohabitation. cohabitation. 411. 433. 441 479 458. 490 511. 544 498. 507 565. 596 524. 584. 534 543. 557 624 629. 650 _ ............................. 562 673 t_ [2_ 4_ _-" Oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE FABLE BI4 (PAGE 4): BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 57 64 70a 77 85b 92 _ ................................................................................................ RAT # DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 99 106 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 13701 13702 13703 166. 227 188. 241 178. 246 187. 254 172. 233 190. 253 180. 234 184. 240 170. 228 190. 259 177. 240 168. 231 171. 226 276. 322 356 261. 293 317 300. 353 386 305. 345 383 274. 300 334 297. 331 353 279. 303 333 269. 315 349 262. 296 310 304. 347 379 284. 320. 351 274. 310. 343 280. 315. 341 369. 329. 413. 410. 356. 376. 350. 372. 322. 403. 362. 355. 354. 392. 345. 433. 429. 386. 411. 366. 394. 343. 433. 387. 381. 371. 414. 356. 450. 460. 409. 442 382 411 354 440 412 385 401 429. 365. 483. 489. 408. 469. 395. 434. 366. 454. 420. 395. 414. 444. 378. 494. 501 42E 481 410 450 383 475 428 415 422 464. 388. 499. 519. 429. 470. 419. 463. 391. 481. 434. 423. 437. 468. 389. 520. 520. 440 479 424 480 405 488 435 435 445 478. 395. 543. 523. 469. 509. 439. 486. 424. 498. 430. 450. 460. 496. 409. 552. 544. 483 520 441 498 430 503 460 459 469 509. 433. 556. 558. 498. 540. 456. 517. 446. 521. 462. 474. 480. 528. 450. 570. 571. 506. 553. 476. 524. 468. 530. 485. 487. 483. 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 175. 240 179. 241 183. 248 171. 233 188. 255 180. 234 181. 232 170. 218 169. 225 176. 240 181. 230 175. 239 183. 238 178. 226 182. 243 285. 339. 385 289. 330. 350 406. 436. 456 367. 396. 414 302. 334. 362 384. 399. 424 281. 324. 363 384. 404. 424 300. 350. 390 413. 433. 453 296. 304. 335 352. 373. 382 253. 275. 290. 300. 305. 316 256. 268. 284. 295. 300. 306 261. 282. 322. 337. 355. 378 280. 289. 317. 334. 323. 378 278. 307. 314. 325. 339. 369 296. 329. 361. 378. 404. 423 293. 321. 340. 351. 380. 400 278. 300. 326. 343. 369. 384 294. 340. 368. 395. 421. 439 482. 489 441. 454 442. 456 440. 459 472. 476 396. 401 328. 335 330. 336 385. 392 404. 420 384. 383 444. 465 417. 433 392. 395 460. 477 510. 523 470. 476 462. 452 467. 487 483. 507 407. 392 347. 352 340. 345 407. 427 423. 434 390. 394 471. 452 440. 448 414. 420 493. 498 549. 580 499. 509 467. 486 499. 514 526. 537 412. 421 371. 372 364. 370 441. 436 450. 462 410. 423 506. 519 481. 494 439. 452 503. 521 598. 540. 513. 535. 552. 437. 381. 383. 449. 478. 439. 533. 514. 467. 521. 620. 551. 519. 541. 538. 443. 390. 393. 435. 484. 434. 544. 521. 477. 519. 13719 13720 171. 233 190. 257 277. 324. 350. 375. 396. 419 288. 339. 363. 393. 421. 444 441. 458 467. 488 477. 483 509. 512 494. 495 535. 542 .................................................................................................................................... = DAY OF STUDY 518. 565. 524. 583. WEIGHTS WERE RECORDED IN GRAMS (G). C/_ Last value recorded before cohabitation. 4_ First value recorded after cohabitation. _-" 0 _0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI4 (PAGE 5): BODY WEIGHTS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... 57 64 70a 77 85b 92 99 106 RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13721 13722 13723 13724 13725 166. 193 178 185 170 220. 229. 212. 193. 203. 263. 268. 252. 243. 235. 299. 307. 254. 281. 259. 331. 316. 260. 296. 256. 358. 315. 263. 298. 259. 381. 335 267 304 274 394. 344. 283. 326. 279. 417. 355. 289. 350. 288. 437. 368. 286. 349. 285. 444. 385. 273. 361. 298. 450. 405. 285. 370. 300. 464. 414. 295. 386. 331. 481. 435. 302. 388. 339. 498. 441. 312. 407. 353. 511. 452. 321. 378. 361. 13726 13727 179 227. 283. 312. 301. 306. 350 373. 378. 380. 394. 345. 419. 438. 451. 465. 182 227. 286. 317. 320. 327. 334 338. 351. 363. 380. 390. 405. 413. 423. 440. 13728 13729 13730 13731 183 224. 268. 293. 306. 315. 324 346. 365. 363. 355. 371. 385. 388. 392. 411. 172 221. 272 298. 309. 317. 329 342. 357. 369. 374. 381. 392. 396. 413. 427. 186 236. 286 339. 372. 392. 410 420. 440. 459. 456. 475. 486. 499. 520. 515. 175 232. 280 296. 321. 341. 360 377. 389. 390. 402. 406. 424. 441. 453. 462. 13732 186 162. 236 208. 278. 311. 192 MORIBUND SACRIFICED ON DAY 45 OF STUDY 13733 13734 13735 13736 13737 13738 13739 13740 171. 198. 254 188. 233. 271 313. 361. 393. 418 442. 475. 480. 506 308. 313. 317 335. 353. 378. 385. 374 178. 205. 249 275. 282. 300 336. 347. 356. 364. 369 181. 214. 253 281. 300. 292 314. 352. 337. 342. 352 171. 206 232 263. 277. 282 290. 302. 320. 327. 345 183. 218 271. 284. 309. 337 354. 373. 386. 399. 412 174. 192 251. 266. 271. 282 304. 303. 331. 337. 334 188. 206 267. 300. 322. 333 368. 377 405. 414. 429 518. 390. 389. 356. 344. 418. 339. 433. 536 396 400 362 269 431 353. 449. 547. 408. 408. 381. 345. 443. 351. 464. 536. 428. 428. 380. 365. 457. 354. 478. 550. 450 437 389 374 464 360 486 13741 13742 13743 13744 171. 211 257. 257. 262. 268 296. 308 185. 216 255. 283. 283. 281 291. 296 169. 187 232. 263 287. 294. 306. 318 176. 191. 243. 268 274 282. 295. 315 315. 302. 331. 328. 310. 304. 343 337 311 306 344 340. 312. 321. 360. 349. 268. 325. 370. 352. 217. 322. 390 359 300. 335. 373. 370. 341 342 390. 386. 13745 13746 176. 217. 259. 277 276 190. 237. 282. 288 311 301. 321. 328 320. 335. 352 353. 358 370. 380 360. 368. 370. 379 386. 391. 415. 419 399. 429. 395. 442. 13747 169. 209. 255. 253 256 13748 185. 190. 266. 319 353 13749 173. 217. 268. 305 321 13750 176. 206. 246. 282 303 ...................................................................................................... 258. 367. 335. 326. 280. 392. 347. 348. 286. 328. 358. 349. 297. 403. 375. 380. 301 448 390 391 305. 475. 400. 404. 302. 485. 383. 390. 301. 306 321. 501. 517 548. 409. 436 442. 399. 414 418. _ ............................. 323. 547. 456. 431. = DAY OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. First value recorded after cohabitation, o0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE BI5 (PAGE I): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 .................................................................................................................................... 13601 13602 13603 13604 13605 13606 13607 13608 13609 13610 13611 148. 166. 183. 172. 164. 179. 154. 166. 168. 177. 189. 195. 209. 207. 211. 185. 203. 199. 182. 175. 209. 218. 190. 217. 225. 220. 207. 195. 198. 197. 201. 208. 221. 178. 208. 212. 210. 198. 216. 193. 187. 196. 196. 229, 188. 201. 198. 210, 195. 213. 181. 201. 200. 212. 214, 196. 196. 204. 215. 195. 220. 192. 196. 207. 230. 218. 208. 198. 202. 217. 198. 220. 205. 191. 210. 228. c 215. 206. 198. 226. 194. 230. 207. 198. 219. 227. 224. 225. 218. 210. 220. 204. 228. 199. 204. 213. 239. 235. 188. 176. 174. 185. 171. 188. 165. 167. 166. c 187. 226. 213. 205. 220. 223. 247. 204. 209. 222, 243. 239. 214. 208. 201. 219. 197. 240. 209. 201. 202. 233. 229. 220. 208. 202. 203. 193. 219. 190. 191. 212. 231. 226. 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 170. 153. 153. 152. 190. 160. 166. 164. 165. 162. 158. 148. 175. 176. 164. 159. 177. 188. 161. 182. 168. 95. 186. 177. 184. 177. 170. 176. 189. 176. 195. 186. 189. 198. 201. 186. 180. 197. 208. 182. 200. 204. 207. 199. 191. 201. 195. 196. 213. 207. 207. 200. 185. 174. 194. 206. 191 187 205 208 190 179 192 183 173 212 187 182 202. 170. 177. 189. 203. 186. 189. 188. 201. 186. 172. 190. 188. 181. 207. 174. 220. 200. 177. 199. 197. 195. 183. 196. 189. 200. 182. 181. 193. 190. 183. 206. 170. 231. 191. 186. 200. 186. 202. 188. 207. 198. 200. 180. 187. 200. 189. 203. 204. 176. 223. 199. 197. 203. 190. 217. 189. 205. c 205. 187. 193. 206. 194. 206. 215. 180. 214. 206. 205. 198. 207. 226. 183. 201. 199. 204. 185. 184. 209. 198. 203. 232. 177. 226. 168. 160. 153. 172 181. 160. 151. 166. 173. 158. 157. 169. 159. 160. 180. 139. 187. 200. 192. 199. 198. 218. 185. 208. 192. 203. 178. 202. 187. c 199. 225. 199. 221. 199. 195. 192. 194. 225. 180. 202. 187. 198. 171. 198. 184. 181. 194. 234. 197. 211. 202. 207. 190. 206. 221. 175. 209. 198. 188. 178. 198, 192. 186. 180. 230. 195. 208. 13629 13630 172. 202. 189. 196 166. 207. 195. 205 195. 213. 197. 214. 213. 219. 205. 219_ 204. 218. 170. 184. 210. 209. 198. 207. 206. 210. ............................................................................................ = DAYS OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. First value recorded after cohabitation. Spilled feed precluded the calculation of this value. ......................................... [/_ 4_ _O-O_ _o O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI5 (PAGE 2) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DAYS i- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 13632 13633 13634 13635 13636 13637 13638 13639 13640 160. 189. 183. 176. 175 182 166 189. 211. 197. 195 197 173 172 188. 186. 178 180 169 190 222. 228. 228 230 156 207 206. 198. 200 207 186 195 230. 210. 212 197 172 206 216. 211, 212 205 176 191 203. 206. 204 217 167 182 229. 217. 216. 210 180. 199. 215. 211. 202. 218 189. 196. 186. 232. 217 219 215 216 210 216 13641 160. 207. 203. 193. 190. 182. 189 1133664423 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 1731. 178. 167. 170, 159. 163. 170. 171. 165. 163. 153. 176. 173. 148. 154. 155. 169. 183. 210887. 193. 178. 180. 172. 171. 188. 179. 182. 177. 163. 176. 182. 158, 177. 183. 184. 186. 211951. 198. 200. 184. 185. 195. 219. 209. 195. 214. 181. 200. 204. 164. 200. 173. 198. 214, 221061.. 203. 215. 193. 190. 199. 196. 210. 197, 219. 174. 190. 205. 156. 187. 192. 207. 220. 1948. 195. 196. 186. 190. 203. 186. 203. 206. 203. 171. 186. 213. 162. c 191. 202. 222. 129063,. 174. 203, 185. 182. 201. 199. 213, 211, 206, 170, 191, 208, 157, 200. 191. 201. 221. 18998. 192. 200. 187. 183. 201. 200, 221. 213. 197. 170. 190. 209. 159. 195. 185. 210. 224. 50- 57 195. 199. 188. 232. 212 230 215 223 210 220 194 129072 196. 204. 197. 190, 217. 196. 216. 210. 200. 175. 205. 226. 167. 194. 280. 200. 233. 57- 64 200. 205. 196, 233. 219. 231. 223. 233 220 235 190 221116 208 197 195. 196. 216. 200. 211. 221. 196. 172. 201. 227. 170. 200. 199. 209. 246. 64- 70a 85b-92 169. 174. 166. 175. 182. 213. c 194. 172 187 164 15784 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 22079 190 203 195. 190. 206, 195. 233. 198. 198. 169. 201. 228. 167, 215. 185. 197. 240. 92- 99 199. 210. 184. 228. 209. 240. 213. 228. 206. 218. 170. 21016. 219. 191. 188. 182. 204. 185. 225. 194. 195. 167. 198. 226. 173. 211. 198. 211. 239. 99-106 193. 219. 169. 224. 210. 235. 218. 221. 202. 220. 189. 20191. 226. 200. 193. 196. 215. 181. 216. 205. 190. 176. 199 218 181 198 220 217 c DAYS = DAYS OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 4_ First value recorded after cohabitation. O0 Spilled feed precluded the calculation of this value. to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI5 (PAGE 3): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DAYS i- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY 50- 57 57- 64 64- 70a 85b-92 92- 99 99-106 .................................................................................................................................... 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 158. 179. 186. 189 178. 191. 203. 201 162. 176. 191. 193 178. 184. 220. 239 169. 197. 215. 199 174. 177. 196. 174 167. 191. 203. 209 172. 197. 204. 176 152. 208. 173. 172 178. 222. 237. 239 168. 185. 207. 189 151. 167. 183. 193 165. 175. 193. 192 161. 190. 198. 173 167. 195. 202. 208 174. c 184. 172 164. c 177. 207 166. 192. 200. 218 166. 162. 201. 207 162. 184. 200. 209 154. 169. 192. 190 166. 184. 210. 215 165. 155. 194. 192 180. 172. 199. 191 161. 155. 188. 193 170. 179. 193. 168 169. 176. 214. 201 184. 204. 200. 200 191. 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. 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. 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. 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. 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. 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. 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. 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. 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. 13689 13690 159. 168. 200. 190 176. 193. 234. 227 200. 244. 200. 251. 203. 259. 204. 261. 203. 274. 180. 237. 209. 268. 214. 274. 209. 267. ...................................................................................................... = DAYS OF STUDY _ ............................. WEIGHTS WERE RECORDED IN GRAMS (G). OO Last value recorded before cohabitation. 4_ First value recorded after cohabitation. _- Oo Spilled feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B15 (PAGE 4): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... 13691 13692 13693 13694 13695 13696 13697 13698 13699 13700 152. 155. 171. 167. 176. 174. 156. 163. 162. 181. 183. 168. 208. 199. 191. 189. 172. 144. 162. 187. 200. 199. 234. 210. 214. 230. 173. 191. 194. 235. 200. 183 233 210 219 207 172 188 182 230 181. 186. 235. 207. 230. 223. 167. 189. 178. 241. 217. 194. 228. 201. 235. 232. 174. 196. 183. 243. 209. 195. c 229. c 238. 177. 194. 184. 233. 13701 163. 177. 219. 195 198. 197. 199. 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 157. 147. 156. 166. 165. 157. 169. 165 172 141 144 164 150 174 143 150 161 176. 176. 174. 196. 195. 186. 185. 191. 180. 156 144 169 174 204 190 184 183 197. 185. 221. 229. 195. 208. 222. 178. 171. 183. 151. 179. 177. 202. 201. 190. 219. 194 179 230 225 188 225 234 176 165 169 162 179 c 204 190 185 218 190. 176. 229. 218 188 226 222 180 178 178 160 178 171 205 191 181 210 194. 161. 221. 223. 198. 215. 209. 185. 179. 170. 161 157 172 207 193 185 217 194. 189. 218. 221. 204. 210. 217. 187. 173. 198. 211. 204. 173. 202. 168. 135. 204. 13719 13720 157 173 215. 207 205 210 222. 183 182 241. 233 238 235 246. 50- 57 200. 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. 57- 64 209. 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. 64- 70a 85b-92 178. 153. 207. 192. 204. 193. 155. 167. 172. 119. 190. 148. 192. 183. 184. 172. 184. 177. c 151. 153. 137. 158. 145. 177. 161. 158. 175. 182. 195. 223. 197. 245. 216. 256. 249. 177. 195. 187. 242. 191. 193. 139. 237. 220. 215. 218. 224. 195. 179. 185. 161. 195. 179. 215. 211. 186. 217. 217. 243. 92- 99 214. 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. 99-106 216. 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 OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 4_ First value recorded after cohabitation. Oo Spilled feed precluded the calculation of this value. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE BI5 (PAGE 5): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - P GENERATION MALE RATS PERFLUOROOCTANOATE DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13721 13722 13723 13724 13725 13726 13727 13728 13729 13730 144. 176. 189 137. 174. 214 132. 170. 146 184. 190. 232 150. 204. 214 162. 213. 217 156. 211. 208 152. 186. 200 156. 186. 204 153, 186. 228 183. 176. 157. 205. 178. 189. 182. 193. 195. 228. 189. 179. 146. 182. 160. 179. 176. 185. 196. 223. 195. 188. 158. 194. 173. 210. 170. 182. 191. 221. 191. 186. 156. 220. 171. 217. 178. 195. 194. 205. 50- 57 200. 168. 156. 228. 165. 203. 189. 200. 208. 219. 57- 64 203. 170. 149. 219. 165 205 202 194 208 240 64- 70a 85b-92 154. 206 162. 197 105. 145 168. 211 156. 185 174. 233 170. 193 160. 201 162, 197 166. 223 92- 99 99-106 201. 179. 146. 207. 175. 217. 181. 187. 200. 224, 192. 180. 205. 111. 168. 206. 190. 187. 201. 203. 1133773312 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 13747 13748 15744.. 108. 159. 116. 140. 124. 145. 130. 123. c 135. 100. 105. 162, 148. 140. 106. 117884.. 151. 164. 157. 154. 133. 184. 174. 169. 194. 172. 158, 173. 179. 177. 182. 163. 17549 202 214 169. 181. 165 169 185 203 180 189 175 191 182 152 175 217. 210785.. 205. 192. 157. 171. 165. 177. 163. 184. 155. 177. 182. 169. 166. 190. 151. 208. 116951.. 200. 174. 169. 161. 145. 176. 172. 191. 165. 171. 177. 169. 189. 180. 154. 209. 17159.. 207. 167. 173. 155. 147. 181. 181. 199. 186. 169. 170. 176. 184. 182. 166. 218. M1O8R2I.BUND 201. 189. 187. 167. 147. 177, 169. 202. 175. 172. 184. 186. 182. 183. 166. c 18S0A.CRIFICED170 206. 212 189. 191 184 190 171. 175 149. 159 183. 180 182 172 205 206 174 166 173 168 182 182 185 197 198 182 181 185 159 161 220 245 ON DA1Y54.45 OF 19S0TUDY 188. 209 157. 169 148 183 147. 185 129. 183 150 190 13{ 160 172 215 139 23 146 177 147 197 143 176 155 177 155 175 129 156 200 221 193. 190. 188. 181. 163. 171. 172. 166. 210. 198. 172. 160. 184. 195. 182. 162. 235. 178. 166. 190. 175. 166, 162. 180. 154. 201. 225. 170. 168. 175. 178. 179. 148. 204. 13749 133. 167. 181. 170. 163. 158. 13750 140. 172. 202. 208. 210. 209. .................................................................................................................................... = DAYS OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded First value recorded before after cohabitation. cohabitation. Spilled feed precluded the calculation of this value. 159. 200. 164 213 166 233 134. 176 181. 199 163. 207, 163. 209, _> [/_ 4_ _" O0 to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (0NE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE BI6 (PAGE i): MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS ...... l ............................................................................................................................. DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... DATE 13601 3 M C 13602 2 M C 13603 4 M C 13604 1 M C 13605 1 M C 13606 3 M C 13607 1 M C 13608 14 M C 13609 2 M C 13610 1 M C 13611 4 M C 13612 13613 4 M 3 M 13614 4 M 13615 8 M 13616 3 M 13617 3 M 13618 2 M 13619 2 M 13620 4 M 13621 4 M 13622 4 M 13623 4 M 13624 4 M 13625 1 M 13626 4 M 13627 1 M 13628 13629 1 M 4 M 13630a C C C C C C C C C C C C C C C C C C .......... FEMALE PREGNANCY STATUS P(13801) P(13802) P(13803) P(13805) P(13806) P(13807) P(13808) P(13809) P(13810) NP(13811) P(13812) P(13813) P(13814) P(13815) P(13816) P(13817) P(13818) P(13819) P(13820) P(13821) P(13822) P(13823) P(13824) P(13825) P(13826) P(13827} P(13828) P(13829) P(13830) M = MATED ( ) ffiFEMALE RAT NUMBER C ffiCONFIRMED NC = NOT CONFIRMED p ffiPREGNANT NP = NOT PREGNANT a. Rat 13630 was not assigned to cohabitation because there were no available female rats. PERFLUOROOCTANOATE > O [_0 4_ 0(9 tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B16 (PAGE 2): MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAYS IN FEMALE PREGNANCY RAT # COHABITATION MATING STATUS MATING DATE STATUS .................................................................................................................................... 13631 13632 3 M 4 M C P{13831) C P(13832} 13633 13634 13635 13636 13637 13638 13639 2 M C P{13833) 2 M C P(13834) 2 M C P(13835) 1 M C P(13837) 1 M C P(13838) 2 M C P(13839) 1 M C NP(13840) 13640 1 M C P{13841) 136412 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 41 MM C P(138423) 1 M C P(13844) 1 M C P(13845) 1 M C P(13846) 1 M C P(13847) 4 M C P(13848) 3 M C P(13849) 1 M C P(13850) 1 M C NP(13851) 1 M C P(13852) 1 M C P(13853) 1 M C P(13854) 1 M C P(13855) 1 M C P(13856) 4 M C P(13857) 1 M C P(13858) 13658 3 M C P(13859) > 13659 4 M C P(13860) 13660a ......... .................................................................................................................................... = MATED ( ) = FEMALE RAT NUMBER _2_ = CONFIRMED NC = NOT CONFIRMED 4_ = PREGNANT NP = NOT PREGNANT OO a. Rat 13660 was not assigned to cohabitation because there were no available female rats. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE B16 (PAGE 3}: MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... DATE 13661 1 13662 14 13663 2 13664 5 13665 1 13666 2 13667 4 13668 4 13669 4 13670 1 13671 2 M C M NC M C M C M C M C M C M C M C M C M C 13672 4 M C 13673 8 M C 13674 2 M C 13675 1 M C 13676 1 M C 13677 3 M C 13678 1 M C 13679 1 M C 13680 1 M C 13681 1 M C 13682 3 M C 13683 1 M C 13684 4 M C 13685 1 M C 13686 1 M C 13687 4 M C 13688 1 M C 13689 1 M C 13690 4 M C .................................................................................................................................... M = MATED C = CONFIRMED ( ) = FEMALE RAT NUMBER NC = NOT CONFIRMED p t PREGNANT NP = NOT PREGNANT FEMALE PREGNANCY STATUS P(13861) P(13862) P(13863) P(13864) P(13865) P(13866) P(13867) P(13868) P(13869) P(13870) P(13871) P(13872) P(13873) P(!3874) 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) PERFLUOROOCTANOATE _> [_O 4A OO O tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITrER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE BI6 (PAGE 4): MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION REPRODUCTION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DAYS IN COHABITATION MATING STATUS MATING DATE .................................................................................................................................... 13691 4 M C 13692 4 M C 13693 1 13694 2 13695 2 13696 2 13697 4 13698 1 13699 3 13700 14 13701 4 13702 2 M C M C M C M C M C M C M C DID NOT MATE M C M C 13703 3 M C 13704 3 M C 13705 4 13706 14 13707 2 13708 1 13709 4 13710 2 13711 1 13712 2 13713 3 13714 3 13715 4 13716 3 13717 14 M C M NC M C M C M C M C M C M C M C M C M C M C M NC 13718 4 M C 13719 3 M C 13720 3 M C .................................................................................................................................... = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED i PREGNANT NC = NOT CONFIRMED NP . NOT PREGNANT FEMALE 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(13905) P(13906) P(13907) P(13908) P(13909) P(13910) P(13911) P(13912} P(13913) P(13914) P(13915) P(13916} P(13917) P(13918) P(13919) P(13920) > _'_ [2_ 4_ _-O_ b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI6 (PAGE 5): MATING AND FERTILITY - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... 13721 13722 2 M C 2 M C 13723a 1 M C 13723b 3 M C 13724 1 M C 13725 4 M C 13726 2 M C 13727 2 M C 13728 1 M C DATE FEMALE PREGNANCY STATUS P(13921) P(13922) P(13923) P(13950) P(13924) P(13925) P(13926) P(13927) P(13928) 13729 13730 13731 13732 13733 13734 13735 13736 13737 13738 13739 13740 13741 13742 13743 13744 13745 13746 3 M C 2 M C 4 M C MORIBUND SACRIFICED ON DAY 45 OF STUDY 3 M C 4 M C 14 M NC 2 M C 4 M C 3 M C 2 M C 2 M C 5 M C 1 M C 1 M C 1 M C 2 M C 6 M C NP(13929) P(13930) P(13931) P(13932) P(13933) P(13934) P_13935) P(13936} P(13937) P(13938) P(13939) P(13940) P(13941) P(13942) P(13943) P(13944) P(13945) 13747 4 M C P(13946) > 13748 1 M C P(13947) _ 13749 4 M C P(13948) 13750 3 M C 'P(13949) .................................................................................................................................... _#_ = MATED ( ) = FEMALE RAT NUMBER 4_ - CONFIRMED NC _ NOT CONFIRMED O0 s PREGNANT NP = NOT PREGNANT a. Result of first cohabitation period. b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION TABLE BIT (PAGE i): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... I 0 13601 DS 106 105 ALL TISSUES 13602 DS 106 105 ALL TISSUES 13603 DS 106 105 ALL TISSUES 13604 DS 106 105 ALL TISSUES 13605 DS 106 105 ALL TISSUES 13606 DS 106 105 ALL TISSUES 13607 13608 13609 13610 DS 107 106 DS 107 106 DS 107 106 DS 107 106 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES 13611 DS 107 106 ALL TISSUES 13612 13613 DS 107 106 DS 108 107 ALL TISSUES ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. _-) 13614 DS 108 107 LUNGS: ALL LOBES, NUMEROUS DARK RED AREAS (PINPOINT TO 2.0 CM X 2.0 CM). ALL OTHER TISSUES APPEARED NORMAL. 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 DS 108 107 DS 108 107 DS 108 107 DS 108 107 DS 109 108 DS 109 108 DS 109 108 DS 109 108 DS 109 108 DS 109 108 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13625 13626 13627 13628 13629 13630 ............................................................................. DS = DAY OF STUDY DS 110 DS Ii0 DS ii0 DS 110 DS ii0 DS ii0 109 109 109 109 109 109 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. ALL TISSUES APPEARED NORMAL. ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. ALL TISSUES APPEARED NORMAL. ....................................................... _'_ [29 OO a. Refer to the individual clinical observations table (Table BI2) for external observations confirmed at necropsy. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B17 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE ...... .............................................................................................................................. DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... II 1 13631 DS 106 105 ALL TISSUES 13632 DS 106 105 ALL TISSUES 13633 DS 106 105 ALL TISSUES 13634 DS 106 105 ALL TISSUES 13635 DS 106 105 ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13636 DS 106 105 TESTES: RIGHT, SMALL AND FLACCID. EPIDIDYMIDES: RIGHT, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL. 13637 13638 DS 107 106 DS 107 106 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. _._ 13639 DS 107 106 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. _O ALL OTHER TISSUES APPEARED NORMAL 13640 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 DS 107 106 DS 107 106 DS 107 106 DS 108 107 DS 108 107 DS 108 107 DS 108 107 DS 108 107 DS 108 107 DS 109 108 DS 109 108 DS 109 108 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL 13652 DS 109 108 ALL TISSUES APPEARED NORMAL 13653 DS 109 108 ALL TISSUES APPEARED NORMAL 13654 DS 109 108 ALL TISSUES APPEARED NORMAL. 13655 DS 110 109 ALL TISSUES APPEARED NORMAL 13656 DS 110 109 ALL TISSUES APPEARED NORMAL U9 13657 DS 110 109 ALL TISSUES APPEARED NORMAL _t_ 13658 DS Ii0 109 ALL TISSUES APPEARED NORMAL O_ 13659 DS 110 109 ALL TISSUES APPEARED NORMAL 13660 DS ii0 109 ALL TISSUES APPEARED NORMAL bO .......................................................................................................... .......................... 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 (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE B17 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... III 3 13661 13662 13663 13664 13665 13666 13667 13668 13669 DS 106 105 DS 106 105 DS 106 105 DS 106 105 DS 106 105 DS 106 105 DS 107 106 DS 107 106 DS 107 106 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. PERFLUOROOCTANOATE 13670 DS 107 106 KIDNEYS: RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13671 DS 107 106 ALL TISSUES APPEARED NORMAL. _O t_ 13672 DS 107 106 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13673 DS 108 107 ALL TISSUES APPEARED NORMAL. 13674 DS 108 107 ALL TISSUES APPEARED NORMAL. 13675 DS 108 107 ALL TISSUES APPEARED NORMAL. 13676 DS 108 107 ALL TISSUES APPEARED NORMAL. 13677 DS 108 107 ALL TISSUES APPEARED NORMAL. 13678 DS 108 107 ALL TISSUES APPEARED NORMAL. 13679 DS 109 108 ALL TISSUES APPEARED NORMAL. 13680 DS 109 i08 ALL TISSUES APPEARED NORMAL. 13681 DS 109 108 ALL TISSUES APPEARED NORMAL. 13682 DS 109 108 ALL TISSUES APPEARED NORMAL. 13683 DS 109 108 ALL TISSUES APPEARED NORMAL. 13684 DS 109 108 ALL TISSUES APPEARED NORMAL. 13685 DS 110 109 ALL TISSUES APPEARED NORMAL. 13686 DS 110 109 ALL TISSUES APPEARED NORMS. 13687 DS 110 109 ALL TISSUES APPEARED NORMAL. [/) 13688 DS ii0 109 ALL TISSUES APPEARED NORMAL. _t_ 13689 DS 110 109 ALL TISSUES APPEARED NORMAL. O0 13690 DS 110 109 ALL TISSUES APPEARED NORMAL. tO .................................................................................................................................... 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 (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE BI7 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE DOSAGE DOSAGE GROUP (MG/KG/DAY) RAT NUMBER DAY OF NECROPSY DOSAGES ADMINISTERED OBSERVATIONS a .................................................................................................................................... IV 10 13691 DS 106 105 ALL TISSUES APPEARED NORMAL. 13692 DS 106 105 ALL TISSUES APPEARED NORMAL. 13693 13694 DS 106 105 DS 106 105 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 13695 DS 106 105 ALL TISSUES APPEARED NORMAL. 13696 DS 106 105 ALL TISSUES APPEARED NORMAL. 13697 DS 107 106 ALL TISSUES APPEARED NORMAL. 13698 DS 107 106 ALL TISSUES APPEARED NORMAL. 13699 DS 107 106 ALL TISSUES APPEARED NORMAL. 13700 DS 107 106 ALL TISSUES APPEARED NORMAL. 13701 DS 107 106 ALL TISSUES APPEARED NORMAL. 13702 13703 DS 107 106 DS 108 107 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. _._ 13704 DS 108 107 ALL TISSUES APPEARED NORMAL. 13705 DS 108 107 ALL TISSUES APPEARED NORMAL. 4_ 13706 DS 108 107 TESTES: RIGHT, SMALL AND FLACCID. EPIDIDYMIDES: RIGHT, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL. 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 DS 108 107 DS 108 107 DS 109 108 DS 109 108 DS 109 108 DS 109 108 DS 109 108 DS 109 108 DS 110 109 DS 110 109 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13717 DS 110 109 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. [/_ 4_ 13718 DS 110 109 ALL TISSUES APPEARED NORMAL. O0 13719 13720 DS Ii0 109 DS 110 109 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. .................................................................................................................................... DS = DAY OF STUDY a. Refer to the indivldual clinical observations table (Table B12) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI7 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... V 30 13721 DS 106 105 ALL TISSUES 13722 DS 106 105 ALL TISSUES 13723 DS 106 105 ALL TISSUES 13724 DS 106 105 ALL TISSUES 13725 DS 106 105 ALL TISSUES 13726 DS 106 105 ALL TISSUES 13727 DS 107 106 ALL TISSUES 13728 DS 107 106 ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13729 DS 107 106 KIDNEYS: ALL OTHER RIGHT, TISSUES PELVIS, SLIGHT DILATION. APPEARED NORMAL. (_ 13730 DS 107 106 ALL TISSUES APPEARED NORMAL. 13731 DS 107 106 ALL TISSUES APPEARED NORMAL. _O t21 13732 DS 45 44 MORIBUND SACRIFICED ON DAY 45 OF STUDY. LIVER : ALL LOBES, TAN AND PALE. TESTES : BILATERAL, RED. ALL OTHER TISSUES APPEARED NORMAL. 13733 DS 108 107 EPIDIDYMIDES: LEFT, SMALL AND FLACCID. KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 13734 DS 108 107 ALL TISSUES APPEARED NORMAL. 13735 DS 108 107 ALL TISSUES APPEARED NORMAL. 13736 DS 108 107 ALL TISSUES APPEARED NORMAL. 13737 DS 108 107 ALL TISSUES APPEARED NORMAL. > 13738 DS 108 107 ALL TISSUES APPEARED NORMAL. 13739 DS 109 108 ALL TISSUES APPEARED NOR_L. 13740 DS 109 108 ALL TISSUES APPEARED NORMAL. .................................................................................................................................... U9 DS = DAY OF STUDY 4_ a. Refer to the individual clinical observations table (Table BI2) for external observations confirmed at necropsy. O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY Nt_BER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI7 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... V 30 (Cont.) 13741 DS 109 108 TESTES: BILATERAL, SMALL EPIDIDYMIDES: BILATERAL, ALL OTHER TISSUES APPEARED AND FLACCID. SMALL AND FLACCID. NORMAL. 13742 13743 13744 13745 13746 13747 13748 13749 DS 109 108 DS 109 108 DS 109 108 DS 110 109 DS 110 109 DS Ii0 109 DS 110 109 DS 110 109 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13750 DS ii0 109 TESTES: LEFT, LARGE. ALL OTHER TISSUES APPEARED NORMAL. _% .................................................................................................................................... DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table B12) for external observations confirmed at necropsy. > O OO t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI8 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - p GENERATION MALE RATS BODY WEIGHT - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. WT. REL. % TBW ABS. WT. REL. % TBW ABS. WT. REL. % TBW .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY L. TESTIS MINUS TUNICA ALBUGINEA ABS. WT. REL. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW .................................................................................................................................... 13601 592. 0.6756 0 11 0.2966 0.05 1.5259 0 26 1.2920 0.22 1.3897 0.23 0.9914 0.17 13602 610. 0.6786 0 11 0.3086 0.05 1.6647 0 27 1.5221 0.25 2.2138 0.36 1.2279 0.20 13603 570. 0.7340 0 13 0.3341 0.06 1.7979 0 32 1.6608 0.29 2.2003 0.39 1.3738 0.24 13604 633. 0.7152 0 11 0.3136 0.05 1.9262 0 30 1.7009 0.27 1.6708 0.26 1.1445 0.18 13605 533. 0.7034 0 13 0.3543 0.07 1.8636 0 35 1.7079 0.32 2.1486 0.40 1.1320 0.21 13606 653. 0.7420 0 11 0.3611 0.06 1.8832 0 29 1.7583 0.27 1.7423a 0.27a 1.2432 0.19 13607 13608 543. 567. 0.6822 0.7947 0 12 0 14 0.3203 0.3453 0.06 0.06 1.8506 1.8574 0 34 0 33 1.7435 1.7354 0.32 0.31 2.1930 2.1517 0.40 0.38 1.0702 1.2132 0.20 0.21 13609 609. 0.5497 0 09 0.2145 0.04 1.6417 0 27 1.4397 0.24 2.6536 0.44 1.4047 0.23 13610 13611 569. 634. 0.6732 0.6526 0 12 0 i0 0.2883 0.3271 0.05 0.05 1.5787 1.7823 0 28 0 28 1.4846 1.6617 0.26 0.26 2.7678 2.1404 0.49 0 34 1.3165 1.1786 0.23 0.18 13612 13613 557. 559. 0.6830 0.6764 0 12 0 12 0.2887 0.3010 0.05 0.05 1.7653 1.7861 0 32 0 32 1.6275 1.6113 0.29 0.29 2.4939 1.9469 0.45 0.35 1.3161 1.3192 0.24 0.24 13614 536. 0.6695 0 12 0.2733 0.05 1.5910 0 30 1.4794 0.28 2.2970 0.43 1.0604 0.20 13615 586. 0.7240 0 12 0.3652 0.06 1.9534 0 33 1.8326 0.31 2.5074 0.43 1.4403 0.24 13616 13617 639. 513. 0.7570 0.7783 0 12 0 15 0.3567 0.3479 0.06 0.07 1.9754 1.7610 0 31 0 34 1.8243 1.6507 0.28 0.32 2.5305 2.1888 0.40 0.43 1.3395 1.2973 0.21 0.25 13618 556. 0.7269 0 13 0.3458 0.06 1.8719 0 34 1.7273 0.31 2.3224 0.42 1.3218 0.24 13619 571. 0.7967 0 14 0.3973 0.07 1.9766 0 35 1.8446 0.32 2.6549 0.46 1.5503 0.27 13620 566. 0.7542 0 13 0 3459 0.06 1.8314 0 32 1.7046 0.30 2.1074 0.37 1.0458 0.18 13621 527. 0.6623 0 12 0 3287 0.06 1.6391 0 31 1.5212 0.29 2.4345 0.46 1.3000 0.25 13622 559. 0.7321 0 13 0 3161 0.06 1.7766 0 32 1.6795 0.30 2.2753 0.41 1.2186 0.22 13623 588. 0.7364 0 12 0 3896 0.07 1.6860 0 29 1.5789 0.27 2.0262 0.34 1.1769 0.20 13624 527. 0.7481 0 14 0 3361 0.06 1.8174 0 34 1.6876 0.32 1.8379 0.35 0.9276 0.18 13625 578. 0.7424 0 13 0 2999 0.05 1.7695 0.31 1.6738 0.29 2.9931 0.52 1.3586 0.24 > 13626 656. 0.8408 0 13 0 3786 0.06 1.9527 0.30 1.8342 0.28 2.6403 0.40 1.4879 0.23 13627 13628 568. 635. 0.7204 0.7515 0 13 0 12 0 3192 0 3760 0.06 0.06 1.6706 1.8851 0.29 0.30 1.5585 1.7864 0.27 0.28 2.4498 2.6437 0.43 0.42 1.3752 1.5575 0.24 0.24 13629 558. 0.6810 0 12 0 3307 0.06 1.6630 0.30 1.5519 0.28 2.3510 0.42 1.3665 0.24 _a_ 13630 628. 0.8494 0 14 0 3993 0.06 2.1140 0.34 1.9567 0.31 2.0128 0.32 1.3021 0.21 4_ .................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses, bo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT TERMINAL BODY RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13601 13602 13603 13604 13605 13606 592. 610. 570. 633. 533. 653. 0.6727 0.6538 0.7422 0.7242 0.7013 0.7714 0.ii 0.II 0.13 0.ii 0.13 0.12 1.5705 1.5701 1.8434 1.8830 1.8294 1.9176 0.26 0.26 0.32 0.30 0.34 0.29 0.9769 1.0477 1.1461 1.2982 0.8545 1.2630 0.16 0.17 0.20 0.20 0.16 0.19 PITUITARY ABS. WT. REL. % TBW a BRAIN ARS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 0.016 0.014 0.012 0.016 0.014 0.009 2.70 2.30 2.10 2.53 2.63 1.38 2.36 2.38 2.19 2.40 2.22 2.24 0.40 0.39 0.38 0.38 0.42 0.34 23.61 22.78 18.43 20.30 15.86 22.82 3.99 3.73 3.23 3.21 2.98 3.49 13607 13608 543. 567. 0.6884 0.7813 0.13 0.14 1.8831 1.9010 0.35 0.34 1.4560 1.3797 0.27 0.24 0.014 0 015 2.58 2.64 2.35 2 33 0.43 0.41 18.53 19.26 3.41 3.40 13609 13610 609. 569. 0.6624 0.6645 0.Ii 0.12 2.3432 1.5825 0.38 0.28 1.2521 1.1033 0.20 0.19 0 029 0 017 4.76 2.99 2 Ii 1 86 0.35 0.33 23.25 22.41 3.82 3.94 13611 634. 0.6452 0.i0 1.8363 0.29 1.1326 0.18 0 018 2.84 2 32 0.36 22.68 3.58 13612 557. 0.7042 0.13 1.8260 0.33 1.0173 0.18 0 012 2.15 2 ii 0.38 17.03 3.06 13613 559. 0.6920 0.12 1.8150 0.32 1.2060 0.22 0 013 2.32 2 51 0.45 21.60 3.86 13614 536. 0.6590 0.12 1.5240 0.28 1.2564 0.23 0 016 2.98 2 19 0.41 20.68 3.86 13615 586. 0.7307 0.12 1.9427 0.33 1.0383 0.18 0 012 2.05 2 25 0.38 20.97 3.58 13616 639. 0.7448 0.12 1.9684 0.31 0.9796 0.15 0.015 2.35 2 52 0.39 25.02 3.92 13617 513. 0.8023 0.16 1.7778 0.35 1.0554 0.20 0.013 2.53 2 52 0.49 16.93 3.30 13618 556. 0.6947 0.12 1.7963 0.32 1.0403 0.19 0.008 1.44 2 27 0,41 19.31 3.47 13619 571. 0.8216 0.14 2.0150 0.35 1.1757 0.20 0.016 2.80 2.33 0.41 21.32 3.73 13620 566. 0.6324 0.11 1.7662 0.31 1.3352 0.24 0.014 2.47 2.21 0.39 20.80 3.67 13621 527. 0.6737 0.13 1.7174 0.32 1.1837 0.22 0.012 2.28 2.15 0.41 16.17 3.07 13622 559. 0.6907 0.12 1.6943 0.30 1.2359 0.22 0.009 1.61 2.22 0.40 18.88 3.38 13623 588. 0.7404 0.12 1 7379 0.30 1.2678 0.22 0.015 2.55 2.45 0.42 19,31 3.28 13624 527. 0.7047 0.13 1 8086 0.34 0.9132 0.17 0.011 2.09 1.83 0.35 18.10 3.43 13625 578 0.7624 0.13 1 7619 0.30 1.1731 0.20 0.014 2.42 2.25b 0.39 19.76 3.42 13626 656 0.8685 0.13 1 9505 0.30 1.6005 0.24 0.018 2.74 2.33 0.36 24.67 3.76 13627 568 0.7318 0.13 1 6434 0.29 1.1031 0.19 0.011 1.94 2.17. 0.38 17.86 3.14 13628 635 0.7165 0.11 1 8347 0.29 0.8151 0.13 0.012 1.89 2.10 0.33 22.09 3.48 13629 558 0.6744 0.12 1.6857 0.30 1.0534 0.19 0.011 1.97 2.10 0.38 18.41 3.30 [/_ 13630 628 0.8078 0.13 2.0934 0.33 0.7730 0.12 0.014 2.23 2.43 0.39 20.24 3.22 _t_ .................................................................................................................................... O_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. a. Value was multiplied by 1O00 I_ b. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... KIDNEY KIDNEY ADRENAL RAT TERMINAL BODY LEFT RIGHT LEFT NUMBER WEIGHT ABS. REL. ABS. RELo ABS. REL. WT. % TBW WT. % TBW WT. % TBW a .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13601 13602 13603 13604 13605 13606 592. 610 570 633 533 653 2.17 2.55 1.90 2.33 2.26 2.25 0.37 0.42 0.33 0.37 0.42 0.34 2.19 2.55 1.96 2.28 2.25 2.39 0.37 0.42 0.34 0.36 0.42 0.37 0.030 0.032 0.031 0.026 0.029 0.044 5.07 5.24 5.44 4.11 5.44 6.74 ADRENAL RIGHT ABS. REL. WT. % TBW a 0.031 0.035 0.026 0.033 0.028 0.039 5.24 5.74 4.56 5.21 5.25 5.97 SPLEEN ABS. WT. REL. % TBW 0.75 0.96 0.69 1.11 1.00 1.20 0.13 0.16 0.12 0.18 0.19 0.18 THYMUS ABS. WT. REL. % TBW 0.38 0.63 0.38 0.69 0.45 0.55 0.06 0.10 0.07 0.11 0.08 0.08 13607 543 13608 567 2.17 2.12 0.40 0.37 2.14 2.15 0.39 0.38 0.046 0.031 8.47 5.47 0.021 0.033 3.87 5.82 0.83 0.90 0.15 0.16 0.41 0.52 0.08 0.09 13609 13610 609 569. 2.33 2.31 0.38 0.40 2.43 2.29 0.40 0.40 0.031 0.028 5.09 4.92 0.029 0 028 4.76 4.92 1.04 0 76 0.17 0.13 0.42 0.32 0.07 0.06 13GII 634. 2.47 0.39 2.38 0.38 0.035 5.52 0 038 5.99 0 94 0.15 0.29 0.04 13612 557. 2.18 0.39 2.21 0.40 0.033 5.92 0 032 5.74 0 79 0.14 0.34 0 06 13613 13614 559. 536. 2.50 2.53 0.45 0.47 2.32 2.31 0.42 0.43 0.029 0.028 5.19 5.22 0 033 0 027 5.90 5.04 0 98 0 98 0.18 0.18 0.49 0.49 0 09 0 09 13615 586. 1.85 0.32 2.03 0.35 0.035 5.97 0 039 6.66 1 01 0.17 0.40 0 07 13616 639. 2.58 0.40 2.61 0.41 0.042 6.57 0.035 5.48 1 26 0.20 0.41 0 06 13617 513. 1.92 0.37 2.05 0.40 0.032 6.24 0.031 6.04 1 12 0.22 0.50 0 10 13618 556. 1.99 0.36 1.89 0.34 0.032 5.76 0.036 6.47 0 80 0.14 0.32 0 06 13619 571. 2.09 0.37 2.03 0.36 0.035 6.13 0.033 5.78 0 93 0.16 0.39 0.07 13620 566. 2.02 0.36 1.99 0.35 0.028 4 95 0.029 5.12 1.32 0.23 0.52 0.09 13621 527. 2.15 0.41 2.12 0.40 0.027 5 12 0.023 4.36 0.85 0.16 0.40 0.08 13622 559. 2.30 0.41 2.20 0.39 0.035 6 26 0.045 8 05 0.68 0 12 0.44 0.08 13623 588. 2.10 0.36 2.30 0.39 0.033 5 61 0.031 5 27 0.80 0 14 0.33 0.06 13624 527. 2.11 0.40 2.15 0.41 0.027 5 12 0.022 4 17 0.87 0 16 0.57 0.11 13625 578. 1.99 0.34 2.09 0.36 0.027 4 67 0.027 4 67 0.87 0 15 0.31 0.05 13626 656. 2.28 0.35 2.34 0.36 0.034 5 18 0.036 5 49 0.96 0 15 0.49 0.07 13627 568. 2.09 0.37 2.05 0.36 0.032 5 63 0.036 6 34 0.94- 0 16 0.42 0.07 13628 635. 2.08 0.33 2.01 0.32 0.035 5.51 0.031 4 88 1.07 0 17 0.50 0.08 13629 558. 2.03 0.36 1.99 0.36 0.029 5.20 0.033 5 91 0.68 0 12 0.26 0.05 0') 13630 628. 2.07 0.33 2.03 0.32 0.032 5.10 0.028 4 46 0.97 0 15 0.46 0.07 _t_ .................................................................................................................................... OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by I000 _CoD PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 4}: TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. .................................................................................................................................... % TBW DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 13631 13632 13633 13634 13635 13636 13637 548. 558. 502. 607. 526 587 645 0.6495 0.7034 0.7044 0.7068 0.6053 0.7697 0.7061 0.12 0.13 0.14 0.12 0.12 0.13 0.ii 0 2998 0 3166 0 3546 0 3369 0 2813 0 3525 0 3434 0.05 0.06 0.07 0,06 0.05 0.06 0.05 1.6770 1.9768 1.7819 1.8226 1.6595 1.8739 1 6545 0.31 0,35 0.35 0.30 0.32 0.32 0.26 1.5445 1.8290 1.6458 1.6586 1.5483 1.6712 1.5240 0.28 0.33 0.33 0.27 0,29 0.28 0.24 2.4075 2.8763 3.2227 1.6848 1.4917 2.3337 2.5335 0.44 0.52 0.64 0.28 0.28 0,40 0.39 1.5081 1.4047 1.5709 1.1637 0.8167 1.2939 1.3047 0.28 0.25 0.31 0.19 0.16 0.22 0.20 13638 624 13639 579 13640 623 13641 548 13642 572 13643 603 13644 592 13645 567 13646 549 13647 577 13648 623 13649 528 13650 584 13651 597 13652 569 13653 520 13654 589 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 0.10 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 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 0.04 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 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 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 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 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 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 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 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 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 13655 647 13656 517 0 8054 0 7198 0.12 0.14 0.3335 0,3468 0.05 0.07 2 1552 1 7050 0.33 0.33 1.9836 1.6041 0.31 0.31 2.8403 2.2805 0.44 0.44 1.4880 1,2083 0.23 0.23 13657 475 0 6277 0.13 0.3055 0.06 1 7519 0.37 1.6518 0.35 2.1178 0.44 1.0602 0.22 13658 576 0 6425 0.ii 0.2637 0.04 1.5617 0.27 1.4618 0.25 2.1529 0.37 1.1517 0.20 13659 531 0 7407 0.14 0.3172 0.06 1.9318 0.36 1.8052 0.34 2,1495 0.40 1.2183 0.23 [29 "13660 697 0 7581 0.11 0.3225 0.05 1.6871 0.24 1.5755 0.23 2.2241 0.32 1,2827 0.18 .................................................................................................................................... _-_ OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. _D tO O PROTOCOL 418"020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 5): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - P GENERATION MALE RATS BODY WEIGHT - .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 13632 13633 13634 13635 13636 548. 558. 502. 607. 526. 587. 0.6184 0.7187 0.7346 0.7092 0.6527 0.3677b 0 Ii 0 13 0 15 0 12 0 12 0 06 1.6665 2.0272 1.8301 1.8432 1.7937 0 8983b 0.30 0.36 0.36 0.30 0.34 0.15 1.2524 1.3965 1.1854 0.9863 1.1001 1.2274 0.23 0.25 0.24 0 16 0 21 0 21 PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 0.016 0.015 0.020 0.015 0.010 0.012 2.92 2.69 3.98 2.47 1.90 2.04 2.22 2.34 2.43 2.13 2.07 2.17 0.40 0.42 0.48 0.35 0 39 0 37 23.73 26.29 20.13 24.69 23.30 27.55 4.33 4.71 4.01 4.07 4.43 4.69 13637 645. 0.7132 0 11 1 6779 0.26 1.1159 0 17 0.016 2.48 2.26 0 35 25.31 3.92 13638 13639 13640 624. 579. 623. 0.6219 0.6966 0.6905 0.I0 0.12 0.ii 1 9129 2 0712 1 9493 0.31 0.36 0.31 1.3568 1.0950 0.9987 0 22 0 19 0.16 0.017 0.008 0.017 2.72 1.38 2.73 2.43 2.42 2.20 0 39 0 42 0 35 26.08 26.73 32.23 4.18 4.62 5.17 13641 548 0.7322 0.13 1 8401 0.34 0.9751 0.18 0.015 2.74 2.26 0.41 25.22 4.60 13642 572 0.7423 0.13 1 7467 0.30 1.2793 0.22 0.012 2.10 2.34 0.41 19.48 3.40 13643 603 0.7523 0.12 2 5181 0.42 1.1153 0.18 0.016 2.65 2.21 0.37 25.04 4.15 13644 592 0 7081 0.12 1 8376 0.31 1.1768 0.20 0.009 1.52 2.44 0.41 24.65 4.16 13645 567 0 6380 0.ii 1.5823 0.28 1.0379 0.18 0.019 3.35 2.25 0.40 23.13 4.08 13646 549 0 6909 0.12 1.7069 0.31 1.4184 0.26 0.012 2.18 2.31 0.42 22.38 4.08 13647 577 0 6756 0.12 2.6503 0.46 0.6843 0.12 0.013 2.25 2.25 0.39 25 86 4.48 13648 623 0 6579 0.10 1.9075 0.31 1.0489 0.17 0.011 1.76 2 33 0.37 22 58 3.62 13649 528 0 6966 0.13 1.6978 0.32 1.4685 0.28 0.015 2.84 2 35 0.44 29 17 5.52 13650 584 0.7426 0.13 2.0238 0.35 1.1363 0.19 0.012 2.05 2 32 0.40 22 99 3.94 13651 597. 0.7281 0.12 1.9809 0.33 0.8039 0.13 0.013 2.18 2 38 0.40 22 73 3.81 13652 569. 0.7464 0.13 1.8349 0.32 0.9861 0.17 0.016 2.81 2 26 0.40 22 86 4.02 13653 520. 0.6316 0.12 1.7942 0 34 1.1095 0.21 0.010 1.92 2 37 0.46 17 07 3.28 13654 589. 0.6388 0.11 1.5501 0 26 1.2735 0.22 0.015 2.55 2 23 0.38 26 32 4.47 13655 13656 647. 517. 0.7879 0.7250 0.12 0.14 2.1403 1.7659 0 33 0 34 0.9730 1.6851 0.15 0.32 0.014 0.014 2.16 2.71 2.33 2.31 0.36 0.45 29.05 19.16 4.49 3.70 13657 475. 0.6460 0.14 1.7433 0 37 1.1798 0.25 0.013 2.74 2.10- 0.44 23.90 5.03 13658 576. 0.6287 0.ii 1.5591 0 27 0.8826 0.15 0.016 2.48 2.31 0.40 22.05 3.83 13659 531. 0.7940 0.15 2.0007 0 38 1.1305 0.21 0.013 2.45 2.17c 0.41 21.10 3.97 [29 13660 697. 0.7865 0.Ii 1.6440 0.24 1.1982 0.17 0.014 2.01 2.28 0.33 27.36 3.92 4_ .................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by I000. _ Rat 13636 had a small and flaccid right epidldymis and right testis. See the individual necropsy observations table (Table BI6). Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT S PLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. % TBW a WT. % TBW a WT. .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY REL. % TBW ABS. WT. REL. % TBW .................................................................................................................................... 13631 13632 13633 13634 13635 13636 13637 548. 558 502 607 526 587 645 2.49 2.97 2.67 2.79 2.32 2,73 2.29 0.45 0.53 0.53 0.46 0.44 0.46 0.36 2.48 2.84 2.62 3.00 2.15 2.97 2.36 0.45 0.51 0.52 0.49 0.41 0.50 0.36 0.034 0 038 0 032 0 037 0 028 0 029 0 036 6.20 6.81 6.37 6.10 5.32 4.94 5.58 0.034 0.038 0.031 0.036 0.028 0.030 0.037 6.20 6.81 6.18 5.93 5.32 5.11 5.74 0.95 0.92 0.68 1.06 0.70 0.94 1.05 0.17 0.16 0.14 0.17 0.13 0.16 0.16 0.39 0.38 0.26 0.50 0.41 0.52 0.47 0.07 0.07 0.05 0.08 0.08 0.09 0.07 13638 624 13639 579 13640 623 13641 548 13642 572 13643 603 13644 592 13645 567 13646 549 13647 577 13648 623 13649 528 13650 584 13651 597 13652 569 13653 520 13654 589 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 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 2.85 2.44b 2.79 2 57 2.15 2.68 2.71 2.77 2.67 2.70 2.56 2.72 2.36 2.80 2.35 2.30 2.20 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 0 027 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 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 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 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 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 0.16 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 0.42 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 0.07 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 13655 647 2 87 0.44 3.18 0.49 0 027 4.17 0.024 3.71 0.88 0.14 0.36 0.06 13656 517 1 89 0.36 1.92 0.37 0 029 5.61 0.025 4.84 0.72 0.14 0.32 0.06 13657 475 2 20 0.46 2.17 0.46 0 029 6.10 0.032 6.74 0.86. 0.18 0.31 0.06 13658 576. 2 20 0.38 2.32 0.40 0 036 6.25 0.027 4.69 0.70 0.12 0.43 0.07 13659 531. 2 ii 0.40 2.10 0.40 0 030 5.65 0.029 5.46 0.87 0.16 0,31 0.06 [2_ 13660 697. 2 67 0.38 2.63 0.38 0 031 4.45 0.030 4.30 1.01 0.14 0.51 0.07 _t_ ................................................................................................................................... - O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by I000. _o Rat 13639 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table BI6). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LIttlER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 7): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW .................................................................................................................................... 13661 13662 13663 13664 13665 13666 13667 585. 539. 567. 511. 511. 481. 550. 0.6912 0.6733 0.7359 0.6819 0.6495 0.6823 0.6787 0.12 0.12 0.13 0.13 0.13 0.14 0.12 0.3254 0.3247 0.3684 0.3250 0.3010 0.2923 0.3297 0 06 0 06 0 06 0 06 0 06 0 06 0 06 1.9614 1.7494 1.8987 1.8210 1.7079 1.8632 1.6308 0.34 0.32 0.33 0.36 0.33 0.39 0.30 1.7444 1.6186 1.7604 1.7070 1.5898 1.7270 1.5095 0.30 0.30 0.31 0.33 0.31 0.36 0.27 2.8329 1.7487 2.1959 2.3292 2.2164 2.1344 2.1297 0.48 0.32 0.39 0.46 0.43 0.44 0.39 1.4299 0.9591 1.1255 1.2339 1.0909 1.0447 1.2414 0 24 0 18 0 20 0 24 0 21 0 22 0 22 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 453. 502. 555. 536. 504. 569. 498. 563. 475. 535. 628. 555. 536. 519. 596. 588. 536. 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 0.13 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 0.2440 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 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 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 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 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 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 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 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 1.0709 1.4370 1.4905 1.3067 1.2914 1.2487 1 3208 1 1959 1 3884 1 2994 1 0874 1 5101 1 2158 1 1777 1 3425 1 3745 1 2772 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 13685 492. 0.6832 0.14 13686 508. 0.6252 0.12 13687 528. 0.6735 0.13 13688 582. 0.7943 0.14 13689 572. 0.6982 0.12 13690 676. 0.6794 0.i0 ............................................................................... 0.3172 0.2874 0.3194 0.3601 0.3340 0.3048 0.06 0.06 0.06 0.06 0.06 0.04 1.8082 1.7667 1.5957 2.0392 1.7096 1.7594 0.37 0.35 0.30 0.35 0.30 0.26 1.6956 1.6740 1.4880 1.9123 1.5964 1.6408 0.34 0.33 0.28 0.33 0.28 0.24 2 6755 2 0154 2 9111 2 2724 2.4406 2.4640 0.54 0.40 0.55 0.39 0.43 0.36 ..................................................... 1 5985 1 1092 1 6056 1 2595 1 2353 1 3996 0 32 0 22 0 30 0 22 0 22 0 21 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. _'_ [/) _t_ _-_ O_ O PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.61 REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 8): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... RAT NUMBER TERMINAL BODY WEIGHT EPIDIDYMIS RIGHT ABS. REL. TESTIS RIGHT ABS. REL. PROSTATE ABS. REL. WT. % TBW WT. % TBW WT. .................................................................................................................................... % TBW DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13661 13662 13663 13664 13665 13666 585. 539. 567. 511. 511. 481. 0.6942 0.6884 0.7462 0.6483 0.6558 0.7041 0.12 0.13 0.13 0.13 0.13 0.15 1.9170 1.7684 1.9026 1.7742 1.7255 1.9202 0.33 0.33 0.34 0.35 0.34 0.40 1.1744 1.0222 0.9513 1.0531 1.0904 1.2313 0.20 0.19 0.17 0.21 0 21 0 26 PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. __. REL. % TBW LIVER ABS. WT. REL. % TBW 0.014 0.018 0.008 0.013 0.013 0.010 2.39 3.34 1.41 2.54 2.54 2.08 2 24 2 11 2 32 2 39 2 40 2 00 0.38 0.39 0.41 0.47 0.47 0.42 28.39 28.59 26.16 28.39 28.78 24.12 4 85 5 30 4 61 5 56 5 63 5 01 13667 550. 0.6941 0.13 1.6840 0.31 1.1857 0 22 0.012 2.18 2.23 0.40 31.05 5 64 1133666689 455032.. 00..57649854 00..1125 11..68578805 00..3377 01..83638178 00 1296 00..000193 12..9599 22..1334 00..4477 2259..2617 55.9516 13670 555. 0.7844 0.14 1.8798 0.34 1.3966 0 25 0.014 2.52 2.12 0.38 27.92 5.03 13671 536. 0.6884 0.13 1.7400 0.32 1.0287 0 19 0.011 2.05 2.36 0.44 24.03 4.48 13672 504. 0.6282 0 12 1.7492 0.35 1.1247 0 22 0.011 2.18 2.22 0.44 26.01 5.16 13673 569. 0.6464 0 11 1.6550 0.29 0.9881 0 17 0.003 0.53 2.07 0.36 28.10 4.94 13674 498. 0.6375 0 13 1.7158 0.34 1.1467 0 23 0.010 2.01 2.36 0.47 24.17 4.85 13675 563. 0.6921 0 12 1.5912 0.28 0.9485 0 17 0.014 2.49 2.22 0.39 28.39 5.04 13676 475 0.6965 0 15 1.9457 0.41 0.9484 0 20 0.010 2.10 2.14 0.45 22.77 4.79 13677 535 0.6481 0 12 1.7060 0.32 1.4671 0 27 0.013 2.43 2.31 0.43 27.65 5.17 13678 628 0.6848 0 11 1.7331 0.28 1.2232 0 19 0.011 1.75 2.35 0.37 26.48 4.22 13679 555 0.7450 0.13 1.7974 0.32 1.4973 0.27 0.011 1.98 2.41 0.43 27.01 4.87 13680 536 0.6700 0.12 1.9337 0.36 0.8157 0.15 0.016 2.98 2.29 0.43 29.45 5.49 13681 519 0.7726 0.15 2.0453 0.39 0.9378 0.18 0.010 1.93 2.42 0.47 29 31 5.65 13682 596 0.7609 0.13 2.0193 0.34 1.1773 0.20 0.012 2.01 2.45 0.41 29 50 4.95 13683 588 0.7217 0.12 1.6827 0.29 1.2601 0.21 0.013 2.21 2.19 0.37 28 45 4.84 13684 536 0 7096 0.13 1.7016 0.32 1.1324 0.21 0.009 1.68 2.20 0.41 22 94 4.28 13685 492 0 6926 0.14 1.8110 0.37 1.1725 0.24 0.014 2.84 2 12 0.43 26 28 5.34 _> 13686 508 0 6045 0.12 1.7715 0.35 1.0562 0.21 0.017 3.35 2 30 0.45 28 94 5.70 13687 528. 0 7076 0.13 1.5732 0.30 1.0888 0.21 0.013 2.46 2 34. 0.44 29 66 5.62 13688 582. 0 7951 0.14 2.0475 0.35 0.9953 0.17 0.014 2.4'0 2 08 0.36 25 96 4.46 13689 572. 0 6814 0.12 1.6739 0.29 1.2406 0.22 0.012 2.10 2 27 0.40 34 16 5.97 C/_ 13690 676. 0 6736 0.I0 1.7440 0.26 0.9884 0.15 0.016 2.37 2 28 0.34 33.85b 5.01 J_ .................................................................................................................................... OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. Io Damaged during processing (weight not affected). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI8 (PAGE 9): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - P GENERATION MALE RATS BODY WEIGHT - ...... .............................................................................................................................. RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY REL. % TBW a ABS, WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. REL. % TBW .................................................................................................................................... 13661 13662 13663 13664 13665 13666 13667 585. 539. 567. 511. 511. 481. 550. 2.49 2.50 2.20 2,26 2,36 2.29 2.43 0.42 0.46 0.39 0.44 0.46 0.48 0.44 2.45 2.45 2.34 2.24 2.50 2.41 2.48 0.42 0.45 0.41 0.44 0.49 0.50 0.45 0.038 0.040 0.031 0.033 0.042 0.027 0.026 6.50 7.42 5.47 6.46 8.22 5.61 4.73 0.044 0.046 0.034 0.032 0.044 0.026 0.021 7.52 8.53 6.00 6.26 8.61 5.40 3 82 1.01 0.89 0.82 0.86 0.74 1.11 0.90 0 17 0 16 0 14 0 17 0 14 0 23 0 16 0.34 0.52 0.45 0.49 0.39 0.44 0.50 0.06 0.i0 0.08 0.10 0.08 0.09 0.09 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 453. 502. 555. 536. 504. 569. 498. 563. 475. 535. 628. 555. 536. 519. 596. 588. 536. 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 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 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 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 0.026 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 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 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 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 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 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 0.25 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 0.06 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 13685 492. 2.65 0 54 2 58 0.52 0.021 4.27 0.019 3 86 0.82 0 17 0.24 0.05 > 13686 508. 2,76 0 54 2 75 0.54 0.030 5.90 0.026 5 12 0.77 0 15 0.29 0.06 13687 528. 2.45 0 46 2 43 0.46 0.029 5.49 0.025 4 73 0.91 . 0 17 0.27 0.05 13688 582. 2,75 0 47 2 55 0.44 0.031 5.33 0.031 5 35 1.02 0 18 0.49 0.08 13689 572. 2.88 0 50 2 82 0.49 0.029 5.07 0,022 3 85 1.07 0 19 0.39 0.07 13690 676. 3.19 0 47 3 03 0.45 0.044 6.51 0.043 6 36 0.96 0 14 0.43 0.06 4_ .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100, a. Value was multiplied by 1000. tO b. Rat 13670 had moderate dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). CD c. Rat 13672 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16) , PROTOCOL 418-020: ORAL (GARAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI8 (PAGE 10) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... L. TESTIS MINDS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... 13691 13692 13693 13694 13695 13696 528. 450. 570 571 506 553 0 6510 0 7089 0 6386 0 7488 0 6307 0 6652 0.12 0,16 0.ii 0.13 0.12 0.12 0.2903 0,3304 0.2740 0.3793 0.2689 0.3142 0.05 0.07 0.05 0.07 0.05 0.06 1 7748 1 8786 1 8515 1 6795 1 6411 1 9205 0.34 0.42 0.32 0.29 0.32 0.35 1.6126 1.7780 1.7107 1.5725 1.5376 1.7789 0.30 0.40 0.30 0.28 0.30 0.32 1.8099 2.3515 1,7267a 2.4684 1.9912 2.0129 0.34 0.52 0.30a 0.43 0.39 0.36 1.1447 1.0306 1.0523 1.5301 1.2054 1.1453 0.22 0.23 0.18 0.27 0.24 0.21 13697 480 0 7278 0.15 0.3255 0.07 1 8740 0.39 1 7521 0.36 2.2800 0.48 1.2851 0.27 13698 13699 13700 13701 533 466 535 490. 0 7380 0.6450 0.7382 0.6860 0.14 0.14 0.14 0.14 0.3381 0.2780 0.3455 0.2982 0.06 0.06 0.06 0.06 2 0329 1.7274 1.8932 1.7259 0.38 0.37 0.35 0.35 1 )220 1 5993 1 7207 1 5848 0.36 0.34 0.32 0.32 2.6892 2.2776 2.4079 1.9875 0.50 0.49 0.45 0,40 1 3437 1 2605 1 2589 1 0487 0.25 0 27 0 24 0 21 13702 498. 0.7634 0.15 0.3364 0.07 1.8769 0.38 1 7673 0.35 2.3722 0.48 1 3402 0 27 13703 501. 0.7196 0.14 0.3232 0.06 1.7387 0.35 1 6197 0.32 2,4935 0.50 1 5376 0 31 13704 624. 0.7761 0.12 0.3537 0 06 1.8951 0.30 i 7609 0.28 2.3446 0.38 1.3177 0 21 13705 551. 0.6684 0.12 0.2734 0 05 1.8277 0.33 1 6738 0.30 1,4559b 0.26b 1.0436 0 19 13706 526. 0.7169 0.14 0.3511 0 07 1.8320 0.35 1 7076 0.32 2.3625 0.45 1.3581 0 26 13707 13708 557. 563. 0.7793 0.7390 0 14 0 13 0.3728 0.3343 0 07 0 06 1.6347 1.8899 0.29 0.34 1.5384 1.7878 0.28 0.32 2.7172 2.6176 0.49 0,46 1.4232 1.4343 0 26 0.25 13709 451. 0.6284 0 14 0.2894 0 06 1.6529 0.37 1.5406 0.34 2.5577 0.57 1.4163 0.31 13710 398. 0.6303 0 16 0.2903 0 07 1.8617 0.47 1.7607 0.44 2.1083 0.53 1.0055 0.25 13711 401. 0.6687 0 17 0.3095 0 08 1.6931 0.42 1.5997 0.40 2.1691 0.54 1.1139 0.28 13712 455. 0.6542 0 14 0.2903 0.06 1.8646 0.41 1.7482 0.38 2.0146 0.44 1.0707 0.24 13713 493. 0.6660 0 14 0.3171 0.06 1.7775 0.36 1.6482 0.33 2.1117 0.43 1.1951 0.24 13714 443. 0.7452 0 17 0.3291 0.07 1.8785 0.42 1.7562 0.40 2.7024 0.61 1.3951 0.31 13715 551. 0.6832 0.12 0.2975 0.05 1.7745 0.32 1.6450 0.30 2.2975 0.42 1.1581 0.21 > 13716 528. 0.7514 0.14 0.3387 0.06 2.0020 0.38 1.8087 0.34 2.3873 0.45 1.2017 0.23 13717 489. 0.7523 0.15 0.3543 0.07 1.8418 0.38 1.7492 0.36 2.4171 0.49 1.3391 0.27 _'_ 13718 543. 0.7349 0.14 0.3363 0.06 1.8380 0.34 1.7356 0.3'2 2.3115 0.42 1.2358 0.23 13719 544. 0.7209 0.13 0.3571 0.06 1.8179 0.33 1.6798 0.31 2.7956 0.51 1.5191 0.28 13720 591 0.7415 0.12 0 3476 0.06 1.8847 0.32 1.7681 0 30 2.9170 0 49 1.5807 0.27 "_ .................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00 CD Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses " _O Damaged during processing (weight affected); values excluded from group averages and statistical analyses. PROTOCOL 418-020: oRAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 11) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT TERMINAL BODY RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL, WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP IV I0 MG/KG/DAY .................................................................................................................................... 13691 13692 13693 13694 13695 13696 528. 450. 570. 571. 506. 553. 0.6462 0.6514 0.4308 0.7073 0.6242 0.6590 0 12 0 14 0 08 0 12 0 12 0 12 1.6959 1.8472 1.5803 1.5982 1 5583 1 9059 0.32 0.41 0.28 0,28 0.31 0.34 1.1002 0.6953 0.9426 0.8671 1.1675 1.1603 0 21 0 15 0 16 0 15 0 23 0 21 PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 0.009 0.013 0.014 0.012 0.016 0.019 1.70 2.89 2.46 2.10 3.16 3.44 2.31 2.35 2.09 2.11 2.05 2.25 0.44 0.52 0.37 0.37 0.40 0.41 30.43 27.20 30.49 28.77 30.35 29.83 5.76 6.04 5.35 5.04 6.00 5.39 13697 13698 480. 533. 0.7200 0.7592 0.15 0.14 1 8881 2 0050 0.39 0.38 1.1685 1.2923 0,24 0,24 0.013 0.008 2 71 1 50 2.26 2.35 0.47 0.44 28.85 27.33 6.01 5.13 13699 13700 13701 466. 535. 490. 0.6287 0.7246 0.6728 0.13 0.14 0.14 1 6871 1 9501 1 7611 0.36 0.36 0.36 1.2763 0.8127 0.9267 0.27 0.15 0.19 0.015 0.014 0.017 3 22 2 62 3 47 2.28 2.46 2.26 0.49 0.46 0,46 19.75 31.22 22.78 4.24 5.84 4.65 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 498. 501. 624. 551. 526. 557. 563. 451. 398. 401. 455. 493. 443. 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 0.14 0.14 0.13 0.12 0.06 0.14 0.13 0.14 0.17 0.16 0.14 0.13 0.17 1.8833 1.7711 1.9822 1.8191 0.8699b 1.6624 1.9331 1.6711 1.8448 1.6398 1.8443 1.7083 1.8709 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 0.9056 1.2401 1.4428 1.0972 1.1747 1.2753 0.8310 1.0523 0.7736 0.9264 0.8620 1.1091 1.0910 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 0.012 0.019 0.020 0.010 0.011 0,011 0.015 0.017 0.019 0.012 0.011 0.014 0.011 2 41 3.79 3.20 1.81 2.09 1.97 2.66 3.77 4.77 2.99 2.42 2.84 2.48 2.05 2.37 2.38 2.32 2.45 2.07 2.13 2.33 2 21 2 16 2 34 2 10 2 17 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 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 4.79 6.23 5.82 6.46 5 53 5 28 5 73 5 65 6 ii 5 59 5 44 6 41 5 88 13715 551. 0.6537 0.12 1.7351 0.31 1.2177 0.22 0.015 2.72 2 22 0.40 34.10 6.19 13716 528. 0.7396 0.14 2.0528 0.39 1.0765 0.20 0.013 2.46 2 25 0.43 28.78 5.45 13717 489. 0.7265 0.15 1.7853 0.36 1.0506 0.21 0.018 3,68 2.43 . 0.50 27.61 5,65 13718 543. 0.7409 0.14 1.8402 0.34 0.6135 0.ii 0.018 3.31 2.18 0.40 28,62 5.27 13719 544. 0.7150 0.13 1.7551 0.32 0.7355 0.14 0.013 2.39 2.21 0.41 32.24 5.93 QF) 13720 591. 0.7717 0 13 1.8332 0.31 1.2191 0 21 0.009 1 52 2.15 0.36 31.49 5.33 _t_ . . . w._ .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by i000. lO_ b. Rat 13706 had a small and flaccid right epldldymis and right testis. See the individual necropsy observations table (Table BI6). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 12): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY REL. % TBW a ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. REL. % TBW .................................................................................................................................... 13691 13692 13693 13694 13695 13696 13697 528. 450. 570. 571. 506. 553. 480. 2.23 2.42 2.34 2.75 2.29 2.99 2.16 0.42 0.54 0.41 0.48 0.45 0.54 0.45 2.27 2.31 2.37 3.01 2.34 2.82 2.16 0.43 0.51 0.42 0.53 0.46 0.51 0.45 0.018 0.026 0.036 0.025 0.028 0.035 0.032 3 41 5 78 6 32 4 38 5 53 6 33 6 67 0.043 0.029 0.038 0.037 0.030 0.033 0.033 8 14 6 44 6 67 6 48 5 93 5 97 6 88 1.01 0,83 0.97 0,81 0.79 1,04 0.90 0 19 0 18 0 17 0 14 0 16 0 19 0 19 0.61 0.55 0.77 0.50 0.40 0.54 0.50 0.12 0.12 0.14 0.09 0.08 0.10 0.I0 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 533. 466 535 490 498 501 624 551 526 557 563 451 398 401 455 493 443 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 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 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 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 0.034 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 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 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 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 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 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 0.52 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.i0 0.09 0.08 0.05 0.05 0.06 0.09 0.10 0.07 0.07 0.06 0.06 0.I0 0,12 0.08 0.05 0.04 13715 551 2.39 0.43 2 45 0.44 0.035 6.35 0.033 5.99 0.98 0 18 0.29 0.05 13716 528 2.49 0.47 2 60 0.49 0.028 5.30 0.026 4.92 0.79 0 15 0.24 0.04 13717 489 2.37 0.48 2 38b 0.49 0.030 6.13 0.032 6.53 0.87" 0 18 0.39 0.08 13718 543 2.42 0.44 2 33 0.43 0.037 6.81 0.033 6.08 0.93 0 17 0.25 0.05 13719 544 2.31 0.42 2 42 0.44 0.033 6.07 0.037 6.80 1,10 0 20 0.47 0.09 [J_ 13720 591 2.48 0.42 2 56 0.43 0.022 3.72 0.026 4.40 1,03 0 17 0.23 0.04 4_ ........................................................................................ b-_ ............................................ OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00 a. Value was multiplied by i000. to b. Rat 13717 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table BI6). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI8 (PAGE 13): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY % TBW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW .................................................................................................................................... 13721 511. 0.6074 0 12 0.2790 0.05 1.6557 0.32 13722 452. 0.6274 0 14 0.2822 0.06 2.0342 0.45 13723 321. 0.6173 0 19 0.2866 0.09 1.7454 0.54 13724 378. 0.6288 0 17 0.2856 0.08 1.7350 0.46 13725 361. 0.5636 0 16 0.2434 0.07 1.5799 0.44 13726 465. 0.5924 0 13 0.2529 0.05 1.6603 0.36 13727 443. 0.6562 0.15 0.3344 0.08 1.6767 0.38 13728 418. 0.6189 0.15 0.2708 0.06 1.8145 0.43 13729 13730 439. 522. 0.6563 0.7344 0.15 0.14 0.2832 0.3692 0.06 0.07 1.8213 1.9206 0.41 0.37 _-_ 13731 468. 0.6264 0.13 0.2816 0.06 1.8082 0.39 tk__ 13732a .... 0.32 .... b .... 1.57 .... 13733 554. 0.4488c 0.08 0.2281 0.04 1.5848 0.29 13734 456. 0.6218 0.14 0.3056 0.07 1.7707 0.39 13735 446. 0.6602 0.15 0.2885 0.06 1.6260 .................................................................................................................................... 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 1.1271 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 ALL WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. a. Rat 13732 was moribund sacrificed b. Value was not recorded. on day 45 of study; values excluded REL. from % TBW group = (ORGAN averages WEIGHT/TERMINAL and statistical BODY WEIGHT) analyses. X 100. c. Rat 13733 had a small and flaccid left epididymis observations table (Table B16). and left testis minus tunica albuginea. See the individual necropsy > C O0 b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 14): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NL_WBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % THW WT. % TBW .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13736 13737 13738 13739 13740 13741 13742 13743 398, 385 475 374 497 358 345 401 0.6673 0.6265 0.7368 0.6346 0.6890 0.4128a 0.6057 0,6398 0.17 0.16 0.16 0.17 0.14 0,12 0.18 0.16 0.3010 0.2859 0,3496 0.2936 0.3195 0.1813a 0.2949 0.3157 0.08 0.07 0.07 0.08 0.06 0.05 0.08 0.08 1 8057 1 8269 1 8806 1 7360 1 8928 0 9095a 1.5689 1.7613 0.45 0.47 0.40 0.46 0.38 0.25 0.45 0.44 L. TESTIS MINUS TUNICAALBUGINEA ABS. REL. WT. % TBW 1.6957 1.7194 1,7560 1.6485 1.7714 0.7763a 1.4689 1.6391 0.43 0.45 0.37 0.44 0.36 0.22 0.42 0.41 SEMINAL WITH ABS, WT. VESICLES FLUID REL. % TBW 2.2496 1.7412 2,2771 2.1199 1.9407 1.5799 2.0911 2.2751 0,56 0.45 0.48 0.57 0.39 0,44 0.61 0.57 SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 1.2149 1.1388 1.1760 1.1596 1.0294 1.0094 1.1513 1.1189 0.30 0.30 0.25 0.31 0.21 0.28 0.33 0.28 1133774445 13746 349143 438. 00,.65391781 0.6928 00..1164 0.16 0.,27485 0.2873 0.07 0.06 1.7837836 1.7150 13747 321. 0.6158 0.19 0.2828 0.09 1.9071 13748 570. 0.7390 0.13 0.3243 0.06 2.0476 13749 469. 0.7383 0.16 0.3499 0.07 1.9514 13750 449, 0.6466 0.14 0.2750 0.06 2,8842b .................................................................................................................................... 0.452 0.39 0.59 0.36 0.42 0.64 1.6930634 1.6329 1.7986 1.9007 1.8267 2.6964b 0.430 0.37 0,56 0.33 0.39 0,60 21 16893213 2 0396 1 8077 2 1969 2 0347 1.6893 0.5451 0,46 0.56 0.38 0.43 0.38 10.29459306 1.1029 0.8948 1.2020 1.1848 1.0501 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) Rat 13741 had small and flaccid epididymides and testes. See the individual necropsy observations table (Table B16). Rat 13750 had a large left epididymis and left testis minus tunica albuginea. See the individual necropsy observations table (Table B16), 0.3223 0.25 0.28 0.21 0.25 0.23 X 100. > C 5_ O_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 15): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION MALE RATS .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13721 13722 13723 13724 13725 13726 13727 13728 511. 452. 321. 378. 361. 465. 443. 418. 0.5828 0.6248 0.6269 0.6778 0.6145 0.5830 0.6714 0.5943 0.11 0.14 0.20 0.18 0.17 0.12 0.15 0.14 1.6442 2.0050 1.6768 1.7229 1.6811 1.6140 1.6811 1.7995 0 32 0 44 0 52 0 46 0 46 0 35 0 38 0.43 0.8431 0.8430 0.5950 0.6971 0.7775 1.1966 1.1502 0.8251 0.16 0.19 0.18 0.18 0.22 0.26 0.26 0.20 PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 0.015 0.013 0.010 0.009 0.005 0.011 0.009 0.011 2.94 2.88 3.12 2.38 1.38 2.36 2.03 2.63 2 32 2 12 2 18 2 22 2 05 2 39 2 09 2 40 0.45 0.47 0.68 0.59 0.57 0.51 0.47 0.57 32.46 26.38 25.29 20.55 24.05 26.25 27.77 33.99 6.35 5.84 7.88 5.44 6.66 5.64 6.27 8.13 13729 13730 439. 522. 0.6131 0.7137 0.14 0.14 1.7874 1.9707 0.41 0.38 0.8078 0.8931 0.18 0.17 0.008 0.011 1.82 2.11 2 26 2.18 0.51 0.42 30.46 36.40 4_ 13731 468. 0.6397 0.14 1.7492 0.37 0.6744 0.14 0.011 2.35 2.10 0.45 27.84 _'_ 13732b .... 0.31 .... 1.54 .... 0.34 .... 0.006 .... 1.83 .... 15.94 13733 554. 0.7056 0.13 1.8567 0.34 0.9479 0.17 0.012 2.17 2.41 0.44 34.60 13734 456. 0.6340 0.14 1.7743 0.39 1.2570 0.28 0.007 1.54 2.25 0.49 28.30 13735 446. 0.6247 0.14 1.6311 0.36 0.9716 .................................................................................................................................... 0.22 0.007 1.57 2.22 0.50 26.33 6.94 6.97 5.95 .... 6.24 6.21 5.90 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. a. Value was multiplied by 1000. b. Rat 13732 was moribund sacrificed on day 45 of study; values excluded REL. % TBW = (ORGAN WEIGHT/TERMINAL from group averages and statistical BODY WEIGHT) X 100. analyses. > C O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 16): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND INDIVIDUAL DATA - P GENERATION MALE RATS RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... RAT NUMBER TERMINAL BODY WEIGHT EPIDIDYMIS RIGHT ABS. REL. TESTIS RIGHT ABS. REL. PROSTATE ABS. REL. WT. % TBW WT. % TBW WT, .................................................................................................................................... % TBW DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13736 13737 13738 13739 13740 13741 398. 385. 475. 374. 497. 358. 0.6535 0.6117 0.7239 0.6380 0.6731 0.3794b 0.16 0.16 0.15 0.17 0.14 0.10 1.7745 1.7991 1.9556 1.7722 1.8953 0.8606b 0.44 0.47 0.41 0.47 0.38 0.24 1.1293 0.6582 0.9491 0.6872 1.0956 0.5990 0.28 0,17 0.20 0.18 0.22 0.17 PITUITARY ABS. WT. REL. % TBW a BRAIN ABS. WT. REL. % TBW LIVER ABS. WT. REL. % TBW 0.010 0.009 0.012 0.015 0.010 0.007 2.51 2.34 2.53 4.01 2.01 1.96 1 95 2 09 2 25 2 16 2 47 2 18 0,49 0.54 0.47 0.58 0.50 0.61 26,04 25.32 27.00 23.10 29.12 27.33 6 54 6 58 5 68 6 18 5 86 7 63 13742 13743 345. 401. 0.6017 0,6511 0.17 0.16 1.5535 1.7824 0.45 0.44 0.7266 0.8984 0.21 0.22 0.007 0.008 2.03 2.00 2 06 2.27 0.60 0.57 25.57 23.40 13744 394. 0.6378 0 16 1.8145 0.46 0.7553 0.19 0.012 3.04 2.25 0.57 24.04 _._ 13745 413. 0.5834 0 14 1.7338 0.42 0.8432 0.20 0.009 2.18 2.32 0.56 29.53 13746 438. 0.6752 0 15 1.6953 0.39 0.8258 0.19 0.015 3.42 2.20 0.50 28.24 13747 321. 0.6142 0 19 1.8456 0.57 0.5597 0.17 0.016 4.98 1,88 0,58 23.29 13748 570. 0.7365 0 13 2.0122 0.35 1.0400 0.18 0.013 2.28 2.28 0.40 31.63 13749 469. 0.7260 0 15 1.8831 0.40 0.8505 0.18 0.011 2.34 2.27 0.48 27.03 13750 449. 0.6502 0 14 1.7065 0.38 0.8981 0.20 0.013 2.90 2.04 0.45 25.92 .................................................................................................................................... 7 41 5 84 6 i0 7 15 6 45 7,26 5,55 5.76 5,77 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN a. Value was multiplied by 1000. b. Rat 13741 had small and flaccid epididymides and testes. WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL See the individual necropsy observations table BODY WEIGHT) (Table B16). X 100. > _n oo t_ o 0_ _._ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 17): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... KIDNEY KIDNEY ADRENAL RAT TERMINAL BODY LEFT RIGHT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW _'_. % TBW WT. % TBW a .................................................................................................................................... ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13721 13722 13723 13724 13725 13726 511. 452. 321. 378. 361. 465. 2.04 1.97 1.96 2.05 1.65 2.21 0.40 0.44 0.61 0.54 0.46 0,48 2.19 2.19 1.94 2.01 1.73 2.20 0.43 0.48 0 60 0 53 0 48 0 47 0.035 0.035 0.033 0.042 0.028 0.029 6.85 7.74 10.28 11.11 7.76 6.24 0.040 0.035 0.028 0.037 0.026 0.039 7.83 7.74 8.72 9.79 7.20 8.39 0.76 0.80 0.72 0.79 0.45 0.93 0.15 0.18 0.22 0.21 0.12 0.20 0.36 0.49 0.37 0.49 0.20 0.51 0.07 0.Ii 0 12 0 13 0 06 0 Ii 13727 13728 443. 418. 2.08 1.89 0.47 0.45 2.16 1.94 0 49 0 46 0.026 0.028 5.87 6.70 0.024 0.025 5.42 5.98 0.75 0.67 0.17 0.16 0.28 0.25 0 06 0 06 13729 439. 2.13 0.48 2.05b 0.47 0.020 13730 522. 2.44 0.47 2.45 0.47 0.035 13731 468. 2.02 0.43 2.05 0.44 0.028 13732C .... 1.22 .... 1.25 .... 0.026 13733 554. 2.19 0.40 2.31d 0.42 0.032 13734 456. 2.22 0,49 2.30 0.50 0.022 13735 446. 2.06 0.46 2.23 0.50 0.030 .................................................................................................................................... 4.56 6.70 5.98 .... 5.78 4.82 6.73 0.014 0.031 0.026 0.026 0.035 0.023 0.014 3.19 5.94 5.56 .... 6.32 5.04 3.14 0.52 0.70 0.57 0,13 0.94 0.69 0.97 0.12 0.13 0.12 .... 0.17 0.15 0.22 0.25 0.38 0.18 0.12 0.28 0.32 0.40 0 06 0 07 0.04 .... 0.05 0.07 0.09 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. a. Value was multiplied by 1000. b. Rat 13729 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations c. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statlstical d. Rat 13733 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table analyses. table (Table B16). B16). > C _n o0 to o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B18 (PAGE 18): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND INDIVIDUAL DATA - P GENERATION MALE RATS RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... KIDNEY KIDNEY ADRENAL RAT TERMINAL BODY LEFT RIGHT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW a .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13736 13737 13738 13739 13740 13741 398. 385. 475. 374. 497. 358. 1.85 1.73 1.98 1.95 1.98 1.82 0.46 0.45 0.42 0.52 0.40 0.51 1.99 1.79 1.95 2.01 2.15 2.02 0.50 0.46 0.41 0.54 0.43 0.56 0.030 0.021 0.037 0.026 0.024 0.009 7.54 5.45 7.79 6 95 4 83 2 51 ADRENAL RIGHT ABS. REL. WT. % TBW a 0.023 0.017 0.032 0.025 0.027 0.014 5.78 4.42 6.74 6.68 5.43 3.91 SPLEEN ABS. WT. REL. % TBW 0.72 0.65 0.73 0.69 0.80 0.42 0.18 0.17 0.15 0.18 0.16 0.12 THYMUS ABS. WT. REL. % TBW 0.28 0.20 0.32 0.25 0.27 0.20 0.07 0.05 0.07 0.07 0.05 0.06 13742 13743 13744 13745 345. 401. 394. 413. 1.60 1.87 1.80 1.92 0.46 0.47 0.46 0.46 1.64 1.93 1.94 2.07 0.48 0.48 0.49 0.50 0.027 0.020 0.029 0.026 7 83 4 99 7 36 6 30 0.029 0.026 0.028 0.026 8.40 6.48 7 Ii 6 30 0.86 0.62 0.58 0.73 0.25 0 15 0 15 0 18 0.17 0.20 0.29 0.28 0.05 0.05 0.07 0.07 13746 13747 438. 321. 2.27 1.89 0.52 0.59 2.20 1.93 0.50 0.60 0.028 0.031 13748 570. 2.20 0.38 2.43 0.43 0.032 13749 469. 1.79 0.38 1.78 0.38 0.029 13750 449. 2.07 0.46 2.04 0.45 0.021 .................................................................................................................................... ALL WEIGHTS WERE RECORDED Value was multiplied IN GRAMS by 1000. (G). ABS. WT. = ORGAN WEIGHT. 6 39 9.66 5.61 6.18 4.68 0.025 0.020 0.030 0.028 0.020 5 71 6 23 5 26 5 97 4 45 0.74 0.51 1.09 0.87 1.06 0 17 0 16 0 19 0 18 0 24 0.35 0.27 0.38 0.29 0.27 REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) 0.08 0.08 0.07 0.06 0.06 X 100. > C O0 4_ _J O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE I): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS DATA - .................................................................................................................................... RAT BRAIN EPIDIDYMIS LEFT CAUDA EPIDIDYMIS LEFT TESTIS LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY REL. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW .................................................................................................................................... 13601 13602 13603 13604 13605 13606 13607 2.36 2.38 2.19 2.40 2.22 2.24 2.35 0.6756 0.6786 0.7340 0.7152 0.7034 0.7420 0.6822 28.63 28.51 33.52 29.80 31.68 33.12 29.03 0 2966 0 3086 0 3341 0 3136 0 3543 0 3611 0 3203 12.57 12.97 15.26 13.07 15.96 16.12 13.63 1.5259 1.6647 1.7979 1.9262 1.8636 1.8832 1.8506 64.66 69.94 82.10 80.26 83.94 84.07 78.75 1.2920 1.5221 1.6608 1.7009 1.7079 1.7583 1.7435 54 74 63 95 75 84 70 87 76 93 78 50 74 19 1.3897 2.2138 2.2003 1.6708 2.1486 1.7423a 2.1930 58 88 93 02 100 47 69 62 96 78 77 78a 93.32 0.9914 1.2279 1.3738 1.1445 1.1320 1.2432 1.0702 42.01 51.59 62.73 47.69 50.99 55.50 45.54 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 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 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 34.11 26.05 36.19 28.13 32.37 26.95 30.57 32.18 30.04 30.88 32.02 34.19 34.13 30.80 32.98 30.06 40.88 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 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 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 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 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 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 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 92 35 125 76 148 81 92 26 118 19 77 56 104 88 111.44 100.42 86 86 102 31 113 94 95 36 113 23 102 49 82 70 100.43 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 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 13625 2.25b 0.7424 33.00 0 2999 13.33 1.7695 78.64 1.6738 74 39 2.9931 133 03 1.3586 60.38 13626 2.33 0.8408 36.08 0 3786 16.25 1.9527 83.81 1.8342 78 72 2.6403 113 32 1.4879 63.86 13627 2.17 0.7204 33.20 0 3192 14.71 1.6706 76.99 1.5585 71 82 2.44_8 112 89 1.3752 63.37 13628 2.10 0.7515 35.78 0 3760 17.90 1.8851 89.77 1.7864 85 07 2.6437 125 89 1.5575 74.17 13629 2.10 0.6810 32.43 0 3307 15.75 1.6630 79.19 1.5519 73 90 2.3510 iii 95 1.3665 65.07 [2] 13630 2.43 0.8494 34.95 0 3993 16.43 2.1140 87.00 1.9567 80 52 2.0128 82 83 1.3021 53.58 4_ ...................................................................... .............................................................. ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW _ (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Damaged during processing (some fluid loss prior to weighing); values excluded from group averages and statistical analyses. Damaged during processing (weight not affected). CD PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 2): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS DATA - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW .................................................................................................................................... 13601 13602 2.36 2.38 0.6727 0.6538 28.50 27.47 1.5705 1.5701 66.55 65.97 0.9769 1.0477 41.39 44.02 0.016 0.014 0.68 0.59 23.61 22 78 1000.42 957.14 2.17 2.55 91.95 107.14 13603 13604 2.19 2.40 0.7422 0.7242 33.89 30.18 1.8434 1.8830 84.17 78.46 1.1461 1.2982 52.33 54.09 0.012 0.016 0.55 0.67 18 43 20 30 841.55 845.83 1.90 2.33 86.76 97.08 13605 13606 13607 13608 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 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 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 31.59 34.44 29.29 33.53 31.39 35.72 27.81 33.37 27.57 30.09 32.48 29.56 31.84 30.60 35.26 28.62 31.33 31.11 30.22 38.51 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 82.40 85.61 80.13 81.59 111.05 85.08 79.15 86.54 72.31 69.59 86.34 78.11 70.55 79.13 86.48 79.92 79.88 76.32 70 93 98 83 0.8545 1.2630 1.4560 1.3797 1.2521 1.1033 1.1326 1.0173 1.2060 1.2564 1.0383 0.9796 1.0554 1.0403 1.1757 1.3352 1.1837 1.2359 1.2678 0.9132 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 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 0.63 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 15 86 22 82 18 53 19 26 23 25 22 41 22 68 17 03 21 60 20 68 20 97 25 02 16 93 19 31 21 32 20 80 16 17 18 88 19 31 18 10 714.41 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 2.26 2.25 2.17 2.12 2.33 2.31 2.47 2.18 2.50 2.53 1.85 2.58 1.92 1.99 2.09 2.02 2.15 2.30 2.10 2.11 101.80 100.45 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 13625 2.25a 0.7624 33.88 1.7619 78 31 1.1731 52.14 0.014 0.62 19 76 878.22 1.99 88 44 13626 2.33 0.8685 37.27 1.9505 83 71 1.6005 68.69 0.018 0.77 24 67 1058.80 2.28 97 85 13627 2.17 0.7318 33.72 1.6434 75 73 1.1031 50.83 0.011 0.51 17 86" 823.04 2.09 96 31 13628 2.10 0.7165 34.12 1.8347 87 37 0.8151 38.81 0.012 0.57 22 09 1051.90 2.08 99 05 13629 2.10 0.6744 32.11 1.6857 80 27 1.0534 50.16 0.011 0.52 18 41 876.67 2.03 96 67 13630 2.43 0.8078 33.24 2.0934 86 15 0.7730 31.81 0.014 0.58 20 24 832.92 2.07 85 18 _t_ .................................................................................................................................... OO ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. Damaged during processing (weight not affected). I_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 3): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS DATA - .................................................................................................................................... RAT BRAIN KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT NUMBER WEIGHT ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13601 13602 13603 13604 13605 13606 2 36 2 38 2 19 2 40 2 22 2 24 2.19 2 55 1 96 2 28 2 25 2 39 92.80 107.14 89.50 95.00 101.35 106.70 0.030 0.032 0.031 0.026 0.029 0.044 1.27 1,34 1.42 1.08 1.31 1.96 0.031 0.035 0.026 0.033 0.028 0.039 1.31 1.47 1.19 1.38 1.26 1.74 SPLEEN ABS. WT. REL. % BRW 0.75 0.96 0.69 1 11 1 00 1 20 31.78 40.34 31.51 46.25 45.04 53.57 THYMUS ABS. WT. REL. % BRW 0.38 0,63 0.38 0.69 0.45 0.55 16.10 26.47 17.35 28.75 20.27 24.55 13607 13608 2.35 2.33 2 14 2 15 91.06 92.27 0.046 0.031 1.96 1,33 0.021 0.033 0.89 1.42 0 83 0 90 35.32 38.63 0.41 0.52 17.45 22.32 13609 13610 2.11 1.86 2 43 2.29 115.16 123.12 0.031 0.028 1.47 1,50 0.029 0.028 1.37 1.50 1 04 0 76 49.29 40.86 0.42 0.32 19.90 17.20 13611 2.32 2.38 102.59 0.035 1.51 0.038 1.64 0 94 40.52 0.29 12.50 13612 2.11 2.21 104.74 0.033 1,56 0.032 1.52 0 79 37.44 0.34 16.11 13613 13614 2.51 2.19 2.32 2.31 92.43 105.48 0.029 0.028 1.16 1,28 0.033 0.027 1.31 1.23 0.98 0.98 39.04 44.75 0.49 0.49 19.52 22.37 13615 2.25 2.03 90.22 0.035 1,56 0.039 1.73 1.01 44.89 0.40 17.78 13616 2.52 2.61 103.57 0.042 1,67 0.035 1.39 1.26 50.00 0.41 16.27 13617 2.52 2.05 81.35 0.032 1,27 0.031 1.23 1.12 44.44 0.50 19.84 13618 2.27 1.89 83.26 0.032 1,41 0.036 1.58 0.80 35.24 0.32 14.10 13619 2.33 2.03 87,12 0 035 1,50 0.033 1.42 0.93 39.91 0.39 16.74 13620 2.21 1.99 90 04 0 028 1,27 0.029 1.31 1.32 59.73 0.52 23.53 13621 2.15 2.12 98 60 0 027 1,26 0.023 1.07 0.85 39.53 0.40 18.60 13622 2.22 2.20 99 i0 0 035 1,58 0.045 2.03 0.68 30.63 0.44 19.82 13623 2.45 2.30 93 88 0 033 1,35 0.031 1.26 0.80 32.65 0.33 13.47 13624 1.83 2.15 117 49 0 027 1,48 0.022 1.20 0.87 47.54 0.57 31.15 13625 2.25a 2.09 92 89 0 027 1,20 0 027 1.20 0.87 38.67 0.31 13.78 > 13626 2.33 2.34 100.43 0.034 1,46 0 036 1.54 0.96 41.20 0.49 21.03 13627 2.17 2.05 94.47 0.032 1,47 0 036 1.66 0.94 43.32 0.42- 19.35 13628 2.10 2.01 95.71 0.035 1,67 0 031 1.48 1.07 50.93 0.50 23.81 13629 2.10 1.99 94.76 0.029 1.38 0 033 1.57 0.68 32.38 0.26 12.38 [29 13630 2.43 2.03 83.54 0.032 1,32 0 028 1.15 0.97 39.92 0.46 18.93 4_ .................................................................................................................................... OC ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00, Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 4): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 13632 13633 13634 13635 13636 2.22 2.34 2.43 2.13 2.07 2.17 0 6495 0 7034 0 7044 0 7068 0 6053 0 7697 29.26 30.06 28.99 33.18 29.24 3S.47 0.2998 0.3166 0.3546 0.3369 0.2813 0.3525 13.50 13.53 14.59 15.82 13 59 16 24 1.6770 1.9768 1.7819 1.8226 1.6595 1.8739 75.54 84.48 73.33 85.57 80.17 86.35 L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW 1.5445 1.8290 1.6458 1.6586 1.5483 1.6712 69.57 78.16 67.73 77.87 74.80 77.01 SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW 2.4075 2.8763 3.2227 1.6848 1.4917 2.3337 108.44 122.92 132.62 79.10 72.06 107.54 SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 1.5081 1.4047 1.5709 1.1637 0.8167 1.2939 67.93 60.03 64.65 54.63 39.45 59.63 13637 2.26 0 7061 31.24 0.3434 15 19 1.6545 73.21 1 5240 67.43 2.5335 112.10 1.3047 57 73 13638 13639 13640 13641 13642 13643 13644 13645 13646 13647 2.43 2.42 2.20 2.26 2.34 2.21 2.44 2.25 2.31 2.25 0 6470 0.7020 0.7283 0.7490 0.7241 0.7330 0.7089 0.6784 0.6822 0.6658 26.62 29.01 33.10 33.14 30.94 33.17 29.05 30.15 29 53 29 59 0.2792 0.2951 0.3536 0.3527 0.3150 0.3398 0.3200 0.3183 0.3463 0.2982 ii 49 12 19 16 07 15 61 13 46 15 38 13 11 14 15 14 99 13 25 1.9344 2.0283 1.8745 1.8714 1.7279 1.9500 1.9383 1.6234 1.6999 1.7814 79.60 83.81 85.20 82.80 73.84 88.24 79.44 72.15 73.59 79 17 1 8105 1 8573 1 7670 1 7242 1 6227 1 8364 1 8199 1.5062 1.5800 1.6328 74.51 76.75 80.32 76.29 69.35 83.10 74.59 66.94 68.40 72.57 2 3501 2 3202 2 6251 2 3899 2 4003 2 5036 2 1300 2 4119 2 0676 2 6220 96.71 95.88 119.32 105.75 102.58 113.28 87.30 107.20 89.51 116.53 1.1924 1.0796 1.3840 1.2356 1.2870 1.2468 1.2740 1.2195 1.1076 1.4890 49 07 44 61 62 91 54 67 55 00 56 42 52.21 S4.20 47.95 66.18 13648 2.33 0.6317 27 11 0.3064 1315 1.8391 78 93 1.7159 73.64 2.1504 92.29 1.1768 50.51 13649 2.35 0.6941 29 54 0.3058 13.01 1.7156 73 00 1.6256 69.17 2.2035 93.76 1.1379 48.42 13650 2.32 0.7437 32 06 0.2876 12.40 1.9510 84 09 1.8355 79.12 2.4213 104.37 1.4614 62.99 13651 2.38 0.7134 29 97 0.3282 13.79 1.9750 82 98 1.8339 77.05 2.5200 105.88 1.4917 62.68 13652 2.26 0.7191 31.82 0 3231 14.30 1.7946 79 41 1.6913 74 84 2.4900 110.18 1.2234 54.13 13653 2.37 0.6303 26.59 0 2784 11.75 1.8551 78 27 1.6992 71 70 1.6932 71.44 1.0140 42.78 13654 2.23 0.6840 30.67 0 2935 13.16 1.5110 67 76 1.4044 62 98 2.3628 105.96 1.1243 50.42 13655 2.33 0.8054 34.57 0 3335 14.31 2.1552 92 50 1.9836 85 13 2.8403 121.90 1.4880 63.86 > 13656 2.31 0.7198 31.16 0 3468 15.01 1.7050 73.81 1.6041 69 44 2.2805 98.72 1.2083 52.31 13657 2.10 0.6277 29.89 0 3055 14.55 1.7519 83.42 1.6518 78 66 2.1178 100.85 1.0602 50.48 13658 2.31 0.6425 27.81 0 2637 11.42 1.5617 67.61 1.4618 63 28 2.1529 93.20 1.1517 49.86 13659 2.17a 0.7407 34.13 0 3172 14.62 1.9318 89.02 1.8052 83 19 2.1495 99.06 1.2183 56.14 [29 13660 2.28 0.7581 33.25 0.3225 14.14 1.6871 74.00 1.5755 69 i0 2.2241 97.S5 1.2827 56.26 _W.td_ ...... .............................................................................................................................. O0 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 5): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS DATA - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 13632 13633 13634 13635 13636 2.22 2.34 2.43 2.13 2.07 2.17 0.6184 0.7187 0.7346 0.7092 0.6527 0.3677a 27.86 30.71 30.23 33.30 31.53 16.94 1.6665 2.0272 1.8301 1.8432 1.7937 0.8983a 75.07 86.63 75.31 86.54 86.65 41.40 1.2524 1.3965 1.1854 0.9863 1.1001 1.2274 56.41 59.68 48.78 46.30 53.14 56.56 PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW 0.016 0.015 0.020 0.015 0.010 0.012 0.72 0.64 0.82 0.70 0.48 0.55 23.73 26.29 20.13 24.69 23.30 27.55 1068.92 1123 50 828 40 1159 15 1125 60 1269 58 2.49 2.97 2.67 2.79 2.32 2.73 112.16 126.92 109.88 130.98 112.08 125.81 13637 13638 2.26 2.43 0.7132 0.6219 31.56 25.59 1.6779 1.9129 74.24 78.72 1.1159 1 3568 49.38 55.84 0.016 0.017 0.71 0.70 25.31 26.08 1119 91 1073 25 2.29 2.64 101.33 108.64 13639 13640 2.42 2.20 0.6966 0.6905 28.78 31.39 2.0712 1.9493 85.59 88.60 1 0950 0 9987 45.25 45.40 0.008 0.017 0.33 0.77 26.73 32.23 1104 54 1465 00 2.72 2.74 112.40 124.54 13641 2.26 0.7322 32.40 1.8401 81.42 0 9751 43.15 0.015 0.66 25.22 1115 93 2.66 117.70 13642 2.34 0.7423 31.72 1.7467 74.64 1 2793 54.67 0.012 0.51 19.48 832 48 2.20 94.02 13643 2.21 0.7523 34.04 2.5181 113.94 1 1153 50.47 0.016 0.72 25.04 1133.03 2.84 128.51 13644 2.44 0.7081 29.02 1.8376 75.31 1.1768 48.23 0.009 0.37 24.65 1010.24 2.58 105.74 13645 13646 2.25 2.31 0.6380 0.6909 28.36 29.91 1.5823 1.7069 70.32 73.89 1.0379 1.4184 46.13 61.40 0.019 0.012 0.84 0.52 23.13 22.38 1028.00 968.83 2.80 2.68 124.44 116.02 13647 2.25 0.6756 30.03 2.6503 117.79 0.6843 30.41 0.013 0.58 25.86 1149.33 2.67 118.67 13648 2.33 0.6579 28.24 1.9075 81.87 1.0489 45.02 0.011 0.47 22.58 969.10 2.41 103.43 13649 2.35 0.6966 29.64 1.6978 72.25 1.4685 62.49 0.015 0.64 29.17 1241.28 2.55 108.51 13650 2.32 0.7426 32.01 2.0238 87.23 1.1363 48.98 0.012 0.52 22.99 990.95 2.22 95.69 13651 2.38 0.7281 30.59 1.9809 83.23 0.8039 33.78 0.013 0.55 22.73 955.04 2.56 107.56 13652 2.26 0.7464 33 03 1.8349 81.19 0.9861 43.63 0.016 0.71 22.86 1011.50 2.55 112.83 13653 2.37 0.6316 26 65 1.7942 75.70 1.1095 46.81 0.010 0.42 17.07 720.25 2.06 86.92 13654 2.23 0.6388 28 64 1 5501 69.51 1.2735 57.11 0.015 0.67 26.32 1180.27 2.22 99.55 13655 2.33 0.7879 33 82 2 1403 91.86 0.9730 41.76 0.014 0 60 29.05 1246.78 2.87 123.18 13656 2.31 0.7250 31 38 1 7659 76.44 1.6851 72.95 0.014 0 61 19.16 829.44 1.89 81.82 13657 2.10 0.6460 30 76 1 7433 83.01 1.1798 56.18 0.013 0 62 23.90. 1138.10 2.20 104.76 13658 2.31 0.6287 27.22 1 5591 67.49 0.8826 38.21 0.016 0 6'9 22.05 954.54 2.20 95.24 13659 2.17b 0.7940 36.59 2 0007 92.20 1.1305 52.10 0.013 0 60 21.10 972.35 2.11 97.24 [2_ 13660 2.28 0.7865 34.50 1 6440 72.10 1 1982 52 55 0.014 0 61 27.36 1200 00 2.67 117.10 .................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Rat 13636had a small and flaccid right epldidymis and right testis. See the individual necropsy observations t_ table (Table BI6). b. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 6): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS DATA - .................................................................................................................................... RAT BRAIN KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 13632 13633 13634 13635 13636 2.22 2.34 2.43 2.13 2.07 2.17 2.48 2 84 2 62 3 00 2 15 2 97 111.71 121.37 107.82 140.84 103.86 136.87 0.034 0.038 0.032 0.037 0.028 0.029 1.53 1.62 1.32 1.74 1.35 1.34 0 034 0 038 0 031 0 036 0 028 0 030 1.53 1.62 1.28 1.69 1.35 1.38 13637 2.26 2 36 104.42 0.036 1.59 0 037 1.64 SPLEEN ABS. WT. REL. % BRW 0.95 0.92 0.68 1.06 0,70 0 94 1 05 42.79 39.32 27.98 49.76 33.82 43.32 46.46 THYMUS ABS. WT. REL. % BRW 0.39 0.38 0.26 0.50 0.41 0.52 0,47 17.57 16.24 10.70 23.47 19.81 23.96 20.80 136389 13640 13641 2.432 2.20 2.26 2.8454a 2.79 2.57 11070.2883 126,82 113.72 0.02376 0.037 0.032 i1.,i4i9 1.68 1.42 0.0229 0.033 0.032 01.920 1.50 1.42 0 980 0 75 1 02 4307.3139 34.09 45.13 0.4225 0.29 0.35 170.2383 13.18 15.49 13642 2.34 2.15 91.88 0.032 1.37 0.031 1.32 1.08 46.15 0.29 12.39 13643 2.21 2.68 121.27 0.034 1.54 0.033 1.49 0.72 32.58 0.45 20.36 13644 2.44 2.71 111 06 0.033 1.35 0.032 1.31 0.75 30.74 0.49 20.08 13645 2.25 2.77 123 11 0.038 1.69 0.036 1.60 1.02 45.33 0.31 13.78 13646 2.31 2.67 115 58 0.026 1.12 0.024 1.04 0.71 30.74 0.32 13.85 13647 2.25 2.70 120 00 0.031 1.38 0,030 1.33 0.95 42.22 0.52 23.11 13648 2.33 2,56 109 87 0.027 1.16 0.026 1.12 0.81 34.76 0.33 14.16 13649 2.35 2.72 115 74 0.032 1.36 0.042 1.79 0.80 34.04 0.44 18,72 13650 2.32 2.36 101 72 0.031 1.34 0.028 1.21 1.01 43.53 0.39 16.81 13651 2,38 2.80 117 65 0.029 1.22 0.025 1.05 0,93 39.08 0.43 18.07 13652 2.26 2,35 103 98 0 033 1.46 0.032 1.42 0.84 37.17 0.30 13.27 13653 2.37 2.30 97.05 0 024 1.01 0.022 0.93 0.74 31.22 0.36 15.19 13654 2.23 2.20 98,65 0 040 1.79 0.041 1.84 0.89 39.91 0.42 18.83 13655 2.33 3.18 136.48 0 027 1.16 0.024 1.03 0.88 37.77 0.36 15.45 > 13656 2,31 1.92 83.12 0 029 1.26 0.025 1.08 0.72 31.17 0.32 13.85 13657 2.10 2,17 103.33 0 029 1.38 0.032 1.52 0.86 40.95 0.31. 14.76 13658 2.31 2.32 100.43 0.036 1.56 0.027 1.17 0.70 30.3_ 0.43 18.61 13659 2.17b 2.10 96.77 0.030 1.38 0.029 1.34 0.87 40.09 0.31 14.28 [2_ 13660 2.28 2.63 115.35 0.031 1.36 0.030 1.32 1.01 44.30 0.51 22.37 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Rat 13639 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). 50 Damaged during processing (weight not affected), PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 7): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13661 13662 13663 13664 13665 13666 13667 2.24 2.11 2.32 2.39 2.40 2.00 2.23 0.6912 0.6733 0.7359 0.6819 0.6495 0.6823 0.6787 30 86 31 91 31 72 28 53 27 06 34 11 30.43 0.3254 0.3247 0.3684 0.3250 0.3010 0.2923 0.3297 14.53 15.39 15.88 13.60 12.54 14.62 14.78 1.9614 1.7494 1.8987 1.8210 1.7079 1.8632 1.6308 87 56 82 91 81 84 76 19 71 16 93 16 73 13 L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW 1.7444 1.6186 1.7604 1.7070 1.5898 1.7270 1.5095 77.87 76.71 75.88 71.42 66 24 86 35 67 69 SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW 2.8329 1.7487 2.1959 2.3292 2.2164 2.1344 2.1297 126.47 82.88 94.65 97.46 92 35 106 72 95 50 SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 1.4299 0.9591 1.1255 1.2339 1.0909 1.0447 1.2414 63.83 45.45 48.51 51.63 45.45 52.24 55.67 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 2.13 2.34 2.12 2.36 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 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 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 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 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 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 76 i0 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 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 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 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 87 14 121 56 134 05 90 06 112 70 113 79 91 24 81 17 108 32 113 39 91 05 115 75 90 86 95 42 103 95 126.80 101.03 1.0709 1.4370 1.4905 1.3067 1.2914 1.2487 1.3208 1.1959 1.3884 1.2994 1.0874 1.5101 1.2158 1.1777 1.3425 1.3745 1.2772 50.28 61.41 70.31 55.37 58.17 60.32 55.97 53.87 64.88 56.25 46.27 62.66 53.09 48.66 54.80 62.76 58.05 13685 2.12 0.6832 32.23 0 3172 14.96 1 8082 85.29 1.6956 79.98 2.6755 126.20 1.5985 75.40 13686 2.30 0.6252 27.18 0 2874 12.50 1 7667 76.81 1.6740 72.78 2.0154 87.63 1.1092 48.23 13687 2.34 0.6735 28.78 0 3194 13.65 1 5957 68.19 1.4880 63.59 2.9111 124.40 1.6056 68.62 _'_ 13688 13689 2.08 2.27 0.7943 0.6982 38.19 30.76 0 3601 0 3340 17.31 14.71 2 0392 1 7096 98.04 75.31 1.9123 1.5964 91._4 70.32 2.2724 2.4406 109.25 107.52 1.2595 1.2353 60.55 54.42 13690 2.28 0.6794 29.80 0 3048 13.37 1 7594 77.17 1.6408 71.96 2.4640 108.07 1.3996 61.38 ...... " ............................................................................................................................. O0 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. tO O PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 8): BRAIN WEIGHTS AND ORGA_I WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL P GENERATION MALE RATS DATA - .................................................................................................................................... RAT BRAIN EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE NI94BER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW HT. % BRW WT. .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW .................................................................................................................................... 13661 13662 13663 13664 13665 13666 13667 2.24 2.11 2.32 2.39 2.40 2.00 2.23 0.6942 0.6884 0.7462 0.6483 0.6558 0.7041 0.6941 30.99 32.62 32.16 27.12 27.32 35.20 31.12 1.9170 1.7684 1.9026 1 7742 1 7255 1 9202 1 6840 85.58 83.81 82.01 74.23 71.90 96.01 75.52 1.1744 1 0222 0 9513 1 0531 1 0904 1 2313 1 1857 52.43 48.44 41.00 44.06 45.43 61.56 53.17 0.014 0.018 0.008 0.013 0.013 0.010 0.012 0.62 0.85 0.34 0.54 0.54 0.50 0.54 28.39 28.59 26.16 28.39 28.78 24.12 31.05 1267.41 1354.98 1127.59 1187.87 1199.17 1206.00 1392 38 2.49 2.50 2.20 2.26 2.36 2.29 2.43 111.16 118.48 94.83 94.56 98.33 114.50 108.97 13668 13669 13670 13671 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 2.13 2.34 2.12 2.36 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 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 26.74 31.98 37.00 29.17 28.30 31.23 27.01 31.18 32.55 28.06 29.14 30.91 29.26 31 92 31 06 32 95 32 25 1 6580 1 8785 1 8798 1 7400 1 7492 1 6550 1 7158 1 5912 1 9457 1 7060 1 7331 1 7974 1 9337 2 0453 2 0193 1 6827 1 7016 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 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 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 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 0.42 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 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 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 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 2.33 112.21 III.ii 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 13685 2.12 0.6926 32 67 1 8110 85.42 1 1725 55.31 0.014 0 66 26.28 1239 62 2.65 125.00 13686 2.30 0.6045 26 28 1 7715 77.02 1 0562 45.92 0.017 0 74 28.94 1258 26 2.76 120.00 13687 2.34 0.7076 30 24 1 5732 67.23 1 0888 46.53 0.013 0 56 29.66. 1267 52 2.45 104.70 13688 2.08 0.7951 38 22 2 0475 98.44 0 9953 47.85 0.014 0 67 25.96 1248 08 2.75 132.21 13689 2.27 0.6814 30 02 1 6739 73.74 1 2406 54.65 0.012 0 53 34.16 1504 84 2.88 126.87 13690 2.28 0.6736 29 54 ...................................................................... 1 7440 76.49 0 9884 43.35 0.016 0 70 33.85a .............................................................. 1484 65 3.19 139.91 _t_ _._ O0 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Damaged during processing (weight not affected), b0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 9): BRAIN WEIGHTS AND ORGAN WEIGHTS AND RATIOS P GENERATION MALE RATS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... RAT BRAIN KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY REL. % BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW .................................................................................................................................... 13661 13662 13663 13664 13665 13666 2.24 2.11 2.32 2.39 2.40 2.00 2.45 2.45 2.34 2.24 2.50 2.41 109.38 116.11 100.86 93.72 104.17 120.50 0.038 0.040 0.031 0.033 0.042 0.027 1 70 1 90 1 34 1 38 1 75 1 35 0.044 0.046 0.034 0.032 0.044 0.026 1.96 2.18 1.46 1.34 1.83 1.30 1.01 0.89 0_82 0.86 0.74 1.11 45.09 42.18 35.34 35.98 30.83 55.50 0.34 0.52 0.45 0.49 0.39 0.44 15.18 24.64 19.40 20.50 16.25 22.00 13667 2.23 2.48 111.21 0.026 1 16 0.021 0.94 0.90 40.36 0 50 22.42 13668 13669 2.13 2.34 2.49 2.50 116.90 106.84 0.026 0.029 1 22 1 24 0.021 0.021 0.98 0.90 0.75 0.90 35.21 38.46 0 25 0 42 11.74 17.95 13670 13671 2.12 2.36 2.31a 2.20 108.96 93.22 0.023 0.034 1 08 1.44 0.021 0.030 0.99 1.27 0.79 0 84 37.26 35.59 0 38 0 24 17.92 10.17 13672 13673 13674 13675 13676 13677 13678 13679 13680 13681 13682 13683 13684 2.22 2.07 2.36 2.22 2.14 2.31 2.35 2.41 2.29 2.42 2.45 2.19 2.20 2.23b 2.60 2.27 2.56 2.37 2.55 2.62 2.67 2.56 2.66 2.62 2.33 2.34 100.45 125.60 96.19 115.32 110.75 110.39 111.49 110.79 111.79 109.92 106.94 106.39 106.36 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 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 0.029 0.022 0.034 0.028 0.032 0.027 0.031 0.034 0.025 0.029 0.024 0.045 0.030 1.31 1.06 1.44 1.26 1.50 1.17 1.32 1.41 1.09 1.20 0.98 2.05 1.36 0 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 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 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 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 13685 2.12 2.58 121.70 0.021 0 99 0.019 0.90 0.82 38.68 0 24 11.32 13686 2.30 2.75 119.56 0.030 1 30 0.026 1.13 0.77 33.48 0 29 12.61 13687 2.34 2.43 103.85 0.029 1 24 0.025 1.07 0.91 38.89 0 27. 11.54 13688 2.08 2.55 122.60 0.031 1 49 0.031 1.49 1.02 49.04 0 49 23.56 13689 2.27 2.82 124.23 0.029 1 28 0.022 0.97 1.07 47.14 0 39 17.18 [2_ 13690 2.28 3.03 132.89 0.044 1 93 0.043 1.88 0.96 42.10 0 43 18.86 4_ .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. a. Rat 13670 had moderate dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). t_ b. Rat 13672 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 10): BRAIN WEIGHTS P GENERATION AND ORGAN MALE RATS WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. .................................................................................................................................... % BRW DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 13691 13692 13693 13694 13695 13696 13697 2.31 2.35 2.09 2.11 2.05 2.25 2.26 0.6510 0.7089 0.6386 0.7488 0.6307 0.6652 0.7278 28.18 30.16 30.56 35.49 30.76 29.56 32.20 0.2903 0.3304 0.2740 0.3793 0.2689 0.3142 0.3255 12.57 14.06 13.11 17.98 13.12 13.96 14.40 1.7748 1.8786 1.8515 1.6795 1.6411 1.9205 1.8740 76.83 79 94 88 59 79 60 80 05 85 36 82 92 1.6126 1.7780 1.7107 1.5725 1.5376 1.7789 1.7521 69.81 75.66 81.85 74.53 75.00 79.06 77.53 1.8099 2.3515 1.7267a 2.4684 1.9912 2.0129 2.2800 78.35 100.06 82.62a 116.98 97.13 89.46 100.88 1.1447 1.0306 1.0523 1.5301 1.2054 1.1453 1.2851 49.55 43.86 50.35 72.52 58.80 50.90 56.86 13698 13699 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 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 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 31.40 28.29 30 01 30 35 37 24 30 36 32 61 28 81 29 26 37 65 34 69 26 97 28 52 30 96 27 96 31 71 34 34 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 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 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 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 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 81.79 70.14 69.95 70.12 86.21 68.34 73.99 72.15 69.70 74.32 83.93 66.12 79.67 74.06 74.71 78.48 80 93 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 114.43 99.89 97.88 87.94 115.72 105.21 98.51 62.75b 96.43 131.26 122.89 109.77 95.40 100.42 86 09 100 56 124 53 1.3437 1.2605 1.2589 1.0487 1.3402 1.5376 1.3177 1.0436 1.3581 1.4232 1.4343 1.4163 1.0055 1.1139 1.0707 1.1951 1.3951 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 13715 13716 2.22 2.25 0.6832 0.7514 30 77 33 40 0.2975 0.3387 13.40 15.05 1.7745 2.0020 79.93 88.98 1.6450 1.8087 74 I0 80 39 2.2975 2.3873 103 49 106 10 1.1581 1.2017 52.17 53.41 13717 13718 2.43 2.18 0.7523 0.7349 30 96 33 71 0.3543 0.3363 14.58 15.43 1.8418 1.8380 75.79 84.31 1.7492 1.7356 71 98 79 61 2.4171 2.3115 99 47 106 03 1.3391 1.2358 55.11 56.69 13719 2.21 0.7209 32 62 0.3571 16.16 1.8179 82.26 1.6798 76 01 2.7956 126 50 1.5191 68.74 13720 2.15 0.7415 34 49 0.3476 16.17 1.8847 87.66 1.7681 82 24 2.9170 135 67 1.5807 73.52 _t_ .................................................................................................................................... O0 ALL WEIGHTS Damaged Damaged WERE RECORDED IN during processing during processing GRAMS. ABS. WT. = ORGAN (some fluid loss prior to (weight affected); values WEIGHT. weighing); excluded REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. values excluded from group averages and statistical from group averages and statistical analyses. analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 11): BRAIN WEIGHTS P GENERATION AND MALE ORGAN RATS WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13691 13692 13693 13694 13695 13696 2.31 2.35 2.09 2.11 2.05 2.25 0.6462 0.6514 0.4308 0.7073 0.6242 0.6590 27.97 27.72 20.61 33.52 30.45 29.29 1.6959 1.8472 1.5803 1.5982 1.5583 1.9059 73.42 78.60 75.61 75.74 76.01 84.71 1.1002 0.6953 0.9426 0.8671 1.1675 1.1603 47.63 29.59 45.10 41.09 56.95 51.57 0.009 0.013 0.014 0.012 0.016 0.019 0.39 0.55 0.67 0.57 0.78 0.84 30.43 27.20 30.49 28.77 30.35 29.83 1317.32 1157.45 1458.85 1363.51 1480.49 1325.78 2.23 2.42 2 34 2 75 2 29 2 99 96.54 102.98 111.96 130.33 111.71 132.89 13697 13698 2.26 2.35 0.7200 0.7592 31.86 32.31 1.8881 2.0050 83 54 85 32 1.1685 1.2923 51.70 54.99 0.013 0.008 0.58 0.34 28.85 27.33 1276.55 1162.98 2 16 2 61 95.58 111.06 13699 13700 13701 2.28 2.46 2.26 0.6287 0.7246 0.6728 27.57 29.46 29.77 1.6871 1.9501 1.7611 74 00 79 27 77 92 1.2763 0.8127 0.9267 55.98 33.04 41.00 0.015 0.014 0.017 0.66 0.57 0.75 19.75 31.22 22.78 866.23 1269.10 1007.96 2 II 2.37 2.03 92.54 96.34 89.82 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 13714 13715 13716 13717 13718 2.05 2.37 2.38 2.32 2.45 2.07 2.13 2.33 2.21 2.16 2.34 2 i0 2 17 2 22 2 25 2 43 2 18 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 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 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 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 0.9056 1.2401 1.4428 1.0972 1.1747 1.2753 0.8310 1.0523 0.7736 0.9264 0.8620 1.1091 1.0910 1.2177 1.0765 1.0506 0.6135 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 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 0.58 0.80 0.84 0.43 0.45 0 53 0 70 0 73 0 86 0 56 0 47 0 67 0.51 0.68 0.58 0.74 0.8"2 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 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 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 42 100.00 106.33 109.66 105.60 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 13719 13720 2 21 2.15 0.7150 0.7717 32.35 35.89 1.7551 1.8332 79.42 85.26 0.7355 1.2191 .................................................................................................................................... 33.28 56.70 0.013 0 009 0.59 0.42 32.24 31.49 1458.82 1464.65 2 31 2 48 104.52 115 35 [2_ 4_ OO ALL WEIGHTS WERE RECORDED IN GRAMS. Rat 13706 had a small and flaccid table (Table B16). ABS. HT. = ORGAN WEIGHT. right epididymis and right REL. % BRW = (ORGAN WEIGHT/BRAIN testis. See the individual necropsy WEIGHT) X I00. observations PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 12) : BRAIN WEIGHTS AND ORGAN WEIGHTS P GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... KIDNEY ADRENAL ADRENAL RAT BRAIN RIGHT LEFT RIGHT NUMBER WEIGHT ABS, REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL, % BRW DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... 13691 13692 13693 13694 13695 13696 13697 2,31 2.35 2.09 2.11 2.05 2.25 2.26 2.27 2 31 2 37 3 01 2 34 2 82 2 16 98.27 98,30 113.40 142.65 114.15 125.33 95.58 0.018 0.026 0.036 0.025 0.028 0.035 0.032 0.78 1.11 1.72 1.18 1.36 1.56 1.42 0.043 0.029 0.038 0.037 0.030 0.033 0.033 1.86 1.23 1.82 1.75 1.46 1.47 1.46 1 01 0 83 0 97 0 81 0 79 1 04 0 90 43.72 35.32 46.41 38.39 38.54 46,22 39.82 0.61 0.55 0.77 0.50 0.40 0 54 0 50 26.41 23.40 36.84 23.70 19.51 24.00 22,12 13698 13699 2.35 2.28 2,63 2.09 111,91 91.67 0,034 0.019 1.45 0 83 0,040 0.016 1,70 0.70 0 82 0 81 34.89 35.53 0 52 0 42 22.13 18.42 13700 13701 13702 13703 13704 13705 13706 13707 13708 13709 13710 13711 13712 13713 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 2.40 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 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 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 1 22 0 97 1 36 1 81 1 51 1.42 1.26 1,54 1.78 1.33 1,31 1.30 1.28 1.19 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 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 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 40.24 31.42 40.98 40.08 48.32 38.79 32.24 38.16 35.68 31.76 29.86 38.42 47.44 34.28 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 17.89 11.50 13.17 13.08 23.53 23.28 15.51 19.32 15.96 12.02 18.10 23.15 15.38 12.38 13714 2,17 2.13 98 16 0.026 1.20 0 051 2.35 0.52 23.96 0.18 8,29 13715 2.22 2.45 110.36 0.035 1.58 0 033 1.49 0 98 44.14 0.29 13.06 13716 2.25 2.60 115.56 0,028 1.24 0 026 1,16 0 79 35.11 0.24 10.67 13717 2.43 2.38a 97.94 0,030 1,23 0 032 1,32 0 87 35.8,0 0.39" 16.05 13718 2.18 2.33 106.88 0,037 1.70 0 033 1.51 0 93 42.66 0.25 11.47 13719 2.21 2.42 109.50 0.033 1.49 0 037 1.67 1 i0 49.77 0.47 21.27 [29 13720 2,15 2.56 119.07 0,022 1.02 0.026 1.21 1 03 47.91 0.23 10.70 4_ ........ - ........................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS, WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. a. Rat 13717 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). |_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 13): BRAIN WEIGHTS AND ORGAN P GENERATION MALE RATS WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... L. TESTIS MINUS TUNICAALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW DOSAGE GROUP V 30 ............................................................... MG/KG/DAY _ .................................................................... 13721 13722 13723 13724 13725 13726 13727 2.32 2.12 2.18 2.22 2.05 2.39 2.09 0.6074 0.6274 0.6173 0.6288 0.5636 0.5924 0.6562 26.18 29.59 28.32 28.32 27.49 24.79 31.40 0.2790 0.2822 0.2866 0.2856 0.2434 0.2529 0.3344 12.02 13.31 13.15 12.86 11.87 10.58 16.00 1.6557 2.0342 1.7454 1.7350 1.5799 1.6603 1.6767 71.37 95.95 80.06 78.15 77.07 69.47 80.22 1.5270 1.9065 1.6102 1.6175 1.4784 1.4205 1.5666 65.82 89.93 73.86 72.86 72.12 59.44 74.96 2.1394 1.9349 1.8187 1.8648 2.0211 2.3913 2.3512 92.22 91.27 83.43 84.00 98.59 100.05 112.50 1.1271 0.9897 1.0162 1.0530 1.1224 1.3574 1.2199 48 58 46 68 46 61 47 43 54 75 56 79 58 37 13728 2.40 0.6189 25.79 0.2708 11.28 1.8145 75.60 1.6036 66.82 1.6491 68.71 0.8819 36 74 _.. t_ 13729 13730 2.26 2.18 0.6563 0.7344 29.04 33.69 0.2832 0.3692 12.53 16.94 1.8213 1.9206 13731 13732a 2.10 1.83 0.6264 0.32 29.83 ..... 0.2816 b 13.41 .... 1.8082 1.57 13733 2.41 0.4488c 18.62 0.2281 9.46 1.5848 13734 2.25 0.6218 27.64 0.3056 13.58 1.7707 13735 2.22 0.6602 29.74 0.2885 13.00 1.6260 .................................................................................................................................... 80.59 88.10 86.10 .... 65.76 78.70 73.24 1.7046 1.7641 1.6879 b 0.7696c 1.6457 1.4871 75.42 80.92 80.38 ..... 31.93 73.14 66.99 2.7535 2.7822 2.2953 0.41 1.9756 1.9533 2.0416 121.84 127.62 109.30 ..... 81.98 86.81 91.96 1.6355 1.3529 1.3058 b 1.0945 1.0168 1.0459 72 37 62 06 62 18 ..... 45.41 45.19 47.11 ALL WEIGHTS WERE RECORDED IN GRAMS. a. Rat 13732 was moribund sacrificed b. Value was not recorded. ABS. WT. = ORGAN WEIGHT. on day 45 of study; values REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) excluded from group averages and statistical X 100. analyses. c. Rat 13733 had a small and flaccld left epidldymis observations table (Table B16). and left testis minus tunica albuginea. See the individual necropsy > C cn 4_ oo tJ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 14) : BRAIN WEIGHTS AND ORGAN WEIGHTS P GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY REL. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW .................................................................................................................................... 13736 13737 13738 13739 13740 1.95 2.09 2.25 2.16 2.47 0.6673 0.6265 0.7368 0.6346 0.6890 34.22 29.98 32.75 29.38 27.89 0.3010 0.2859 0.3496 0.2936 0.3195 15.44 13 68 15 54 13 59 12 94 1.8057 1.8269 1.8806 1.7360 1.8928 92.60 87.41 83.58 80.37 76.63 13741 2.18 13742 2.06 _I_ 13743 2.27 0.4128a 0.6057 0.6398 18.94 29.40 28.18 0.1813a 0.2949 0.3157 8 32 14 32 13 91 0.9095a 1.5689 1.7613 41.72 76.16 77.59 _-. tO2O_ 13744 2.25 0.6318 28.08 0.2745 12 20 1.7873 79.44 13745 2.32 0.5971 25.74 0.2785 12 00 1.7386 74.94 13746 2.20 0.6928 31.49 0.2873 13 06 1.7150 77.95 13747 1.88 0.6158 32.76 0.2828 15 04 1.9071 101.44 13748 2.28 0.7390 32.41 0.3243 14 22 2.0476 89.81 13749 2.27 0.7383 32.52 0.3499 15 41 1.9514 85.96 13750 2.04 0.6466 31.70 0.2750 13 48 2.8842b141.38 .................................................................................................................................... 1.6957 1.7194 1.7560 1.6485 1.7714 86.96 82.27 78.04 76.32 71.72 0.7763a 1.4689 1.6391 35.61 71.30 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 2.6964b132.18 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 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 WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = 0RGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN a. Rat 13741 had small and flaccid epididymides and testes. See the individual necropsy observations b. Rat 13750 had a large left epididymis table (Table BI6). and left testis minus tunica albuginea. See the individual WEIGHT) table necropsy X I00. (Table BI6). observations > O_ O0 C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B19 (PAGE 15): BRAIN WEIGHTS P GENERATION AND MALE ORGAN RATS WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13721 13722 13723 13724 13725 13726 2.32 2.12 2.18 2.22 2.05 2.39 0.5828 0.6248 0.6269 0.6778 0.6145 0.5830 25.12 29.47 28.76 30.53 29.98 24.39 1.6442 2.0050 1.6768 1.7229 1.6811 1.6140 70.87 94.58 76.92 77.61 82.00 67.53 0.8431 0,8430 0.5950 0.6971 0.7775 1.1966 36.34 39.76 27.29 31.40 37 93 50 07 PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW 0.015 0.013 0.010 0,009 0.005 0.011 0.65 0.61 0.46 0.40 0.24 0.46 32.46 26.38 25.29 20.55 24.05 26,25 1399.14 1244.34 1160.09 925.68 1173.17 1098.33 KIDNEY LEFT ABS. REL. WT. % BRW 2.04 1.97 1.96 2.05 1.65 2.21 87.93 92.92 89.91 92.34 80.49 92.47 13727 13728 2.09 2.40 0.6714 0.5943 32.12 24.76 1.6811 1 7995 80.44 74.98 1.1502 0.8251 55 03 34 38 0.009 0.011 0.43 0.46 27.77 33.99 1328.71 1416.25 2.08 1.89 99.52 78.75 13729 2.26 0.6131 27.13 1 7874 79.09 0 8078 35 74 0.008 0 35 30.46 1347 79 2.13 94.25 _.A 13730 2.18 tJ_ 13731 2.10 0.7137 0.6397 32.74 30.46 1 9707 1 7492 90.40 83.30 0.8931 0.6744 40 97 32 11 0.011 0.011 0.50 0.52 36.40 27.84 1669.72 1325.71 2.44 2.02 111.93 96.19 13732a 1.83 0.31 ..... 1 54 .... 0.34 .... 0,006 ..... 15.94 ....... 1.22 ..... 13733 2.41 0.7056 29.28 1 8567 77.04 0.9479 39.33 0.012 0.50 34.60 1435.68 2.19 90.87 13734 2.25 0.6340 28.18 1 7743 78.86 1.2570 55.87 0.007 0.31 28.30 1257.78 2.22 98.67 13735 2.22 0.6247 28.14 1.6311 73.47 0.9716 .................................................................................................................................... 43.76 0.007 0.32 26.33 1186.04 2.06 92.79 ALL WEIGHTS WERE RECORDED a. Rat 13732 was moribund IN GRAMS. sacrificed ABS. WT. = ORGAN WEIGHT. on day 45 of study; values REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) excluded from group averages and statistical X 100. analyses. > C ca 4_ oo to PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 16): BRAIN WEIGHTS AND ORGAN P GENERATION MALE RATS WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13736 13737 13738 13739 13740 13741 13742 13743 1.95 2.09 2.25 2.16 2.47 2.18 2.06 2.27 0.6535 0.6117 0.7239 0.6380 0.6731 0.3794a 0.6017 0.6511 33.51 29.27 32.17 29.54 27.25 17.40 29.21 28.68 1.7745 1.7991 1.9556 1.7722 1.8953 0.8606a 1.5535 1.7824 91.00 86.08 86.92 82.05 76.73 39.48 75.41 78.52 1.1293 0.6582 0.9491 0.6872 1.0956 0.5990 0.7266 0.8984 57 91 31 49 42 18 31 81 44 36 27 48 35 27 39 58 0.010 0.009 0.012 0.015 0.010 0.007 0.007 0.008 0.51 0.43 0.53 0.69 0.40 0.32 0 34 0 35 26.04 25.32 27.00 23.10 29.12 27.33 25.57 23.40 1335.38 1211.48 1200.00 1069.44 1178.95 1253.67 1241.26 1030.84 1.85 1.73 1.98 1.95 1.98 1.82 1.60 1.87 94.87 82.78 88.00 90.28 80.16 83.49 77.67 82.38 13744 13745 2.25 2.32 0.6378 0.5834 28.35 25.15 1 8145 1 7338 80.64 74.73 0.7553 0.8432 33 57 36 34 0.012 0.009 0 53 0 39 24.04 29.53 1068.44 1272.84 (_ 13746 2.20 0.6752 30.69 1 6953 77.06 0.8258 37 54 0.015 0 68 28.24 1283.64 13747 1.88 0.6142 32.67 1 8456 98.17 0.5597 29 77 0.016 0 85 23.29 1238.83 13748 2.28 0.7365 32.30 2 0122 88.25 1.0400 45 61 0.013 0 57 31.63 1387.28 13749 2.27 0.7260 31.98 1 8831 82.96 0.8505 37 47 0.011 0 48 27.03 1190.75 13750 2.04 0.6502 31.87 1 7065 83.65 0.8981 .................................................................................................................................... 44 02 0.013 0 64 25.92 1270.59 1.80 1.92 2.27 1.89 2.20 1.79 2.07 80.00 82.76 103.18 100.53 96.49 78.85 101.47 ALL WEIGHTS WERE RECORDED IN GRAMS. a. Rat 13741 had small and flaccid ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN epldidymides and testes. See the individual necropsy WEIGHT/BRAIN observations WEIGHT) X 100. table (Table B16). > C OC PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 17): BRAIN WEIGHTS P GENERATION AND MALE ORGAN RATS WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... RAT NUMBER BRAIN WEIGHT KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS . REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW SPLEEN ABS . WT. REL. % BRW THYMUS ABS. WT. REL. % BRW .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY ...... _ ............................................................................................................................. 13721 2.32 2.19 94.40 0.035 1 51 0.040 1.72 13722 2.12 2.19 103.30 0.035 1 65 0.035 1.65 13723 2.18 1.94 88.99 0.033 1 51 0.028 1.28 13724 2.22 2.01 90.54 0.042 1 89 0.037 1.67 13725 2.05 1.73 84.39 0.028 1 36 0.026 1.27 13726 2.39 2.20 92.05 0.029 1 21 0.039 1.63 13727 2.09 2.16 103.35 0.026 1 24 0.024 1.15 13728 2.40 1.94 80.83 0.028 1 17 0.025 1.04 13729 2.26 2.05a 90.71 0.020 0 88 0.014 0.62 _._ 13730 2.18 2.45 112.38 0.035 1 60 0.031 1.42 (_h 13731 2.10 2.05 97.62 0.028 1 33 0.026 1.24 _-_ 13732b 1.83 1.25 ..... 0.026 .... 0.026 .... 13733 2.41 2.31c 95.85 0.032 1.33 0.035 1.45 13734 2.25 2.30 102.22 0.022 0.98 0.023 1.02 13735 2.22 2.23 100.45 0.030 1.35 0.014 0.63 .................................................................................................................................... 0 76 0 80 0 72 0 79 0 45 0 93 0 75 0 67 0 52 0 70 0 57 0 13 0 94 0 69 0 97 32.76 37.74 33.03 35.58 21.95 38.91 35.88 27.92 23.01 32.11 27.14 ..... 39.00 30.67 43.69 0.36 0.49 0.37 0.49 0.20 0 51 0 28 0 25 0 25 0 38 0 18 0 12 0 28 0 32 0 40 15.52 23.11 16.97 22.07 9.76 21.34 13.40 10.42 11.06 17.43 8.57 .... 11.62 14.22 18.02 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. a. Rat 13729 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). b. Rat 13732 was moribund sacrificed on day 45 of study; values excluded from group averages and statistical analyses. c. Rat 13733 had slight dilation of the pelvis of the right kidney. See the individual necropsy observations table (Table B16). > C 4_ OO 6, 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LI%_I'ER PER GENERATION) (APFO} IN RATS (SPONSOR'S STUDY NL_4BER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE BI9 (PAGE 18} : BRAIN WEIGHTS AND ORGA}I WEIGHTS P GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - C_ _') .................................................................................................................................... RAT NUMBER BRAIN WEIGHT KIDNEY RIGHT ABS. REL. ADRENAL LEFT ABS. REL. ADRENAL RIGHT ABS. REL. WT. % BRW WT. % BRW WT. .................................................................................................................................... % BRW DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13736 1.95 1.99 102.05 0 030 1.54 0.023 13737 2.09 1.79 85.64 0 021 1.00 0.017 13738 2.25 1.95 86.67 0 037 1.64 0.032 13739 2.16 2.01 93.06 0 026 1.20 0.025 13740 2.47 2.15 87.04 0 024 0.97 0.027 13741 2.18 2.02 92.66 0 009 0.41 0.014 13742 2.06 1.64 79.61 0 027 1.31 0.029 13743 2.27 1.93 85.02 0.020 0.88 0 026 13744 2.25 1.94 86.22 0.029 1.29 0 028 13745 2.32 2.07 89.22 0.026 1.12 0 026 13746 13747 2.20 1.88 2.20 1.93 100.00 102.66 0.028 0.031 1.27 1.65 0 025 0 020 13748 2.28 2.43 106.58 0.032 1.40 0 030 13749 2.27 1.78 78.41 0.029 1.28 0.028 13750 2.04 2.04 100.00 0.021 1.03 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 ALL WEIGHTS WERE RECORDED IN GRAMS. ABS. WT. = ORGAN WEIGHT. REL. SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW 0.72 0.65 0.73 0.69 0.80 0.42 0.86 0.62 0.58 0.73 0.74 0.51 1.09 0.87 1.06 36.92 31.10 32.44 31.94 32.39 19.27 41.75 27.31 25.78 31.46 33.64 27.13 47.81 38.32 51.96 0.28 0.20 0.32 0.25 0.27 0.20 0.17 0.20 0.29 0.28 0.35 0.27 0.38 0.29 0.27 % BRW = (ORGAN WEIGHT/BRAIN 14.36 9.57 14.22 11.57 i0 93 9 17 8 25 8 81 12 89 12 07 15.91 14.36 16.67 12.78 13.24 WEIGHT) X 100. > _n 4= oo 5.) o PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B20 (PAGE 1): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID (See footnotes at the end of this table.} COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS .___E.9..R._.................................L._...G...L._.G.L._....................................................... RAT NUMBER MOTILE STATIC COUNT TOTAL SPERM SPERM SPERMATID SPERMATID _..BE.R......M.g.!.5..L.E....P.E._...C_.....!.N.g.._g!.._.L.E._..2.9.._ia.......C.g...T_.b.....D.E.N.SSLIc ....._...-._.!....._...9._.-.N._!.Y.-_.... 13601 267 92 22 289 79 770,5 38 85.1 13602 189 87 29 218 111 1040.5 36 68.4 13603 392 86 64 456 89 770.6 45 78.4 13604 408 92 37 445 77 710.3 33 56.3, 13605 400 85 72 472 118 963.4 66 111.8 13606 502 84 93 595 136 1089.5 36 59.2 13607 380 92 34 414 128 1156.0 75 124.4 13608 359 88 50 409 143 1198.0 68 113.3 13609 13610 13611 13612 13613 13614 13615 13616 13617 13618 13619 13620 13621 13622 13623 13624 13625 13626 13627 13628 13629 13630 123 409 247 458 360 428 375 269 548 229 155 372 413 286 267 398 392 454 355 373 394 417 34 240 363 38 512.5 27 54.2 88 58 467 132 1324.4 59 115.0 76 76 323 91 804.8 91 158.4 89 54 512 120 1202.4 56 99.5 88 50 410 95 913.0 67 120.3 79 112 540 60 635.1 52 101.7 89 47 422 145 1148.5 67 105.8 80 68 337 129 1046.1 71 112.6 81 127 675 117 972.8 47 82.4 85 42 271 117 978.7 38 63.6 63 91 246 89 648.0 50 78.4 77 113 485 95 794.5 53 89.9 87 60 473 146 1284.9 29 161.0 88 40 326 147 1345.2 82 141.2 83 53 320 137 1017.2 50 91.6 > 89 47 445 205 1764.4 45 77.1 91 38 430 83 800.6 56 96.8 85 83 537 63 '481.4 37 58.4 U_ 85 61 416 83 752.2 44 81.7 84 73 446 133 1023.2 37 59.9 _" OO 75 131 525 125 1093.4 37 69.0 76 133 550 88 637.5 30 44.4 |_ PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) , REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B20 (PAGE 2): CAUDA EPIDIDYMJtL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID (See footnotes at the end of this table.) COUNT - INDIVIDUAL DATA P GENERATION MALE RATS ..m_. 999_E.. RAT 992_.P..{ _ ...................................................... NUMBER MOTILE STATIC COUNT 13631 13632 13633 13634 13635 13636 13637 13638 1133663490 13641 13642 13643 13644 13645 13646 13647 13648 13649 13650 13651 13652 13653 13654 13655 13656 13657 13658 13659 13660 530 274 403 264 178 440 554 350 214948 541 407 302 177 272 225 328 430 410 305 300 205 370 227 562 470 417 490 280 243 87 82 84 51 89 49 83 56 70 77 82 96 88 75 78 101 9825 2315 86 89 84 78 93 22 80 45 84 52 69 101 67 159 80 110 79 109 84 56 92 27 95 10 89 48 88 31 89 66 93 37 91 43 84 95 88 39 89 31 _._.G. _9./.99.Y. TOTAL ............................................................................... SPERM SPERM SPERMATID 612 325 452 320 255 536 629 451 226353 630 485 324 222 324 326 487 540 519 361 327 215 418 258 628 507 460 585 319 274 I01 974.5 40 i01 922.8 45 69 562.9 44 103 884,4 56 98 1007.8 49 93 763.2 42 98 825.5 42 54 559.5 39 114370 11404613..05 5516 104 853.0 47 114 1046.9 40 138 1174,8 49 112 1012,4 49 130 1181,4 32 199 1662,3 31 104 1008,9 68 135 1274,5 48 132 1248.7 28 78 784.5 65 180 1586.5 59 212 1898.0 50 117 1215.7 62 99 975.7 60 162 1405.2 72 170 '1418.0 41 ii0 1041.6 40 72 789.8 24 152 1386.2 30 71 636.8 18 SPERMATID 74.9 71.2 77.3 97.7 91,5 72.7 79.7 62.3 19113..75 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 > _'_ _n O__'_ bO PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B20 (PAGE 3): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID (See footnotes at the end of this table.) COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS DOSAGE RAT GROUP III NUMBER MOTILE STATIC COUNT 3 MG/KG/DAY TOTAL SPERM SPERM SPERMATID SPERMATID ..N_B..oER........... MOTI.LE 13661 261 13662 387 13663 258 13664 288 13665 424 13666 392 13667 508 13668 423 .......... PE_R.CENT ........(NO_NMOT ILEJ ......... CO.UNT. _a .......... _COUN_T_.b ........ DENS_I.TY. c ........ COUNT. 94 17 278 87 773 .4 40 87 59 446 132 1176.0 48 87 40 298 118 926.5 48 63 172 460 95 845.6 49 82 94 518 86 826.5 53 89 46 438 77 762 .0 43 93 37 545 78 684.4 39 92 37 460 72 853.6 56 d......... .D_E_NSIT.Y__e.. 66 .3 85.8 78 .9 83 0 96 4 72 .0 74 .7 108 1 13669 424 86 70 494 117 1053.4 63 114 .0 1133667701 259083 9912 3413 352496 18753 1834628..94 9580 18681..32 13672 270 83 54 324 64 671 0 29 51 0 13673 451 13674 549 90 48 499 83 112 661 90 944 .6 47 87 .6 87 885.8 64 119.9 13675 512 90 56 568 131 1132 9 32 62 .7 13676 523 92 47 570 121 1076.0 59 93 .3 13677 376 93 27 403 139 1319.2 46 83 .6 13678 358 79 94 452 76 704 .9 39 71 .2 13679 293 90 33 326 134 1177.5 27 47.3 13680 269 88 36 305 107 971.5 43 70.2 13681 235 73 85 320 79 678 .9 80 119.8 13682 391 87 60 451 183 1520.7 50 75 .1 13683 453 13684 549 13685 221 91 44 497 214 2099.2 54 100 .5 > 87 84 633 105 1033 8 42 77.0 94 13 234 180 1641.5 43 73 .4 _'_ 13686 411 88 57 468 82 825 ,3 57 98 .5 Cn 13687 357 81 83 440 107 969.1 34 66.1 13688 245 82 54 299 i00 803 3 37 56.0 _'_ O_ 13689 252 85 45 297 138 11952 26 47 1 ....1.3.6.9.0..........3......I..L...........2....{.............2.4..........3.4.1.........7.8.........7.4.0_.3...................2..4...................4..2..3...............o.... PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B20 (PAGE 4): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID (See footnotes at the end of this table.) COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS 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 NUMBER 353 328 368 202 517 305 248 467 283 334 237 355 385 305 456 241 401 334 251 535 294 396 302 247 447 273 210 412 397 264 MOTILE 85 86 89 83 82 83 86 88 91 89 81 93 86 88 90 85 93 92 85 87 94 93 89 80 86 87 83 87 96 86 STATIC COUNT 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 TOTAL 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 SPERM DENSITY c 1026.3 884.3 823.5 1197.4 1011.2 662.9 968.7 1163.6 SPERMATID COUNT d 26 40 63 46 30 33 62 59 SPERMATID DENSITY e 46.6 65.1 106.5 84.6 56.4 53.7 102.4 88.8 106 1103.0 48 86.8 100 837.3 86 834.2 70 117.7 36 65.7 121 1040.5 51 83.5 129 1154.6 55 98.2 278 2273.6 42 69.0 92 973.4 46 79.5 89 733.3 71 120,3 162 1257.0 59 110.9 152 1315,3 52 84.1 69 689.7 51 95.8 86 857.0 143 1336.5 69 113.4 43 77.8 84 837.0 55 91.0 139 1268.0 121 1063.6 72 700.1 128 _093.2 160 1306.3 81 696.7 58 101.8 > 38 62.6 30 52.8 _'_ 59 94.4 OO 29 48,0 4_ 19 31.7 _-" OO 179 1450.0 26 44.8 105 873.8 25 40.9 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B20 (PAGE 5): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID (See footnotes at the end of this table.) COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS ..D_._P._.9_._?.._ RAT ...................................................... NUMBER MOTILE STATIC COUNT _2. _P. d_.D. TOTAL _Y. .............................................................................. SPERM SPERM SPERMATID SPERMATID 13721 498 13722 375 13723 386 13724 208 13725 457 13726 368 13727 243 13728 420 92 44 542 82 850.2 40 75.8 82 81 456 87 891.8 44 66.8 84 71 457 64 646.0 39 70.1 75 68 276 105 1063.5 48 85.8 81 105 562 57 677.4 41 80.2 77 107 475 80 915.1 36 73.3 89 29 272 134 1159.2 82 151.4 88 59 479 70 747.7 43 77.6 13729 188 80 46 234 107 1092.9 49 83.2 13730 345 90 37 382 157 1230.1 51 83.6 13731 477 86 78 555 118 1212.1 52 89.1 13732 MORIBUND SACRIFICED ON DAY 45 OF STUDY 13733 106 90 12 118 1 12.7 2 7.5 13734 321 90 34 355 115 1088.6 74 130.1 13735 320 81 73 393 69 691.8 44 85.6 13736 710 92 60 770 85 816.9 66 112.6 13737 294 65 158 452 122 1234.4 52 87.5 13738 266 78 73 339 173 1431.5 55 90.6 13739 262 86 41 303 105 1034.5 38 66.7 13740 388 86 61 449 101 914.4 41 67.0 13741 108 58 79 187 13 207.4 3 11.2 13742 179 68 83 262 113 1108.4 42 82.7 13743 320 96 15 335 119 1090.4 41 72.4 > 13744 392 93 31 423 91 959.0 41 70.2 13745 440 89 53 493 130 1350.3 37 65.4 13746 273 13747 228 90 31 304 102 '1027.0 41 72.6 OO 82 49 277 77 787.6 39 62.7 13748 218 84 42 260 131 1168.5 39 59.4 OO 13749 470 90 51 521 125 1033.4 34 53.8 13750 235 91 23 258 113 1188.6 23 24.7 t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER PER GENERATION) (APFO} IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE B20 (PAGE 6) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - P GENERATION MALE RATS FOOTNOTES : 20 fields were evaluated. b. Sperm count used in the calculation of sperm density. Ten fields were evaluated. c. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10 "6mL), multiplying by 2 (dilution factor) and multiplying by 10.6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table B17 for the weight of the left cauda epididymis) to obtain the sperm density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. d. Spermatid count used in the calculation of spermatid density. Ten flelds were evaluated. e. The spermatid density was calculated by dividing the spermatid count by the volume in the image area (34.3 x 10.6mL), multiplying by 2 (dilution factor) and multiplying by 10.6 to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis minus tunica albuginea (see Table B18 for the weight of the left testis minus tunica albuginea) to obtain the spermatid density. _'_ The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image 0% OO evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an overestimate of the concentration. > C U_ 0o O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B21 (PAGE 1): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION STUDY OF AMMONIUM PERFLUOROOCTANOATE MALE RATS .................................................................................................................................... BROKEN EXCES- COILED RAT DETACHED NO FLAGEL- NO SIVE FLAGEL- NUMBER NORMAL HEAD HEAD LUM HOOK HOOK LUM .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13601 193 6 1 0 0 0 0 13602 199 0 1 0 0 0 0 13603 192 3 4 1 0 0 0 13604 189 9 2 0 0 0 0 13605 189 8 3 0 0 0 0 13606 190 13607 197 7 3 0 0 0 0 2 1 0 0 0 0 13608 194 4 1 1 0 0 0 13609 60 64 75 1 0 0 0 13610 189 6 5 0 0 0 0 13611 179 15 6 0 0 0 0 13612 186 9 5 0 0 0 0 13613 197 2 1 0 0 0 0 13614 187 6 7 0 0 0 0 13615 189 9 2 0 0 0 0 13616 188 10 2 0 0 0 0 13617 193 6 1 0 0 0 0 13618 181 10 9 0 0 0 0 13619 192 5 2 1 0 0 0 13620 191 8 1 0 0 0 0 13621 193 5 2 0 0 0 0 13622 191 3 4 1 1 0 0 13623 192 6 2 0 0 0 0 13624 191 6 3 0 0 0 0 13625 196 2 2 0 0 0 0 13626 195 4 1 0 0 0 0 13627 195 13628 197 2 2 1 0 0 0 2 1 0 0 0 0 13629 196 1 3 0 0 0 0 13630 192 5 3 0 0 0 0 .................................................................................................................................... BENT FLAGEL- LUM 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 SHORT SPERM HEAD 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 OTHER 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 3.5 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 O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6} REPRODUCTION TABLE B21 (PAGE 2): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION .................................................................................................................................... BROKEN EXCES- COILED RAT DETACHED NO FLAGEL- NO SIVE FLAGEL- NUMBER NORMAL HEAD HEAD LUM HOOK HOOK LUM .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13631 194 13632 191 3 3 0 0 0 0 6 3 0 0 0 0 13633 193 5 2 0 0 0 0 13634 185 4 8 3 0 0 0 13635 188 7 2 3 0 0 0 13636 195 3 2 0 0 0 0 13637 195 3 2 0 0 0 0 13638 160 20 19 1 0 0 0 13639 196 1 2 1 0 0 0 BENT FLAGEL- LUM 0 0 0 0 0 0 0 0 0 SHORT SPERM HEAD 0 0 0 0 0 0 0 0 0 STUDY OF AMMONIUM MALE RATS OTHER 0 0 0 0 0 0 0 0 0 PERFLUOROOCTANOATE PERCENT ABNORMAL 3.0 4,5 3.5 7.5 6,0 2.5 2.5 20.0 2.0 136401 18975 13642 196 61 74 0 0 0 0 0 0 0 2 2 0 0 0 0 0 0 0 13643 197 3 0 0 0 0 0 0 0 0 13644 194 3 2 1 0 0 0 0 0 0 13645 197 13646 195 1 1 1 0 0 0 0 0 0 2 3 0 0 0 0 0 0 0 13647 197 0 3 0 0 0 0 0 0 0 13648 186 8 6 0 0 0 0 0 0 0 13649 197 2 1 0 0 0 0 0 0 0 13650 192 4 3 1 0 0 0 0 0 0 13651 190 5 4 1 0 0 0 0 0 0 13652 191 5 4 0 0 0 0 0 0 0 13653 185 i0 2 2 0 1 0 0 0 0 13654 191 4 2 3 0 0 0 0 0 0 13655 196 1 2 1 0 0 0 0 0 0 13656 196 1 3 0 0 0 0 0 0 0 13659 193 13658 191 7 0 0 0 0 0 0 0 0 2 6 1 0 0 0 0 0 0 13659 189 7 4 0 0 0 0 0 0 0 13660 191 5 3 0 0 1 0 0 0 0 .................................................................................................................................... 62.5 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 Cn OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B21 (PAGE 3): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION STUDY OF AMMONIt_ PERFLUOROOCTANOATE MALE RATS BROKEN EXCES- COILED RAT DETACHED NO FLAGEL- NO SIVE FLAGEL- NUMBER NORMAL HEAD HEAD LUM HOOK HOOK LUM .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13661 198 13662 195 13663 196 13664 185 13665 190 2 0 0 0 0 0 4 1 0 0 0 0 2 2 0 0 0 0 5 8 1 0 0 1 4 5 1 0 0 0 13666 189 13667 193 13668 194 13669 193 6 2 2 1 0 0 0 6 1 0 0 0 2 4 0 0 0 0 4 2 1 0 0 0 13670 188 13671 189 4 8 0 0 0 0 4 7 0 0 0 0 13672 194 4 2 0 0 0 0 13673 191 7 2 0 0 0 0 13674 172 13 13 1 0 1 0 13675 194 4 1 1 0 0 0 13676 189 8 3 0 0 0 0 13677 194 2 4 0 0 0 0 13678 195 1 4 0 0 0 0 13679 187 7 5 1 0 0 0 13680 195 2 2 1 0 0 0 13681 197 2 1 0 0 0 0 13682 194 5 1 0 0 0 0 13683 187 7 6 0 0 0 0 13684 191 6 2 1 0 0 0 13685 195 3 2 0 0 0 0 13686 181 11 8 0 0 0 0 13687 194 13688 194 3 1 2 0 0 0 3 3 0 0 0 0 13689 193 4 3 0 0 0 0 13690 189 7 4 0 0 0 0 .................................................................................................................................... BENT FLAGEL- LUM 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 SHORT SPERM HEAD 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 O 0 0 0 OTHER 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 10 25 20 75 50 55 35 30 35 60 55 30 45 14 0 30 55 30 25 65 25 15 30 65 45 25 95 30 30 35 _'_ 55 _#_ 4= o_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE B21 (PAGE 4) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION STUDY OF AMMONIUM PERFLUOROOCTANOATE MALE RATS BROKEN EXCES- COILED RAT NUMBER NORMAL DETACHED HEAD NO HEAD FLAGELLUM NO HOOK SIVE HOOK FLAGELLUM .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13691 195 13692 193 13693 193 13694 186 13695 193 13696 186 13697 194 13698 194 13699 192 5 0 0 0 0 0 7 0 0 0 0 0 5 1 0 1 0 0 6 8 0 0 0 0 2 5 0 0 0 0 9 4 0 1 0 0 3 3 0 0 0 0 4 2 0 0 0 0 6 1 0 0 0 0 13700 192 5 2 1 0 0 0 13701 184 11 4 1 0 0 0 13702 196 2 2 0 0 0 0 13703 189 9 2 0 0 0 0 13704 191 8 0 0 0 1 0 13705 193 4 3 0 0 0 0 13706 187 9 4 0 0 0 0 13707 190 10 0 0 0 0 0 13708 183 8 9 0 0 0 0 13709 189 5 6 0 0 0 0 13710 188 9 1 1 0 0 1 13711 194 3 2 1 0 0 0 13712 192 7 1 0 0 0 0 13713 194 1 4 1 0 0 0 13714 194 1 5 0 0 0 0 13715 185 11 3 1 0 0 0 13716 193 2 5 0 0 0 0 13717 193 13718 193 5 2 0 0 0 0 6 1 0 0 0 0 13719 193 5 2 0 0 0 0 13720 188 8 4 0 0 0 0 .................................................................................................................................... BENT FLAGEL- LUM 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 SHORT SPERM HEAD 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 OTHER 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 2.5 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 4= O0 _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6| REPRODUCTION TABLE B21 (PAGE 5): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - P GENERATION .................................................................................................................................... BROKEN EXCES- COILED RAT DETACHED NO FLAGEL- NO SIVE FLAGEL- NUMBER NORMAL HEAD HEAD LUM HOOK HOOK LUM .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13721 195 13722 193 13723 187 13724 196 13725 193 13726 196 13727 190 13728 190 4 1 0 0 0 0 4 2 1 0 0 0 7 5 1 0 0 0 1 3 0 0 0 0 2 3 2 0 0 0 3 1 0 0 0 0 8 2 0 0 0 0 3 6 1 0 0 0 13729 194 13730 190 13731 191 3 2 1 0 0 0 7 3 0 0 0 0 5 4 0 0 0 0 13732 MORIBUND SACRIFICED ON DAY 45 OF STUDY 13733 4 6 3 0 0 0 0 13734 196 1 3 0 0 0 0 13735 188 ii 1 0 0 0 0 13736 190 5 3 2 0 0 0 13737 189 3 7 1 0 0 0 13738 191 2 7 0 0 0 0 13739 194 2 2 1 0 1 0 13740 191 5 4 0 0 0 0 13741 3 83 94 17 1 1 1 13742 192 5 2 1 0 0 0 13743 191 7 2 0 0 0 0 13744 192 6 1 1 0 0 0 13745 194 4 2 0 0 0 0 13746 187 9 3 0 0 0 0 13747 197 1 1 0 1 0 0 13748 198 1 1 0 0 0 0 13749 194 2 2 0 1 0 0 13750 175 15 8 2 0 0 0 .................................................................................................................................... BENT FLAGEL- LUM 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 SHORT SPERM HEAD 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 STUDY OF AMMONIUM MALE RATS OTHER 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 PERFLUOROOCTANOATE PERCENT ABNORMAL 25 35 65 20 35 20 50 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 > _'_ 4_ O0 6 ARGUS 418-020 APPENDIX C REPORT TABLES - P GENERATION FEMALE RATS Page 174 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C1 (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE ...... - ............................................................................................................................. DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION): MAXIMUM POSSIBLE INCIDENCE 2098/ 30 2089/ 30 2100/ 30 2100/ 30 2100/ 30 MORIBUND SACRIFICED la lb 0 0 0 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 13/ 3 12/ 2 1/ la 6/ 1 6/ 1 0/ 0 16/ 1 0/ 0 16/ 1 26/ 1 13/ 1 13/ 1 48/ 2 27/ 2 39/ 1 CHROMORHINORRHEA i/ la 6/ 1 5/ 3 i/ 1 2/ 1 UNGROOMED COAT _- SCAB(S) c La CHROMODACRYORRHEA LOCALIZED ALOPECIA: TOTAL LIMBS UNDERSIDE 0/ 0 71 1 i/ la 84/ 2 84/ 2 0/ 0 0/ 0 01 0 0/ 0 51/ 2 39/ 1 12/ 1 0/ 0 01 0 3/ 1 0/ 0 0/ 0 0/ 0 0/ 0 71 1 13/ 1 0/ 0 0/ 0 0/ 0 LEFT FORELIMB AND FOREPAW: SWOLLEN 0/ 0 3/ lb 0/ 0 0/ 0 SOFT OR LIQUID FECES 0/ 0 3/ 1 0/ 0 0/ 0 LEFT FORELIMB: FRACTURED 0/ 0 I/ ib 0/ 0 0/ 0 PALATE : BROKEN i/ la 0/ 0 0/ 0 0/ 0 SWOLLEN SNOUT 1/ la 0/ 0 ............................................................................................ STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED N/N _ TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13804 was moribund sacrificed on day 68 of study. b. Rat 13836 was moribund sacrificed on day 59 of study. c. Located on the back, right forelimb or left forelimb, TO THE NUMBER PER GROUP. 0/ 0 0/ 0 OF RATS ,........................................ WITH OBSERVATIONS. 1/ 1 01 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 O/ 0 0/ 0 0/ 0 0/ 0 > O [/9 ___4_ O0 tOO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C1 (PAGE 2): CLINICAL OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... PRESUMED GESTATION: a III 3 STUDY OF AMMONIUM PERFLUOROOCTANOATE IV V 10 30 MAXIMUM POSSIBLE MORTALITY INCIDENCE 640/ 29 0 642/ 29 0 641/ 29 0 595/ 27 0 640/ 29 0 LOCALIZED ALOPECIA: RIGHT OR BOTH EARS: TOTAL LIMBS UNDERSIDE SWOLLEN 26/ 3 26/ 3 o/ o 18/ 1 37/ 2 22/ 1 151 1 0/ 0 7/ 1 7/ 1 o/ o 15/ 1 17/ 1 17/ 1 o/ o 15/ i 15/ 2 15/ 2 o/ o 28/ 2 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 19/ 1 0/ 0 19/ 1 0/ 0 0/ 0 0/ 0 22/ 1 0/ 0 22/ I 42/ 3 20/ 2 22/ 1 21/ 1 13/ i 21/ 1 0% CHROMORHINORRHEA 0/ 0 0/ 0 0/ 0 i/ 1 i/ 1 HEAD: MASS 01 0 01 0 01 0 01 0 31 i CHROMODACRYORRHEA 19/ 1 0/ 0 3/ 1 4/ 2 0/ 0 DRIED, RED PBRINASAL SUBSTANCE 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 BOTH FOREPAWS: DRIED, RED SUBSTANCE 0/ 0 0/ 0 0/ 0 1/ 1 0/ 0 LEFT HINDPAW: SWOLLEN 0/ 0 0/ 0 18/ 1 0/ 0 0/ 0 LEFT HINDPAW OR LOWER MIDLINE: SCAB 0/ 0 6/ 1 4/ 1 0/ 0 0/ 0 > LEFT HINDPAW: ABRASION 0/ 0 0/ 0 3/ I 0/ 0 0/ 0 ........................................................................................... STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Restricted to rats with a confirmed mating date. TO THE NUMBER PER GROUP. OF RATS _ ........................................ WITH OBSERVATIONS. [2_ 4_ Oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C1 (PAGE 3}: CLINICAL OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... LACTATION: III 3 STUDY OF AMMONIUM PERFLUOROOCTANOATE IV V i0 30 MAXIMUM POSSIBLE MORTALITY SACRIFICED a INCIDENCE 602/ 28 lb 583/ 27 lc 638/ 29 0 638/ 29 0 617/ 29 0 LOCALIZED ALOPECIA: RIGHT OR BOTH EARS: TOTAL LIMBS UNDERSIDE HEAD SWOLLEN 34/ 3 34/ 3 0/ 0 01 0 27/ 2 49/ 3 42/ 3 22/ 1 01 0 19/ 1 2/ 2 2/ 2 0/ 0 01 0 0/ 0 22/ 1 22/ 1 0/ 0 01 0 32/ 3 30/ 4 23/ 3 0/ 0 71 1 49/ 3 _._ INCISORS: TOTAL --_ MISSING/BROKEN "_ MISALIGNED 22/ i 0/ 0 22/ 1 0/ 0 0/ 0 0/ 0 22/ 1 16/ 1 22/ 1 31/ 2 9/ 1 22/ 1 16/ 1 16/ 1 14/ 1 CHROMODACRYORP/4EA 22/ 1 0/ 0 0/ 0 4/ 1 I0/ 1 HEAD OR RIGHT AXILLA: HEAD: SCAB MASS 0/ 0 01 0 0/ 0 01 0 0/ 0 01 0 3/ 1 01 0 4/ 1 71 1 SOFT OR LIQUID FECES TRAUMATIZED CORNEA 8/ 5 0/ 0 4/ 2 0/ 0 2/ 1 19/ 1 6/ 2 0/ 0 0/ 0 0/ 0 RIGHT EYE: SWOLLEN 0/ 0 0/ 0 I0/ i 0/ 0 0/ 0 TEAT: SWOLLEN 0/ 0 0/ 0 2/ 1 0/ 0 0/ 0 .................................................................................................................................... STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. [29 N/N = TOTAL NT24BER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed OO because it was not possible to identify to which litter the pups belonged. b. Dam 13822 was sacrificed c. Dam 13852 was sacrificed on day on day 8 of lactation. 11 of lactation. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C2 (PAGE 1): BODY WEIGHTS - PRECOHABITATION - SUMMARY - P GENERATION FEMALE RATS ...... - ............................................................................................................................. DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 30 30 30 30 30 BODY WEIGHT (G) DAY 1 MEAN+S.D. 147.8 + 7.3 148.0 + 5.7 149.3 6.5 149.4 6.5 148.9 + 6.7 DAY 8 MEANS.D. 177.7 9.1 175.3 7.3 181.3 + 8.2 180.6 + 9.3 178.8 7.0 DAY 15 MEAN+S.D. 202.4 + 12.2 199.2 ii.i 206.9 + 11.8 205.9 + 12.0 202.7 + 8.2 DAY 22 MEAN+S.D. 218.5 15.0 214.5 + 14.1 224.1 + 15.8 223.1 + 14.7 217.4 9.6 DAY 29 0_ DAY 36 -U O0 DAY 43 MEAN+S.D. MEAN+S.D. MEAN+S.D. 234.5 18.5 243.7 + 18.2 252.8 + 20.9 228.0 + 15.5 236.7 + 16.6 245.9 + 16.1 239.8 19.6 249.2 + 21.5 259.7 + 24.2 238 4 _ 15.8 247.9 + 16.9 257.8 + 17.2 233.0 10.2 238.9 + 10.1 250.1 11.1 DAY 50 MEAN+S.D. 262.8 + 20.4 255.8 + 17.6 269.0 + 25.5 268.3 + 18.0 258.8 + 11.7 DAY 57 MEAN+S.D. 268.9 + 22.4 261.3 + 17.4 276.9 + 25.9 272.8 + 19.0 264.0 + 13.3 ...... DAY 64 MEAN+S.D. 274.4 f 22.2 268.5 + 18.2 [ 29]a DAY 70b MEAN+S.D. 276.8 + 22.7 271.8 + 18.1 [ 29] a [ 29] a . ............................................................................................................................. 284.2 27.1 287.2 27.6 279.7 19.2 284.4 + 21.8 267.5 + 13.0 271.8 + 14.0 DAY = DAY OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were moribund sacrificed. > b. Last value recorded before cohabitation. _% C 4= o_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C3 (PAGE i) : BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 30 30 30 30 30 BODY WEIGHT CHANGE (G) DAYS 1- 8 MEAN+S.D. +30.0 + 7.5 +27.3 5.2 +32.0 + 4.7 +31.2 4.8 +30.0 4.1 DAYS 8 - 15 MEAN+S.D. +24.6 + 6.0 +23.9 f 5.4 +25.6 4.9 +25.3 + 5.8 +23 8 + 4.7 DAYS 15 - 22 MEAN+S.D. +16.1 + 5.5 +15.3 + 5.2 +17.2 + 7.0 +17.2 + 6.0 +14 7 f 4.8 DAYS 22 - 29 MEAN+S.D. +16.0 + 7.0 +13.5 + 4.0 +15.7 + 5.6 +15.3 3.9 +15 6 4 1 DAYS 29 - 36 MEAN+S.D. +9.2 + 6.9 +8.8 i 5.4 +9.5 + 4.5 +9.5 i 3.6 +6 0 + 4 9* _._ DAYS 36 - 43 MEANS.D. +9.1 + 5.3 +9.1 + 5.3 +10.5 + 5.2 +9.9 + 4.1 +ii 1 + 4 6 k_ DAYS 43 - 50 MEAN+S.D. +I0.0 + 5.8 +9.9 + 4.5 +9.2 + 5.1 +10.4 + 4.8 +8 7 + 5 1 DAYS 50 - 57 MEAN+S.D. +6.1 + 5.7 +5.5 + 4.4 +7.9 + 5.1 +4.6 + 5.0 +5.2 + 3 8 DAYS 57 - 64 MEANS.D. +5.5 + 5.8 +6.4 4.9 ( 29] a DAYS 64 - 70b MEANfS.D. +2.6 + 5.4 [ 29]a +3.3 3.6 [ 29]a DAYS 1 - 70b MEANfS.D. +129.3+ 21.7 +124.1 17.1 [ 29]a [ 29]a .................................................................................................................................... +7.3 3.8 +3.1 + 5.0 +138.0+ 24.1 +6.9 5.9 +4.7 5.6 +134.9 18.7 +3.5 5 9 +4.3 5.5 +123.0 13.4 DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were moribund sacrificed. > b. Last value recorded before cohabitation. * Significantly different from the Group I value (p<0.05). 5_ 4_ O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION} T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C4 (PAGE i) : MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 I0 30 .................................................................................................................................... RATS TESTED N 29a 29a 30 30 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 28 27 29b 27b 28b MATERNAL BODY WEIGHT (G) DAY 0 MEANS.D. 280.3 + 24.2 272.0 + 19.2 283.5 + 27.3 279.7 + 22.7 269.8 + 14.8 DAY 7 MEANS.D. 310.3 24.9 299.6 21.8 313.6 4- 30.0 309.6 + 22.2 295.1 f 15.5" SD DAY i0 MEAN+S.D. 320.6 + 25.5 310.5 + 22.6 325.4 31.3 322.7 23.7 306.4 + 16.2 DAY 14 OO MEANIS.D. 337.7 + 26.3 324.7 22.2 DAY 18 MEAN+S.D. 377.4 + 29.3 [ 27] c 371.6 + 26.8 DAY 21 MEAN+S.D. 405.4 + 46.0 389.0 + 51.5 [ 27] d .................................................................................................................................... DAY [] a. b. c. d. * = DAY OF GESTATION = NUMBER OF VALUES AVERAGED Excludes rats that were moribund sacrificed prior to cohabitation. Excludes Excludes rats that did not have a confirmed values that were not recorded. mating date. Excludes values for rats that delivered. Significantly different from the Group I value (p<0.05). 343.3 + 32.8 386.4 + 35.6 414.7 + 47.2 337.3 + 24.4 378.8 + 26.8 415.3 29.8 [ 26] d 320.5 + 19.7" 363.3 + 25.7 381.4 + 43.1 > 4= OO b_ 0 (_ OO _-_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C5 (PAGE 1) : MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 29a 29a 30 30 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 28 27 29b 27b 28b MATERNAL BODY WEIGHT CHANGE (G) DAYS 0- 7 MEANS.D. +30.0 + 9.3 +27.6 + 7.1 +30.1 9.0 +29.9 + 10.4 +25.3 + 8.3 DAYS 7 - i0 MEANS.D. +10.3 6.0 +10.9 + 6.3 +11.8 + 5.3 +13.1 5.2 +11.3 + 6.4 DAYS 10 - 14 MEANS.D. +17.1 6.2 +14.2 + 4.3 DAYS 14 - 18 MEANiS.D. +39.1 11.2 [ 27] c +46.9 8.9 DAYS 18 - 21 MEANiS.D. +29.5 31.6 [ 26]c,d +17.4 38.2 DAYS 0 - 21 MEANS.D. +126.0 33.2 +117.1 40.8 [ 27]d .................................................................................................................................... DAYS DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed b. Excludes rats that did not have a confirmed c. Excludes values that were not recorded. d. Excludes values for rats that delivered. prior to cohabitation. mating date. +17.9 + 5.4 +43.0 12.1 +28.3 24.6 +131.2 29.4 +14.6 + 6.2 +41.5 + 9.3 +36.6 f 12.0 [ 26]d +134.8 20.5 [ 26]d +14.0 9.4 +42.8 15.0 +18.1 35.7 +111.5 38.9 > C 4_ O_ d:, 0 _._ OO t,O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C6 (PAGE i): MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY} 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 29a 29a 30 30 30 PREGNANT N 28 27 30 29 29 DELIVERED A LITTER N 28 27 29 29 29 MATERNAL BODY WEIGHT (G) DAY 1 MEAN+S.D. 313.1 24.7 303.2 + 19.8 321.2 + 28.8 312.2 + 24.1 300.3 19.9 DAY 5 MEAN+S.D. 322.8 28.6 310.2 + 22.0 327.3 + 29.1 DAY 8 DAY Ii MEAN+S.D. MEANS.D. 341.0[ 24]b26.3 351.5 28.2 [ 25]b,c 327.8[ 23+]b24.3 339.4 _ 29.7 [ 22]b,c DAY 15 MEAN+S.D. 354.4 29.5 345.3 26.8 [ 27]c [ 26]c DAY 22 MEAN+S.D. 345.0 + 29.1 339.5 23.6 [ 27]C [ 26]C .................................................................................................................................... 337.7[ 351.4 [ 357.7 25]b27.6 31.2 28]b + 28.9 351.4 23.0 DAY -- DAY OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values that were not recorded. c. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. 318.8 25.4 339.8[ 21i]b28.2 345.2 24.9 349.9 + 27.8 342.1 26.1 308.3 18.8 [ 27]b,c 322.8[ 25+]b,1c9.4 332.3 + 20.5 [ 27]b,c 344.2 f 18.1 [ 28]c 345.0 17.7 [ 28]C > 4_ oo h_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C7 (PAGE I) : MATERNAL BODY WEIGHT C}[ANGES - LACTATION - SUMMARY - P GENERATION .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 29a 29a III 3 30 PREGNANT N 28 27 30 DELIVERED A LITTER N 28 27 29 INCLUDED IN ANALYSES N 28 27 29 MATERNAL BODY WEIGHT CHANGE (G) STUDY OF AMMONIUM FEMALE RATS IV 10 30 29 29 29 PERFLUOROOCTANOATE V 30 30 29 29 28b DAYS 1- 5 MEANS.D. +9.7 + 11.8 +7.0 + 14.5 +6.1 11.0 +6.6 i 12.8 +7.4 + 13.0 [ 27] C (_ DAYS 5 - 8 MEAN+S.D. +12.4 + 13.1 +16.0 i0 6 +14.1 + 10.7 +18.8 8.4 +12.5 + 9.8 _-_ 24] C 23] C [ 25] c [ 21] C [ 24] c OO DAYS 8 - Ii MEAN+S.D. +14.9 + 12.9 +9.8 + 14 9 +9.6 + 13.2 +7.1 + 22.6 +9.1 15.2 L_ 21]b,c 18]h,c [ 24]c [ 21]c [ 24]c DAYS ii - 15 MEAN+S.D. +4.3 + 15.9 +8.5 + 19 3 +6.0 + 16.1 +4.8 _ 19.1 +12.6 + 13.4 25]b,c 22]b,c [ 28]c [ 27]c DAYS 1 - 15 MEANS.D. +41.8 + 14.5 +42.8 17 5 +36.5 13.0 +37.8 16.0 +42.9 + 17.2 27]b 26]b DAYS 15 - 22 MEANS.D. -9.4 + 25.2 27]b -5.8 22 5 26]b -6.3 + 16.5 -7.9 + 22.9 +0.8 16.8 DAYS 1 - 22 MEANS.D. +32.4 + 23.0 27]b +37.0 21 7 26]b .................................................................................................................................... DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED +30.2 + 19.4 +29.9 + 21.3 +43.7 + 15.8 a. Excludes values for rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. > c. Excludes values that were not recorded. _n Oc tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C8 (PAGE 1}: ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION __ .................................................................................................................................. DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS TESTED N 30 30 - SUMMARY - P GENERATION FEMALE RATS III IV V 3 10 30 30 30 30 FEED CONSUMPTION (G/DAY} DAYS 1- 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 MEANfS.D. MEAN+S.D. MEAN+S.D. MEANfS.D. MEAN+S.D. 18,8 1.8 20.8 2.4 21.5 + 2.0 [ 28]a 21.3 2.2 [ 28]a 21.4 2.4 19.2 2.1 [ 29]a 21.0 2.9 [ 29_ a 21.2 + 2.3 [ 29]a 20,7 2,2 21.0 + 1.8 DAYS 36 - 43 MEANiS.D. 21 6 2.5 21.5 1.9 OO 29]a [ 29]a 4_ DAYS 43 - 50 MEAN+S.D. 22.6 2.8 21.7 1.8 27]a [ 29]a DAYS 50 - 57 MEANS.D. 21.0 + 2.3 28]a 21.2 + 2.0 DAYS 57 - 64 MEAN+S.D. 21.8 2.8 21.1 + 1.6 27]a [ 29]b DAYS 64 - 70c MEANS,D, 21.3 2.0 21.1 2.3 27]a,b [ 29]b DAYS 1 - 70c MEANiS.D. 21.3 1.6 21.0 + 1.7 27]a,b [ 29]b .................................................................................................................................... 19.9 1.4 21.8 2.7 [ 29] a 21.8 2.2 [ 29]a 22.3 2.8 21.8 2.1 [ 29]a 22.6 2.7 22.8 2.5 [ 29]a 22.2 f 2.2 [ 27]a 22.1 + 1.8 21.4 2.0 21.9 2,0 19,7 1.7 21.7 2.4 22.2 [ 29]a 22.1 [ 29]a 22 0 [ 291a 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 23 2.2 2.4 2.8 2.2 2.4 1.9 19.6 1,5 [ 29]a 21.2 1.8 20.9 + [ 25]a 21.2 [ 28]a 21.0 [ 291a 21.4 [ 29]a 22.0 1.6 1.6 19 1.8 3.0 21.2 + [ 28]a 20.5 + 2.3 1.7" 20.1 2.0 21.0 1.5 DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded or appeared incorrectly recorded, as well as those associated with spillage. _ bc.. ELxacsltudevsalue valrueecsordefdor rbaetfsore thactohawbeirteatiomno.ribund sacrificed. _ * Significantly different from the Group I value (p<0 05) O0 b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C9 (PAGE i) : RELATIVE FEED CONSUMPT_.ON VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 FEED CONSUMPTION (G/EG/DAY) III 3 30 - P GENERATION IV 10 3O FEMALE RATS V 30 30 DAYS 1- 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 MEANS.D. MEAN+S.D. MEAN+S.D. MEANS.D. 115.6 + 9.4 110.0 14.4 102.4 8.4 [ 28]a 94.3 + 8.9 [ 28]a 118.9 + 11.6 [ 29]a 112.0 + 13.7 [ 29]a 102.2 i [ 29]a 93.5 + 7.4 67 120.4 + 6.5 112.8 + 13.5 [ 29]a 101.3 + 7.6 [ 29]a 96.0 + 9.1 119.6 + 78 112.1 _ 95 103.7 + 71 [ 29]a 95.2 10 7 [ 29]a 120.0 8.0 [ 29]a 111.2 + 8.9 100.0 + 6.0 [ 25]a 94.1 6.4 [ 28]a DAYS 29 - 36 MEAN+S.D. 89.3 + 5.8 90.7 + 59 DAYS 36 - 43 MEAN+S.D. 86. f 6.9 88.8 + 64 Ot0a 29]a [ 29]a DAYS 43 - 50 MEAN+S.D. 87.8 + 7.2 86.7 53 27]a [ 29]a DAYS 50 - 57 MEANS.D. 79.6 + 6.4 82.1 _ 62 28]a DAYS 57 - 64 MEANS.D. 81.1 _ 9.2 27]a 79.7 [ 29]b 50 DAYS 64 - 70c MEAN+S.D. 76.6 5.4 78.1 + 78 27]a,b [ 29]b DAYS 1 - 70c MEANS.D. 91.1 + 4.1 92.2 54 27]a,b [ 29]b .................................................................................................................................... DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED 89.2 + 4.8 [ 29]a 88.7 + 7.2 86.0 6.2 [ 29]a 80.7 + 5.8 [ 27]a 78.9 4.8 75.3 f 6.3 91.8 5.7 90.5 + [ 29]a 87.6 [ 29]a 85.6 + [ 28]a 82.1 [ 29]a 78.7 , [ 29]a 75,2 [ 29]a 91.9 + [ 29]a 64 61 58 72 58 52 48 89.2 [ 87.5 [ 86.3 + 29]a 29]a + 8.0 5.6 10.3 81.0 7.0 [ 28]a 77.3 4.8 74.3 + 5.7 91.0 4.7 a. Excludes values that were not recorded or appeared incorrectly b. Excludes values for rats that were moribund sacrificed. c. Last value recorded before cohabitation. recorded, as well as those associated with spillage. Cn Oo O PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C10 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 29a 29a - GESTATION - SUMMARY III 3 30 - P GENERATION IV i0 30 FEMALE RATS V 30 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 28 27 29b 27b 28b MATERNAL FEED CONSUMPTION (G/DAY) DAYS 0- 7 DAYS 7 - i0 MEAN+S.D. MEAN+S.D. 25.9 + 3.2 I 27]c 27.0 + 3.7 25.7 + 2.4 25.7 + 2.5 DAYS I0 - 14 MEAN+S.D. 27.6 + 3.5 25.8 + [ 26]c 2.4* OO DAYS 14 - 18 MEAN+S.D. 26.1 + 2.8 26.8 + 2.7 _% [ 26]c DAYS 18 - 21 MEAN+S.D. 23.6 + 2.4 [ 25]d 23.2 + 3.1 [ 23]d DAYS 0 - 21 MEANS.D. 26.1 + 2.6 25.6 + 1.9 [ 25]d [ 23]d .................................................................................................................................... DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes rats that did not have a confirmed mating date. c. Excludes values that were associated with spillage. d. Excludes values for rats that delivered. * Significantly different from the Group I value - (p<0.05). 26.0 + 3.1 [ 26]c 28.0 + 2.9 28.4 + 3.5 [ 28]c 27.3 + 3.1 24.5 + 2.8 [ 28]d 26.7 + 2.3 [ 28]d 25.0 i 2.5 26.8 + 2.8 26.2[ 26+] c 3.3 [ 26]c 26.1 + 2.5 [ 26]c 23.5 + 3.6 [ 26]d 25.6 2.2 [ 26]d 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* > C 50 4_ OO d:, tO 0 _-_ OO "_] PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C11 (PAGE i): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 29a 29a - GESTATION III 3 30 - SUMMARY - P GENERATION IV i0 30 FEMALE RATS V 30 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 28 27 29b 27b 28b MATERNAL FEED CONSUMPTION (G/KG/DAY) DAYS 0- 7 DAYS 7 - I0 MEAN+S.D. MEANIS.D. 87.5 f 9.5 [ 27]C 85.4 f 8.3 90.1 8.3 84.5 + 7.0 87.0 + 7.6 [ 26]C 87.7 7.1 DAYS I0 - 14 MEAN+S.D. 84.0 f 7.7 81.5 + [ 26]c DAYS 14 - 18 MEAN+S.D. 73.3 6.2 77.1 [ 27]c [ 26]c DAYS 18 - 21 MEAN+S.D. 59.7 f 8.5 59.9 24]c,d t 23]d DAYS 0 - 21 MEANS.D. 77.0 + 5.5 77.3 + [ 25]d [ 23]d .................................................................................................................................... 7.3 7.7 7.7 5.7 DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes rats that did not have a confirmed mating date. c. Excludes values that were not recorded, as well as those associated d. Excludes values for rats that delivered. with 84.4 + [ 28]c 75.1 + 61.3 t 77.7 [ 28]d + 28]d spillage. 8.0 8.6 6.0 4.4 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 85.3 7.1 [ 27]C 84.8 + 6.4 81.0 + 7.6 74.7 + 9.4 61.7 + 9.2 [ 27]d 76.0 + 5.3 [ 27]d > Cn C O0 4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C12 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - LACTATION - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 29a 29a III 3 30 - P GENERATION IV I0 30 FEMALE RATS V 30 30 PREGNANT N 28 27 30 29 29 DELIVERED A LITTER N 28 27 29 29 29 INCLUDED IN ANALYSES N 28 27 29 29 28b MATERNAL FEED CONSUMPTION (G/DAY) DAYS 1- 5 MEANS.D. 31.8 6.4 [ 25]c 31.9 4.6 33.1 7.1 [ 28]c 31.0 6.3 [ 25]c 29.6 6.1 [ 26]c _._ OO OO DAYS 5- 8 MEANiS.D. 51.2[ 26]b,c 8.6 49.6 7.2 DAYS 8 - ii MEANS.D. 61.8 10.6 58.7 10.5 [ 25]b,c [ 25]b,c DAYS ii - 15d MEANS.D. 69.4 Ii.i 68.2 8.6 [ 26]b,c [ 25]b,c DAYS 1 - 15d MEANiS.D. 54.1 7.5 51.8 5.7 [ 26]h,c [ 25]b,c .................................................................................................................................... 50.0 10.8 62.2 + 13.1 69.0 [ 53.6 [ 28]c 28]c 14.0 10.7 50.9[ 59.6 [ 67.6 28]c + 28]c f 8.9 8.4 12.8 53.1 f 9.3 47.6 55.2 [ 66.2 27]c i0.0 10.6 7.7 50.0 7.3 DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that were sacrificed or sacrificed due to no surviving c. Excludes values that were associated with spillage. d. Because it is presumed that the pups begin to consume maternal feed after day were not tabulated on days 15 to 22 of lactation. pups. 15 of lactation, maternal feed consumption values > C OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE C13 (PAGE i): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS TESTED N 29a 29a PREGNANT N 28 27 DELIVERED A LITTER N 28 27 INCLUDED IN ANALYSES N 28 27 MATERNAL FEED CONSL_4PTION (G/KG/DAY) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE - LACTATION - SUMMARY - P GENERATION FEMALE RATS III IV V 3 10 30 30 30 30 30 29 29 29 29 29 29 29 28b DAYS 1- 5 MEAN+S.D. 100.3 + 17.5 [ 25]C 104.0 + 13.6 102.9 + 21.8 [ 28]c 98.1 + 19.6 [ 25]C 96.4 20.5 [ 25]c DAYS 5- 8 MEAN+S.D. 152.3 + 21.9 [ 22]b,c 153.3 i 15.8 { 23]c OO DAYS 8 - Ii MEAN+S.D. 175.9 i 27.4 176.6 + 27.6 [ 19]b,c [ 17]b,c DAYS ii - 15d MEANS.D. 194.2 27.5 197.9 21.4 [ 24]b,c [ 21]b,c DAYS 1 - ISd MEANfS.D. 161.0 18.7 159.9 13.8 [ 26]b,c [ 25]h,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 154.4 [ 176.7 [ 194.2 20]c 20]c 22.6 19.8 33.6 159.8 26.2 151.5 + 30.6 [ 24]c 168.3 29.0 [ 23]c 196.7 22.4 [ 27]c 155.5 20.6 DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that were sacrificed or sacrificed due to no surviving pups. c. Excludes values that were not recorded, as well as those associated with spillage. d. Because it is presumed that the pups begin to consume maternal feed after day 15 of lactation, maternal feed consumption values were not tabulated on days 15 to 22 of lactation. > C U9 OO 6 tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) [APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE FABLE C14 (PAGE 1): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 i0 30 ESTROUS CYCLING OBSERVATIONS PRECOHABITATION ESTROUS CYCLING RATS EVALUATED N 29a 29a 30 30 30 ESTROUS STAGES/ 21 DAYS MEAN+S.D. 5.2 + 1.0 5.2 + 0.6 5.0 + 0.8 4.9 + 1.0 5.2 + 0.7 RATS WITH 6 OR MORE CONSECUTIVE DAYS OF DIESTRUS N 2 0 0 1 0 RATS WITH 6 OR MORE CONSECUTIVE DAYS OF ESTRUS N 0 0 2 1 1 ESTROUS STAGE AT SACRIFICE RATS EVALUATED N 28b 28b 30 30 29b DIESTRUS N 7 9 13 11 8 PROESTRUS N 21 16 14 16 20 ESTRUS N 0 2 1 1 1 METESTRUS N 0 1 2 2 0 .................................................................................................................................... a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Excludes values for rats that did not have a value recorded. > CD oo _b PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C14 (PAGE 2): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS IN COHABITATION N 29a 29a 30 30 30 DAYS IN COHABITATION b MEAN+S.D. 3.3 + 2.6 1.9 + 1.2" 2.4 + 1.7 [ 29] 3.1 + 2.4 [ 28] 2.6 + 1.4 [ 29] RATS THAT MATED N(%) 29(100.0) 29(100.0) 30(100.0) 29(96.7) 30(100.0) FERTILITY INDEX c RATS WITH CONFIRMED MATING DATES RATS MATING d DAYS DAYS 1-7 8-14 N/N (%) N N(%) N(%) 28/ 29 96.6) 29 27 93.1) 2 6.9) 27/ 29 (93.1) 29 29(i00.0) 0( 0.0) 30/ 30 (100.0) 29 28(96.6) I( 3.4) 29/ 29 (100.0) 27 27(100.0) 0( 0.0) 29/ 30 (96.7) 29 29(100.0) 0( 0.0) RATS PREGNANT/RATS IN COHABITATION N/N 28/ 29 27/ 29 (%) (96.6) 93.1) .................................................................................................................................... [ ] = NUMBER OF VALUES AVERAGED a. Excludes rats that were moribund sacrificed prior to cohabitation. b. Restricted to rats with a confirmed mating date and rats that did not mate. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date. * Significantly different from the Group I value (p<0.05). 30/ 30 (I00.0) 29/ 30 (96.7) 29/ 30 (96.7) > O C 4= O0 I,J 0 b-_ kO tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C15 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 10 30 RATS EXAMINED a N 30 30 30 30 30 MORIBUND SACRIFICED N ib lc 0 0 0 SACRIFICED d N le if 0 0 0 APPEARED NORMAL N 29e 29f 29 30 30 KIDNEYS: LEFT, PELVIS, MARKED DILATION N 0 0 1 0 0 LEFT FORELIMB: ULNA ANDRADIUS, BROKEN N 0 lc 0 0 0 .................................................................................................................................... a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. b. Rat 13804 was moribund sacrificed on day 68 of study. c. Rat 13836 was moribund sacrificed on day 59 of study. d. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. e. Rat 13822 was sacrificed on day 8 of lactation. f. Rat 13852 was sacrificed on day 11 of lactation. > 5_ O0 tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C16 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 III 3 30 IV V 10 30 29a 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 27b 26b 29c 29 28b TERMINAL BODY WEIGHT MEAN+S.D. 345.0 + 29.1 339.5 + 23.6 351.4 23.0 342.1 + 26.1 345.0 17,7 PITUITARY BRAIN MEANS.D. MEAN+S.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 0.016 + 0.006 [ 27]d 2.17 + 0.11 LIVER KIDNEY LEFT MEAN+S.D. MEAN+S.D. 18,69 + 1.57 2.49 0.16 17.97 1,58 + 2.13 0.14 17.85 + 1.78 1.58 + 0.18 17.25 + 1.94 1.52 + 0.14 18.08 1.44 1.71 0.10"* t_ KIDNEY RIGHT MEANS.D. 1,57 i 0.18 1.61 + 0.14 1.62 + 0.16 1.55 + 0.13 1.49 0.10" ADRENAL LEFT MEAN+S.D. 0.045 + 0.010 0.051 + 0.009 0.048 + 0.010 0.046 + 0.007 0.046 + 0.010 ADRENAL SPLEEN RIGHT MEAN+S.D. MEANfS,D, 0.045 + 0.007 0,67 0.i0 0.046 0.008 0.69 + 0.09 0.043 0.006 0.71 0.II 0.042 + 0.009 0.69 + 0.09 0.042 + 0.010 [ 27] d 0,72 + 0.i0 CERVIX MEAN+S.D. 0.22 + 0.12 0.19 + 0.05 0.20 + 0.08 0.20 + 0.i0 0,17 + 0.06 OVARY LEFT MEAN+S.D. 0.052 + 0.011 0.055 + 0.016 0.054 + 0.014 0.049 + 0.010 0.053 0,016 OVARY RIGHT MEANS.D. 0.053 + 0.011 0.057 0,018 0.057 + 0.013 0.054 + 0.012 0.049 0.014 > UTERUS NON-GRAVID MEAN_S.D. 0.52 + 0.14 0.59 + 0.21 0,53 + 0.15 0.58 + 0.19 0,50 + 0.ii ...................................................................... ............................................................. [ ] = NUMBER OF VALUES AVERAGED _0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes rat 13900, which did not have organ weight values recorded. 4_ b. Excludes values for rats that were sacrificed, moribund sacrificed or sacrificed due to no surviving pups. Oo c. Excludes dam 13862, which was pregnant but did not deliver a litter. d. Excludes values that appeared incorrectly recorded. * Significantly different from the Group I value (p_<0.05). ** Significantly different from the Group I value (p__0.01). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C17 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 III 3 30 IV V 10 30 29a 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 27b 26b 29c 29 28b TERMINAL BODY WEIGHT MEAN+S.D. 345.0 + 29.1 339.5 23.6 351.4 + 23.0 342.1 + 26.1 345.0 + 17.7 PITUITARY d BRAIN MEAN+S.D. MEAN+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 LIVER _._ KIDNEY LEFT _t_ KIDNEY RIGHT MEANS.D. MEANS.D. MEAN+S.D. 5.405 0.455 + 0.425 + 0.042 0.456 f 0.044 5.284 0.465 0.422 + 0.041 0.474 + 0.042 5.088 0.449 + 0 481" + 0 040 0.461 + 0 037 5.047 0.443 i 0.455** + 0.032 0.454 + 0.032 5.244 0.418 + 0.461 + 0.032** 0.431 0.029* ADRENAL LEFT d MEAN+S.D. 13.162 2.855 14.963 2.401 13.614 + 2 787 13.438 t 2.221 13.312 + 3.037 ADRENAL SPLEEN RIGHT d MEANS.D. MEANS.D. 13.042 + 2.341 0.195 + 0.026 13.642 + 2.274 0.204 + 0.026 12.230 + 1.775 0.203 + 0.029 12.418 2.418 0.200 0.023 12.042 + 2.869 [ 27] e 0.207 0.028 CERVIX MEANS.D. 0.063 * 0.031 0.057 0.014 0.058 0.026 0.058 0.027 0.049 0.017 OVARY LEFT d MEANS.D. 15.227 3.484 16.053 f 4.570 15.333 + 4.080 14.289 + 3.173 15.446 4.566 OVARY RIGHT d MEAN+S.D. 15.417 + 2.965 16.886 + 5.250 16.271 + 3.379 15.903 3.306 14.108 + 3,631 UTERUS NON-GRAVID MEANS.D. 0.154 0.043 ...................................................................................................... 0.175 0.063 0.151 0.044 0.170 0.049 0.146 . ............................. 0.033 [] ALL a. b. c. d. e. * = NUMBER OF VALUES AVERAGED WEIGHTS WERE RECORDED IN GRAMS (G). Excludes Excludes rat 13900, which did not have organ weight values recorded. values for rats that were sacrificed, moribund sacrificed or Excludes dam 13862, which was pregnant but did not deliver a litter. Value was multiplied Excludes values that by 1000 appeared incorrectly recorded. significantly different from the Group I value (p<0.05). Significantly different from the Group I value (p<_0.01). RATIOS (%) sacrificed = (ORGAN WEIGHT/TERMINAL due to no surviving pups. BODY WEIGHT) X 100. _.,4_ O0 tOo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C18 (PAGE I) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 30 III 3 30 IV V I0 30 29a 30 PREGNANT N 28 27 30 29 29 INCLUDED IN ANALYSES N 27b 26b 29c 29 28b BRAIN WEIGHT MEAN+S.D. 2.22 f 0.13 2.21 0.14 2.22 + 0.13 2.22 + 0.08 2.17 + 0 11 PITUITARY LIVER MEAN+S.D. MEAN+S.D. 0.82 + 0.20 [ 26]d 839.90 +101.30 0.85 + 0.23 814.22 + 93.64 0.78 + 0.16 806.07 + 98.78 0.71 + 0.27 776.69 + 90.72 0.72 + 0 28 [ 27]d 834.10 + 80 85 KIDNEY LEFT MEAN+S.D. 70.57 + 7.47 71.66 + 7.89 71.24 + 8.32 68.35 6.17 66.42 + 4 29* KIDNEY RIGHT MEAN+S.D. 70.80 + 7.55 73.06 + 7.36 73.00 + 7.24 69.80 + 6.03 68.59 + 4 86 t21 ADRENAL LEFT MEAN+S.D. 2.03 + 0.42 2.31 + 0.44 2 14 + 0.43 2.06 + 0.30 2.11 + 0 48 ADRENAL SPLEEN RIGHT MEAN+S.D. MEAN+S.D. 2.01 + 0.33 30.28 3.63 2.10 + 0.39 31.47 + 4.70 1 94 + 0.31 32 14 + 5.27 1.91 0.38 30.94 + 3.74 1.92 + 0.46 [ 27] d 33.18 + 4.83 CERVIX MEAN+S.D. 9.76 5.09 8.80 + 2.28 9 21 3.79 9.00 4.37 7.90 + 2.68 OVARY LEFT MEAN+S.D. 2.35 + 0.49 2.48 + 0.74 2 43 + 0.65 2.19 + 0.46 2.46 0.76 OVARY RIGHT MEAN+S.D. 2,40 + 0.55 2.58 + 0.78 2 58 + 0.57 2.45 + 0.54 2.25 + 0.59 UTERUS NON-GRAVID MEAN+S.D. 23,74 + 6.45 26.97 + 10.31 23.93 + 6.55 26.16 + 8.39 23.15 + 5.23 .................................................................................................................................... [ ] = NUMBER OF VALUES AVERAGED ALL WEIGHTS WERE RECORDED IN GRAMS (G). RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. a. Excludes rat 13900, which did not have organ weight values recorded. b. Excludes values for rats that were sacrificed, moribund sacrificed or sacrificed due to no surviving pups. C/_ C. Excludes dam 13862, which was pregnant but did not deliver a litter. 4_ d. Excludes values that appeared incorrectly recorded. O0 * Significantly different from the Group I value (p<__0.05) . O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C19 (PAGE 1): NATURAL DELIVERY OBSERVATIONS - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS ASSIGNED TO NATURAL DELIVERY N 29a 29a 30 30 30 PREGNANT N(%) 28(96.6) 27(93.1) 30(i00.0) 29(96.7) 29(96.7) DELIVERED A LITTER N(%) 28[i00.0) 27(i00.0) 29(96.7) 29(i00.0) 29(i00.0) DURATION OF GESTATION b MEANfS.D. IMPLANTATION SITES PER DELIVERED LITTER N MEAN_S.D. 22.6 + 0.5 428 15.3 1.9 22.5 + 0.5 421 15.6 + 2.1 22.8 + 0.5 442 15.2 + 2.3 22.6 + 0.6 [ 27] C 453 15.6 + 2.0 22.7 + 0.5 [ 28] C 445 15.3 + 2.0 DAMS WITH STILLBORN PUPS DAMS WITH NO LIVEBORN PUPS N(%) N(%) _D 0% GESTATION INDEX d % N/N 3(10.7) 0( 0.0) i00.0 28/ 28 4(14.8) 0( 0.0) i00.0 27/ 27 5(17.2) 0( 0.0) 96.7 29/ 30 3(10.3) 0( 0.0) 100.0 29/ 29 4(13.8) 0( 0.0) i00.0 29/ 29 DAMS WITH DAYS 1-4 ALL PUPS POSTPARTUM DYING N(%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0} i( 3.4) DAMS WITH ALL PUPS DYING DAYS 5-21 POSTPARTUM N(%) 0( 0.0) 0( 0.0) .................................................................................................................................... 0( 0.0) 0( 0.0) 0( 0.0) [] a. b. c. d. = NUMBER OF VALUES AVERAGED Excludes rats that were moribund sacrificed prior to cohabitation. Calculated as the time (in days) elapsed between confirmed mating (arbitrarily the first pup was delivered. Excludes values for rats that did not have a confirmed mating date. Number of rats with live offspring/number of pregnant rats. defined as day 0) and the time (in days) C _n 4_ tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C20 (PAGE i): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE DOSAGE GROUP (MG/KG/DAY) I II III IV V 0 1 3 i0 30 .................................................................................................................................... DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 27 29 29 29 PUPS DELIVERED (TOTAL) N MEAN+S.D. 402 14.4 + 2.1 395 14.6 + 2.2 393 13.6 f 3.6 404 13.9 f 3.0 394 13.6 f 3.3 LIVEBORN STILLBORN MEAN+S.D. N(%) MEAN+S.D. N(%) 14.2 + 2.2 397(98.8) 0.i 0.3 3( 0.7) 14.2 2.6 384(97.2) 0.4 i0( + 1.4 2.5} 13.4 f 3.6 388(98.7) 0.2 + 0.4 5( 1.3) 13.8 f 3.0 400(99.0) 0.I f 0.4 4( 1.0) 13.4 3.3 388(98.5) 0.2 f 0.6 6( 1.5) UNKNOWN VITAL STATUS N 2 1 0 0 0 PUPS FOUND DEAD OR PRESUMED CANNIBALIZED "_ DAY 1 DAYS 2- 5 DAYS DAYS 6- 8 9-15 DAYS 16-22 VIABILITY INDEX c 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 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 3/388( 7/385( 5/378( 1/373( 1/372( 0.8} 1.8) 1.3)* 0.3) 0.3) 97.4 378/388 0/400 ( 5/400( 2/395( 3/393( 0/390( 0.0) 1.2) 0.5) 0.8) 0.0) 98.8 395/400 3/388( 11/385( 10/374( 2/364( 0/362( 0.8) 2.8) 2.7)** 0.5) 0.0) 96.9 376/388 LACTATION INDEX d % 99.7 98.9 N/N 375/376a 361/365b .................................................................................................................................... 98.1" 371/378 DAY(S) = DAY(S) POSTPARTUM a. Excludes litter 13822; b. Excludes litter 13852; c. Number of live pups on d. Number of live pups on * Significantly different ** Significantly different all pups were sacrificed all pups were sacrificed day 5 postpartum/Number day 22 postpartum Number from the Group I value from the Group I value due to sacrifice due to sacrifice of liveborn pups of llve pups on (p<_0.05). (p<_0.01). of dam. of dam. on day 1 postpartum. day 5 postpartum. 98.7 390/395 96.3** 362/376 C/_ /_ O_ d:, t-O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NIR_BER. PER GENERATION) T-6889.6} REPRODUCTION STUDY OF /%MMONIUM PERFLUOROOCTANOATE TABLE C20 (PAGE 3): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 27 29 29 29 LIVE LITTER SIZE AT WEIGHING DAY 1 DAY 5 DAY 8 DAY 15 MEANS.D. MEANfS.D. MEI_NS.D. MEAN+S.D. DAY 22 MEAN+S.D. %0 %0 PUP WEIGHT/LITTER (GRAMS) 14.1 + 2.2 13.8 2.1 13.9 + 2.0 [ 27]b 13.9 + 2.0 [ 27]b 13.9 + 2.0 [ 27]h 14.1 + 2.7 13.9 f 2.5 13.8 2.5 13.9 2.5 [ 26]b 13.9 2.5 [ 26]b 13.3 3.6 13.0 + 3.4 12.9 3.4 12.8 + 3.3 12.8 + 3.4 13.8 3.0 13.6 + 2.8 13.6 + 2.9 13.4 _ 2.8 13.4 f 2.8 13.8 + 2.5 [ 28] a 13.4 + 2.8 [ 28]a 13.0 + 2.7 [ 28]a 12.9 + 2.8 [ 28]a 12.9 2.8 [ 28]a DAY 1 MEAN+S.D. 6.3 + 0.5 6.0 + 0.4* DAY 5 MEAN+S.D. 9.4 + 1.3 8.8 + 0.8 DAY 8 MEAN+S.D. 13.3 + 2.0 [ 27]b 12.7 + 1.3 DAY 15 MEAN+S.D. 25.0 + 4.0 [ 27]b 24.2 + 2.8 [ 26]b DAY 22 MEAN+S.D. 37.4 + 6.5 36.7 [ 27]b [ 26]b .................................................................................................................................... 5.5 DAY [] a. b. * ** = DAY POSTPARTUM = NUMBER OF VALUES AVERAGED Excludes litter 13947, which had no surviving pups on day Excludes litters in which the dam was sacrificed. Significantly different from the Group I value (p<0.05). Significantly different from the Group I value (p<0.01). 1 of lactation. 6.2 + 0.5 9.5 + 1.5 13.5 + 2.2 26.4 4.7 39.7 + 8.3 6.2 + 0.4 9.3 + 0.9 13.0 + 1.6 24.8 + 4.0 38.8 + 6.1 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 O_ __/_ Oo d:, b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C21 (PAGE 1): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II III IV V MATERNAL DOSAGE (MG/KG/DAY) 0 1 3 10 30 LITTERS EXAMINED (N) 28 27 29 29 29 .................................................................................................................................... TRANSIENT CLINICAL OBSERVATIONS: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS COLD TO TOUCH N/N 22/5 5/4 29/5 3/2 81/4 BRUISE b N/N 0/0 0/0 0/0 6/1 12/4"* NO MILK IN STOMACH N/N i/i 0/0 0/0 3/2 2/2 UMBILICAL PALE HERNIA N/N NIN 0/0 010 2/1 010 0/0 010 i/i 111 14/2 111 LEFT FORELIMB NOT NESTING BACK: SCAB OR MOUTH: MASS N/N NIN N/N 010 311 0/0 2/1 010 0/0 0/0 010 0/0 0/0 111 I/I 11/1 010 0/0 RED PERIANAL SUBSTANCE N/N 0/0 0/0 i/i 0/0 0/0 NOT NURSING N/N 3/1 0/0 0/0 0/0 0/0 PERSISTENT CLINICAL OBSERVATIONS: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS TIP OF TAIL MISSING N/N 0/0 18/1 2/1 22/1 0/0 LEFT EYE: TRAUMATIZED CORNEA N/N 0/0 0/0 0/0 2/1 0/0 TIP OF TAIL BLACK N/N 0/0 0/0 20/1 0/0 0/0 > HINDLIMBS ROTATED INWARD N/N 0/0 22/1 0/0 0/0 0/0 NO TAIL PRESENT N/N 0/0 22/1 0/0 0/0 0/0 -- .................................................................................................................................. _#] STATISTICAL ANALYSES WERE RESTRICTED TO THE NUMBER OF LITTERS WITH OBSERVATIONS. 4_ a. Tabulation restricted to adverse observations; all other pups appeared normal. O_ b. Located on the head, back, chest and/or lower midline. - O ** Significantly different from the vehicle control group value (p<0.01). bO _,) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTAMOATE TABLE C22 (PAGE 1): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II III IV V MATERNAL DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... LITTERS EXAMINED N 28 27 28 28 29 TOTAL PUPS STILLBORN OR FOUND DEAD a,b STILLBORN FOUND DEAD N 6 N 3 N 3 8 10 i 5 7 5 8 17 4 6 4 11 NO MILK IN STOMACH c N(%) 2(66.7) 2(28.6) .................................................................................................................................... PUPS SACRIFICED AND NECROPSIED ON DAYS 8, 11 AND 22 POSTPARTUM b 0( 0.0) 2(50.0) 5(45.4) LITTERS EVALUATED PUPS EVALUATED APPEARED NORMAL LII-I_R INCIDENCE PUP INCIDENCE N 28 N 163 N(%) N(%) 28(100.0) 163(100.0) 27 156 27(100.0) 156(I00.0) 28 148 28(100.0) 148(100.0) 28 16_ 28(100.0) 161(100.0) 28 145 27(96.4) 144(99.3) KIDNEYS : RIGHT, PELVIS, MODERATE LITTER INCIDENCE DILATION N(%) 0( 0.0) 0( 0.0) PUP INCIDENCE N(%) 0( 0.0} 0( 0.0) .................................................................................................................................... 0( 0.0) 0( 0.0) a. Restricted to pups in which complete necropsies were performed. Complete necropsies were autolysis or cannibalization precluded evaluation. b. Refer to the individual pup clinical observations table (Table C39) for external clinical c. Analysis restricted to pups found dead and necropsied. 0( 0.0) 0( 0.0) not performed observations on pups confirmed i( 3.6) 1( 0.7) in which at necropsy. O _n o_ 6 C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE C23 (PAGE 1): PUP ORGAN WEIGHTS - SUMMARY - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II MATERNAL DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... LITTERS EXAMINED N 27 26 TERMINAL BODY WEIGHT WEIGHT/LITTER MALE PUPS FEMALE PUPS BRAIN MEAN+S.D. MEAN+S.D. - MEAN+S.D. - 36.84 + 6.61 I 25]a 38.26 + 6.52 [ 23]a,b 35.63 + 7.11 [ 25]a 35.52 + 5.41 [ 22)a 36.82 + 5.08 [ 22]a 34.23 + 6.42 [ 22]a REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE III 3 28 39.21 + 8.24 [ 26]a 40.01 + 8.36 [ 25]a,b 37.92 + 7.73 [ 23]a,c IV i0 28 36.68 + 5.84 [ 24]a 37.78 + 6.82 [ 23]a 35.59 + 5.25 [ 23]a V 30 28 34.25 + 6.60 [ 22]a 35.53 + 6.79 [ 21]a 33.22 + 7.23 [ 21]a,c WEIGHT/LITTER [,O MALE PUPS [") FEMALE PUPS SPLEEN MEAN+S.D. MEAN_+S.D. MEAN+S.D. 1.40 + 0.i0 1.42 _+ 0.ii [ 26]b 1.38 + 0.12 1.43 _+ 0.i0 1.45 + 0.12 1.41 + 0.I0 1.42 + 0.ii 1.45 + 0.13 [ 24]b 1.40 + 0.ii [ 26]c 1.40 + 1.42 + 1.38 + 0.09 0.12 0.09 1.38 + 0.12 1.40 + 0.13 [ 26]b 1.36 + 0.II [ 27)c WEIGHT/LITTER MALE PUPS FEMALE THYMUS PUPS MEAN+S.D. MEAN+S,D. MEAN+S.D. 0.14 _+ 0.05 0,15 + 0.06 [ 26]b 0.13 + 0.05 0.12 + 0.03 0.12 + 0.04 0.12 + 0.04 0.13 + 0.05 0.13 + 0.06 [ 24]b 0.13 + 0.04 [ 26] c 0.14 + 0.13 + 0.04 0.05 0.14 + 0.05 0.12 + 0.04 0.ii + 0.04 [ 26]b 0.12 _+ 0.04 [ 27] c WEIGHT/LITTER > MEAN+S.D. 0.16 + 0.05 0.16 + 0.04 0.14 + 0.05 0.17 _+ 0.05 0.14 + 0.05 MALE PUPS MEAN+S,D. 0.16 + 0.05 0.16 + 0.04 0.14 + 0.05 0.17 + 0.05 0.14 + 0.05 FEMALE PUPS -MEAN+S.D. [ 26]b 0.16 + 0.06 0.15 + 0.05 [ 231b 0.14 + 0.04 0.16 + 0.05 [ 26]b 0.14 + 0.05 - - - [ 26) c - [ 27) c __" .................................................................................................................................. ALL WEIGHTS WERE RECORDED IN GRAMS (G). O0 [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification was not recorded [5 or appeared incorrectly recorded. b. Excludes values for lltter(s) that had no male pups examined. c. Excludes values for lltter(s) that had no female pups examined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C23 (PAGE 2): PUP ORGAN WEIGHTS - SU_L_RY - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II III IV V MATERNAL DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... LITTERS EXAMINED N 27 26 28 28 28 INCLUDED IN ANALYSES N 25a 22a 26a 24a 22a RATIOS (%) OF BRAIN TO TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D. 3.93 + 0.64 4.07 + 0.43 3.77 + 0.61 3.88 + 0.48 4.11 + 0.62 MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D. 3.83 + 0.63 [ 24]b 4.02 + 0.70 RATIOS (%) OF SPLEEN TO TERMINAL BODY WEIGHT WEIGHT/LITTER O MEAN+S.D. 0.38 _+ 0.ii t_ MALE PUPS MEAN+S.D. 0.40 [ 24]b FEMALE PUPS MEAN+S.D. 0.37 + 0.ii RATIOS (%) OF THYMUS TO TERMINAL BODY WEIGHT 3.95 + 0.36 4.18 + 0.59 0.33 + 0.33 0.07 0.33 + 0.09 3.75 + 0.56 [ 22]b 3.84 + 0.65 [ 24]c 0.33 + 0.i0 0.31 + 0.Ii [ 22]b 0.34 + 0.I0 [ 24] c 3.82 + 0.50 3.94 + 0.58 0.36 + 0.35 + 0.09 0.ii 0.38 + 0.I0 4.00 [ 4.23 + 21]b + 0.51 0.86 [ 21]c 0.33 + 0.06 0.31 [ 0.34 [ + 0.08 21]b + 0.07 21] c WEIGHT/LITTER MEAN+S.D. 0.44 + 0.12 0.42 _+ 0.07 0.36 _+ 0.09* 0.45 _+ 0.12 0.39 + 0.09 MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D. 0.42 + 0.ii [ 24]b 0.46 + 0.16 0.42 + 0.09 0.42 + 0.10 .................................................................................................................................... 0.35 + 0.09 [ 22]b 0.37 + 0.10 [ 24] C 0.46 + 0.13 0.45 + 0.13 0.37 + 0.ii [ 21]b 0.41 + 0.I0 [ 21] C ALL WEIGHTS WERE RECORDED IN GRAMS (G). RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for pups in which the terminal body weight could not be determined because pup identification was not recorded or appeared incorrectly recorded. b. Excludes values for litter(s) that had no male pups examined. [/) C. Excludes values for litter(s) that had no female pups examined. /_ * Significantly different from the Group I value (p<0.05). O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C23 (PAGE 3) : PUP ORGAN WEIGHTS - SUMMARY - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II III IV V MATERNAL DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 10 30 LITTERS EXAMINED N 27 26 28 28 28 RATIOS (%) OF SPLEEN TO BRAIN WEIGHT WEIGHT/LITTER MALE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D. MEAN+S.D. 9.74 + 3.30 10.42 + 4.21 [ 26]a 9.26 + 2.95 8,34 8.60 + 2.60 8.08 + 2.74 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 RATIOS (%) OF THYMUS TO BRAIN WEIGHT (IQ WEIGHT/LITTER MEAN+S.D. 11 17 + 3.28 10.80 + 2.35 9 84 + 2 94 11.88 + 3 33 9 82 + 2.86 MALE PUPS MEAN+S.D. 11.02 + 3.45 10.95 + 2.60 4_ [ 26]a FEMALE PUPS MEAN+S.D. 11.46 + 3.69 10.66 + 3.07 .................................................................................................................................... 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 ALL [] a. b. WEIGHTS = NUMBER Excludes Excludes WERE RECORDED IN GRAMS (G). OF VALUES AVERAGED values for litter(s) that had no male pups examined. values for litter(s) that had no female pups examined. RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. > C _n oo o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM C24 (PAGE I): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13801 13802 13803 13804 DS( 48- 56) DS( 59- 72) DG( 0- 20) DL( I- 22) DL( 5} DL( 14 ) DS 68 DS 68 DS 68 DS 68 DS 68 LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINORRHEA a CHROMODACRYORP/4EA a PALATE: BROKEN a SWOLLEN SNOUT INCISORS: MISALIGNED 13805 DS 68 MORIBUND SACRIFICED NO ADVERSE FINDINGS 13806 DS( 15- 17) INCISORS: MISSING/BROKEN DL( 20- 21) LOCALIZED ALOPECIA: LIMBS 13807 NO ADVERSE FINDINGS 13808 DS( 37- 45) INCISORS: MISSING/BROKEN 13809 NO ADVERSE FINDINGS 13810 DS( 8- 71) LOCALIZED ALOPECIA: LIMBS DO( 0 13811 LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS 13812 NO ADVERSE FINDINGS 13813 NO ADVERSE FINDINGS 13814 13815 DL( 18- 22 RIGHT EAR: SWOLLEN a NO ADVERSE FINDINGS 13816 DL( 9 SOFT OR LIQUID FECES .................................................................................................................................... DAY OF STUDY DO = DAY OF PRESUMED Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE _n O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C24 (PAGE 2): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13817 13818 13819 13820 13821 13822 DL( 12 ) DL( 14 ) DG( 3- 21) DG( 3- 21) DL( 1- 22) DL( 1- 22) DL( 11- 12) DS( 15- 16} DS( 22- 26) DL{ 8) NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA a INCISORS: MISALIGNED SOFT OR LIQUID FECES LEFT FORELIMB: SCAB RIGHT FORELIMB: SCAB SACRIFICED b a (0.5 CM X 0.5 CM) (0.2 CM X 0.2 CM) 13823 13824 DL( 14 ) NO ADVERSE FINDINGS SOFT OR LIQUID FECES O 13825 DG( 4- 21) BOTH EARS: SWOLLEN C_ DL( I- 22) BOTH EARS: SWOLLEN a 13826 NO ADVERSE FINDINGS 13827 DG( 3- 6) LOCALIZED ALOPECIA: LIMBS 13828 DL( 13- 22) LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a 13829 NOADVERSE FINDINGS 13830 NO ADVERSE FINDINGS .................................................................................................................................... DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. because it was not possible to identify to which litter the pups belonged. Both dams and litters were sacrificed > C 4= 0c 0 PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO} IN RATS {SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM C24 (PAGE 3): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 DS( 40- 45} DS( 57- 59) DS ( 59 ) DS ( 59 ) DL( 17- 21} DS( 32- 71) DG( 0- 21} INCISORS: NO ADVERSE MISSING/BROKEN FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LEFT FORELIMB AND FOREPAW: LEFT FORELIMB : FRACTURED MORIBUND SACRIFICED LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS SWOLLEN 13840 DL( i- 22) LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a 1133884412 NNOO AADDVVEERRSSEE FFIINNDDIINNGGSS 13843 NO ADVERSE FINDINGS 13844 NO ADVERSE FINDINGS 13845 DL( 12 ) SOFT OR LIQUID FECES 13846 NO ADVERSE FINDINGS 13847 DS ( 1- 5 } CHROMORHINORRHEA DS ( 7) CHROMORHINORR/4EA .................................................................................................................................... DAY OF STUDY DG = DAY OF PRESUMED Observation confirmed at necropsy. GESTATION DL = DAY a OF LACTATION PERFLUOROOCTANOATE > C 4_ oo O _I_ _O O OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C24 (PAGE 4): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 DL( 11 ) DG( 16- 21) DL( 4- 22) DL ( 8) DL( 12- 13) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SACRIFICED NO ADVERSE b FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOWER MIDLINE: SCAB (0.5 CM X 0.2 CM) RIGHT EAR: SWOLLEN a SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS 13859 13860 DS( 30- 32) DS( 59- 73) SOFT OR LIQUID FECES LOCALIZED ALOPECIA: UNDERSIDE DG( 0- 13) LOCALIZED ALOPECIA: UNDERSIDE DG( 20 ) LOCALIZED ALOPECIA: UNDERSIDE DL( 1- 22) LOCALIZED ALOPECIA: UNDERSIDE a DL( 8- 22) LOCALIZED ALOPECIA: LIMBS a .................................................................................................................................... DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. because it was not possible to identify to which litter the pups belonged. Both dams and litters were sacrificed O 4_ 0_ b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C24 (PAGE 5): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13861 13862 13863 13864 13865 13866 13867 13868 13869 DS(77-109) DS ( DS ( DG( DG{ 5) 73 ) 0 o 17) 4- 6) NO ADVERSE FINDINGS BOTH EARS: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHI NORRHEA LEFT HINDPAW: SWOLLEN LEFT NINDPAW: SWOLLEN LEFT HINDPAW: ABRASION (0.3 CM X 0.2 CM) DG( 7- i0) LEFT NINDPAW: SCAB (0.3 CM X 0.2 CM) DG( Ii- 17) LOCALIZED ALOPECIA: LIMBS O DL( 4- 13) RIGHT EYE: SWOLLEN %_ DL( 4- 22} TRAUMATIZED CORNEA a 13870 NO ADVERSE FINDINGS 13871 NO ADVERSE FINDINGS 13872 DL( 7- 8) TEAT: SWOLLEN 13873 NO ADVERSE FINDINGS 13874 DL( 22 ) LOCALIZED ALOPECIA: LIMBS a .................................................................................................................................... DS = DAY OF STUDY DG = DAY OF PRESUMED a. Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION > 4= o C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION CONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM C24 (PAGE 6): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 DS ( 8- 9) DG( 7- 21) DS( 55- 73) CHROMORHINORRBEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT EAR: SWOLLEN INCISORS: MISALIGNED DS( 68- 73) DG ( 0 - 2 ) CHROMODACRYORRHEA CHROMODACRYORRHEA DG( 0- 21) DL( i- 22) INCISORS: INCISORS: MISALIGNED MISALIGNED a DL( 7- 22) INCISORS: MISSING/BROKEN a 13885 NO ADVERSE FINDINGS 13886 DL( 14- 15) SOFT OR LIQUID FECES 13887 DS ( 2- 3 ) CHROMORHINORRHEA 13888 DL( 22 ) LOCALIZED ALOPECIA: LIMBS 13889 NO ADVERSE FINDINGS 13890 NO ADVERSE FINDINGS .................................................................................................................................... DAY OF STUDY DG = DAY OF PRESUMED Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE _n 4_ O0 O _O _-_ _'_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE C24 (PAGE 7): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13891 NO ADVERSE FINDINGS 13892 13893 13894 DG( 2) DG( 3- 20) DL( 1- 9) DL 12- 14) CNROMODACRYORR/4EA INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN NO ADVERSE FINDINGS RIGHT AXILLA: MASS (2.5 CM X 1.0 13895 13896 DG 19- 20) DS 37- 49) DS 58- 71) DS 58- 71) DG 0- 2) DG 0- 21) INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA INCISORS: MISALIGNED CM X 1.0 CM) DL i- 22) INCISORS: MISALIGNED a 13897 DL 19- 22} DS 7) CHROMODACRYORRHEA a CHROMORHINORRHEA DG II ) CHROMORHINORRHEA 13898 DG 7- 21) RIGHT EAR: SWOLLEN DL I- 22) RIGHT EAR: SWOLLEN a 13899 NO ADVERSE FINDINGS 13900 NO ADVERSE FINDINGS 13901 DL( 22 ) RIGHT EAR: SWOLLEN a 13902 NO ADVERSE FINDINGS 13903 NO ADVERSE FINDINGS .................................................................................................................................... DS = DAY OF STUDY DG = DAY OF PRESUMED a. Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE > C O0 O_ tO O PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM C24 (PAGE 8): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13904 13905 13906 13907 13908 13909 13910 13911 13912 DL( 5) DS( 87- 95) DL( 12- 16) DG( 14 ) DG( 14 ) DL( 14- 22) DG( 5- 21) DL( i- 22) SOFT OR LIQUID FECES NO ADVERSE FINDINGS BOTH EARS: SWOLLEN SOFT OR LIQUID FECES DRIED, RED PERINASAL SUBSTANCE BOTH FOREPAWS: DRIED, RED SUBSTANCE RIGHT EAR: SWOLLEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a 13913 13914 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 13915 NO ADVERSE FINDINGS 13916 13917 DS( 22- 28) BACK: NUMEROUS SCABS NO ADVERSE FINDINGS 13918 NO ADVERSE FINDINGS 13919 NO ADVERSE FINDINGS 13920 NO ADVERSE FINDINGS .................................................................................................................................... DAY OF STUDY DG = DAY OF PRESUMED Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE > C O_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE C24 (PAGE 9): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS PERFLUOROOCTANOATE _) _-_ DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929 DS( 24 ) DG( 7- 21) DL{ 1- 22) DL( 6- 10) NO ADVERSE FINDINGS NO ADVERSE FINDINGS UNGROOMED COAT NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT EAR: SWOLLEN RIGHT EAR: SWOLLEN a RIGHT EAR: NO ADVERSE SWOLLEN FINDINGS 13930 DG( 12- 21) DL( 1- 10) LOCALIZED A LOPECIA: LOCALIZEDALOPECIA: LIMBS LIMBS 13931 NO ADVERSE FINDINGS 13932 13933 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 13934 DS( 46- 54) INCISORS: MISSING/BROKEN 13935 DG( 4- 8) LOCALIZED AIX)PECIA: LIMBS DG( 14 ) CHROMORHINORRHEA DG( 19- 21) HEAD: MASS (0.7 CM X 0.5 CM X 0.3 DL( 1- 4} HEAD: MASS (0.7 CM X 0.5 CM X 0.3 DL( 5- 11) HEAD: SCAB (DID NOT EXCEED 0.5 CM DL( 12- 18) LOCALIZED ALOPECIA: HEAD .................................................................................................................................... CM) CM) X 0.5 CM) DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. 4_ O0 CD _O _.d 4_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE C24 (PAGE I0): CLINIC_L OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 DL( 13- 22) DS( 16- 17) DL( 12- 22) DG 9- 21) DL I- 22) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA a CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a NO ADVERSE FINDINGS BOTH EARS: SWOLLEN BOTH EARS: SWOLLEN a 13947 DL I) SACRIFICED DUE TO NO SURVIVING PUPS 13948 DS 30- 50} DS 53- 73} INCISORS: INCISORS: MISALIGNED MISSING/BROKEN DS 53- 73) INCISORS: MISALIGNED DG 0- 12) INCISORS: MISSING/BROKEN DG 0- 20) INCISORS: MISALIGNED DL 7- 22) INCISORS: MISSING/BROKEN a DL 9- 22) INCISORS: MISALIGNED a 13949 NO ADVERSE FINDINGS 13950 DL( 8- 9} LOCALIZED ALOPECIA: LIMBS .................................................................................................................................... DS = DAY OF STUDY DG = DAY OF PRESUMED a. Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE > C O0 4_ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C25 (PAGE 1): BODY WEIGHTS- PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 57 64 70a .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 131. 149 177. 187. 194. 205 154. 183 216. 240. 260. 262 154. 177 216. 227. 242. 256 155. 187 209. 227. 250. 257 141. 173 194. 216. 256. 240 155. 182 200. 217. 229. 236 149. 186 215. 234. 254. 264 145. 181. 204. 224. 239. 250 140. 168. 190. 202. 218. 226 154. 194. 225. 249. 261. 265 217. 227 282. 297 272. 283 263. 270 248. 267 245. 261 275. 281 256. 264 237. 242 279. 297 225. 296. 288. 279. 275. 258. 290. 266. 245. 296. 238. 293. 301. 281. 280. 264. 290. 267. 258. 298. 246. 308. 303. b 278. 268. 301. 270. 253. 309. 13811 13812 13813 145. 177. 200. 215. 214. 23{ 152. 178. 195. 209. 224. 233 136. 167. 187. 203. 218. 230 238. 251 241. 254 240. 248 266. 262. 255. 264. 278. 265. 271. 278. 266. 13814 13815 13816 13817 13818 13819 155. 177. 204. 225. 240. 251 147. 186 214 239. 256. 264 152. 171. 197. 202. 223. 216 138. 164. 187. 204. 213. 222 156. 179. 212. 219. 229. 236 143. 174. 195. 210. 222. 232 257. 274 283. 292 227. 233 226. 233 236. 251 236. 253 274. 308. 239. 227. 253. 256. 280. 310 239. 235. 260. 250. 280. 315. 239. 239. 264. 261. 13820 13821 13822 13823 13824 13825 13826 13827 13828 134. 187. 216. 233. 251. 265 144. 170. 196. 212. 227. 240 151. 186. 215. 232. 254. 265 148. 175. 199. 217. 240. 254 154. 186. 216. 232. 248. 262 142. 175. 193. 219. 237. 254 160. 188. 216. 230. 248. 258 147. 188. 214. 229. 253. 266 153. 176. 196. 213. 226. 233 278. 288 251. 252 273. 268 263. 268 284. 285 260. 274 261. 271 277. 280 236. 252 293. 261. 278. 279. 296. 283. 288. 290. 263. 299. 267. 286. 290. 303. 292. 285. 307. 268. 300. 268. 283. 292. 299. 288. 292. 298. 273. 13829 13830 145. 153. 175. 173. 185. 188. 198. 191. 209. 200. ...................................................................................................... = DAY OF STUDY 221 211 227. 242 216. 225 249. 229. 250. 235. 252. 234. _ ............................. WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 4_ Rat 13804 was moribund sacrificed on day 68 of study. O0 bo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C25 (PAGE 2): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 139. 159. 147. 150. 142. 155. 144. 149 138 156 171 191 173 179 177 171 163 179. 166. 185. 193. 219. 205. 204. 197. 188. 179. 202. 194. 209. 214. 241 216 221 212 197 195 222 210 225 219. 249 233 230 224 207 209 234 226 240 242. 263. 233. 230. 226. 214. 217. 251. 227. 242. 260. 263. 249. 249. 242. 217. 219 256 242 252 264. 268. 255. 266. 252. 227. 230. 275. 254. 260. 13841 150 174. 195. 215 227 235. 245 258. 57 259. 269. 258. 269. 255. 237. 236. 284. 260. 259. 266. 64 70a 266. 273. 283. 283. 260. 267. 267. 274. 256. 268. MORIBUND SACRIFICED 244 249. 300 307. 263 272. 264 265. 272 273. ON DAY 59 OF STUDY 138423 15430 117662.. 210779.. 211835. 212997.. 2305. 224134 25105. 25261. 25287. 26219. 13844 13845 157 189. 216 234. 253. 262. 266 276. 283 286. 287. 153 179. 200 207. 224. 230. 234 241. 244 251. 252. 13846 149. 167. 186 198. 210. 221. 230 250. 252 256. 256. 13847 141. 175. 194 211. 224. 238 249. 260. 261 274. 276. 13848 156. 185. 215 227. 245. 257 273. 280. 285 292. 294 13849 146. 176. 204 220. 235. 253 268. 283. 283 297. 306 13850 147. 176. 199 212. 229. 243 252. 267. 274 278. 280 13851 141. 167. 187. 202. 211. 223 234. 237. 240 251. 257 13852 149. 172. 192. 211. 232. 240 246. 257. 271. 283. 280 13853 145. 176. 197. 214. 233. 244 249. 262. 264. 271. 272 13854 152. 190. 225. 249. 266. 272 276. 288. 296. 302. 302 13855 143. 177. 206. 233. 247. 254 257. 267. 278. 278. 280 13856 151. 174. 207. 227. 241. 251. 256. 268. 278. 284. 289 13857 145. 172. 202. 215. 222. 233. 245. 254. 258. 267. 266. 13858 151. 174. 194. 210. 227. 235. 238. 244. 259. 265. 265. 13859 144. 171. 193. 204. 212. 216. 229. 235. 245. 241. 248. > 13860 148. 171. 187. 195. 204. 210. 223. 231. 238. 251. 252. ...................................................................................................... _ ............................. = DAY OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 4_ O0 t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE C25 (PAGE 3}: BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 130. 157. 177. 189 198 161. 193. 227. 248 269 149. 177. 207. 215 222 149. 181. 207. 212 234 141. 181. 202. 219 236 161. 194. 223. 257 277 149. 176. 199. 215 230 146. 173. 203. 212 223 145. 178. 210. 226 249 154. 180. 200. 221 237 148. 185. 209. 225 238 154. 182. 207. 216 233 142. 174. 192. 215 221 156. 200. 234. 249 278 143. 174. 190. 208 225 155. 192. 220. 249 278 144. 185. 214. 241 256 149. 179. 205. 221 233 144. 176. 195. 215 222 155. 188. 216. 232 253 146. 173. 192. 198 213 158. 190. 220. 239 258 152. 179. 197. 212 226 150 188. 216. 237 248 147 183. 208. 232 245 155 184. 210. 223 236 144 174. 200. 206 218 153 181. 209. 233 248 206. 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. 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. 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. 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. 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 70a 236. 315. 264. 265. 291. 334. 269. 269. 290. 283. 273. 276. 263. 337. 267. 351. 326. 289. 280. 327. 248. 306. 270. 296. 297. 269. 257. 298. 13889 13890 148 183. 210. 233 248 256. 264. 272. 150 178. 208. 225 241 253. 263. 268. .................................................................................................................................... = DAY OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 283. 275. 286 285 289. 282. [/) 4_ w.d O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C25 (PAGE 4): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... 13891 136 160. 178 190. 210. 218, 227 234. 13892 13893 13894 13895 13896 13897 13898 13899 13900 160 192. 215 233. 250. 260. 268 274. 155 192. 225 249. 273. 281. 286 297. 152 186. 214 237. 252. 265. 283 298. 141 176. 208 223. 236. 238. 248 264. 157 191. 215 229. 247. 255. 270 287. 151 192. 225 231. 251. 262. 276 283. 159 191, 220 248. 264. 279. 287 293. 140 165. 185 203. 210. 213. 223 233. 155 184. 210 222. 237. 247. 255 263. 57 234 289 305 301 262 290 293 299 239 266 64 70a 246. 292. 312. 303. 265. 277. 304. 304. 239. 272. 243. 294. 321. 320. 265. 283. 310. 310. 244. 272. 13901 150 174. 197 214. 225. 237. 250 260. 255 262. 267. 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 145 171. 196 212. 227. 236. 253 263. 274 281. 286. 140 173. 198 216. 229. 240. 251 269. 276 285. 295. 151 174. 185 201. 214 224. 232 250. 246. 261. 271. 149 188. 207 230. 249 251. 267 273. 278 " 280. 291 " 153 193. 216 231. 248 263. 271 271. 282. 294. 296. 140 167. 190 206. 227 235. 241 256. 263. 262. 269. 155 188. 212 240. 260 266. 274 290, 293, 301. 303. 147 177. 200 211. 229 241. 249 251. 261. 268. 268. 151 186. 219 249. 258 270. 282 300. 300. 315. 323. 145 177. 202 213. 231 244. 252 257. 263. 271. 275. 159 189. 211 234. 248 258. 263 278. 283. 285. 294. 142 173. 199 215. 229 243. 252 260. 258. 270. 276. 153 183. 212 235. 250 257. 264 275. 284. 291. 301. 148 182. 204 218. 236 246. 246 253. 264. 277, 263. 156 191. 215 234. 247 264. 278 290. 287. 304. 312. 146 176. 218 227. 237 245. 251 263. 270. 276. 277. 154 182. 206 215. 228 236. 245 255. 257. 261. 260. 13919 143 167. 196 215. 226 233. 244 252. 253. 262. 269. > 13920 150 179. 199 212. 224 231. 247 256. 260. 271. 273. ....................................................................................................... = DAY OF STUDY ............................. WEIGHTS WERE RECORDED IN GRAMS (G). [/_ Last value recorded before cohabitation. 4= O0 to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C25 (PAGE 5): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 141, 164. 146. 150, 138. 158. 153. 152. 140. 160. 147. 147. 174. 191 178 180 169 190 181 183 163 191 178 169 203. 204. 202. 203. 189. 216. 207, 200. 185. 222. 205. 195. 224. 219. 216. 221. 199. 228. 232. 216 198 233 207 213 240. 237. 228. 237. 212. 237. 250. 231 214 247 231 223 244 239 238 243 220 238 246 245. 220. 253. 238. 224. 258, 249. 246. 247. 228. 256. 265. 247. 224. 265. 251. 241. 270, 263. 261. 261. 230 267 270 270 235 275 257 248 13933 139. 173 195. 212 227 13934 13935 13936 13937 13938 156. 186. 206. 215 233 149. 181. 207. 217 234 155 188. 210. 225 239 137 167. 189. 199. 211 145 174. 199. 220. 232 13939 13940 148 185. 218 230. 249 148 185. 210 230. 245. 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 146 181. 204 149 176. 195 148 179. 194 152 173. 202 148 178. 206 152 178. 200 144 179. 201 159, 182, 208 142. 173. 205 153. 180. 200 224. 209, 207. 217. 229. 210. 218. 223. 217. 214. 250. 224, 231. 235. 241. 225. 230. 232. 236. 228. ...................................................................................................... = DAY OF STUDY WEIGHTS WERE RECORDED Last value recorded IN GRAMS (G). before cohabitation. 223. 247. 239. 245, 222. 235. 250, 254. 258. 235, 235. 234. 248. 233. 234. 249. 244. 235. 236. 255. 255. 258 236 251 265 263 265 246 251 242 259 241. 240. 260. 261. 241. 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. 70a 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 27S 298 268 _ ............................. > [2_ /_ O_ 6, bO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C26 (PAGE i) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... PREGNANCY STATUS DAY 0 7 10 14 18 21 ...... _ ............................................................................................................................. RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 P 238. 276. 289. 310. 310. 350. 13802 P 306. 352. 372. 380. 418. 468. 13803 P 319. 348. 356. 378. 421. 464. 13804 - MORIBUND SACRIFICED ON DAY 68 OF STUDY 13805 P 278. 324 334. 352. 396. 421. 13806 P 267. 305 313. 334. 379. 318. 13807 P 306. 324 330. 354. 408. 13808 P 272. 293 298. 317. 361. 312 13809 P 276. 297 308. 322. a 397 13810 P 13811 NP 13812 P 13813 P 300. 340 264. 297 275. 295 279. 306 350. 365. 407. 458 304. 302 301. 305. 307. 328. 362. 409 328. 348. 381. 421 13814 P 290. 316 325. 336. 360. 416 13815 P 324. 345 366. 378. 411. 438 13816 P 238. 271 284. 295. 338. 388 13817 P 241. 270 281. 292. 340. 389 13818 P 266. 297 312. 332. 376. 425 13819 P 261. 291 300. 312. 360. 347 13820 P 292. 299 319. 322. 362. 41_ 13821 P 268. 306 308. 336. 374. 417 13822 P 292. 327 330. 354. 385. 421 13823 P 302. 327 342. 359. 385. 415 13824 P 299. 339 350. 368 407. 449 13825 P 290. 313 327. 342 385. 422 13826 P 290. 326 325. 343 405. 437 13827 P 311. 338 339. 370 414. 459 13828 P 13829 P 13830 P 274. 315 252. 286 243. 262 320. 330 291. 305 273. 293 ....................................................................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED = DAY OF PRESUMED GESTATION 370. 410 349. 389 326. 293 FROM AVERAGES) WEIGHTS WERE RECORDED IN GRAMS Value was not recorded. (G). 25 309. - ........................ _'_ [_0 4_ OO b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C26 (PAGE 2): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... PREGNANCY STATUS DAY 0 7 i0 14 18 21 .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 P 283. 323. 337. 354. 403. 438. 13832 P 13833 P 13834 P 13835 P 13836 13837 P 13838 P 13839 P 13840 NP 294. 271. 275. 272. MORIBUND 244. 303. 258. 260. 324. 291. 298. 296. SACRIFICED 275. 333. 292. 282. 332. 298. 305. 318. ON DAY 280. 344. 304. 288. 348. 306. 315. 329. 59 OF 303. 366. 314. 286. 390. 358. 352. 380. STUDY 341. 428. 356. 282. 447. 404. 388. 429. 303 467 390 284 13841 P 278. 298. 309. 322. 374. 396 13842 P 13843 P 262. 224. 284. 247. 289. 258. 303. 282. 13844 P 13845 P 287. 245. 304. 274. 312. 290. 322. 307. 13846 P 253. 285. 296. 311. 13847 P 271. 297. 303. 313. 13848 P 295. 333. 341. 354. 13849 P 298. 334. 341. 359. 13850 P 276 286. 320. 331. 13851 NP 259 267. 270. 270. 13852 P 282 308. 324 335. 13853 P 273 306. 316 330. 13854 P 289 328. 342 353. 13855 P 276 310. 326 337 13856 P 292 321. 332 348 13857 P 278 303. 310 329 13858 P 270. 293. 296 306 13859 P 13860 P 246. 268. 278 294 248. 278. 282 297 ............................................................................................ = PREGNANT NP - NOT PREGNANT DAY _ DAY OF PRESUMED GESTATION (VALUES EXCLUDED 353. 312. 379. 352. 359. 370. 408. 389. 377. 276. 390. 381. 410. 386. 398. 365. 356. 342. 325. 400 282 406 388. 394. 402. 455. 425. 324. 275. 413. 303. 455. 339. 417. 417. 309. 378. 335. FROM AVERAGES) ALL WEIGHTS WERE RECORDED IN GRAMS (G). 25 287. 278. _ ....................................... {29 f %.2 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C26 (PAGE 3): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... PREGNANCY STATUS DAY 0 7 10 14 18 21 25 .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 P 13862 P 234. 257. DID NOT DELIVER 265. A LITTER 282. 312. 339. 13863 P 249. 281. 291. 312. 362. 416 13864 P 261. 296. 310. 328 340. 358 13865 P 286. 339. 347. 363 423. 420 13866 P 328. 358, 379, 397 438. 488 13867 P 275. 296. 308. 326 369. 416 13868 P 275. 302. 310. 335 373. 407 13869 P 292. 304. 326. 356 389. 437 13870 P 282. 307. 310. 336 373. 399 13871 P 262. 294. 301. 319 385. 351 13872 P 13873 P 281. 281. 311. 289. 316. 335 301. 310 379. 417 370. 424 13874 P 334. 366. 374. 390 438. 487 13875 P 265. 301 323. 338 399. 436 13876 P 349. 385 401. 422 474. 520 13877 P 324. 357 372. 391 433. 482 13878 P 274. 293 305. 323 358. 388 13879 P 273. 304 322. 334 376. 41_ 13880 P 321. 364 376. 404 450, 496 13881 P 244. 277 294. 306 348. 355 13882 P 301. 335 347. 374 403. 433 13883 P 265. 302 311. 320 372. 409 13884 P 292. 314 329. 340. 371. 403 13885 P 284. 320 336. 352. 374. 367 13886 P 256. 287 291. 310. 358. 372 13887 P 266. 290 300. 318. 352. 390 13888 P 13889 P 293. 320 296. 325 330. 347. 403. 430 328. 341. 389. 343 13890 P 278. 320 334. 348. 394. 432 ........................................................................................... PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) = DAY OF PRESUMED GESTATION WEIGHTS WERE RECORDED IN GRAMS (G) > . ....................................... _O-0- O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C26 (PAGE 4): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS PREGNANCY STATUS DAY 0 7 10 14 18 21 25 .................................................................................................................................... RAT # DOSAGE GROUP IV I0 MG/KG/DAY .................................................................................................................................... 13891 P 246. 260. 273 283. 316. 348. 13892 P 301. 315. 325 341. 388. 413. 13893 P 319. 330. 337 349. 396. 427. 13894 P 305. 337. 355 364. 414. 448. 13895 P 261, 294. 302 319. 333. 379. 13896 P 248. 303. 322 332. 367. 403. 13897 P 316. 340. 351 376. 411. 449. 13898 P 300. 336. 355 366. 417. 457. 13899 P 246. 270. 271 290. 336. 372. 13900 NP MATING NOT CONFIRMED 13901 P 13902 P 13903 P 13904 P 13905 P 13906 P 13907 P 13908 P 13909 P 13910 P 13911 P 13912 P 13913 P 13914 P 13915 P 13916 P 13917 P 274. 277. 310. 305. 321. 320. 293. 309. 327. 254 289. 299. 327. 314 338. NO CONFIRMED MATING DATE 257. 288. 307 302. 342. 356 273. 302. 316 309. 353. 366 269. 301. 316 284. 311. 321 271. 309. 326 296. 318. 323 269. 306. 312 307. 326. 349. NO CONFIRMED MATING DATE 339. 328. 339. 339. 352. 325. 364. 328. 383. 320. 333. 334. 356. 325. 370. 386. 370. 382. 375 . 389. 381. 387. 371. 424. 364. 375. 364. 410. 369. 418. 432. 418. 419. 411. 430. 384. 407. 463. 381. 417. 386. 455. 419. 459, 13918 P 268. 290. 305. 319. 359. 410. _> 13919 P 250. 281. 289. 305. 357. 388. 13920 P 267. 296. 315. 328. 368. 423. ............................................................................................ PREGNANT NP _ NOT PREGNANT (VALUES EXCLUDED = DAY OF PRESUMED GESTATION FROM AVERAGES) _ ....................................... 4_ WEIGHTS WERE RECORDED IN GRAMS (G). O0 tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C26 (PAGE 5): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... PREGNANCY STATUS DAY 0 7 i0 14 18 21 .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13921 P 13922 P 13923 P 13924 P 13925 P 13926 P 13927 P 13928 P 13929 NP 276. 257. 273. 268. 241. 272. 277. 284. 249. 296. 296. 297. 295. 252. 294. 310. 313. 252. 310. 303. 304. 298. 265. 317. 319. 317. 249. 328. 312. 321. 322. 282. 332. 339. 344. 254. 390. 323. 373 370 327 380 386 400 243 428. 282. 316. 421. 358. 333. 412. 439. 243. 13930 P 279. 311. 328. 341. 13931 P 13932 P 13933 P 276. 268. 249. 302. 287. 268. 311. 306. 278. 330. 284. 285. 13934 P NO CONFIRMED MATING DATE 13935 P 268 291. 308 314. 13936 P 297 309. 338 359. 13937 P 248 268. 276 295. 13938 P 262 286. 299 308 13939 P 292 307. 317 327 13940 P 278 310. 310 328 13941 P 286. 315. 325 346 13942 P 253. 292. 295 319 13943 P 252. 299. 302 316 13944 P 263. 289 305 312 13945 P 281. 309 320 331 13946 P 258. 281 296 314 13947 P 248. 278 289. 293 13948 P 281. 297 313. 320 13949 P 289. 316 325. 346 13950 P 279. 296 306. 325 ............................................................................................ = DAY ALL PREGNANT NP = NOT PREGNANT (VALUES = DAY OF PRESUMED GESTATION WEIGHTS WERE RECORDED IN GRAMS (G). EXCLUDED 367 427. 375 388. 345 368. 329 373. 357. 400. 347. 372. 374. 370. 398. 373. 360. 337. 376. 349. 304. 324. 393. 373. 402. 430. 393. 310. 407. 414. 450. 411. 381. 375 395 375 306 368 348 368 FROM AVERAGES) 25 246. '........................................ [29 4_ OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C27 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... DAM # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 294. 365. 346. MORIBUND 320. 302. 315. 302. 298. 355. 287. 302. 309. 322. 376. 386. 390. 396. 366. 372. 372. 402. SACRIFICED ON DAY 68 OF STUDY 336. 346. 352. 370. 308. 337. a 341. 344. 369. 376. 376. 298. 316. a 331. 316. 348. 345. 354. 357. 382. 389. 394. 338. 367. 366. 348 340 367 286 355 370 13811 NOT PREGNANT 1133881123 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 13829 13830 239196. 301. 340. 285. 272. 296 299 312 304 327 338 330 317 328 351 306 284 265 3242. 313. 332. 294. 271. 303. 314. 337. 334. 342. 348. 342. 318. 349. 347. 297. 280. 265. 33673. a 332. 292. a a 331. 343. 352 330 336 351 342 341 368 328 279 a 34910. 343. 35449. 351. 356. 367 321. 326 293. 314 336. 328 327. 321 369. 381 364. 344 SACRIFICED ON DAY 364. 379. 353. 400. 355. 338. 356. 380. 394. 404. 340. 351. 324. 303. 312. 309. 32963. 359. 370. 320. 302. 376. 344. 317. 328. 8 OF 339. 385. 350. 376. 377. 309. 301. 306. LACTATION ........................................................................................... DAY ffiDAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). value was not recorded. _ ........................................ 4_ o_ b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION} T-6889.6) REPRODUCTION TABLE C27 (PAGE 2): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION .................................................................................................................................... DAY 1 5 8 ii 15 22 .................................................................................................................................... DAM # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 321. 322. a 375. 365. 342. 329. 373. 368. 380. 293. 307. 310. 343. 344. 294. 293. 304. 320. 316. 304. 326. 336. 336. 360. MORIBUND SACRIFICED ON DAY 59 OF STUDY 289. 293. 307. a 329. 335. 331. 355. 385. 382. 301. 314. 327. 335. 340. NOT PREGNANT 290. 320. 312. 332. 362, 361. 357. 343. 310. 318. 359. 375. 361. 347. STUDY OF AMMONIUM PERFLUOROOCTANOATE FEMALE RATS 138423 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 29630. 237066.. 292. 283. 315. 277. 290. 292. 289, 296. 319. 335. 314. 320. 320. 296. NOT PREGNANT 322. 301. 296. 309. 340. 358. 317. 338. 238274.. 332. 298. 297. 314. 353. a 322. 317. 322. 375. 356. 323989 331 305 276 322 385 349. a 336021.. 361. 323. 326. 338. 377. 319. 350. 335117. 368 352 336 314 331 336 341 SACRIFICED ON DAY a 331. 372. 379. 371. 379. 11 OF 331. 381. 330. LACTATION 13856 13857 13858 13859 13860 318. 305. 301. 282. 277. 342. 328. 288. 295. 268. 358, 335. 325. a a 347. 358. a 320. 299. 386. 337. 314. 323. 294. 367. 295. 338. 316. 293. ....................................................................................................... DAY = DAY OF LACTATION ALL WEIGHTSWERE RECORDED IN GRAMS Value was not recorded. (G). .............................. 4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C27 (PAGE 3}: MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... DAM # DOSAGE GROUP III 3 MG/KG/DAY ...... _ ............................................................................................................................. 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 275. PREGNANT; 297. 312. 340. 368. 293. 304. 318. 319. 274. 285. DID NOT DELIVER 320. 336. 310. 311. 332. 339. 366. 392. 302. 322. 308 a 337 349. 320 330. 276. A LITTER 335. 344. 344. 406. 328. 348. 361. 327. 305. 334. 334. 364. 408. 355. 354. 372. 366. 312. 352. 335 353 401 335 356 357 386 13871 13872 13873 315. 313 308. 322 301. 324 343. 335. 334. 323. 344. 355. 337. 353. 350 366 347 346. 13874 368. 379 a 401. 403 368. 13875 309. 306 327. 332. 360 358. 13876 398. 413 427. 438. 441 399. 13877 373. 376 a 388. 404 383. 13878 309. 312 335. 330. 352 352. 13879 308 329. 342. 337. 360 328. 13880 368 366. 366. 374. 377 363. 13881 291 298. 313. 321. 318 323. 13882 332 341. a 381. 361 355. 13883 303 322. 343. 347. 331 342. 13884 316 335. 325 347. 363 368. 13885 323 336. 340 351. 349. 336. 13886 300 299. 338 364. 340. 322. 13887 295 309. 316 341. 322. 310. 13888 327 303. 306 339. 337. 335. 13889 333 326. 352 a 367. 340. > 13890 312 315. 336 356. 357. 364. ............................................................................................ DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). value was not recorded....4_ ,........................................ [/) oo tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C27 (PAGE 4): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION STUDY OF AMMONIUM PERFLUOROOCTANOATE FEMALE RATS DAY 1 5 8 11 15 22 .................................................................................................................................... DAM # DOSAGE GROUP IV I0 MG/KG/DAY .................................................................................................................................... 13891 264. 260. 275. 285. 285. 300 13892 336. 334. a 361. 364. 366 13893 13894 319. 330 332. 350 352. 380. 370. 332 371. 389. 399. 386 13895 13896 13897 13898 13899 13900 301. 310 339. 352. 354. 334 311. 329 334. 347. 363. 376 351. 338 359. 368. 376. 361 350. 369 405. 328. 408. 395 268. 284 a 288. 308. 320 NOT PREGNANT MATING NOT CONFIRMED 13901 303. 313 329. 348. 344. 350 139023 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 30147. 306. 321. 316. 301. 343. 294. 350. 294. 316. 305. 326. 281. 356. 312. 290. 30319 316 338 317 308 343 317 361 276. 324. 321. 340. 293. 336. 288. 309. 32429. 342. 364. 337. 317. 343. 331. 382. 297. 337. a a 316. a a 335. 31546. 359. 350. 359. 315. 359. 347. 371. 320. 351. 336. 365. 346. 379. 325. 342. 3336. 364. 360. 352. 318. 374. 355. 381. 325. 341. 363. 371. 335. 371. 330. 336. 3118 354 351 355 337 366 356 353 327 355 317 294 323 376. 327. 302. 13919 13920 285. 301. 287. 315. a 330. 324. 329. a 340. 308. 349. .................................................................................................................................... '_ = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). Value was not recorded. 4_ Oo O PROTOCOL 418-020. ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C27 (PAGE 5): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - P GENERATION STUDY OF AMMONIUM PERFLUOROOCTANOATE FEMALE RATS DAY 1 5 8 11 15 22 .................................................................................................................................... DAM # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13921 311 310. 320 346. 368 357. 13922 274 304. 307 318. 334 352. 13923 13924 305 287. 303 a 325 320. 291 316. 327 342. 350 341. 13925 13926 13927 13928 13929 273 278. 298 324 320. 338 289 293. 298 317 330. 346 NOT PREGNANT 310. 311 349. 366 308. 334 358. 359 318. 353. 331. 368. 13930 318 321. 325. 341. 369 350. 13931 318 300. a 324. 339 368. 139323 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 2756 29875. 286a. 32293. 33218 303 306. 322 327. 327 294 313. 308 313. 315 321 337. 353 352. 360 286 303. 317 311. 318 298 290. 301 316. 343 301 308. 331 342. 370 304 324. 316 352. 351 341 353. 352 304. 335 298 313. 334 361. 345 308 316. 337 350. 359 291 279. 302 299. 336. 312 a 341 351. 360. 292 312. 327 338. 327. 273 SACRIFICED DUE TO NO SURVIVING PUPS 267 289. 322. 338. 346. 13949 13950 345 342. 359. 366. 304 298. a 340. ....................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). Value was not recorded. 374. 357. 35276. 340. 318. 349. 306. 343. 349. 353. 383. 344. 349. 341. 342. 353. ON DAY 323. 365. 361. 1 OF LACTATION .............................. ' [2_ 4_ O0 _O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C28 (PAGE 1): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 13802 100 188 126 109. 120. 124 133. 132 161 168 167. 160. 177 181. 13803 133 158 154 156. 159. 151 172. 13804 13805 13806 13807 13808 13809 13810 148 148 162 162. 161. 159 b 111 122 154 152. 150. 175 177 140 143 147 146. 147. 154 165 133 148 152 151. 159. 143 158 142 158 158 160. 158. 156 158 131 142 143 146. 140. 149 152 142 156 218.c 157. 167. 179 176 50- 57 119. b 150. 154 158 144 146 144 146 159 57- 64 64- 70a 136. 149.c 158.c 156. 162 147 145 148 151 174 119. 137. 145. MORIBUND 133 133 124 123 120 152 SACRIFICED ON DAY 68 OF STUDY 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 125 133 126 130 123 143 125 154 147 156 164 193 121 123 132 149 126. 137 143. 158 116. 137 139. 144 131. 144 130. 138 143. 144 140. 142 138. 149 114. 127 163 154 142 160 165 126 124 150 138 165 137 152 145 154 155 139 168 b 140. 155. 146. 145. 174. 137. 123. 141. 134. b 136. 153. 145. 152. 157. 141. 173. b 144. 147. 147. 145. 171. 123. 129. 143 147 184 143 173 157 149. 166. 144. 174. 117. 141 144 160 167 183 130 117 140 146 178 b 150 149 148 163 140 166 129. 168 154 159 169 181 132 115 149 161 191 143 140 148 202 166 145 b 147. 152 141 157 149 177 128 110 143 136 173 137 138 14_ . 153. 163. 143. b 182. 152 172 216 151 175 130 117 144 138 163 144 b 150 148 173 139 179 140 119. 134. 133. 135. 141 108. b 117. 133. 139. 110. 115. 123. 118. 127. 124. 145. 130. 13829 13830 137. 133 124. 120 178. 184. 144. 142. b 135. 153 129. 139. 122. 126. 138. 134. 126 b 106. ........................................................................................... = DAYS OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. _ ........................................ [29 4_ Spilled feed precluded the calculation of this value. O0 Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C28 (PAGE 2): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 139. 146. 148. 149 166 163. b 134. 145. 146. 144 148 141. 141. 133. 145. 142. 145 146 156. 153. 158. 154. 172. 151 145 165. 178. 145. 142. 144. 140 140 148. 146. 13836 13837 13838 13839 13840 13841 125. 134. 134. 127 134 b 146. 110. 117. 138. 123 123 122. 135. 127. 136. 141. 136 147 145. 159. 129. 136. b 139 145 149. 148. 141. 160. 164. 149 151 151. 149. " 136. 142. 151. 146 142 163. 160. 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 139. 156. 142. 155 137 160. 158. 131. 133. 129. 121 139 134. 138. 165. 176. 169. 176 172 176. 174. 139. 149. 144. 142 138 142. 148. 118. 125. 123. 125 130 134. 143. 109. 128. 140. 130 137 138. 142. 153. 149. 147. 150 150 147. 152. 134. 149. 149. 153 166 167. 166. 147. 203. 148. 182 174 163. 178. 124. 132. 146. 146 155 150. 134. 120. 130. 158. 140 149 141. 157. 135. 141. 146. 147 148 150. 153. 139. 155. 206. 173 159 156. 169. 139. 153. 160. 157 151 150. 154. b 211. 149. 159 166 183. 164. 111. 146. 143. 130 150 142. 138. 170. b 158. 151 147 150. 152. 13859 13860 133. 147. 139. 138 139 125. 128. 124. 125 130 ......................... = DAYS OF STUDY ................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 142. 138. 138. 139. Spilled feed precluded the calculation of this value. 50- 57 181. 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. 57- 64 64- 70a 166. 146. 148. 146. 141. MORIBUND 133. 158. 151. 141. 141. 123. 119. 135. 126. 125. SACRIFICED 120. 129. 136. 114. 146. ON DAY 59 OF STUDY 135. 129. 166. 147. 134. 136. 144. 168. 170. 142. 155. 154. 151. 148. 159. 134. 154. 102. 112. 136. 130. 106. 122. 122. 141. 130. 118. 132. 120. 127. 129. 175. 111. 137. 149. 145. 128. 114. .-_ _ ....... _ ............................. _'_ [/_ 4_ Oo tJ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE yABLE C28 (PAGE 3): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 123. 136. 131. 136. 133. 136. 142. 13862 13863 13864 13865 13866 13867 13868 13869 13870 149. 142. 132. 148. 159. 135. 133. 145. 139. 152. 154. 142. 147. b 140. 148. 161. 155. 169. 145. 139. 170. 180. 144. 176. 166. 162. 177. 143. 149. 159. 191. 145. 157. 194. 158. 160. 149. 147. 160. 181. 141. 160. 162. 160. 163. 161. 159. 153. 194. 152. 167. 165. 172. 168. 150. 154. 175. 184. 136. 166. 173. 168. 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 128. 136. 124. 152. 130. 145. 150. 125. 131. 143. 127. 140. 141. 158. 140. 136. 135. 139. 139. 161. 134. 163. 154. 164. 161. 145. 148. 160. 120. 153. 145. 158. 141. 141. 159. 159. 143. 141. 124. 161. 150. 173. 168. 137. 147. 151. 131. 161. 147. 154. 150. 142. 136. 174. 138. 144. 138. 170. 145. 178. 162. 148. 127. 162. 130. 162. 142. 161. 142. 143. 137. 167. 131. 141. 134. 177. 152. 171. 174. 153. 145. 162. 115. 171. 145. 160. 156. 145. 141. 154. 133. 147. 138. 175. 158. 196. 186. 146. 143. 170. 129. 157. 149. 153. 143. 137. 136. 166. 132. b 136. 178. 158. 198. 167. 155. 158. 186. 127. 163. 154. 153. 150. 139. 144. 163. 50- 57 142. 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. 57- 64 145. 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. 64- 70a 119. 144. 133. 118. 142. 142. 124. 133. 129. 112. 148. iii. 116. 146. 132. 141. 142. 126. 122. 137. 104. 129. 127. 121. 128. 113. 110. 138. 13889 149. 160. 162. 166. 152. 158. 161. 157. 157. 130. _> 13890 149. 235. 250.c 213, b 202. 184. b 174. 144. .................................................................................................................................... = DAYS OF STUDY ' WEIGHTS WERE RECORDED IN GRAMS (G). O0 Last value recorded before cohabitation. Spilled feed precluded the calculation of this value. O0 Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C28 (PAGE 4): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAYS i- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY ...... _ ............................................................................................................................. 13891 13892 13893 13894 13895 13896 13897 13898 129. 131 165 b 147. 143. 147. 152. 162 179 172. 167. 167. 176. 155. 178 188 193. 183. 182. 180. 145. 163 169 166. 174. 188. 193. 149. 163 161 163. 157. 153. 172. 139. 150 156 159. 164. 167. 180. 153. 166 156 155. 166. 159. 162. 147. 159 167 171. 179. 171. 175. 13899 13900 131. 140 141 135. 142. 146. 146. 145. 148 147 151. 150. 156. 151. 50- 57 139. 181. 174. 228. 157. 170. 158. 160. 148. 151. 57- 64 136. 162. 172. 186. 155. 121. 158. 158. b 163. 64- 70a 109 134 144 167 131 118 128 133 118 120. 13901 125. 134 137 142. 147. 136. 138. 131. 138. 113. 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 126. 142 138 129. 163 141 116. 104 145 156. 178 165 167. 184 177 121. 133 149 133. 140 154 124. 147 136 146. 160 170 139. 143 150 144. 147 163 130. 152 151 133. 139. 159 146. 151 152 143. 174 155 135. 168 158 134. 156 143 137. 142. ii0. 170. 173. 143. 156. 138. 166. 154. 159. 155. 158. 156. 109. 185. 122. 150. 133. 109. 159. b 141. 147. 133. 167. 148. 157. 157. 161. 148. 188. 159. 140. 154. 149. 131. 187. 163. 137. 159. 132. 165. 142. 163. 159. 157. 136. 163. b 145. 140. 160. 141. 183. 161. 140. 169. 130. b 143. 168. 153. 162. 141. 166. b 141. 147. 154. 132. 172. 167. 141. 155. 138. 180. 136. 150. 144. 167. 161. 156. b 142. 162. 158. 137. 162. 172. 128. 156. 139. 171. 128. 151. 153. 166. 148. 168. 151. 135. b 129. 115. 147. 139. 120. 129. 115. 152. 116. 128. 118. 149. 110. 139. 123. 108. 13919 13920 123. 138 135. 144 148 b 189. 156. 150. 144. 163. 133. .................................................................................................................................... = DAYS OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). Last value recorded before cohabitation. 144. 148. 136. 147. 145. 158. 118. 122. _> [29 Spilled feed precluded the calculation of this value. OO 6 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C28 (PAGE 5) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS DAYS I- 8 8- 15 15- 22 22- 29 29- 36 36- 43 43- 50 .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 144 152 155. 150. 142. 157 159 154 149 153. 161. 156. 167 153 149 164 163. 165. 167. 172 191 141 162 162. 157. 157. 156 185 128 138 136. 132. 135. 132 130 138 146 146. 150. 149. 163 157 126 141 151. 156. 143. 153 152 160 145 165. 130. 157. 156 169 120 131 128. 133. 138. 130 131 141 152 149. 139. 155. 160 156 13931 138 169 b b 140. 142 149 50- 57 148 146 191 179 126 149 141 147 132 161 140 57- 64 147 150 170 165 126 155 140 154 137 149 142 64- 70a 124 127 147 140 104 133 110 129 112 122 ii0 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 13948 123 139 137. 138. 128. 144 141 136 136 120. 154 163 133. 143. 181. 135 139 138 134 i00. 146 155 151. 162. 178. 161 169 163 156 123. 144 154 148. 148. 152 142 150 151 143 132. 141 142 156. 150. 134. 136 135 143 138 118. 121 123 136. 138. 133. 130 124 125 135 104. 125 131 142. 137. 134. 143 139 135 131 113. 144 153 b 174. 145. 150 153 145 138 127. 134 155 c 143. 146. 144 228 150 136 117. b 182 b b 156. 163 150 b 153 135. 134 144 142. 141. 144. 151 160 156 129 120. 140 134 141. 157. 140. 144 144 167 144 118. 128 162 b 158. 142. 150 149 141 138. 112. 137 150 166. 151. 156. 169 176 163 160 137 125 138 131. 153. b 145 141 133 132 109 134 132 133. 136. 123. 133 129 127 121 95 144 149 147. 144. 140. 161 155 151 150 119 13949 131 148 149. 164. 158. 163 161 166 162 132 > 13950 149 154 140. 141. 144. b 145 b 145 122 ...................................................................................................... = DAYS OF STUDY WEIGHTS WERE RECORDED IN GRAMS (G). _ ............................. Last value recorded before cohabitation. 4_ Spilled feed precluded the calculation of this value. O0 Value was not recorded. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C29 (PAGE 1): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - i0 10 - 14 14 - 18 18 - 21 21 - 25 .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 P 180. 82. 113. 79. 82. 13802 P 221. 103. 135. 119. 73. 13803 P 187. 93. 118. 110. 71. 13804 - MORIBUND SACRIFICED ON DAY 68 OF STUDY 13805 P 208 97. 134. 122. 67. 13806 P 207 81. 115. 110. 13807 P 157 66. 103. 102. 13808 P 157 72. 108. 116. 13809 P 173 66. 84. 91. 84. 13810 P 218 97. 131. 120. 79. 13811 NP 180 74. 108. 67. 55. 90. 13812 P 160 85. 119. 113. 79. 13813 P 207 92. 125. 117. 76 13814 P 183 79. 102. 90. 74 13815 P 187 95. 117. 108. 63 13816 P 164 72. 102. 102. 71 13817 P a 67. 82. 94. 74 13818 P 173 76. 102. 97. 75 13819 P 164 81. 98. 113. 83 13820 P 133 64. 92. 100. 65 13821 P 172 76. 115. 91. 65 13822 P 182 85. 114. 103. 68 13823 P 180 85. 118. 106. 67 13824 P 197 89. 124. 108. 61 13825 P 176 78. 112. 104. 62 13826 P 168 69. 100. 102. 64 13827 P 218 96. 126. 119. 76 13828 P 13829 P 204 80. 113. 107. 176 72. 9G. 94. 13830 P 153 68. 99. 84. ............................................................................................ PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED DAYS = DAYS WEIGHTS Spilled OF PRESUMED GESTATION WERE feed RECORDED precluded IN GRAMS (G) the calculation of this 66 66 58 FROM AVERAGES) value. ,........................................ 4_ _" O0 to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE C29 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - P GENERATION FEMALE RATS PREGNANCY STATUS DAYS 0- 7 7 - i0 i0 - 14 14 - 18 18 - 21 21 - 25 .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 P 13832 P 13833 P 13834 P 13835 P 13836 13837 P 215. 201. 185. 177. 221. MORIBUND 170. 94. 81. 72. 70. 85. SACRIFICED 70 120. a i00. 95. 115. ON DAY 99. 102 107. 114. 99. 113. 59 OF 112. 74. 70. 81. 68. 75. STUDY 13838 P 13839 P 176. 83 115. 125. 82. 184. 79 107. 111. 71. 13840 NP 154. 68 88. 77. 61. 79. 138412 P 13843 P 13844 P 13845 P 13846 P 13847 P 13848 P 13849 P 13850 P 13851 NP 13852 P 13853 P 13854 P 13855 P 13856 P 13857 P 16526. 731 1050. 104a. 578. 166. 72 107. i00. 69. 180. 90 109. 115. 51. 180. 80 112. 120. 65. 149. 76 97. 110. 68. 159. 59 78. 99. 69. 177. 78 96. 118. 86. 202. 76 111. 88. 63. 199. 80 115. 114. 150. 61 80. 82. 50. 58. 180. 80 102. 114. 70. 176. 77 106. 108. 189. 89 106. 101. 85. 177. 84 105. 130. 73. 182. 182. 79 104. 107. 69. 74 99. 92. 56. 13858 P 13859 P 13860 P 171. 77 183. 68 160. 68 93. 98. 94. 94. 63. 88. 89. 55. .................................................................................................................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION WEIGHTS Spilled WERE feed RECORDED precluded IN GRAMS (G). the calculation of this value. _'_ [29 4_ O0 _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE C29 (PAGE 3} : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - I0 10 - 14 14 - 18 18 - 21 21 - 25 .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 P 13862 P 140. 76. a 113. 66. DID NOT DELIVER A LITTER 13863 P 13864 P 13865 P 13866 P 13867 P 13868 P 13869 P 168. 82. 111 110. 79. a 89. 105 82. 69. 224. 98. 125 125. 71. 194. 87. 111 101. 81. 178. 77. 103 100. 80. a 84. 118 105 70. 177. 93. 128 116 70. 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 173. 87. 128 136 82. 158. 72. i00 106 74. 173. 87. 112 105 71. 157. 68. 77 95 77. 194. 91. 123 119. 83. 197. 93. 123 122 74. 193. 92. 136 121 94. 204. 99. 125 116 91. 158. 70. 101 103 83. 170. 83. 98 110 69. 202. 91. 128 125 73. 159. 79. 94 106 63. 214. 92. 136. 113 66. 178. 76. 107. 110 74. 217. 79. 103. 85 67. a 89. 120. 121 55. 155. 66. 97. 104 71. 176. 80. 120. 90 68. 13888 P 13889 P 13890 P 176. 196. 208. 86. 120. 117 66. 80. 109. 114. 87. 123. 97. 74. ............................................................................................ PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED DAYS = DAYS OF PRESUMED GESTATION FROM AVERAGES) WEIGHTS Spilled WERE feed RECORDED precluded IN GRAMS (G) the calculation of this value. REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - P GENERATION FEMALE RATS L ....................................... > _'_ [2_ 4_ _O'0_ O PRoToCoL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE C29 (PAGE 4 4) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - 10 10 - 14 14 - 18 18 - 21 21 - 25 .................................................................................................................................... RAT # DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 P 13892 P 13893 P 13894 P 13895 P 13896 P 13897 P 13898 P 13899 P 139. 168. 167. 207. 202. 186. 172. 185. 153. 72. 93. 89. 64 72. 104. 110. 71 74. 97. 95. 59 a 130. a 96 82. 108. 95. 57 84. 111. 107. 67 82. 115. 116. 75 99. a 117. 80 69. 87. 99. 77 13900 NP MATING NOT CONFIRMED 139012 P 13903 P 13904 P 17645. 708. 10951. 10853. 783. 147. 75. 99. 107. 76. 170. 81. 108. 128. 71. 13905 P 207. 92. 125. 107. 67. 13906 P NO CONFIRMED MATING DATE 13907 P 164 74. 94 106. 13908 P 193 94. 115 112 46. 13909 P 169 74. 90 97 63. 13910 P 208 97. 132 121 77. 13911 P 163 81. 88 93 48. 13912 P 173 80. 106 110 76. 13913 P 185. 94. 115 97 64. 13914 P 170. 84. 114 108 76. 13915 P 174. 79. 99. 103 71. 13916 P 175. 78. 112. 113 83. 13917 P NO CONFIRMED MATING DATE 13918 P 172. 73. 102. 95. 73. 13919 P 157. 72. 81. 102. 68. 13920 P 173. 82. 103. 101. 70. .................................................................................................................................... p= DAYS ALL a. PREGNANT - DAYS WEIGHTS spilled NP . NOT PREGNANT (VALUES OF PRESUMED GESTATION WERE RECORDED IN GRAMS (G). feed precluded the calculation EXCLUDED FROM AVERAGES) of this value. REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - P GENERATION FEMALE RATS > [2_ _t_ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE C29 (PAGE 5): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - i0 I0 - 14 14 - 18 18 - 21 21 - 25 .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY ...... - ............................................................................................................................. 13921 P 13922 P 13923 P 13924 P 13925 P 13926 P 13927 P 13928 P 13929 NP 164. 187. 196. 196. 140. 176. 176. 181. 135. 73. 104. 115 75. 87. IIi. 99 35. 87. 95. 130 78. 128 111 75. 63. 84 95 66. 82. 116 111 78. 86. 103 101 62. 74. 108 124 77. 58. 84 61. 48. 69. 13930 P 181. 82. 113 108. 87. 139312 P 1761. 7840. 10765. 11054. 13933 P 13934 P 139. 61. 86. 84. NO CONFIRMED MATING DATE 13935 P 157. 72 92. 95. 13936 P 165. 84 119. 102. 13937 P 134. 63 87. 98. 13938 P 149. 70 94. 102. 13939 P 159. 76 89. 102. 13940 P 169. 71 95. 88. 13941 P 171 85 108. 115. 13942 P 167 75 106. 116. 13943 P 185 79. 112. 110. 13944 P 183 84. 105. 98. 13945 P 184 88. 107. 101. 13946 P 164 74. 103. 88. 13947 P 157 75. 92. 90. 13948 P 13949 P 155 72. 96. 51. 177 83. 116. 113. 13950 P a 68. 95. 97. ............................................................................................ 712. 65. 67. 67. 72. 71. 61. 68. 90. 72 77 80 56 66 53 72 83 49 = DAYS ALL PREGNANT = DAYS WEIGHTS Spilled NP = NOT PREGNANT (VALUES OF PRESUMED GESTATION WERE RECORDED IN GRAMS (G). feed precluded the calculation EXCLUDED FROM AVERAGES) of this value. REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - P GENERATION FEMALE RATS '........................................ _u [/) 4_ _.. OO CD PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C30 (PAGE 1): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1- 5 5- 8 8 - 11 11 - 13 13 - 15a .................................................................................................................................... DAM # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 86. 126. 165. 112. 143. 13802 171. 163. 215. 147. 138. 13803 152. 187. 126. 109. 141. 13804 MORIBUND SACRIFICED ON DAY 68 OF STUDY 13805 b b 207. 128. 152. 13806 135. 178. 229. 146. 168. 13807 161. 177. 208. 134. 156. 13808 116. 144. 188. 142. 139. 13809 156. 156. b 148. 140. 13810 117. 167. 226. 153. 157. 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 13828 NOT PREGNANT b 189. 198. 132. 98. 173 193. 229. 46. 300. 130 166. 214. 164. 174. 101 142. 147. 133. 160 148 109. 165. 118. b 106 134. 160. 125. 136. 122 169. 180. 85. 111. 140 148. 164. 69. 89. 138 151. 214. 137. 172. 128 171. 220. 134. 166. b SACRIFICED ON DAY 8 OF LACTATION 122 123. 153. 96. 144 145 169. 210. 143. 170 101 139. 193. 150. 157 141 131. 122. 119. 139 117 180. b 177. 172 84 149. 184. 138. 148 13829 13830 107 85. 156. 118. 136 89 148. 165. 87. 141 .................................................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). It is presumed that the pups begin to consume the maternal feed after day 15 of lactation. 4_ Spilled feed precluded the calculation of this value. _O" tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C30 (PAGE 2): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1- 5 5- 8 8 - 11 11 - 13 13 - 15a .................................................................................................................................... DAM # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 154. 204. 222. 153. 165. 107. 159. 169. 133. 170, 138. 154. 219. 135. 145. 109. 127. 181. 124. 123. 138. 171. 212. 140. 162. MORIBUND SACRIFICED ON DAY 59 OF STUDY 115. 136. 164. 128. 128. 123. 168. b 158. 173, 137. 167. 183. 77. 121. NOT PREGNANT 129. 112. 131, 132. 151, 138423 13844 14201. 162. 14238. 168. 19502. 174 13293. 112 13845 107. 139. 172 138 13846 116. 131. 142 117 13847 104. 119, 152 107 13848 133. 178. 221 135 13849 103. 140. 173 120 13850 152. 117. 193 139 13851 NOT PREGNANT 13852 100. 127. SACRIFICED ON DAY 13853 13854 129. 147. 151. 168. 194. 172. 139. 103. 13855 158. 159. 205. 149. 13856 145. 144. 121. 115. 13857 127. 164. 201. 148. 13858 114. 156. 205. 150. 13859 132. 152. 102. 111. 13860 103. 132. 154. 98. ...................................................................................................... 1371, b 150, 122, 129, 189. 121, 148. 11 OF 138. 118, 160. 154. 155, 146. 134. 144. LACTATION DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). It is presumed that the pups begin to consume the maternal Spilled feed precluded the calculation of this value. feed after day 15 of lactation. _ ............................. _4_ O_ _b 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C30 (PAGE 3}: MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1- 5 5- 8 8 - 11 11 - 13 13 - 15a .................................................................................................................................... DAM # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 93. PREGNANT; 151. 100. 114. b 148. 131. 138. 109. 121. 141. DID NOT DELIVER 178. 208. 126 144. 129 133. 225 276. 133 148. 188 216. 121 171. 114 141. 86. A LITTER 92. 111. 93. 135. 126. 161. 140. 111. 122. 116. 117. 119. 195. 159. 187. 159. 122. 13871 117 151 148. 84. 104. 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 151 169 188 128 126 119 152 137 135 122 198 165 133 99. 126. 114. 64. 127. 154. 154 162 209. 161. 155. 159. 157. 152. 127. 131. 194. 181. 118. 87. 153. 130. 92. 173. 166. 166. 199. 232. 196. 197. 196. 189. 183. 204. 157. 238. 246. 172. 101 196 174 181 244 214 141. 137. 161. 146. 145. 159. 130. 115. 141 127 155 124 141 62 128 128 140 167 160 157. b 167 164 152 177 148 145 205 119. 167. 162. 172. 65. 95. 147. 137. 149. 191. ............................................................................................ DAY = DAY OF LACTATION ......................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). It is presumed that the pups begin to consume the maternal feed after day 15 of lactation. 4_ Spilled feed precluded the calculation of this value. Oo tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C30 (PAGE 4): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1 - 5 5- 8 8 - 11 11 - 13 13 - 15a ........................ _ ........................................................................................................... DAM # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... 13891 b 138. 164. 139. 124. 13892 13893 132. 152. 187. 143. 155 130. 150. b 146. 151 13894 13895 13896 13897 13898 13899 13900 b 156. 217. 142. 193 b 203. 227. 138. 169 128. 141. 175. 110. 123 101. 136. 186. 153. 179 133. 157. 171. 136. 151 130. 134. 133. 91. 118 NOT PREGNANT; MATING NOT CONFIRMED 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 13918 127 112 140 123 133 139 149 94 115 157 76 131 148 154. 137. b 49. 147. 132. 153. 156. b 159. 158. 176. 115. 163. 183. 107. 157. 173. 217. 139. 191. 107. 173. 190. 186. 173. 175. 170. 208. 160. 136. 167. 185. 162. 184. 198. 198. 190. 220. 116. 194. 129. 129. 105. b 132. 146. 85. 92. 141. 90. 128. 131. 143. 138. 131. 149. 88. 137. 165 164 158 161 158 168 99 99. 166 127 137 132 162 156 168 158 99. 155. 13919 13920 102. 109. 124. 126. 174. 158. 122. 57. 143. 66. ........................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). it is presumed that the pups begin to consume the maternal Spilled feed precluded the calculation of this value. _ .......... feed after day 15 of lactation. _ ............................. [29 4_ W.d O0 b_ PROTOCOL 418-020: ORAL (GARAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C30 (PAGE 5): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DAY 1- 5 5- 8 8 - 11 11 - 13 13 ........................................................................................................ - 15a DAM # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 108. 120. 92. 97. 80. 116. 147. 149. 122. 135. 91. 147. 112, 123. b 170. NOT PREGNANT 121. 143. 68. 98. 124. 159. 172. 106. 174. 199. 147. 164. 127. 217. 158. 126. 168. 114. 82. 95. 148. 126. 144. 103, 152. 119. 94. 134. 140. 90. 136. 132. 146. 145. 122. 171. 138 111 142 13933 13934 b 94. 118. 103. 180 89. 249. b 108. 183 _ .......................... 1133993356 13937 113359.. 158. 115415.. 168. 210532.. 168. 111302. 122 112563 158. 13938 92. 123. 126. 115 133. 13939 103. 167 221. 138 162. 13940 121. 133 166. 135 130. 13941 140. 153 198. 148 141. 13942 157. 166 201. 137 144. 13943 131. 128 166. 118 127. 13944 140. 150 108. 115 142. 13945 141. 168 184. 147. 136. 13946 137. 131. 166. 128, 141. 13947 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 13948 118. 139. 170. 126. 151. 13949 120. 151. 193. 129. 155. > 13950 88. 127. 171. 126. 136. ...................................................................................................... _ ............................. DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). It is presumed that the pups begin to consume the maternal feed after day 15 of lactation. 4_ Spilled feed precluded the calculation of this value. Oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C31 (PAGE i}: MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 5 13802 6 13803 5 13804 5a 13805 5 13806 4 13807 5 13808 5 13809 6 13810 5 3 2 4 MORIBUND 1 1 3 1 14 2 SACRIFICED M M M ON DAY M M M M M M 68 OF STUDY MATING DATE C C C C C C C C C - INDIVIDUAL DATA - P GENERATION FEMALE RATS PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE P PRO P PRO P D P PRO P PRO P PRO P PRO P D P PRO 1133881112 43bb 14 MM 13813 6 4 M 13814 4 3 M 13815 5 4 M 13816 5 8 M 13817 6 3 M 13818 5 3 M 13819 5 2 M 13820 7 2 M 13821 6 4 M 13822 5 4 M 13823 6 4 M 13824 7 4 M 13825 3 4 M 13826 6 1 M 13827 6 4 M 13828 5 1 M 13829 5 1 M 13830 6 4 M ...... - ..................................................................................... M= PRO a. MATED C PROESTRUS Rat 13804 statistical = CONFIRMED NC = NOT CONFIRMED E = ESTRUS MET = METESTRUS was moribund sacrificed on day 68 analyses. P = PREGNANT D = DIESTRUS of study (day b. Six or more consecutive days of diestrus were observed. c. Estrous stage was not recorded. CC C C C C C C C C C C C C C C C C C C NP = NOT PREGNANT 19 of estrous evaluation); NPP P P P P P P P P P P P P P P P P P P ........................................ DD D PRO PRO D PRO PRO PRO PRO PRO c PRO PRO PRO D PRO PRO PRO PRO values excluded from group averages and [29 O_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C31 (PAGE 2): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... MATING DATE PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 5 13832 6 13833 5 13834 5 13835 5 13836 3a 13837 6 13838 3 13839 5 13840 5 13841 5 3 M C 4 M C 2 M C 2 M C 2 M C MORIBUND SACRIFICED ON DAY 59 OF STUDY 1 M C 1 M C 2 M C 1 M C 1 M C P PRO P PRO P PRO P PRO P PRO P PRO P D P D NP E P MET 13842 5 13843 6 13844 5 1 M 4 M 1 M C P D C P PRO C P D 13845 5 13846 5 I M 1 M C P D C P D 13847 5 1 M C P PRO 13848 6 4 M C P PRO 13849 5 3 M C P PRO 13850 6 1 M C P PRO .13851 6 1 M C NP E 13852 5 1 M C P b 13853 5 1 M C P PRO 13854 5 1 M C P D 13855 5 1 M C P D 13856 5 1 M C P D 13857 5 4 M C P PRO 13858 5 1 M C P PRO > 13859 5 3 M 13860 6 4 M ............................................................................................ C P PRO C P PRO '........................................ M = MATED C = CONFIRMED NC = NOT CONFIRMED P = pREGNANT NP = NOT PREGNANT PRO PROESTRUS E _ ESTRUS MET = METESTRUS D = DIESTRUS 4_ a. Rat 13836 was moribund sacrificed on day 59 of study (day ii of estrous evaluation); values excluded from group averages and O0 statistical analyses. b. Estrous stage was not recorded, bOO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C31 (PAGE 3): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 4 1 M 13862 6 14 M 13863 5 2 M 13864 5 5 M 13865 5 1 M 13866 4 2 M 13867 5 4 M 13868 6 4 M 13869 6 4 M 13870 5 1 M 13871 5 2 M 13872 6 4 M 13873 6 8 M 13874 4 2 M 13875 5 1 M 13876 5 1 M 13877 5 3 M 13878 5 1 M 13879 6 1 M 13880 5 1 M 13881 5 1 M 13882 5a 3 M 13883 5 1 M 13884 5 4 M 13885 2b 1 M 13886 4b 1 M 13887 6 4 M 13888 5 1 M 13889 5 1 M 13890 6 4 M ............................................................................................ M= PRO a. b. MATED C = CONFIRMED NC = NOT CONFIRMED = PROESTRUS E = ESTRUS MET = METESTRUS Estrous stage was not recorded on day 19 of Six or more consecutive days of estrus were P = PREGNANT NP D = DIESTRUS estrous evaluation, observed. = NOT MATING DATE C NC C C C C C C C C C C C C C C C C C C C C C C C C C C C C PREGNANT PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P _ ....................................... D PRO PRO D D D PRO PRO PRO PRO PRO D D PRO D MET D PRO E PRO D D PRO PRO PRO D D D PRO MET [2_ 4_ oo <D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C31 (PAGE 4): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... GROUP IV 10 MG/KG/DAY .................................................................................................................................... MATING DATE PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE 13891 6 13892 6 13893 5 13894 5 13895 5 13896 5 13897 6 13898 5 13899 5 4 M 4 M 1 M 2 M 2 M 2 M 4 M 1 M 3 M C P PRO C P PRO C P D C P MET C P D C P PRO C P PRO C P D C P PRO 13900 3a 14 13901 5 4 DID NOT MATE - M C E P PRO 13902 5 13903 5 13904 2 2 M 3 M 3 M C P D C P PRO C P D 13905 4 4 13906 6 14 13907 4 2 13908 5 1 13909 6 4 13910 5 2 13911 5 1 13912 5 2 M C P PRO M NC P PRO M C P D M C P D M C P D M C P PRO M C P D M C P PRO 13913 4b 3 M 13914 4 3 M C P PRO C P PRO 13915 6 13916 5 4 M 3 M C P MET C P D 13917 3 14 M NC P PRO 13918 6 13919 5 13920 5 4 M 3 M 3 M C P PRO C P PRO C P D ........................................................................................... _ ........................................ M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP = NOT PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS w.d a. Six or more consecutive days of estrus were observed, o0 b. Six or more consecutive days of diestrus were observed. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C31 (PAGE 5): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION .................................................................................................................................... ESTROUS STAGES/ DAYS IN RAT # 21 DAYS COHABITATION .............................................................................................. GROUP V 30 MG/KG/DAY MATING STATUS .................................................................................................................................... 13921 5 2 M 13922 5 2 M 13923 5 1 M 13924 6 1 M 13925 7 4 M 13926 5 2 M 13927 5 2 M 13928 5 1 M 13929 3a 3 M 13930 5 2 M 13931 6 13932 5 4 M 3 M 13933 5 4 M 13934 6 14 M 13935 5 2 M 13936 6 4 M 13937 5 3 M 13938 4 2 M 13939 5 2 M 13940 5 5 M 13941 5 1 M 13942 4 1 M 13943 5 13944 5 1 M 2 M 13945 5 6 M 13946 6 4 M 13947 5 1 M 13948 6 13949 5 13950 6 4 M 3 M 3 M ............................................................................................ M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS a. Six or more consecutive days of estrus were observed. b. Estrous stage was not recorded. = NOT MATING DATE C C C C C C C C C C C C C NC C C C C C C C C C C C C C C C C PREGNANT - INDIVIDUAL DATA - P GENERATION FEMALE RATS PREGNANCY ESTROUS STAGE STATUS AT SACRIFICE _ ..................................... P PRO P D P PRO P D P PRO P PRO P PRO P PRO NP E P PRO P PRO P PRO P PRO P D P PRO P D P PRO P PRO P D P D P PRO P PRO P PRO P PRO P D P PRO P b P P P _ ....................................... PRO D PRO > _'_ [29 4_ 0_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE C32 (PAGE i): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - p GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... I 0 13801 DL 22 P 114 13802 DL 22 P 114 13803 DL 22 P 116 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 13804 DS 68 67 MORIBUND SACRIFICED ON DAY 68 OF STUDY. ALL TISSUES APPEARED NORMAL. 13805 DL 22 P 114 13806 DL 22 P 112 13807 DL 22 P 114 13808 DL 22 P 112 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 13809 DL 22 P 126 13810 DL 22 P 113 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 13811 DG 25 NP 95 ALL TISSUES APPEARED NORMAL. 13812 DL 22 P 116 ALL TISSUES APPEARED NORMAL. t21 13813 DL 22 P 116 ALL TISSUES APPEARED NORMAL. 13814 DL 22 P 115 ALL TISSUES APPEARED NORMAL. 13815 DL 22 P 116 ALL TISSUES APPEARED NORMAL. 13816 DL 22 P 119 ALL TISSUES APPEARED NORMAL. 13817 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13818 DL 22 P 115 ALL TISSUES APPEARED NORMAL. 13819 DL 22 P 113 ALL TISSUES APPEARED NORMAL. 13820 DL 22 P 113 ALL TISSUES APPEARED NORMAL. 13821 DL 22 P 116 ALL TISSUES APPEARED NORMAL. .................................................................................................................................... DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. > _n 4_ oo tO t_ _'_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C32 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... I 0 13822 DL 8 P 101 OBSERVATIONS a SACRIFICED ON DAY 8 OF LACTATION.b ALL TISSUES APPEARED NORMAL. 13823 DL 22 P 116 13824 DL 22 P 115 13825 DL 22 P 115 13826 DL 22 P 112 13827 DL 22 P 116 13828 DL 22 P 113 13829 DL 22 P 113 13830 DL 22 P 114 .................................................................................................................................... ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P= a. b. PREGNANT NP = NOT PREGNANT Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. > C o0 6 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C32 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... II 1 13831 DL 22 P 115 13832 DL 22 P 115 13833 DL 22 P 113 13834 DL 22 P 114 13835 DL 22 P 114 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13836 DS 59 59 MORIBUND SACRIFICED ON DAY 59 OF STUDY. LEFT FORELIMB: ULNA AND RADIUS, BROKEN. ALL OTHER TISSUES APPEARED NORMAL. 13837 13838 13839 13840 DL 22 P DL 22 P DL 22 P DG 25 NP 112 113 113 95 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 13841 DL 22 P 113 t_ 13842 DL 22 P 113 b_ 13843 DL 22 P 115 13844 DL 22 P 112 13845 DL 22 P 113 13846 DL 22 P 113 13847 DL 22 P 113 13848 DL 22 P 115 13849 DL 22 P 114 13850 DL 22 P 112 13851 DG 25 NP 95 .................................................................................................................................... ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. > 4_ OO t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C32 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY} NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... II 1 13852 DL 11 P 102 OBSERVATIONS a SACRIFICED ON DAY 11 OF LACTATION.b ALL TISSUES APPEARED NORMAL. 13853 DL 22 P 112 13854 DL 22 P 113 13855 DL 22 P 113 13856 DL 22 P 113 13857 DL 22 P 115 13858 DL 22 P 112 13859 DL 22 P 115 13860 DL 22 P 114 .................................................................................................................................... ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT tO a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. tn b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed t_ because it was not possible to identify to which litter the pups belonged. > O 4_ oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C32 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS _I_ t_) t_ 4_ ...... - ............................................................................................................................. DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... III 3 13861 DL 22 P 112 13862 DG 25 P 108 13863 DL 22 P 114 13864 DL 22 P 116 13865 DL 22 P 112 13866 DL 22 P 113 13867 DL 22 P 116 13868 DL 22 P 114 13869 DL 22 P 116 13870 DL 22 P 113 13871 DL 22 P 112 13872 DL 22 P 116 13873 DL 22 P 120 13874 DL 22 P 114 13875 DL 22 P 113 13876 DL 22 P 112 13877 DL 22 P 114 13878 DL 22 P 114 13879 DL 22 P 113 13880 DL 22 P 113 13881 DL 22 P 112 13882 DL 22 P 114 13883 DL 22 P 113 13884 DL 22 P 116 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL.b NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13885 DL 22 P 114 KIDNEYS: ALL OTHER LEFT, PELVIS, MARKED DILATION. TISSUES APPEARED NORMAL. 13886 DL 22 P 112 ALL TISSUES APPEARED NORMAL. 13887 DL 22 P 116 ALL TISSUES APPEARED NORMAL. 13888 DL 22 P 112 ALL TISSUES APPEARED NORMAL. 13889 DL 22 P 112 ALL TISSUES APPEARED NORMAL. 13890 DL 22 P 116 ALL TISSUES APPEARED NORMAL. .................................................................................................................................... [_ DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION 4_ P = PREGNANT NP = NOT PREGNANT O0 a. Refer to the individual clinical observations table (Table C24) for external observations confirmed at necropsy. b. Rat 13862 had one implantation site present, t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C32 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS -_ .................................................................................................................................. DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... IV OBSERVATIONS a I0 _I_ 13891 DL 22 P 115 13892 DL 22 P 114 13893 DL 22 P 113 13894 DL 22 P 114 13895 DL 22 P 113 13896 DL 22 P 114 13897 DL 22 P 115 13898 DL 22 P 112 13899 DL 22 P 114 13900 DS109 NP 108 13901 DL 22 P 116 13902 DL 22 P 113 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13903 DL 22 P 115 13904 DL 22 P 115 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 13905 DL 22 P 115 ALL TISSUES APPEARED NORMAL. t21 13906 DL 22 P 115 ALL TISSUES APPEARED NORMAL. t2_ 13907 DL 22 P 112 ALL TISSUES APPEARED NORMAL. 13908 DL 22 P 113 ALL TISSUES APPEARED NORMAL. 13909 DL 22 P 116 ALL TISSUES APPEARED NORMAL. 13910 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13911 DL 22 P 113 ALL TISSUES APPEARED NORMAL. 13912 DL 22 P 114 13913 DL 22 P 114 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 13914 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13915 DL 22 P 116 ALL TISSUES APPEARED NORMAL. 13916 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13917 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13918 DL 22 P 116 ALL TISSUES APPEARED NORMAL. 13919 DL 22 P 114 ALL TISSUES APPEARED NORMAL. 13920 DL 22 ................................................................................ DS = DAY OF STUDY DG = DAY OF PRESUMED P = PREGNANT NP = NOT PREGNANT GESTATION a. Refer to the individual clinical observations P 115 DL = DAY OF LACTATION ALL TISSUES APPEARED NORMAL. 7 ................................................... table (Table C24) for external observations confirmed at necropsy. > [/) O0 rO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE C32 (PAGE 7) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - P GENERATION FEMALE RATS PERFLUOROOCTANOATE t21 0% .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... V 30 13921 DL 22 P 114 13922 DL 22 P 113 13923 DL 22 P 112 13924 DL 22 P 113 13925 DL 22 P 115 13926 DL 22 P 112 13927 DL 22 P 114 13928 DL 22 P 113 13929 DG 25 NP 97 13930 DL 22 P 114 13931 DL 22 P 114 13932 DL 22 P 114 13933 DL 22 P 115 13934 DL 22 P 115 13935 DL 22 P 114 13936 DL 22 P 116 13937 DL 22 P 115 13938 DL 22 P 112 13939 DL 22 P 113 13940 DL 22 P 117 13941 DL 22 P 112 13942 DL 22 P 113 13943 DL 22 P 113 13944 DL 22 P 113 13945 DL 22 P 118 13946 DL 22 P 116 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13947 DL 1 P 93 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION. ALL TISSUES APPEARED NORMAL. > 13948 DL 22 P 115 13949 DL 22 P 113 13950 DL 22 P 114 -_ .................................................................................................................................. ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. DS I DAY OF STUDY DG I DAY OF PRESUMED GESTATION P - PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations DL = DAY OF LACTATION table (Table C24) for external observations confirmed at necropsy, [2_ OO tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE i)." TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - PITUITARY BRAIN LIVER RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 13802 13803 13804c 13805 13806 13807 338. 367. 366. --348. 340. 367. 0.020 0.014b 0.021 0.008 0.013 0.019 0.106d 5.92 3.81 5.74 .... 3.74 5.59 28.88d 2.20 2.30 2.18 1.95 2.22 2.13 2.39 0.65 0.63 0.60 .... 0.64 0.63 0.65 17.78 21.16 20.36 11.13 16.85 20.35 19.10 5.26 5.76 5.56 .... 4 84 5 98 5 20 13808 286. 0.013 4.54 2.27 0.79 13.72 4 80 KIDNEY LEFT ABS. REL. WT. % TBW 1.70 1.92 1.44 1.21 1.85 1.61 1.45 1.45 0.50 0.52 0.39 .... 0.53 0.47 0.40 0.51 KIDNEY RIGHT ABS. REL. WT. % TBW 1.86 2.08 1.54 1.14 1.64 1.48 1.58 1.55 0.55 0.57 0.42 .... 0.47 0.44 0.43 0.54 ADRENAL LEFT ABS. REL. WT. % TBW a 0.040 0.043b 0.045 0.031 0.042 0.051 0.072 0.047 11.83 11.72 12.30 ..... 12.07 15.00 19.62 16.43 1380190 35750. 0.01351 48.2328 2 0287 0.5681 1280.474 5 2502 1.2774 0.3467 1.3617 0.3475 0.0367 108.4121 13811e 13812 --326. 0.130 0.013 .... 3.99 2 i0 2 21 .... 0.68 13.44 15.92 .... 4.88 1.35 1.48 .... 0.45 1.31 1.44 .... 0.44 0.035 0.034 ..... 10.43 13813 393. 0.022 5.60 2 18 0.55 22 84 5.81 1.61 0.41 1.70 0.43 0.045 11.45 13814 359 0.017 4.74 2 26 0.63 19 92 5.55 1.67 0.46 1.70 0.47 0.032 8.91 13815 370 0.017 4.59 2 26 0.61 20 15 5.44 1.77 0.48 1.60 0.43 0.045 12.16 13816 320 0.018 5.62 2 15 0.67 17 21 5.38 1.52 0.48 1.46 0.46 0.059 18.44 13817 302 0.018 5.96 2 31 0.76 17 80 5.89 1.30 0.43 1.33 0.44 0.043 14.24 13818 376 0.014 3.72 2 53 0.67 24 99 6.65 1.75 0.46 1.92 0.51 0.059 15.69 13819 344 0.018 5.23 2.30 0.67 19 63 5.71 1.49 0.43 1 52 0.44 0.041 11.92 13820 317. 0.012 3.78 2.06 0.65 16.32 5.15 1.57 0.50 1 50 0.47 0 038 11.99 13821 328. 0.016 4.88 1.86 0.57 17.26 5.26 1.53 0.47 1 58 0.48 0 043 13.11 13822f --- 0.023 .... 2.31 .... 13.61 .... 1.15 .... 1 13 .... 0 048 ..... 13823 339. 0.018 5.31 2.30 0 68 17.43 5.14 1.45 0.43 1 54 0.45 0 035 10.32 13824 385. 0.016 4.16 2.31 0 60 20.80 5.40 1.60 0.42 1 61 0.42 0 040 10.39 13825 350. 0.018 5.14 2.19 0 62 16.81 4.80 1.58 0.45 1 47 0.42 0 047 13.43 13826 376. 0.027 7.18 2.21 0 59 21.80 5.80 1.74 0.46 1.71 0.45 0 046 12.23 13827 377. 0.025 6.63 2.40 0 64 18.52 4.91 1.49 0.40 1.53 0.40 0.056 14.85 13828 309. 0.022 7.12 2.28 0 74 16.69 5.40 1.50 0.48 1.43. 0.46 0.050 16.18 13829 301. 0.015 4.98 2.07 0 69 15.27 5.07 1.34 0.4'4 1.32 0.44 0.041 13.62 13830 306. 0.023 7.52 2.18 0 71 17.04 5.57 1.51 0.49 1.44 0.47 0.026 8.50 4_ .................................................................................................................................. b-_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. OO Value was multiplied by I000. Fixed weight. O c. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages and statistical analyses. value appeared incorrectly recorded and was excluded from group averages and statistical analyses. e. Rat was not pregnant; values excluded from group averages and statistical analyses. f. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - P GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... RAT TERMINAL BODY ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. .................................................................................................................................... REL. % TBW DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 13802 13803 13804c 13805 13806 13807 338. 367. 366. --348. 340. 367. 0.042b 0.040b 0.038 0.032 0.038 0.058 0.056 12.43 10.90 10.38 ..... 10.92 17.06 15.26 0.68 0 78 0 72 0 56 0 66 0 74 0 74 0.20 0.21 0.20 .... 0.19 0.22 0.20 0.24 0.70 0.18 0.55 0.26 0.09 0.06 0.07 0.19 0.05 .... 0.07 0.03 0.02 OVARY LEFT ABS. WT. REL. % TBW a OVARY RIGHT ABS. WT. REL. % TBW a UTERUS NON-GRAVID ABS. WT. REL. % TBW 0.060b 0.047b 0.061 0.054 0.045 0.049 0.040 17.75 12.81 16.67 ..... 12.93 14.41 10.90 0.072b 0.061b 0.036 0.061 0.046 0.056 0.046 21.30 16.62 9.84 ..... 13.22 16.47 12.53 0.52 0.54 0.51 0.29 0.68 0.51 0.45 0.15 0.15 0.14 .... 0.20 0.15 0.12 13808 13809 13810 286. 355. 370. 0.046 0.042 0.051 16.08 11.83 13.78 0 72 0 52 0 75 0.25 0.15 0.20 0.20 0 07 0 26 0.07 0.02 0.07 0.054 0.038 0.062 18.88 10.70 16.76 0.047 0.044 0.052 16.43 12.39 14.05 0.57 0.42 0.73 0.20 0.12 0.20 13811d --- 0.032 ..... 0.73 .... 0 46 .... 0.033 ..... 0.055 ..... 0.54 .... 13812 326. 0.037 11.35 0.53 0.16 0 14 0.04 0.046 14.11 0.042 12.88 0.48 0.15 13813 393. 0.047 11.96 0.60 0.15 0 28 0.07 0.055 13.99 0.056 14.25 0.63 0.16 13814 359. 0.050 13.93 0.73 0.20 0 21 0.06 0.041 11.42 0.064 17.83 0 51 0.14 13815 370. 0.041 11.08 0.86 0.23 0 23 0.06 0.038 10.27 0.062 16.76 0 58 0.16 13816 320. 0.051 15.94 0.52 0.16 0.26 0.08 0.047 14.69 0.047 14.69 0 47 0.15 13817 302. 0.041 13.58 0.55 0.18 0.13 0.04 0.043 14.24 0.036 11.92 0 52 0.17 13818 376. 0.057 15.16 0.75 0.20 0.15 0.04 0.070 18.62 0.051 13.56 0 05 0.01 13819 344. 0.040 11.63 0.73 0.21 0.19 0.06 0.044 12.79 0.042 12.21 0 51 0.15 13820 317. 0.047 14.83 0.66 0.21 0.17 0.05 0.040 12.62 0.051 16.09 0 54 0.17 13821 328. 0.042 12.80 0.57 0.17 0.22 0.07 0.058 17.68 0.072 21.95 0.61 0.18 13822e --- 0.059 ..... 0.65 .... 0.23 .... 0.063 ..... 0.076 ..... 0.53 .... 13823 339. 0.032 9.44 0.73 0.22 0.19 0.06 0.071 20.94 0.049 14.45 0.53 0.16 13824 385. 0.038 9.87 0.70 0.18 0.26 0.07 0.068 17.66 0.071 18.44 0.41 0.11 13825 13826 350. 376. 0.047b 0.043 13.43 11.44 0.74 0.62 0.21 0.16 0.26 0.18 0 07 0 05 0.052 0.056 14.86 14.89 0.053 0.073 15.14 19.41 0.65 0.30 0.18 0.08 13827 377. 0.047 12.47 0.81 0.21 0.36 0 10 0.049 13.00 0.069 18.30 0.65 0.17 13828 309, 0.050 16.18 0.70 0.23 0.22 0 07 0.080 25.8'9 0.054 17.48 0.54 0,17 13829 301. 0.054 17.94 0.54 0.18 0.17 0 06 0.054 17.94 0.048 15.95 0.48 0.16 [2_ 13830 306. 0.032 10 46 0.57 0.19 0.19 0 06 0.042 13 72 0.037 12 09 0.77 0.25 .................................................................................................................................... OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) Value was multiplied by i000. Fixed weight. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages and statistical analyses. Rat was not pregnant; values excluded from group averages and statistical analyses. e. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. X i00. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - P GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... PITUITARY BRAIN LIVER RAT TERMINAL BODY Nt_4BER WEIGHT ABS. ?.EL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a .................................................................................................................................... 13831 13832 13833 13834 13835 13836b 13837 138389 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. 37651. --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 0.02113 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 53.60 .... 4.61 4.84 4.73 6.25 7.39 3.87 6.05 5.44 8.04 5.86 .... .... 5.44 3.67 5.45 6.81 3.05 3.25 7.59 7.85 2.17 2.31 2.23 2.26 2.38 1.91 2.07 2.4350 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 0.654 .... 0.63 0.63 0.69 0.59 0.68 0.67 0.72 0.53 0.65 0.70 .... .... 0.61 0.61 0.68 0.60 0.69 0.64 0.66 0.76 21.35 18.12 17.51 16.32 20.02 10.07 20.19 189.9873 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 5.0469 .... 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 1.7538 1.28 1.75 1 62 1 41 1 86 1 56 1 64 1 51 1 67 1 57 1 79 1 19 1 32 1 64 1.70 1 39 1 43 1 29 1 60 1 58 1 57 0.45 0.41 0.43 0.42 0.55 .... 0.42 0.464 .... 0.50 0.46 0.44 0.50 0.44 0.49 0.48 0.50 0.47 0.52 .... .... 0.50 0.45 0.42 0.39 0.44 0.47 0.50 0.54 1 67 1 51 1 57 1 38 1 61 1 24 1 60 1.5870 1.52 1.81 1.73 1.51 1.86 1.67 1.49 1.68 1.58 1.50 1.87 1.16 1.28 1.63 1.80 1.29 1.49 1.53. 1.53 1.59 1.58 0.46 0.42 0.46 0.44 0.51 .... 0.44 0.483 .... 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 0505 0 053 0 077 0 052 0 039 0 061 0 047 0 050 0 033 0 051 0 039 0 058 0 034 0 058 0 053 0 059 0 040 0 059 0 044 0 057 0 050 0 048 13.30 13.72 16.03 12.90 18.55 ..... 13.65 13.33 15.24 ..... 22.19 14.81 12.30 16.58 13.35 14.88 10.51 15.41 11.61 17.01 ..... ..... 16.01 15.48 12.12 16.08 14.92 16.86 15.82 16.38 .................................................................................................................................... O_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by 1000. _o Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses. O Rat was not pregnant; values excluded from group averages and statistical analyses. Rat 13852 was sacrificed on day II of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... RAT NUMBER TERMINAL BODY WEIGHT ADRENAL RIGHT ABS. REL. SPLEEN ABS. REL. THYMUS ABS. REL. WT, % TBW a WT. % TBW WT. .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS, REL. WT. % TBW .................................................................................................................................... 13831 361, 0.040 11.08 0.74 0.20 0.14 0.04 0.072 19.94 0,065 18.00 0.58 0.16 13832 357. 0.040 11.20 0.79 0.22 0.14 0.04 0,051 14.28 0 041 11.48 0.62 0.17 13833 343. 0.052 15.16 0.72 0.21 0.24 0.07 0.050 14.58 0 065 18.95 0.41 0.12 13834 310. 0.038 12.26 0.67 0.22 0.15 0.05 0.050 16.13 0 074 23.87 0.37 0,12 13835 318. 0.046 14.46 0.64 0.20 0.21 0,07 0.037 11.64 0 045 14.15 0.50 0,16 13836b --- 0.039 ..... 0.49 .... 0.34 .... 0.049 ..... 0 057 ..... 0.53 .... 13837 13838 359. 375. 0.042 0.055 11.70 14.67 0.81 0.66 0.22 0.18 0.29 0.20 0.08 0.05 0.055 0.062 15.32 16.53 0 065 0 050 18.10 13.33 i.i0 0.60 0.31 0.16 13839 13840c 361. --- 0.051 0.049 14.13 ..... 0.82 0.59 0.23 .... 0.21 0.35 0.06 .... 0.046 0.064 12.74 ..... 0 051 0 064 14.13 ..... 0.48 0.59 0.13 .... 13841 347. 0.060 17.29 0.65 0.19 0.18 0.05 0.066 19.02 0 iii 31.99 0.55 0 16 13842 351. 0,046 13.10 0.67 0.19 0.22 0.06 0.077 21.94 0 050 14.24 0.75 0 21 13843 317. 0.030 9.46 0,54 0.17 0.19 0.06 0.047 14.83 0 057 17.98 0.63 0 20 13844 368. 0.047 12.77 0.79 0.21 0,15 0.04 0 042 11.41 0 051 13.86 0.51 0 14 13845 352. 0.049 13.92 0.51 0.14 0.17 0.05 0 094 26.70 0 102 28.98 0.32 0 09 13846 336. 0.042 12.50 0.48 0.14 0.14 0.04 0 037 11.01 0 036 10.71 0.64 0 19 13847 314. 0.034 10.83 0.71 0.23 0.24 0.08 0 054 17.20 0 060 19,11 0.72 0 23 13848 331. 0.046 13,90 0.61 0.18 0.21 0.06 0 049 14.80 0 046 13.90 0.36 0 11 13849 336. 0,035 10.42 0.68 0.20 0.10 0.03 0 034 10.12 0 043 12.80 0.43 0 13 13850 13851c 341. --- 0.050 0.039 14.66 ..... 0.64 0.60 0.19 .... 0.20 0.27 0.06 .... 0 034 0 033 9.97 ..... 0 066 0 039 19.35 ..... 0.84 1.24 0 25 .... 13852d --- 0,043 ..... 0.59 .... 0.24 .... 0.049 ..... 0 066 ..... 0.45 .... 13853 331. 0.061 18.43 0,70 0.21 0.22 0.07 0.082 24.77 0 037 11.18 1.23 0 37 13854 381. 0.052 13.65 0.83 0.22 0.29 0.08 0.075 19.68 0 043 11.29 0.54 0 14 13855 330. 0.048 14.54 0.78 0.24 0.16 0.05 0,077 23.33 0 066 20.00 0.64 0 19 > 13856 367. 0,059 16.08 0.79 0.22 0.22 0.06 0.045 12,26 0 055 14.99 0.52 0 14 13857 295. 0.036 12.20 0.69 0.23 0.21 0.07 0.032 10.85 0 041 13.90 0.47 0 16 13858 338. 0,043 12.72 0.71 0.21 0.22 0.06 0.053 15.6_ 0 062 18.34 0.47 0 14 13859 316. 0,050 15.82 0.75 0,24 0.13 0.04 0,046 14.56 0 044 13.92 0.43 0 14 O_ 13860 293. 0.052 17.75 0.62 0.21 0.20 0.07 0.053 18.09 0 060 20.48 0.70 0 24 _t_ .................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by 1000. _ Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses, O Rat was not pregnant; values excluded from group averages and statistical analyses. Rat 13852 was sacrificed on day 11 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 5): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... PITUITARY BRAIN LIVER RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a .................................................................................................................................... 13861 13862b 13863 13864 13865 13866 13867 312. --352. 335. 353. 401. 335. 0.014 0.014 0.014 0.011 0.014 0.018 0.014 4.49 .... 3.98 3.28 3.97 4.49 4 18 2.11 2.16 2.12 2.03 2.28 1.94 2.19 0.68 .... 0.60 0.60 0.64 0.48 0.65 17.99 15.04 20.98 16.43 17.78 20.32 15.19 5.77 .... 5 96 4 90 5 04 5 07 4 53 1.59 1.58 1.48 1.33 1.53 1.86 1.54 0.51 .... 0.42 0.40 0.43 0.46 0.46 1.58 1.66 1.67 1.35 1.59 1.75 1.56 0.51 .... 0.47 0.40 0.45 0.44 0.46 0.044 0.033 0.044 0.039 0.049 0.031 0.052 14.10 ..... 12.50 11.64 13.88 7.73 15.52 13868 13869 356. 357. 0.028 0.016 7 86 4 48 2.22 2.25 0.62 0.63 18.68 17.99 5 25 5 04 1.69 1.63 0.47 0.46 1.77 1.62 0.50 0.45 0.073 0.045 20.50 12.60 13870 386. 0.020 5 18 2.36 0.61 21.82 5 65 2.11 0.55 2.03 0.52 0.048 12.44 13871 13872 366. 347. 0.014 0.022 3 82 6 34 2.30 2.33 0.63 0.67 19.76 17.22 5 40 4 96 1.55 1.44 0.42 0.41 1.65 1.48 0.45 0.43 0.065 0.050 17.76 14.41 13873 346. 0.016 4 62 2.15 0.62 17.19 4 97 1.54 0.44 1.64 0.47 0.065 18.79 13874 13875 368. 358. 0.023 0.018 6 25 5 03 2.46 2.07 0.67 0.58 15.63 18.99 4 25 5 30 1.61 1.48 0.44 0.41 1.70 1.58 0.46 0.44 0.050 0.056 13.59 15.64 13876 13877 399. 383. 0.020 0.024 5 01 6 27 2.48 2.29 0.62 0.60 17.31 17.66 4 34 4 61 1.84 1.79 0.46 0.47 1.88 1.81 0.47 0.47 0.047 0.044 11.78 11.49 13878 13879 352. 328. 0.017 0.020 4 83 6 10 2.22 2.37 0.63 0.72 18.85 17.67 5 36 5 39 1.78 1.61 0.50 0.49 1.77 1.69 0.50 0.52 0.045 0.044 12.78 13.41 13880 363. 0.016 4 41 2.29 0.63 17.99 4 96 1.39 0.38 1.52 0.42 0.032 8.82 13881 323. 0.022 6 81 2.24 0.69 18.95 5 87 1.57 0.49 1.60 0.50 0.045 13.93 13882 355. 0.018 5 07 2.35 0.66 18.41 5 18 1.57 0.44 1.47 0.41 0.052 14.65 13883 342. 0.011 3 22 2.26 0.66 18.20 5 32 1.49 0.44 1.63 0.48 0.040 11.70 13884 368. 0.019 5 16 2.07 0.56 18.27 4 96 1.40 0.38 1.37 0.37 0.048 13.04 13885 336. 0.014 4 17 2.23 0.66 13.77 4 10 1.72 0.51 1.60 0.48 0.044 13.10 > 13886 322. 0.019 5 90 2.24 0.70 16.87 5 24 1.37 0.42 1.58 0.49 0.051 15.84 13887 310. 0.015 4 84 2.14 0.69 15.59 5 03 1.31 0.42 1.31. 0.42 0.030 9.68 13888 335. 0.015 4 48 2.25 0.67 19.46 5 81 1.50 0.45 1.61 0.48 0.048 14.33 13889 340. 0.015 4 41 2.25 0.66 14.98 4 40 1.46 0.43 1.44 0.42 0.059 17.35 [23 13890 364. 0.016 4 40 2.00 0.55 17.82 4 90 1.67 0.46 1.75 0.48 0.043 11.81 _t_ .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. I_ Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... RAT TERMINAL BODY ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT. % TBW DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 13862b 13863 13864 13865 13866 13867 312. --352. 335. 353. 401. 335. 0.032 0.032 0.047 0.037 0.045 0.043 0.043 10.26 ..... 13.35 11 04 12 75 10 72 12 84 0.66 0.80 0 72 0 60 0 63 0 85 0 76 0.21 .... 0.20 0.18 0.18 0.21 0.23 0.i0 0.51 0.19 0.12 0.18 0.23 0.20 0.03 .... 0 05 0 04 0 05 0 06 0 06 0.035 0.040 0.042 0.045 0.047 0.066 0.064 11.22 ..... 11.93 13.43 13.31 16.46 19.10 0.024 0.054 0.050 0.047 0.051 0.074 0.053 7.69 .... 14.20 14.03 14.45 18.45 15.82 0.32 0.83 0.54 0.47 0.51 0.48 0.50 0.i0 .... 0.15 0.14 0.14 0.12 0.15 13868 356. 0.050 14 04 0 64 0.18 0.12 0 03 0.046 12.92 0.049 13.76 0.46 0.13 13869 13870 357. 386. 0.043 0.043 12 04 11.14 0 49 0 90 0.14 0.23 0.14 0.35 0 04 0.09 0.049 0.069 13.72 17.88 0.058 0.079 16.25 20 47 0.38 0.72 0.11 0.19 13871 366 0.048 13.11 0 89 0.24 0 19 0.05 0.037 I0.ii 0.059 16 12 0.40 0.11 13872 347 0.041 11.82 0 69 0.20 0 16 0.05 0.050 14.41 0.047 13 54 0.44 0.13 13873 346 0.055 15.90 1.02 0.29 0 18 0.05 0.074 21.39 0.068 19 65 0.44 0.13 13874 368 0.045 12.23 0.72 0.20 0 16 0.04 0.056 15.22 0.074 20 11 0.39 0.10 13875 358 0.046 12.85 0.56 0.16 0 19 0.05 0.054 15.08 0.058 16 20 0.56 0.16 13876 399 0.037 9.27 0.64 0.16 0 22 0.06 0.061 15.29 0.069 17 29 0.69 0.17 13877 383 0.050 13.05 0.75 0.20 0 30 0.08 0.046 12.01 0.051 13 32 0.62 0.16 13878 352 0.039 11.08 0.70 0 20 0 09 0.02 0.031 8.81 0.046 13 07 0.66 0.19 13879 328. 0.035 10.67 0.69 0 21 0.30 0.09 0.077 23.48 0.087 26.52 0.50 0.15 13880 363. 0.035 9.64 0.78 0 21 0.19 0.05 0.045 12.40 0.049 13.50 0.78 0.21 13881 323. 0.049 15.17 0.65 0 20 0.12 0.04 0.049 15.17 0.053 16.41 0.20 0.06 13882 355. 0.049 13.80 0.60 0 17 0.12 0.03 0.056 15.77 0.062 17.46 0.76 0.21 13883 342. 0.038 11.11 0.75 0 22 0.25 0.07 0.093 27.19 0 060 17.54 0.52c 0.15 13884 368. 0.038 10.33 0.66 0 18 0.22 0.06 0.059 16.03 0 078 21.20 0.44 0.12 13885 336. 0.040 11.90 0.78 0 23 0.43 0.13 0.055 16.37 0 058 17.26 0.59 0.18 13886 322. 0.037 11.49 0.68 0 21 0.17 0.05 0.064 19.88 0 053 16.46 0.73 0.23 13887 310. 0.030 9.68 0.75 0 24 0.29 0.09 0.035 11.29 0 046 14.84 0.77 0.25 13888 335. 0.050 14.92 0.72 0.21 0.40 0.12 0.049 14.63 0 049 14.63 0.67 0.20 13889 340. 0.051 15.00 0.70 0.20 0.16 0.05 0.039 11.47 0 059 17.35 0.31 0.09 [/) 13890 364. 0.049 13.46 0.68 0.19 0.17 0.05 0.068 18.68 0 052 14.28 0.57 0.16 .................................................................................................................................... O_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. _ ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. tC_D Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses. c. Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 7): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - PITUITARY BRAIN LIVER RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... REL. % TBW DOSAGE GROUP IV 10 MG/KG/DAY KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a .................................................................................................................................... 13891 300. 0.013 4.33 2 26 0.75 15.62 13892 13893 13894 13895 13896 13897 366. 332. 386. 334, 376. 361. 0.023 0.022 0.017 0.018 0,016 0,006 6.28 6.63 4.40 5.39 4.26 1.66 2 20 2 19 2 28 2 17 2 16 2 15 0.60 0.66 0.59 0.65 0.57 0.60 21.99 16.27 16.90 17.85 18.63 17.38 5.21 6.01 4.90 4.38 5.34 4.95 4,81 1.36 1.75 1.42 1.83 1.46 1.60 1.73 0.45 0.48 0.43 0.47 0.44 0.42 0.48 1.34 1.83 1.47 1.81 1.56 1.64 1.75 0.45 0.50 0.44 0.47 0.47 0.44 0.48 0.048 0.047 0.038 0,058 0.041 0.045 0.043 16.00 12.84 11.44 15,02 12.28 11.97 11.91 13898 13899 13900b 395. 0.018 4.56 2 27 0.57 320. 0.010 3.12 2 19 0.68 ....................................................... 22.41 18.65 5.67 5.83 1.60 1.57 0.40 0.49 1.69 1.62 0.43 0.51 0.060 0.042 15.19 13.12 13901 350 13902 311 13903 318 13904 354 13905 351 13906 355 13907 337 13908 366 13909 356 13910 353 13911 327 13912 355 13913 317 13914 294 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 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 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 0.66 0.68 0.64 0.68 0.61 0.61 0.66 0.61 0.61 0.62 0.69 0.63 0.71 0.78 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 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 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 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 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 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 0.048 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 13.71 11.58 15.09 12.43 15.10 10.98 18.10 12.30 11.52 14.16 12.84 11.27 14.83 20.41 13915 323 0.012 3.72 2 i0 0.65 14.92 4.62 1.40 0.43 1.51 0.47 0.040 12.38 > 13916 376 0.013 3.46 2 40 0.64 18.53 4.93 1.61 0.43 1.60 0.42 0.038 10.11 13917 327 0.022 6.73 2 31 0.71 17.29 5.29 1.55 0.47 1.44 . 0.44 0.046 14.07 13918 302 0.021 6.95 2 22 0.74 14.35 4.75 1.30 0.43 1.39 0.46 0.042 13.91 13919 329 0.025 7.60 2 30 0.70 17.02 5.17 1.32 0.40 1.34 0.41 0.045 13.68 [J_ 13920 349 0.007 2,00 2 28 0.65 18.54 5.31 1.63 0.47 1.62 0.46 0.040 11.46 4_ .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 a, Value was multiplied by I000. |_ b, Rat was not pregnant; values were not recorded. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY Nt_4BER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 8} : TERMINAL BODY WEIGHTS _/_D ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... ADRENAL SPLEEN THYMUS RAT TERMINAL BODY RIGHT Nt_4BER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 13892 13893 13894 13895 13896 300. 366. 332. 386. 334. 376. 0.042 0,048 0.048 0.057 0.034 0.040 14 00 13 11 14 46 14 77 i0 18 10 64 0.61 0.80 0 58 0 77 0 77 0 69 0.20 0.22 0.17 0.20 0.23 0.18 0.ii 0.30 0.21 0.33 0.31 0.20 0 04 0 08 0 06 0 08 0 09 0 05 OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT. % TBW 0.035 0.057 0.033 0.047 0,056 0.048 11.67 15 57 9 94 12 18 16 77 12 76 0.044 0.054 0.050 0.086 0.054 0.048 14.67 14.75 15.06 22.28 16.17 12.76 0.41 0.99 0.55 1.03 0.40 0,51 0 14 0 27 0 16 0 27 0 12 0 14 1133889978 13899 13900b 336915.. 00..004732 1118 9213 00 7902 00..1293 320. 0.034 I0 62 0 74 0.23 ......................................................... 00..1186 0.13 00 0054 0 04 00,.004470 0,047 1130 0123 14 69 00..004517 0.046 1141..4336 14.38 00..4596 0.44 00 1144 0 14 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 350. 311. 318. 354. 351. 355. 337. 366. 356. 353. 327. 355. 317. 294. 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 11 14 10 93 9 43 12 71 13 96 10 70 13 35 10 93 i0 67 13 31 10 70 12 11 12 62 20 07 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 0.20 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 0.17 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 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 0.058 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 16 57 11 90 10 06 13 56 16 24 12 39 18.40 18 03 9 27 17 85 15 60 11 27 19 87 17 35 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 17.43 18.65 18.24 18.36 21.08 13 52 19 58 17 76 16 01 14 73 8 56 14 93 18 61 18 03 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 ii 0 16 0 16 0 18 0 14 0 16 0 11 0 30 0 15 0 13 0 22 0 23 0 21 0.15 13915 323. 0.045 13 93 0.67 0.21 0.29 0 09 0.054 16 72 0.071 21 98 0.69 0.21 13916 376. 0.038 i0 ii 0.69 0.18 0.14 0 04 0.033 8 78 0,050 13 30 0.61 0.16 13917 327. 0.038 Ii 62 0.68 0.21 0.20 0 06 0.061 18 65 0,052 15 90 0.46 0.14 13918 302. 0.038 12 58 0.65 0.22 0.18 0 06 0.046 15 2'3 0.049 16.22 0.57 0.19 13919 329. 0,040 12 16 0.48 0.14 0.09 0 03 0,056 17 02 0.038 11.55 0.52 0.16 [2_ 13920 349. 0.032 9 17 0.66 0.19 0.08 0 02 0.045 12 89 0.038 10.89 0.47 0.13 4_ ................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. _o Rat was not pregnant; values were not recorded. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 9): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - P GENERATION FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... RAT TERMINAL BODY PITUITARY BRAIN LIVER NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY REL. % TBW KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929b 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 357. 352. 320. 341. 318. 353. 331. 368. --350. 368. 357. 326. 340. 318. 349. 306. 343. 349. 353. 383. 344. 349. 341. 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 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 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 0 65 0 61 0 67 0 62 0 67 0 62 0 62 O 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 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 5.38 4.63 6.26 6.14 4.78 5.82 5.62 5.14 .... 5.91 5.20 5.76 5.26 4.41 5.52 5.17 5.47 5.54 4.71 5.36 5.06 5.00 5.07 4.80 1.54 1.37 1.41 1.47 1.31 1.63 1.47 1.58 1.20 1.47 1 29 1.53 1.28 1.42 1.39 1.37 1.51 1.58 1.49 1.34 1.55 1.46 1.52 1.43 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 1.59 1.37 1.38 1.61 1.34 1.58 1.60 1.60 1.27 1.62 1.33 1.53 1.43 1.50 1.46 1.38 1.40 1.63 1.51 1.46 1.65 1 37 1 45 1 53 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 0.052 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 14 56 i0 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 13945 342. 0.021 6.14 2.29 0.67 17.42 13946 353. 0.009 2.55 2.04 0.58 17.13 13947d --- 0.015 .... 2.05 .... 11.28 13948 323. 0.017 5.26 2.20 0.68 15.10 13949 365. 0.013 3.56 2.09 0.57 18.90 13950 361. 0.016 4.43 2.02 0.56 18.17 ........................................................................................................................... 5.09 4.85 .... 4.67 5.18 5.03 1.45 1.22 1.18 1.35 1.53 1.39 0.42 0.34 .... 0.42 0.42 0.38 1 57 1 33 1 11. 1.36 1.55 1.52 0.46 0.38 ---0.42 0.42 0.42 0 051 0 032 0 048 0 044 0 046 0 037 14.91 9.06 ..... 13.62 12.60 10.25 ......... ALL WEIGHTS WERE RECORDED IN GRAMS Value was multiplied by i000. (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) Rat was not pregnant; values excluded from group averages and statistical analyses. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. Rat 13947 was sacrificed statistical analyses. due to no surviving pups on day 1 of lactation; values excluded from group averages and X i00. _'_ [2_ O0 to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C33 (PAGE 10) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... RAT TERMINAL BODY ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. _qT. REL. % TBW .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY OVARY LEFT ABS. WT. REL. % TBW a OVARY RIGHT ABS. WT. REL. % TBW a UTERUS NON- GRAVID ABS. WT. REL. % TBW .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929b 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 357. 352. 320. 341. 318. 353. 331. 368. --350, 368. 357. 326. 340. 318. 349. 306. 343. 349. 353. 383. 344. 349, 341. 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 11.76 11.65 12.81 13.20 10.38 13.88 15.71 9.78 .... 10.57 10.60 12.88 18.40 8.53 17.61 12.61 10.13 14.28 10.60 11.05 15.40 10.17 12.03 15.25 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 0.20 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 0.15 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 0.04 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 0.069 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 19.33 20.74 9.38 31.08 12.58 17.28 18.73 13.32 .... 9.71 15.22 11.48 15.95 15.29 17.61 15.76 19.28 14.58 15.76 9.35 14.62 7.85 16.90 19.35 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 9.24 17.04 6.25 16.13 13.52 19.83 17.52 16.30 ..... 13.43 13.59 13.72 11.04 12.65 14.46 11.46 9.80 11.37 21.20 11.05 22.45 17.44 14.90 15.84 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 0.15 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 13945 342. 0.039 11.40 0.69 13946 353. 0.024 6.80 0.89 13947c --- 0.040 .... 0.66 13948 323. 0.810d 250,77d 0.80 13949 365. 0.023 6.30 0.62 13950 361. 0.041 11.36 0.72 ........................................................................................ 0.20 0.25 .... 0.25 0.17 0.20 0.28 0.17 0,26 0.22 0.17 0.18 0.08 0.05 .... 0.07 0.05 0.05 0 047 0 058 0 085 0 035 0 050 0 060 13.74 16.43 .... i0.84 13.70 16.62 0.050 0.044 0.058 0.047 0.038 0.046 14.62 12.46 ..... 14.55 10.41 12.74 ............................................ 0.28 0.45 2.00 0.65 0.39 0.65 0.08 0.13 .... 0.20 0.11 0.18 ALL WEIGHTS WERE RECORDED IN GRAMS Value was multiplied by I000. (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Rat was not pregnant; values excluded from group averages and statistical analyses. Rat 13947 was sacrificed statistical analyses. due to no surviving pups on day 1 of lactation; values excluded from group averages and Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. [/_ 4_ _-_ O_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 1) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... PITUITARY LIVER KIDNEY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 13802 13803 13804b 13805 13806 2.20 2.30 2.18 1.95 2.22 2.13 0.020 0.014a 0.021 0.008 0.013 0.019 0.91 0.61 0.96 .... 0.58 0.89 17.78 21.16 20.36 11.13 16.85 20.35 808.18 920.00 933.94 ...... 759.01 955.40 1.70 1.92 1.44 1.21 1.85 1.61 77.27 83.48 66.06 ..... 83.33 75.59 KIDNEY RIGHT ABS. REL. WT. % BRW 1.86 2.08 1.54 1.14 1.64 1,48 84.54 90.43 70.64 ..... 73.87 69.48 ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. WT. REL. % BRW 0.040 0.043a 0.045 0.031 0.042 0.051 1.82 1.87 2.06 .... 1.89 2.39 0.042a 0.040a 0.038 0.032 0.038 0.058 1.91 1.74 1.74 .... 1.71 2.72 13807 13808 2.39 2.27 0.i06c 0.013 4.44c 0.57 19.10 13.72 799.16 604.40 1.45 1,45 60.67 63.88 1.58 1.55 66.11 68.28 0.072 0.047 3.01 2.07 0.056 0.046 2.34 2.03 13809 2.08 0.015 0.72 18.47 887 98 1.27 61 06 1.31 62 98 0.037 1.78 0.042 2.02 13810 2.27 0.031 1.36 20.44 900.44 1.74 76.65 1.67 73.57 0.067 2.95 0.051 2.25 13811d 2.10 0.130 .... 13.44 ...... 1.35 ..... 1.31 ..... 0.035 .... 0.032 .... 13812 2.21 0.013 0 59 15.92 720.36 1.48 66.97 1.44 65.16 0.034 1.54 0.037 1.67 13813 2.18 0.022 1 01 22.84 1047.71 1.61 73.85 1.70 77.98 0.045 2.06 0.047 2.16 13814 2.26 0.017 0 75 19.92 881.42 1.67 73.89 1.70 75.22 0.032 1.42 0.050 2,21 13815 2.26 0.017 0 75 20.15 891.59 1.77 78.32 1.60 70.80 0.045 1.99 0.041 1.81 13816 13817 2.15 2.31 0.018 0.018 0 84 0 78 17 21 17 80 800.46 770.56 1.52 1.30 70.70 56.28 1.46 1.33 67.91 57.58 0.059 0.043 2.74 1.86 0.051 0.041 2.37 1.77 13818 2.53 0.014 0.55 24 99 987.75 1.75 69,17 1.92 75,89 0,059 2,33 0.057 2.25 13819 2.30 0.018 0.78 19 63 853.48 1.49 64.78 1.52 66.09 0.041 1.78 0,040 1.74 13820 2.06 0.012 0.58 16 32 792,23 1.57 76.21 1.50 72.82 0.038 1.84 0.047 2.28 13821 1 86 0.016 0.86 17 26 927.96 1 53 82.26 1,58 84.95 0,043 2.31 0.042 2.26 13822e 2 31 0.023 .... 13 61 ...... 1 15 ..... 1.13 ..... 0.048 .... 0 059 .... 13823 2 30 0.018 0.78 17 43 757,83 1 45 63.04 1.54 66.96 0.035 1.52 0 032 1.39 13824 2 31 0.016 0.69 20 80 900,43 1 60 69,26 1,61 69.70 0.040 1.73 0 038 1.64 13825 2 19 0.018 0.82 16.81 767.58 1 58 72.15 1.47 67.12 0 047 2.15 0 047a 2.15 13826 2 21 0.027 1.22 21.80 986.42 I 74 78.73 1.71 77.38 0 046 2.08 0 043 1.94 _U 13827 2,40 0.025 1.04 18.52 771.67 1.49 62.08 1.53 63.75 0 056 2.33 0 047 1.96 13828 2.28 0.022 0.96 16.69 732.02 1.50 65.79 1.43 62.72 0 050 2.19 0 050 2.19 13829 2.07 0.015 0.72 15.27 737.68 1.34 64.73 1.32 63.77 0 041 1.98 0 054 2.61 C/] 13830 2.18 0,023 1.06 17.04 781.65 1.51 69.27 1 44 66.06 0 026 1.19 0 032 1.47 4_ .................................................................................................................................... C_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Fixed weight. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages and statistical analyses. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses, d. Rat was not pregnant; values excluded from group averages and statistical analyses, e. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 2) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... SPLEEN THYMUS OVARY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY REL. % BRW OVARY RIGHT ABS. WT. REL. % BRW UTERUS NON- GRAVID ABS. REL. WT. % BRW .................................................................................................................................... 13801 13802 13803 13804b 13805 13806 13807 2.20 2.30 2.18 1.95 2.22 2.13 2.39 0.68 0.78 0.72 0.56 0.66 0.74 0.74 30.91 33.91 33.03 ..... 29,73 34.74 30.96 0.24 0.70 0.18 0.55 0.26 0.09 0.06 10.91 30.43 8.26 .... 11.71 4.22 2.51 0.060a 0.047a 0,061 0.054 0.045 0.049 0.040 13808 13809 13810 13811c 2.27 2,08 2.27 2.10 0.72 0.52 0.75 0.73 31.72 25.00 33,04 ..... 0.20 0.07 0.26 0.46 8.81 3.36 11.45 .... 0,054 0.038 0.062 0.033 13812 13813 13814 13815 2.21 2.18 2.26 2.26 0.53 0.60 0.73 0.86 23,98 27.52 32.30 38.05 0.14 0.28 0.21 0.23 6 33 12 84 9 29 i0 18 0.046 0.055 0.041 0.038 13816 13817 2.15 2.31 0.52 0.55 24.19 23,81 0.26 0.13 12 09 5 63 0,047 0,043 13818 13819 13820 13821 13822d 13823 13824 2.53 2.30 2.06 1.86 2.31 2.30 2.31 0.75 0.73 0.66 0.57 0.65 0.73 0.70 29.64 31,74 32,04 30.64 ..... 31.74 30,30 0.15 0.19 0.17 0.22 0.23 0.19 0.26 5 93 8 26 8 25 11 83 .... 8 26 11 26 0.070 0.044 0.040 0.058 0.063 0.071 0,068 2.73 2.04 2.80 .... 2.03 2.30 1.67 2.38 1.83 2.73 .... 2.08 2.52 1.81 1.68 2.19 1.86 2.77 1.91 1.94 3.12 .... 3.09 2.94 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 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 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 23.64 23.48 23.39 ..... 30.63 23.94 18.83 25.11 20.19 32,16 ..... 21,72 28.90 22.57 25.66 21,86 22.51 1,98 22,17 26.21 32.80 ..... 23.04 17,75 13825 2.19 0.74 33,79 0.26 11 87 0.052 2.37 0.053 2.42 0 65 29.68 13826 2.21 0.62 28.05 0.18 8 14 0.056 2.53 0.073 3.30 0 30 13.57 13827 2.40 0.81 33,75 0.36 15 00 0.049 2.04 0,069 2.88 0 65 . 27.08 C_ 13828 2.28 0.70 30.70 0.22 9 65 0.080 3.51 0,054 2.3_ 0 54 23,68 13829 2.07 0.54 26.09 0.17 8 21 0.054 2.61 0.048 2.32 0 48 23,19 13830 2.18 0.57 26.15 0.19 8 72 0.042 1.93 0.037 1.70 0 77 35,32 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. a. Fixed weight. |_ b. Rat 13804 was moribund sacrificed on day 68 of study; values excluded from group averages c. Rat was not pregnant; values excluded from group averages and statistical analyses. and statistical analyses. d. Rat 13822 was sacrificed on day 8 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 3) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... PITUITARY LIVER KIDNEY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. WT. REL. % BRW ADRENAL RIGHT ABS. WT. REL. % BRW .................................................................................................................................... 13831 13832 13833 13834 13835 13836a 2.17 2.31 2.23 2.26 2.38 1.91 0.026 0.015 0.019 0.013 0.019 0.017 1.20 0.65 0.85 0.58 0.80 .... 21 35 18 12 17 51 16 32 20 02 10 07 983.87 784.42 785.20 722.12 841.18 ...... 1.63 1.48 1.48 1.32 1.74 1.28 75.12 64.07 66.37 58.41 73.11 ..... 1.67 1.51 1.57 1.38 1.61 1.24 76.96 65.37 70.40 61.06 67.65 ..... 0.048 0.049 0.055 0.040 0.059 0.038 2.21 2.12 2.47 1.77 2.48 .... 0.040 0.040 0.052 0.038 0.046 0.039 1.84 1.73 2.33 1.68 1.93 .... 13837 13838 13839 13840b 2.07 2.45 2.30 1.98 0.024 0.021 0.013 0.018 1.16 0.86 0.56 .... 20 19 18 97 19 83 11 67 975.36 774.28 862.17 ...... 1.49 1.73 1.58 1.28 71.98 70.61 68.70 ..... 1.60 1.80 1.57 1.52 77.29 73.47 68.26 ..... 0.049 0.050 0.055 0.053 2.37 2.04 2.39 .... 0.042 0.055 0.051 0.049 2.03 2.24 2.22 .... 13841 13842 13843 13844 2.18 2.20 2.20 2.18 0.016 0.017 0.015 0.023 0.73 0.77 0.68 1.06 18 14 18 85 14 05 22 15 832.11 856.82 638.64 1016.06 1.75 1.62 1.41 1.86 80.28 73.64 64 09 85 32 1.81 1.73 1.51 1.86 83.03 78 64 68 64 85 32 0.077 0.052 0.039 0.061 3.53 2.36 1.77 2.80 0.060 0.046 0.030 0.047 2.75 2.09 1.36 2.16 13845 13846 13847 13848 13849 13850 13851b 13852c 2.40 2.26 2.26 1.75 2.20 2.39 1.91 2.15 0.026 0.013 0.019 0.018 0.027 0.020 0.017 0.017 1.08 0.58 0.84 1.03 1.23 0.84 .... .... 19.06 16.47 16.51 15.39 18.37 19.60 10.61 13.39 794.17 728.76 730.53 879.43 835.00 820.08 ...... ...... 1.56 1.64 1.51 1.67 1.57 1.79 1.19 1.32 65 00 72 57 66 81 95 43 71 36 74 90 ..... ..... 1.67 1.49 1.68 1.58 1.50 1.87 1.16 1.28 69 58 65 93 74 34 90.28 68.18 78.24 ..... ..... 0.047 0.050 0.033 0.051 0.039 0.058 0.034 0.058 1.96 2.21 1.46 2.91 1.77 2.43 .... .... 0.049 0.042 0.034 0.046 0.035 0.050 0.039 0.043 2.04 1.86 1.50 2.63 1.59 2.09 .... .... 13853 13854 2.03 2.32 0.018 0.014 0.89 0 60 16.88 20.77 831.53 895.26 1.64 1.70 80 79 73 28 1.63 1.80 80 30 77 59 0.053 0.059 2 61 2 54 0.061 0.052 3.00 2.24 13855 2.23 0.018 0 81 15.43 691.93 1.39 62 33 1.29 57 85 0.040 1 79 0.048 2.15 13856 2.19 0.025 1 14 18.95 865.30 1.43 65 30 1.49 68 04 0.059 2 69 0.059 2.69 13857 2.04 0.009 0 44 15.95 781.86 1.29 63 24 1.53 75 00 0.044 2 16 0.036 1.76 13858 2.15 0.011 0 51 17.69 822.79 1.60 74 42 1.53 71 16 0.057 2 65 0.043 2.00 13859 2.10 0.024 1 14 16.36 779.05 1.58 75 24 1.59 75 71 0.050 2.38 0.050 2.38 [2_ 13860 2.22 0.023 1 04 14.25 641.89 1.57 70 72 1.58 71 17 0.048 2.16 0.052 2.34 _t_ .................................................................................................................................... _.d O0 ;iLL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW (ORGAN WEIGHT/BRAIN WEIGHT} X 100. Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses, to Rat was not pregnant; values excluded from group averages and statistical analyses. O Rat 13852 was sacrificed on day 11 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 4) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... SPLEEN THYMUS OVARY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836a 2.17 2.31 2.23 2.26 2.38 1.91 0.74 0.79 0.72 0.67 0.64 0.49 34.10 34.20 32.29 29.65 26.89 ..... 0.14 0.14 0.24 0.15 0.21 0.34 6.45 6.06 10.76 6.64 8.82 .... 0.072 0.051 0.050 0.050 0.037 0.049 3.32 2.21 2.24 2.21 1.55 .... OVARY RIGHT ABS. WT. REL. % BRW 0.065 0.041 0.065 0.074 0.045 0.057 3.00 1.77 2.91 3.27 1.89 .... UTERUS NON-GRAVID ABS. REL. WT. % BRW 0.58 0.62 0.41 0.37 0.50 0.53 26.73 26.84 18.38 16.37 21.01 ..... 13837 13838 13839 2.07 2.45 2.30 0.81 0.66 0.82 39.13 26.94 35.65 0.29 0.20 0.21 14.01 8.16 9.13 0.055 0.062 0.046 2.66 2.53 2 00 0.065 0.050 0.051 3.14 2.04 2 22 1.10 0.60 0.48 53.14 24.49 20 87 13840b 1.98 0.59 ..... 0.35 .... 0.064 .... 0.064 .... 0.59 ..... 13841 13842 13843 13844 2.18 2.20 2 20 2 18 0.65 0.67 0.54 0.79 29.82 30.45 24.54 36.24 0.18 0.22 0.19 0.15 8.26 i0.00 8.64 6.88 0 066 0 077 0 047 0 042 3.03 3.50 2.14 1.93 0.iii 0.050 0.057 0.051 5.09 2.27 2.59 2.34 0.55 0.75 0.63 0.51 25.23 34.09 28.64 23.39 13845 13846 13847 13848 13849 13850 13851b 13852c 13853 13854 2 40 2 26 2 26 1 75 2.20 2.39 1.91 2.15 2.03 2.32 0.51 0.48 0.71 0.61 0.68 0.64 0.60 0.59 0.70 0.83 21.25 21.24 31.42 34.86 30.91 26.78 ..... ..... 34.48 35.78 0.17 0.14 0.24 0,21 0.10 0.20 0.27 0.24 0.22 0.29 7.08 6.19 10.62 12.00 4.54 8.37 .... .... 10.84 12.50 0 094 0 037 0 054 0 049 0.034 0.034 0.033 0,049 0.082 0.075 3.92 1.64 2.39 2.80 1.54 1.42 .... .... 4.04 3.23 0.102 0 036 0 060 0 046 0 043 0 066 0 039 0.066 0.037 0,043 4.25 1.59 2.65 2.63 1.95 2.76 .... .... 1.82 1.85 0.32 0.64 0.72 0.36 0.43 0.84 1.24 0.45 1.23 0.54 13.33 28.32 31.86 20.57 19.54 35.15 ..... ..... 60.59 23.28 13855 2.23 0.78 34.98 0.16 7.17 0.077 3.45 0.066 2.96 0.64 28.70 13856 2.19 0.79 36.07 0.22 10.04 0.045 2.05 0.055 2.51 0,52 23.74 13857 2.04 0.69 33.82 0.21 10.29 0.032 1.57 0.041 2.01 0.47. 23.04 13858 2.15 0.71 33.02 0.22 10.23 0.053 2.46 0.062 2.8'8 0.47 21.86 13859 2.10 0.75 35.71 0.13 6.19 0.046 2.19 0.044 2.10 0.43 20.48 00 13860 2.22 0.62 27.93 0.20 9.01 0.053 2.39 0.060 2.70 0.70 31.53 _t_ .................................................................................................................................... _0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Rat 13836 was moribund sacrificed on day 59 of study; values excluded from group averages and statistical analyses, b_ Rat was not pregnant; values excluded from group averages and statistical analyses. O c. Rat 13852 was sacrificed on day ii of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 5) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... RAT BRAIN PITUITARY LIVER KIDNEY LEFT NUMBER WEIGHT ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY KIDNEY RIGHT ABS. WT. REL. % BRW ADRENAL LEFT ABS. WT. REL. % BRW ADRENAL RIGHT ABS. WT. REL. % BRW .................................................................................................................................... 13861 13862a 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 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 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 0.66 .... 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 17.99 15.04 20.98 16.43 17.78 20.32 15.19 18.68 17.99 21.82 19.76 17.22 17.19 15.63 18.99 17.31 17.66 18.85 17.67 17.99 18.95 18.41 18.20 18.27 852.61 ...... 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 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 75.36 ..... 69.8.1 65.52 67.10 95.88 70.32 76.13 72.44 89.41 67.39 61.80 71.63 65.45 71.50 74.19 78.16 80.18 67.93 60.70 70.09 66.81 65.93 67.63 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 74.88 ..... 78.77 66.50 69.74 90.21 71.23 79.73 72.00 86.02 71.74 63.52 76.28 69.10 76.33 75.81 79.04 79.73 71.31 66.38 71.43 62.55 72.12 66.18 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 2.08 .... 2.08 1.92 2.15 1.60 2.37 3.29 2.00 2.03 2.83 2.14 3.02 2.03 2.70 1.90 1.92 2.03 1.86 1.40 2.01 2.21 1.77 2.32 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 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 13885 13886 2.23 2.24 0.014 0.019 0.63 0.85 13.77 16.87 617 49 753 12 1.72 1.37 77.13 61.16 1.60 1.58 71.75 70.54 0 044 0 051 1.97 2.28 0.040 0.037 1 79 1 65 13887 13888 2.14 2.25 0.015 0.015 0.70 0.67 15.59 19.46 728 50 864 89 1.31 1.50 61.21 66.67 1.31 1.61 61.21 71.56 0 030. 0 048 1.40 2.13 0.030 0.050 1 40 2 22 13889 2.25 0.015 0.67 14.98 665 78 1.46 64.89 1.44 64.00 0 059 2.62 0.051 2 27 [29 13890 2.00 0.016 0.80 17.82 891 00 1.67 83.50 1.75 87.50 0 043 2.15 0.049 2.45 4_ .................................................................................................................................... OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. a. Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses, b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 6) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... RAT BRAIN SPLEEN THYMUS OVARY LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW OVARY RIGHT ABS. WT. REL. % BRW UTERUS NON-GRAVID ABS. REL. WT. % BRW DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 13862a 13863 13864 13865 13866 13867 13868 2.11 2.16 2.12 2.03 2.28 1.94 2.19 2.22 0.66 0.80 0.72 0.60 0.63 0,85 0.76 0.64 31.28 ..... 33 96 29 56 27 63 43 81 34 70 28 83 0.10 0.51 0.19 0.12 0.18 0,23 0.20 0.12 4.74 .... 8.96 5.91 7.89 11.86 9.13 5.40 0.035 0.040 0,042 0.045 0.047 0,066 0.064 0.046 1.66 .... 1,98 2 22 2 06 3 40 2 92 2 07 0.024 0.054 0.050 0.047 0.051 0,074 0.053 0.049 1.14 .... 2,36 2 32 2 24 3 81 2 42 2 21 0.32 0.83 0,54 0.47 0.51 0,48 0.50 0.46 15.16 ..... 25.47 23.15 22.37 24,74 22.83 20.72 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 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 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 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 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 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 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 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 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 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 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 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 13885 13886 2.23 2.24 0.78 0.68 34.98 30.36 0.43 0.17 19.28 7.59 0.055 0.064 2.47 2.86 0 058 0 053 2.60 2.37 0 59 0 73 26.46 32.59 13887 2.14 0.75 35.05 0.29 13.55 0.035 1.64 0 046 2.15 0 77. 35.98 13888 2.25 0.72 32.00 0.40 17.78 0.049 2.18 0 049 2.28 0 67 29.78 13889 2.25 0.70 31.11 0.16 7.11 0.039 1.73 0 059 2.62 0 31 13.78 13890 2.00 0.68 34.00 0.17 8.50 0.068 3.40 0 052 2.60 0 57 28.50 _t_ ..................................................................................................................................... O_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Rat 13862 was pregnant, but did not deliver a litter; values excluded from group averages and statistical analyses, to Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 7) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... PITUITARY LIVER KIDNEY RAT BRAIN LEFT N-UMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 2.26 0.013 0.58 15.62 691.15 1.36 13892 13893 2.20 2.19 0.023 0.022 1.04 1.00 21.99 16.27 999.54 742.92 1.75 1.42 13894 13895 13896 13897 13898 13899 13900a 2.28 0.017 0.74 16.90 741.23 2.17 0.018 0.83 17.85 822.58 2.16 0.016 0.74 18.63 862.50 2.15 0.006 0.28 17.38 808.37 2.27 0.018 0.79 22.41 987.22 2.19 0.010 0.46 18.65 851.60 ............................................................ 1.83 1.46 1.60 1.73 1.60 1.57 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 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 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 0.69 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 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 18.53 640.09 836.97 749.01 650.63 817.29 871.56 847.77 728.83 766.20 842.27 742.48 752.68 673.21 667.25 710.48 772.08 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 13917 13918 13919 13920 2.31 2.22 2.30 2.28 0.022 0.021 0.025 0.007 0 95 0 94 1 09 0 31 17.29 14.35 17.02 18.54 748.48 646.40 740.00 813.16 1.55 1.30 1.32 1.63 60 18 79 54 64 84 80 26 67 28 74 07 80 46 70 48 71 69 65 09 65 40 64 85 67 36 66 36 79 36 61 61 67 12 67 59 70 91 69 91 71 88 60 27 67 25 66 67 67 08 67 i0 58 56 57 39 71 49 ................................................................................................................................... ALL WEIGHTS WERE RECORDED Rat was not pregnant; IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. values were not recorded. REL. KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW 1.34 1.83 1.47 1.81 1.56 1.64 1.75 1.69 1.62 1.56 1.40 1.38 1.63 1.52 1.50 1.35 1.55 1.50 1.63 1.59 1.66 1.52 1.58 1.51 1.60 1.44 1.39 1.34 1.62 59 29 83 18 67 12 79 38 71 89 75 92 81.40 74.45 73.97 67.24 66.35 68.32 68.20 71.03 68.81 60.27 69.82 69.44 74.09 70 35 74 11 67 86 69 00 71 90 66 67 62 34 62 6'1 58.26 71.05 0.048 0.047 0.038 0.058 0.041 0.045 0.043 0.060 0.042 0.048 0.036 0.048 0.044 0.053" 0.039 0.061 0.045 0.041 0.050 0.042 0.040 0.047 0.060 0.040 0.038 0.046 0.042 0.045 0.040 % BRW = (ORGAN WEIGHT/BRAIN 2 12 2 14 1 74 2 54 1 89 2 08 2 00 2 64 1 92 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 WEIGHT) ADRENAL RIGHT ABS. REL. WT. % BRW 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 X i00. 1.86 2.18 2.19 2.50 1.57 1.85 2.00 3.17 1.55 1.68 1.61 1.48 1.88 2.29 1.74 2.01 1.80 1.76 2.14 1.55 1.92 1.78 2.58 2.14 1.58 1.64 1.71 1.74 1.40 _'_ [25 _t_ OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 8): BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - ..... i .............................................................................................................................. SPLEEN THYMUS RAT BRAIN _BER WEIGHT ABS. REL. ABS. REL. WT. % BRW WT. % BRW ......................................................................................... OVARY LEFT ABS, WT. REL. % BRW DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 13892 13893 13894 13895 13896 2.26 2.20 2.19 2,28 2.17 2.16 0.61 0.80 0.58 0.77 0.77 0.69 26.99 36.36 26.48 33.77 35.48 31.94 0.11 0 30 0 21 0 33 0 31 0 20 4.87 13.64 9.59 14.47 14.28 9.26 0.035 0.057 0.033 0.047 0.056 0.048 1.55 2.59 1.51 2.06 2.58 2.22 13897 2,15 0.70 32.56 0 18 8.37 0.047 2.19 OVARY RIGHT ABS. WT. UTERUS NON-GRAVID REL. ABS. REL. % BRW WT. % BRW _ .......................................... 0.044 0.054 0.050 0.086 0.054 0.048 0.041 1.95 2.45 2.28 3.77 2.49 2.22 1.91 0.41 0.99 0.55 1.03 0.40 0.51 0.49 18 14 45 00 25 11 45 18 18 43 23 61 22 79 1133889989 13900a 22..2179 00..9724 4303..5739 00..1163 ................................................ 75..0954 00..004407 12..7165 00..005476 22..5110 00..5464 2240 6079 13901 2,32 0.72 31.03 0.17 7.33 0.058 2.50 0.061 2.63 0.39 16.81 13902 2.11 0.55 26.07 0.19 9.00 0.037 1.75 0 058 2.75 0.49 23.22 13903 2.02 0.57 28.22 0.12 5.94 0.032 1.58 0 058 2.87 0.51 25.25 13904 2.39 0.76 31.80 0.31 12.97 0.048 2.01 0 065 2.72 0.62 25.94 13905 2.14 0.62 28.97 0.27 12.62 0.057 2.66 0 074 3.46 0.50 23.36 13906 2.18 0.64 29.36 0.15 6.88 0.044 2.02 0 048 2.20 0 57 26.15 13907 2.24 0.70 31.25 0.06 2.68 0.062 2.77 0 066 2.95 0 37 16.52 13908 2,22 0.76 34.23 0.54 24.32 0.066 2.97 0 065 2.93 1 09 49.10 13909 2.16 0.71 32.87 0.16 7.41 0.033 1.53 0.057 2.64 0 55 25.46 13910 2.20 0.65 29.54 0.16 7.27 0.063 2.86 0.052 2.36 0 45 20.45 13911 2.26 0.70 30 97 0.23 10.18 0.051 2.26 0.028 1.24 0 71 31.42 13912 2.24 0.67 29 91 0.16 7.14 0.040 1 78 0.053 2.37 0.81 36.16 13913 2.24 0.80 35 71 0.19 8.48 0.063 2 81 0.059 2.63 0.66 29.46 13914 2.29 0.69 30 13 0.17 7.42 0.051 2 23 0.053 2.31 0.44 19.21 13915 13916 2.10 2.40 0.67 0.69 31 90 28 75 0.29 0.14 13.81 5.83 0.054 0.033 2 57 1 38 0.071 0.050 3.38 2.08 0.69 0.61 32.86 25.42 13917 2.31 0.68 29.44 0.20 8.66 0.061 2 64 0,052 2,25 0.46- 19.91 13918 2.22 0.65 29.28 0.18 8.11 0.046 2.07 0.049 2.2i 0.57 25.68 13919 2.30 0.48 20.87 0.09 3.91 0.056 2.43 0.038 1.65 0.52 22.61 _29 13920 2.28 0.66 28.95 0.08 3.51 0.045 1.97 0,038 1.67 0.47 20.61 4_ .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Rat was not pregnant; values were not recorded, bO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE 9) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... RAT BRAIN PITUITARY LIVER KIDNEY LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW DOSAGE GROUP V 30 MG/KG/DAY KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW ADRENAL RIGHT ABS. REL. WT. % BRW .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929a 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 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 0.019 0.010 0.012 0.020 0.009 0.027 0.011 0.028 0.015 0.019 0.022 0.016 0.018 0.012 0.010 0.017 0.005 0.016 0.016 0.030 0.017 0.006 0.011 0.092b 0.82 0 46 0 56 0 95 0 42 1 23 0 53 1.22 .... 0.85 1.05 0.73 0 90 0 56 0 48 0 74 0 25 0 71 0 70 1 34 0 71 0 27 0 48 4 58b 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 38 824.46 755.09 932.09 992.89 716.51 937.44 898.55 823.04 ...... 923.66 915.79 942.66 861.81 694.44 844.71 787.77 824.63 844.44 718.34 844.64 810.88 785.84 769.56 814.92 1.54 1.37 1.41 1.47 1.31 1.63 1.47 1.58 1.20 1.47 1.29 1.53 1.28 1.42 1.39 1.37 1.51 1.58 1.49 1.34 1.55 1.46 1.52 1.43 66.09 63.42 65.58 69.67 61.79 74.43 71.01 68.70 ..... 65.62 61.72 70.18 64 32 65 74 66 83 59 82 74 38 70 22 65 06 59.82 64.85 66.67 66.09 71.14 1.59 1.37 1.38 1.61 1.34 1.58 1.60 1.60 1.27 1.62 1.33 1.53 1.43 1.50 1.46 1.38 1.40 1.63 1.51 1.46 1.65 1.37 1.45 1.53 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 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 2.23 1 76 1 95 2 51 1 89 3 24 3 33 2 17 .... 1 74 2 01 2 34 2 26 1 80 2 55 2 31 1 43 2 49 1 70 2 14 1 88 1 37 1 48 2 79 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 1.80 1.90 1.91 2.13 1.56 2.24 2.51 1.56 .... 1.65 1.87 2.11 3.02 1.34 2.69 1.92 1.53 2.18 1.62 1.74 2.47 1.60 1.83 2.59 13945 13946 2.29 2.04 0.021 0.009 0 92 0 44 17 42 17 13 760.70 839.70 1.45 1.22 63.32 59.80 1.57 1.33 68 56 65 20 0.051 0.032 2 23 1 57 0.039 0.024 1.70 1.18 13947c 13948 2.05 2.20 0.015 0.017 .... 0.77 11 28 15 i0 ...... 686.36 1.18 1.35 ..... 61.36 1.11 1.36 ..... 61.82 0.048 0.044 .... 2.00 0.040 0.810b .... 36.82b 13949 2.09 0.013 0.62 18 90 904.31 1.53 73.20 1.55 74.16 0.046 2.20 0.023 i. I0 [2_ 13950 2.02 0.016 0.79 18 17 899.50 1.39 68.81 1.52 75.25 0.037 1.83 0.041 2.03 _t_ .................................................................................................................................... O0 ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. HT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Rat was not pregnant; values excluded from group averages and statistical analyses, t_ Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. Rat 13947 was sacrificed due to no surviving pups on day 1 of lactation; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C34 (PAGE I0) : BRAIN WEIGHTS, ORGAN WEIGHTS P GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - RAT BRAIN SPLEEN THYMUS OVARY LEFT NUMBER WEIGHT ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY REL. % BRW OVARY RIGHT ABS. WT. REL. % BRW UTERUS NON-GRAVID ABS. REL. WT. % ERW .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 2 33 2 16 2 15 2 ii 2 12 2 19 2 07 0.71 0.72 0.74 0.52 0.56 0.90 0.79 30.47 33.33 34.42 24.64 26.42 41.10 38.16 0.15 0.08 0.10 0.16 0.10 0.19 0.20 6.44 3.70 4.65 7.58 4.72 8.68 9.66 0 069 0 073 0 030 0 106 0 040 0 061 0 062 2.96 3.38 1.40 5.02 1.89 2.78 3.00 0.033 0.060 0.020 0,055 0.043 0.070 0.058 1,42 2.78 0.93 2.61 2.03 3.20 2.80 0.54 0.52 0.45 0.40 0.40 0.47 0.27 23.18 24.07 20.93 18.96 18.87 21.46 13.04 13928 13929a 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 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 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 36.52 ..... 35.71 39.23 28.44 33.16 31.48 29.33 32.31 24.63 36.89 32.75 29.46 29.71 31.96 32.61 40.80 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 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 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 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 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 2.61 .... 2.10 2 39 2.25 1.81 1.99 2.21 1.75 1.48 1.73 3.23 1.74 3.60 2.74 2.26 2.69 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 26.09 ..... 20.54 27.75 25.69 25.63 23.61 36.54 24.45 24.14 19.11 18.78 26.78 18.83 24.66 22.17 28.36 13945 13946 13947b 2 29 2 04 2 05 0.69 0.89 0.66 30.13 43.63 ..... 0.28 0.17 0.26 12.23 8.33 .... 0,047 0,058 0.085 13948 13949 2 20 2 09 0.80 0.62 36.36 29.66 0.22 0.17 i0.00 8.13 0,035 0,050 13950 2 02 0.72 35.64 0.18 8.91 0,060 ............................................................................................................................... 2.05 2.84 .... 1.59 2.39 2.97 0,050 0.044 0.058 0.047 0,038 0.046 2.18 2.16 .... 2.1_ 1.82 2.28 0.28 0.45 2.00. 0.65 0.39 0.65 12.23 22.06 - .... 29.54 18.66 32.18 [_ 4_ _.d ..... OO ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % BRW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Rat was not pregnant; values excluded from group averages and statistical analyses, b_ Rat 13947 was sacrificed due to no surviving pups on day 1 of lactation; values excluded from group averages and O statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C35 (PAGE i): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... 13801 13802 13803 13804 22 22 23 MORIBUND 9 14 16 SACRIFICED 0 0 0 ON DAY 9 14 16 68 OF STUDY 4 5 8 6 6 10 4 5 8 6 6 i0 OF LIVE OF DAY 8 M F PUPS AT POSTPARTUM 15 M F 4 5 8 6 6 9 4 5 8 6 6 9 22 M F 4 5 8 6 6 9 TOTAL IMPLANTATIONS N 11 14 16 13805 23 13 0 13 6 7 6 7 6 7 6 7 6 7 13 13806 22 17 0 17 6 11 5 II 5 ii 5 ii 5 11 17 13807 22 17 0 17 8 9 8 9 8 9 8 9 8 9 17 13808 22 12 1 13 6 6 6 6 6 6 6 6 6 6 16 13809 23 13 0 13 94 9 4 9 4 9 4 9 4 14 13810 23 14(1) 1 15 5 8 4 8 4 8 4 8 4 8 18 13811 NOT PREGNANT 13812 23 14 0 14 9 5 9 5 9 5 9 5 9 5 15 13813 23 12 0 1311] 5 7 5 7 5 7 5 7 5 7 16 13814 22 17 0 17 11 6 11 5 11 5 11 5 11 5 18 13815 23 15 0 15 i0 5 10 5 10 5 10 5 10 5 16 13816 23 15 0 16ti] 5 10 5 10 5 10 5 10 5 10 17 13817 23 15 0 15 8 7 8 6 8 6 8 6 8 6 16 13818 23 16 0 16 8 8 8 6 8 6 8 6 8 6 17 13819 22 13(1} 0 13 4 8 4 8 4 8 4 8 4 8 14 13820 23 14 0 14 5 9 5 9 5 9 5 9 5 9 16 13821 22 17 0 17 8 9 8 9 8 9 8 9 8 9 17 13822a 23 12 0 12 3 9 3 9 3 9 - - 12 13825 25 9 0 9 4 5 4 5 4 5 4 5 4 5 11 13824 23 16 0 16 8 8 8 8 8 8 8 8 8 8 16 13825 23 15 0 15 2 13 2 13 2 13 2 13 2 13 15 15826 23 16 0 16 8 8 8 8 8 8 8 8 8 8 16 13827 23 16 0 16 10 6 9 6 9 6 9 6 9 6 16 13828 23 14 0 14 5 9 5 9 5 9 5 9 5 9 16 13829 22 13 0 13 8 5 8 5 8 5 8 5 '8 5 13 13830 22 13 1 14 7 6 7 6 7 6 7 6 7 6 15 [/) .................................................................................................................................. = MALE F - FEMALE ) . NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. _'_ O0 ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. tO a. Dam 13822 was sacrificed on day 8 of lactation. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C35 (PAGE 2) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... OF LIVE OF DAY 8 M F PUPS AT POSTPARTUM 15 M F 13831 13832 13833 13834 13835 13836 13837 13838 22 23 22 22 22 MORIBUND 22 23 17 14 15 13 18 SACRIFICED 11 18 0 17 0 14 0 15 0 13 0 18 ON DAY 59 OF STUDY 1 12 0 18 13 4 10 4 6 9 4 9 6 12 5 6 7 11 13 4 10 4 6 8 4 9 6 10 5 6 7 10 13 4 10 4 6 8 4 9 6 10 5 6 7 10 13 4 10 4 6 8 4 9 6 10 5 6 7 10 1133883490 N2O3T PREGNANT 12 0 12 6 6 6 6 13841 22 13842 22 13843 22 13844 23 13845 23 13846 23 13847 23 13848 23 11 (1) 0 13 0 10 0 17 0 12 0 14 0 8 7 16 0 12 [1] 13 10 17 12 14 15 16 5 5 6 7 5 5 6 11 7 5 7 7 4 4 12 4 5 5 6 7 5 5 6 11 7 5 7 6 4 4 12 4 13849 13850 13851 23 16 22 12 NOT PREGNANT 0 16 1 13 11 5 6 6 11 5 6 6 13852a 23 13853 22 13854 23 13855 22 12 0 12 17 0 17 17 0 17 16 (1) 0 16 8 4 10 7 11 6 96 8 4 10 7 11 6 9 5 13856 22 13857 23 16 0 16 14 1 15 9 7 4 i0 9 7 4 i0 13858 22 17 0 17 9 8 9 8 13859 23 15 0 15 6 9 6 9 13860 22 13 0 13 94 9 4 .................................................................................................................................. 6 6 5 5 5 7 5 5 6 10 7 5 7 6 4 4 12 4 11 5 6 6 8 4 i0 7 ii 6 9 5 9 7 4 I0 9 8 6 9 9 4 6 6 5 5 5 7 5 5 6 10 7 5 7 6 4 4 12 4 11 5 66 10 7 11 6 9 5 9 7 4 i0 9 8 6 8 9 4 - MALE F - FEMALE ) . NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR a. Dam 13852 was sacrificed on day 11 of lactation. 1 POSTPARTUM. AUTOLYSIS PRECLUDED THE DETERMINATION 22 M F 13 4 10 4 6 8 4 9 6 10 5 6 7 10 6 6 5 5 57 55 6 10 7 5 76 4 4 12 4 11 5 66 10 7 ii 6 9 5 9 7 4 i0 9 8 6 8 9 4 OF VIABILITY. TOTAL IMPLANTATIONS N 17 16 17 15 18 13 20 13 14 14 10 17 13 14 17 17 17 15 15 17 17 17 17 15 17 15 14 [2_ OO bO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C35 (PAGE 3): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS DOSAGE GROUP III 3 MG/KG/DAY ........................ i ........................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... 13861 13862 23 PREGNANT; i0 0 10 DID NOT DELIVER A LITTER 8 2 8 2 OF LIVE OF DAY 8 M F PUPS AT POSTPARTUM 15 M F 8 2 8 2 22 M F 8 2 TOTAL IMPLANTATIONS N 12 13863 23 16 0 16 5 11 5 10 5 10 5 10 5 10 17 13864 23 6 1 7 4 2 4 2 4 2 4 2 4 2 13 13865 22 17(I) 0 17 7 9 7 9 7 9 7 9 7 9 17 13866 23 18 0 18 8 I0 8 10 8 9 7 9 7 9 18 13867 23 15 1 16 9 6 9 6 7 5 7 5 7 5 16 13868 22 16 0 16 8 8 8 8 8 8 8 8 8 8 16 13869 23 16 0 16 7 9 7 8 7 8 7 8 7 8 16 13870 23 8 0 8 2 6 2 6 2 6 2 6 2 6 Ii 13871 22 15 0 15 5 10 4 9 4 8 4 8 4 7 16 13872 23 17 0 17 9 8 9 8 9 8 9 8 9 8 17 13873 23 17 0 17 8 9 8 8 8 8 8 8 8 8 18 13874 23 17 0 17 5 12 5 11 5 11 5 11 5 11 18 13875 23 16 0 16 8 8 8 8 8 8 8 8 8 8 17 13876 23 14(1) 1 15 7 6 7 6 7 6 7 6 7 6 18 13877 23 13 1 14 7 6 7 6 7 6 7 6 7 6 17 13878 23 9 0 9 2 7 2 7 2 7 2 7 2 7 11 13879 23 11 0 11 6 5 6 5 6 5 6 5 6 5 14 13880 23 13 0 13 9 4 94 94 9 4 9 4 16 13881 22 11 0 11 6 5 6 5 6 5 6 5 6 5 12 13882 22 16 0 16 10 6 10 5 10 5 10 5 10 5 16 13883 23 15(i) 0 15 7 7 7 7 7 7 7 7 7 7 15 13884 23 11 0 11 6 5 6 5 6 5 6 5 6 5 11 13885 24 3 0 3 2 1 2 1 2 1 2 1 2 1 16 13886 22 12 0 12 7 5 7 5 7 5 7 5 7 5 13 13887 23 Ii 0 11 8 3 8 3 8 3 8 3 8 3 13 13888 23 14 1 15 2 12 2 12 2 12 2 12 2 12 16 13889 22 16 0 16 i0 6 I0 6 i0 6 I0 6 I0 6 16 13890 23 15 0 15 1 14 1 14 1 14 1 14 1 14 16 .................................................................................................................................... = MALE F - FEMALE ) . NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. _'_ [/_ ._A w-d O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C35 (PAGE 4): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... 13891 23 13892 22 13893 22 13894 23 13895 22 13896 23 10 1 11 15 1 16 15 0 15 14 0 14 15 0 15 12 0 12 4 6 7 8 7 8 7 7 11 4 5 7 4 6 7 8 7 8 6 7 11 4 5 7 13897 23 12 0 12 6 6 6 6 13898 23 17 0 17 7 10 7 9 OF LIVE OF DAY 8 M F 4 6 7 8 7 8 6 7 11 4 5 7 6 6 7 9 PUPS AT POSTPARTUM 15 M F 4 6 7 8 7 8 6 7 11 4 5 7 6 6 7 9 22 M F 4 6 7 8 7 8 6 7 11 4 5 7 6 6 7 9 13899090 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 2N2OT PREGNANT; 23 23 23 23 23 a 21 23 23 22 23 22 22 23 23 MATIiNiG 16 15 14 14 16 14 16 4 14 15 12 14 13 18 17 NOT 0CONFIRM1E1D 0 16 0 15 0 14 0 14 0 16 2 16 0 16 0 4 0 14 0 15 0 12 0 14 0 13 0 18 0 17 6 5 6 5 6 5 6 7 9 7 9 7 8 7 7 8 7 8 7 8 7 4 10 4 10 4 10 4 9 5 9 5 9 5 9 5 11 5 11 5 11 5 6 8 5 8 5 7 5 10 6 10 6 10 6 10 2 2 2 2 2 2 2 5 9 5 9 5 9 5 6 9 6 9 6 9 6 8 4 8 4 8 4 8 7 7 7 7 7 7 7 7 6 7 6 7 6 7 8 10 8 9 8 9 8 9 8 9 8 9 8 9 13916 23 13917 a 16 0 16 7 0 7 7 9 7 9 7 9 7 34 3 4 3 4 3 13918 23 14 0 14 5 9 5 9 5 9 5 13919 22 14 0 14 6 8 6 8 6 8 6 13920 23 16 0 16 7 9 7 8 7 8 6 . ............................................................................................................................... = MALE F - FEMALE a. Dam did not have a confirmed mating date, which precludes the calculation of the 5 6 5 8 7 8 8 7 8 I0 4 10 5 9 5 11 5 11 7 5 7 6 10 6 2 2 2 9 5 9 9 6 9 4 84 7 7 7 6 7 6 9 8 9 8 9 8 9 7 9 4 3 4 9 5 9 8 6 8 6 6 6 duration of gestation. TOTAL IMPLANTATIONS 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 ii 15 17 17 [2_ O0 rO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C35 (PAGE 5): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ LITTER GESTATION (DAYS) LIVE BORN STILLBORN TOTAL BORN COMPLETION 1 5 NUMBER N N N N M F M F .................................................................................................................................... 13921 23 13922 22 13923 22 13924 23 13925 23 13926 22 13927 23 13928 23 15 0 15 9(2} 0 9 14 0 14 17 0 17 13 0 13 14 1 15 16 0 16 16 0 16 96 52 7 7 i0 7 6 7 8 6 7 9 6 i0 9 6 4 7 7 10 7 6 7 8 6 7 9 5 i0 OF LIVE OF DAY 8 M F 8 6 4 7 7 10 7 6 7 86 7 8 4 10 PUPS AT POSTPARTUM 15 M F 8 6 4 7 7 10 7 6 7 8 6 7 8 4 i0 22 M F 8 6 4 7 7 I0 7 6 7 8 6 7 8 4 i0 13929 13930 NOT PREGNANT 22 18 0 18 9 9 9 8 13931 22 15 0 15 8 7 8 6 13932 23 14 0 14 8 6 8 6 13933 23 13 0 13 5 8 5 8 13934 a 15 0 15 3 12 2 12 13935 23 15 0 15 7 8 7 8 13936 23 14 0 14 ii 3 11 3 13937 23 15 0 15 6 9 6 9 13938 22 16 0 16 8 8 7 8 13939 23 14 1 15 7 7 7 7 13940 23 15 0 15 6 9 6 9 13941 23 13 1 14 9 4 9 4 13942 23 16 0 16 Ii 5 II 5 13943 23 7 0 7 2 5 2 5 13944 22 12 0 12 4 8 3 8 13945 23 14 0 14 9 5 9 5 13946 23 11 0 11 5 6 5 6 13947b 24 I(I) 0 1 13948 22 12 0 12 7 5 7 4 13949 22 13 0 13 94 9 4 13950 22 11 3 14 6 5 6 4 - ............................................................................................................................... 8 7 64 8 6 5 8 2 11 7 8 ii 3 6 9 7 8 7 7 6 9 9 4 ii 5 2 5 3 8 9 5 5 6 7 4 9 4 6 4 M = MALE ( ) . NUMBER F ffiFEMALE OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. a. Dam did not have a confirmed mating date, which precludes the calculation b. Dam 13947 was sacrificed due to no surviving pups on day 1 of lactation. 8 6 8 5 1 7 11 6 7 7 6 9 11 2 3 9 5 7 9 6 of the 7 8 7 4 64 6 8 6 8 5 8 11 1 11 8 7 8 3 Ii 3 9 6 9 8 7 8 7 7 7 9 6 9 4 9 4 5 Ii 5 5 2 5 7 3 7 5 9 5 6 5 6 4 74 4 9 4 4 6 4 duration of gestation. TOTAL IMPLANTATIONS N 15 13 16 17 13 19 17 18 19 15 14 13 18 15 15 15 17 16 15 14 17 13 13 16 11 15 17 14 15 > {29 O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C36 (PAGE i) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION LITTERS MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT/ LITTER DAY 1 DAY 5 DAY 8 NUMBER M F T M F T M F T .................................................................................................................................... 13801 13802 13803 13804 5.5 5.3 5.4 6.9 6.2 6.6 7.4 7.0 7,1 MORIBUND SACRIFICED 8.8 12.1 11.3 ON 8.5 11.2 10.8 DAY 68 8.6 13,2 11.7 17.5 11.0 15.8 OF STUDY 13.2 16.8 15.4 13.2 17.2 15.6 DAY 15 M F T 29.2 30.8 23.2 28.7 30.1 23.0 28.9 30.5 23.1 DAY 22 M F T 45.6 43.9 42.0 43.6 41.9 40.8 44.4 43.0 41.3 13805 13806 13807 13808 13809 7.2 6.8 7.0 10.6 10.0 10.3 15.4 14.0 14.6 5.8 5.7 5.7 8.3 8,2 8.2 11.9 12.2 12.1 6.3 6.0 6.2 9.1 8.8 9.0 12.2 12.0 12.1 6.5 5.8 6.2 10.2 9.9 10.0 14.5 14.3 14.4 6.7 6.2 6.5 9.9 9.2 9.7 13.9 13.0 13.6 28.8 24.4 23.1 29.7 28,4 26.4 24.6 23.0 29.3 26.5 27.5 24.5 23.0 29.5 27.8 45 7 33 9 25 6 40 9 36 0 41 4 34 4 24 8 40 2 34 2 43 4 34 2 25 2 40 5 35 5 13810 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 6.4 6.0 6.1 NOT PREGNANT 6.5 6.4 6.5 7.4 7.0 7.2 5.8 5.2 5.6 5.8 5.5 5.7 6.5 6.1 6,3 6.8 6.4 6.6 6.2 5.5 5.8 6.3 5.5 5.8 6,7 6.2 6.4 5.7 5,3 5.5 7.2 6.7 6.8 7.0 6.9 6.9 6.6 6.1 6.4 6.4 6.3 6.3 6.8 6.2 6.5 9.8 10.5 11.6 8.0 8.2 8.9 9.3 7.4 9.7 9.0 9.5 12.1 12.8 9,7 8.1 9.9 9.4 10.4 11.6 7.4 7.9 8.4 8.6 7.0 8.4 8.7 8.9 11.3 12.8 8.9 8.2 9.0 9.6 10.4 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 14.7 14.0 14.2 31.2 29.8 30.3 15.3 15.0 17.2 17.0 11.1 10,5 11.2 10.5 11,5 10.9 12.6 12.0 11.0 9.8 13.6 12.3 13.5 12.1 14.0 13.0 SACRIFICED 18.8 18.7 13.2 12.8 12.0 11.9 12.9 12.2 15.2 17.1 10.9 10.9 11.1 12.4 10.5 12.8 12.6 13.5 ON DAY 18.7 13.0 11.9 12.6 27.2 32.2 22.8 21.0 20.0 23.9 18.4 21.0 26.9 26.3 8 OF 33.2 25.8 24.8 20.0 26.4 31.1 21.5 19.8 17.4 22.7 16.9 19.6 24.7 25.0 LACTATION 32.9 24.7 23,7 18.2 26,9 31.6 22.4 20.6 18.3 23.4 17.8 20.1 25.5 25.6 33.0 25.2 23.9 19.1 45 6 43,3 43 8 34 0 32 8 33 1 38 2 28 6 30 5 26 8 40 5 42 7 41 2 43 3 32 6 31 0 29 3 37 0 26 6 28 9 29 0 38 5 43 6 42 6 43 5 33 5 32 2 30 6 37 7 27 8 29 4 28 2 39 5 54,0 40,4 35,5 32.0 53.3 39.1 34.2 28.7 53 6 39 7 34 3 30 4 13827 6.4 5.6 6.1 9.6 9.1 9.4 13.9 13.3 13.6 26.2 25.1 25.7 41.7 39.9 41 0 > 13828 6.6 6.3 6.4 8.7 8.4 8.5 12.5 12.0 12.2 25.4 24.5 24.8 41.3 39.3 40 0 13829 6.7 6.3 6,5 i0.0 9.5 9.8 11.9 ii.i 11.6 23.8 21.4 22.9 41.2 37.5 39 8 13830 5.5 5.3 5.4 8.0 7.8 7.9 11.4 11.6 11.5 22.7 22.7 22.7 35'.5 35.1 35 3 .................................................................................................................................... MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS} DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O0 6bO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C36 (PAGE 2): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION LITTERS MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT/ LITTER DAY 1 DAY 5 DAY 8 NUMBER M F T M F T M F T .................................................................................................................................... DAY 15 M F T DAY 22 M F T 13831 13832 13833 13834 13835 13836 6.3 5.9 6.2 6.8 6.5 6.7 5.7 5.6 5.6 6.3 5.9 6.0 6.0 5.4 5.6 MORIBUND SACRIFICED 9.4 9.9 9.0 10.0 8.7 ON 8.6 9.8 8.7 9.5 8.2 DAY 59 9.2 13.1 9.9 14.2 8.8 12.8 9.7 14.0 8.4 12.9 OF STUDY 12.3 13.7 12.2 13.7 12.2 12.9 14.0 12.4 13.8 12.5 25.1 25.4 26.2 26.6 25.4 24.2 23.9 25.1 25.6 23.8 24.9 25.0 25.6 25.9 24.4 34.6 41.8 43.0 37.3 35.9 32.6 39.1 40.0 35.9 32.8 34.1 41.0 41.3 36.3 34.0 13837 13838 13839 6.2 5.7 5.9 6.5 5.8 6.1 6.6 6.4 6.5 8.5 7.8 8.1 9.1 8.2 8.6 9.4 i0.i 9.7 12.6 13.3 15.5 11.7 11.6 14.3 12.1 12.3 14.9 26.4 25.3 24.7 25.4 23.3 22.9 25.8 24.2 23.8 39.6 36.7 36.1 37.6 34.0 33.1 38.5 35.1 34.6 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 NOT PREGNANT 5.9 5.6 5.8 6.1 5.9 6.0 6.7 5.9 6.3 6.0 5.7 5.8 6.7 6.6 6.7 6.1 5.6 5.8 5.7 5.9 5.8 6.7 6.2 6.6 6.2 5.9 6.1 5.9 5.5 5.7 NOT PREGNANT 94 85 80 78 97 92 10 5 9.4 8.2 8.5 9.1 8.1 7.2 7.2 9.8 8.6 10.1 9.0 7.7 8.2 9.2 8.3 7.6 7.4 9.7 9.0 10.3 9.3 8.1 8.3 12.7 12.9 11.2 11.8 13.8 12.6 15.8 13.7 11.4 12.0 12.5 12.1 10.1 10.5 14.1 12.2 15.0 13.3 11.0 II.I 12.6 12.4 10.6 11.0 13.9 12.4 15.4 13.6 11.3 11.5 23 7 27 0 23 7 21 7 27 8 23 4 31 9 26 0 21 2 25 2 22 5 24 6 22 7 19 8 28 8 22 2 31 3 25 4 20 5 24 1 23.1 25.6 23.2 20.5 28.2 22.8 31.6 25.8 21.0 24.6 41.6 40.5 34.5 35.4 43.1 35.3 54.6 42.6 26.2 38.0 39.2 36.6 32.4 29.1 43.3 32.7 52.3 39.7 26.0 34.9 40.4 38.2 33.4 31.4 43.2 34.1 53.4 41.8 26.2 36.4 13852 13853 13854 13855 13856 6.3 6.2 6.3 5.2 4.6 5.0 6.1 6.0 6.1 5.7 5.5 5.6 5.7 5.1 5.4 9.3 9.2 9.3 7.8 7.6 7.7 9.4 9.0 9.2 9.6 9.4 9.6 9.2 8.1 8.7 13.3 11.1 13.5 14.3 13.2 13.6 10.8 12.6 14.4 11.8 13.4 10.9 13.2 14.4 12.6 SACRIFICED 21.9 20.2 20.0 18.2 28.4 28.0 21.0 18.8 ON DAY 21 2 19 3 28 2 20 0 11 OF 32.7 29.5 39.2 33.5 LACTATION 29.9 31.5 27.2 28.7 38.8 39.0 28.7 31.4 13857 6.8 6.3 6.4 10.2 9.8 9.9 14.9 14.4 14.6 13858 5.5 5.2 5.3 7.8 7.5 7.6 11.1 11.2 11.2 13859 6.1 5.7 5.9 8.6 8.3 "8.4 12.6 11.8 12.2 13860 5.7 5.7 5.7 8.5 8.4 8.5 11.9 12.2 12.0 .................................................................................................................................... 27.4 23.0 22.7 23.4 26.6 22.6 22.1 22.8 26 9 22 8 22.4 23.2 43.0 33.2 40.4 36.7 40.6 33.6 39.2 37.5 41.3 33.4 -39.7 37.0 MALE F = FEMALE T z TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O0 6 PROTOCOL 418-020: ORAL (GARAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C36 (PAGE 3): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION LITTERS MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT/ LITTER NUMBER DAY 1 M F T DAY 5 M F T DAY 8 M F T DAY 15 M F T DAY 22 M F T 13861 13862 6.0 5.5 5.9 9.8 9.0 9.6 PREGNANT; DID NOT DELIVER A LITTER 14.2 12.9 14.0 26.8 26.0 26.7 34.6 33.6 34,4 13863 13864 13865 13866 13867 13868 13869 6.0 5.5 5.7 9.3 9.1 9.2 13.8 13.6 13.7 22.0 22.0 22.0 6.4 6.4 6.4 11.4 11 3 11.4 18.3 18.5 18.4 38.8 38,2 38,6 5.4 5.4 5.4 8.4 85 8.4 11.5 11.6 11.6 19.0 18.6 18.8 6.6 6.2 6.3 8.9 85 8.7 10.8 10.4 10.6 22.2 21.4 21.8 6.0 5.9 5.9 6.5 68 6.7 9.6 96 9.6 20.8 21.2 20.9 5.7 5.4 5.6 9.2 86 8.9 13 5 12 7 13.1 26.0 25.9 25.9 6.4 6,1 6.3 8.3 81 8.2 i0 8 10 6 10.7 20.7 18.0 19.3 32.1 59.6 29.9 35.1 29.4 34.4 31.9 31.4 60.6 29.0 31.7 29.1 33.9 27.7 31,6 60.0 29.4 33,2 29,3 34.1 29.6 13870 13871 13872 13873 13874 13875 13876 13877 13878 13879 7.2 6.6 6.8 6.3 6.0 6.1 5.7 5.4 5.6 6.2 59 6.0 73 63 6.6 61 60 6.0 66 62 6.4 71 64 6.7 75 73 7,4 71 67 6.9 9.2 7.9 7.7 86 11.7 8.9 10.2 9.8 9.9 11.6 91 75 7.5 88 10.2 8.6 9.9 83 i0 6 11 4 9.2 7.6 7.6 8.7 10.6 8.7 10.1 9.1 10.4 11.5 13 2 12 2 ii 2 12 5 17 2 12 5 15 7 13 5 14 8 15 7 13 1 ii 8 I0 7 13.2 14.7 12.5 15.0 12.0 15.4 16.0 13.1 11.9 ii.0 12 8 15.5 12.5 15.4 12.8 15.3 15.8 27.9 19.7 21.4 23.3 32.1 25.4 30.1 30.0 31.2 31.8 28.0 19.0 20.2 24.5 28.2 24.0 29.0 27.0 32.0 31.2 27.9 19.2 20.8 23 9 29.4 24.7 29.6 28.6 31.9 31.5 39.6 28.0 31.0 35.1 50.7 37.3 48.2 46.2 48.8 48.4 40.1 28.3 28.7 35,4 44.5 37.4 45.9 41.6 48.4 48.7 40,0 28.2 29,9 35,2 46.4 37.3 47,1 44.1 48,5 48,6 13880 13881 67 6.4 6.6 65 60 6.2 11.7 11.0 11 6 10 0 11.7 10.5 15 5 15 4 15.3 14.5 15.4 15.0 29.6 29.3 30.2 29.3 29.7 29.3 48.3 39.7 47.9 38.1 48.2 39,0 13882 13883 13884 13885 13886 58 52 5.6 68 66 6.7 65 61 6.3 7.4 74 7.4 6.3 62 6.3 9.5 10.3 9.8 13.9 9.4 89 10.3 8.9 13.7 9.3 9.3 10.3 9.4 13.8 9.3 14 4 14 6 12 0 19.0 13.9 13.1 14.8 11.1 18.5 13.4 14 0 14 7 11 6 18 9 13 7 27.2 27.2 28.2 33.8 25.8 26.2 27.5 26.4 32.0 24.4 26,9 27.3 27.4 33.2 25.2 41.6 46.3 43.2 53.5 42.9 39.2 46.4 39.5 53.5 40.2 40.8 46,3 41,5 53,5 41,8 13887 6.3 59 6.2 11.2 10,2 i0,9 16.0 15.1 15 7 13888 6.6 61 6.2 9.2 8.7 8.8 11.2 10.8 I0 9 13889 5.6 53 5.5 8.7 7.8 8.3 12.5 11.8 12 2 13890 6.5 59 5.9 9.5 9.1 9.1 13.6 12.6 12 7 .................................................................................................................................... 32.2 25.1 26.3 26.9 30.2 22.3 24.7 24.8 31.7 22.7 25.7 24.9 50.8 36.4 35.6 43.1 47.3 30.7 32.2 38.1 49,9 31,5 .34,3 38,5 MALE P = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. OO bO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C36 (PAGE 4) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION LITTERS MATER.NAL..DO.SAG.E .G.ROU.P .IV......10.M.G/K.G/D.AY .......................................... LITTER NUMBER DAY 1 M F T DAY 5 M F T DAY 8 M F T .................................................................................................................................... 13891 13892 13893 13894 13895 13896 13897 13898 6.9 6.8 6.9 11.1 10.8 10.9 15.4 15.3 15.3 5.8 5.6 5.7 9.0 B.6 8.8 13.0 12.4 12.7 6.7 6.1 6.4 10.4 9.8 10.1 14.9 13.9 14.4 6.7 5.9 6.3 8.6 7.6 8.1 12.6 11.1 11.8 5.5 5.4 5.5 7.9 8.0 7.9 12.0 12.4 12.1 6.8 6.3 6.6 10.5 9.8 10.1 14.8 14.2 14.5 7.0 6.5 6.7 10.1 9.5 9.8 14.3 14.1 14.2 6.4 5.9 6.1 8.9 8.4 8.6 12.0 10.9 11.4 13899 6.4 . 5.9 6.2 I0.0 9.4 9.7 13.5 12.7 13.1 DAY 15 M F T 30.5 25.4 26.9 25.7 24.9 26.5 29.8 22.3 21.7 29.2 24.5 25.6 23.1 26.0 24.7 28.3 20.7 20.1 29.7 24.9 26.2 24.3 25.2 25.5 29.1 21.4 21,0 DAY 22 M F T 48.6 39.2 43.0 38.5 38.4 42.2 46,8 29.9 34.8 45.8 37.0 41.0 34.9 39.2 38.1 43.0 27.5 32.5 46.9 38.0 41.9 36.6 38.6 39.8 44.9 28.6 33.8 139001 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 N6O.T3 PRE5G.N9ANT; 6.1MATING 7 N8OT C7O.N0FIRME7D.3 6.7 6.7 6.7 99 9.2 9.5 6.7 6.7 6.7 I0 9 10.7 i0 8 6.8 6.3 6.6 98 9.1 9.6 6.1 5.3 5.6 97 9.0 9.2 6.3 6.0 6.1 10 0 9.5 9.7 5.7 5.4 5.6 86 8.2 8.4 7.2 7.0 7.1 11 2 11.2 11 2 5.6 5,5 5.5 87 8.6 86 6.1 5.8 5.9 10 0 10.0 10 0 6.5 6.2 6.4 97 9.4 96 5.9 5.4 5.7 87 8.0 83 6.1 5.7 5.9 10,4 9.8 10 1 5.9 5.7 5.8 88 8.5 86 6.2 6.0 6,0 89 8.8 8.8 6.2 5.8 6.0 88 8.0 8.3 10.5 13.7 14.6 11.6 14.3 15.1 12.4 16.7 12.8 14.9 12.5 12.6 15.1 12.0 12.0 13.2 9.3 12.7 14,4 10.0 13.2 14.8 12.1 16.4 12.5 14.9 12.0 11.5 14.3 11.7 11.8 12.1 9.9 13.2 14.5 11.0 13.6 15.0 12.3 16.5 12.6 14.9 12.4 12.0 14.8 11.8 11.9 12.6 22,2 26.6 26.0 19.6 25.3 30.5 18.6 36.3 24.2 22.1 26.6 25.8 29.1 23.5 22.1 27.6 19.8 23.9 25.6 17.3 23.9 30.3 18.2 36.0 23.5 23.4 25.6 24.4 28.6 22.9 21.3 24.3 20.9 25.2 25.7 18.8 24.3 30.4 18.5 36.1 23.7 22.9 26.2 25.1 28.9 23.2 21.7 25.7 31.7 42.4 40.3 35 1 38 0 48 3 27 9 55 4 39 4 36 8 42 4 39 5 45 4 32 5 36 2 44 4 28.7 39.2 41.0 31.5 37.4 48.1 27.0 55.0 38 3 37 5 41 1 37 8 43 2 31 9 34 2 39.0 30 1 40 7 40 8 33 8 37 6 48 2 27 6 55 2 38 7 37 2 42 0 38 7 44 4 32 2 35 3 41 4 13917 6.6 6.3 6.4 I0 0 9.2 9.5 13.7 13.1 13.3 13918 6.4 6.1 6.2 10 3 9.6 9.9 15.7 14.6 15.0 13919 6.1 5.9 6.0 96 8.6 9.1 11.9 10.6 11.2 13920 6.3 6.1 6.2 88 8.3 8.5 10.3 i0.0 i0.i .................................................................................................................................... 28.1 29.0 24.0 16.9 27.3 27.1 21.8 15.2 27.6 27.8 22.7 16.1 43 9 44 6 39 0 3i.8 43.5 40.8 35.7 30.0 43 7 42 2 37 1 30 9 MALE F -- FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C36 (PAGE 5) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION LITTERS .................................................................................................................................... MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT/ LITTER DAY 1 DAY 5 DAY 8 DAY 15 DAY 22 NUMBER M F T M F T M F T .................................................................................................................................... M F T M F T 13921 13922 13923 13924 13925 13926 13927 13928 6.3 5.6 6.1 4.3 4.0 4.2 6.0 5.6 5.8 5.8 5.8 5.8 6.0 5.5 5.7 5.5 5.2 5.4 5.7 5.4 5.6 6.9 6.4 6.6 8.7 7.6 8.3 11.8 10.2 11.1 23 8 20.4 22.3 40.0 33.3 37.1 6.7 --- 6.7 9.0 --- 9.0 22 2 --- 22.2 39.0 --- 39.0 8.4 8.2 8.3 11.1 10.8 10.9 21 0 19.4 20.2 32.6 30.2 31.4 8.5 8.0 8.3 12.3 11.1 11.8 22 4 20.7 21.7 33.0 29.9 31.7 7.9 7.4 7.7 10.4 10.5 10.5 20 3 20.4 20.4 33.2 32.8 33.0 7.3 7.2 7.2 11.0 10.8 10.9 23 3 23.0 23.2 32.8 32.0 32.5 8.9 8.1 8.4 11.5 11.3 11.4 15 3 14.3 14.8 24.8 23.2 23.9 9.1 8.5 8.7 13.1 11.6 12.0 26 9 25.0 25.5 41.6 38.3 39.2 13929 NOT PREGNANT 13930 13931 13932 5.7 5.2 5.4 5.2 5.0 5.1 6.1 5.6 5.9 6.6 6.1 6.4 6.2 6.0 6.1 9.8 9.0 9.4 19.2 18 8 19 1 24.8 23.2 24.1 7.1 6.8 7.0 17.2 16 6 16 9 26.1 25.7 25.9 8.7 8.0 8.4 12.5 11.5 12.0 23.0 22 2 22 6 33.4 32.6 33.0 13933 13934 13935 13936 6.6 6.0 6.2 5.3 5.3 5.3 5.6 5.4 5.5 5.8 5.4 5.7 9.4 9 0 9.1 12.0 11.6 11.7 17.2 17 2 17 2 28.5 27.6 27.9 6.5 6.9 6.8 7.9 9.7 9.4 15 4 20 0 19 6 29.4 32.5 32.3 8.9 8.4 8.6 12.4 11.5 12.0 22 0 20 7 21 3 33.6 32.0 32.8 9.6 9.2 9.6 13.6 13.3 13.6 25 1 23 9 24 9 41.2 37.3 40.4 13937 13938 7.3 6.8 7.0 11.2 10.6 10.9 15.3 14.4 14.7 5.6 5.4 5.4 7.1 7.1 7.1 10.1 10.3 10.2 26 0 17 0 24 2 17 1 24 9 17 0 41.7 27.0 40.4 27.6 40.9 27.3 13939 13940 13941 5.6 5.5 5.5 5.7 5.4 5.5 6.2 5.9 6.1 8.6 8.3 8.4 13.0 12.4 12.7 9.1 8.4 8.7 12.4 11.3 11.7 9.7 9.1 9.5 13.6 13.0 13.4 25 6 23 4 24 7 24 2 21 3 22 8 24 8 22 2 24 1 41.4 32.2 39.4 39.9 29.1 35.1 40.6 30.3 38.1 13942 13943 13944 13945 13946 5.8 5.4 5.6 9.3 8.9 9.2 13.4 13.0 13.2 24 1 23 4 23 9 36.3 35.5 36.0 7.2 6.7 6.8 12.6 11.4 11.7 18.7 16.4 17.1 36.5 35 8 36 0 57.4 54.1 55.0 5.8 5.5 5.6 7.0 6.5 6.7 10.2 9.2 9.5 22.2 21 5 21 7 37.3 34.8 35.5 5.5 5.7 5.6 9.4 9.6 9.5 13.9 14.0 13.9 25.7 25 3 25 5 39.3 39.4 39.4 6.5 6.1 6.3 10.2 9.4 9.8 15.0 14.0 14.4 30.0 27 8 28 8 44.8 42.4 43.5 13947 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 13948 5.9 5.5 5.7 8.8 8.1 8.6 12.8 11.4 12.3 13949 5.6 5.4 5.5 9.2 8.8 9.1 13.3 12.6 13.1 13950 6.0 5.5 5.8 9.2 9.0 9.1 13.4 13.3 13.4 .................................................................................................................................... 26.4 27.8 28.2 25.1 27.2 27.2 26.0 27.6 27.8 43.2 42.2 4'5.2 40.8 40.1 44.7 42.3 .41.6 45.0 _'_ MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O0 tO O PROTOCOL418-020: ORAL(GAVAGE) (APFO) IN _TS _O-GENE_TION(ONELITERPERGENE_TION) (SPONSOR'S STaY NUMBER: T-6889.6) REPRODU_IONST_YOFAMMONI_ PERFLUOR_OATE T_LE C37 (PAGE I): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F1 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITER # _TE_ DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... POSTP_T_ DAY 1 13801 13802 13803 13804 13805 13806 13807 13808 13809 5.5 5.5 5.2 5.9 5.1 5.4 5.6 5,3 5.1 7.0 6.8 7.1 6.7 7.0 7.1 6.7 7.0 5.8 5.9 6.6 6.7 5.9 6.1 7.6 6.6 7.6 8.7 5.4 8.3 7.8 7.2 6.4 7.4 6.0 7.7 8.0 5.6 6.8 6.6 MORIBUND SACRIFICED ON DAY 68 OF STaY 7.1 6.5 6.9 7.4 7.4 7.8 6.7 6.1 7.3 6.7 7.3 6.7 6.7 5.9 5.6 6.0 5.9 6.2 5.1 5.5 5.1 6.0 5.8 5.4 5.5 6.1 5.5 6.1 5.5 6.0 6.7 6.8 6.1 6.2 6.1 6.0 6.4 6.0 6.5 6.2 6.0 6.0 6.6 6.4 5.4 5.4 5.8 7.1 6.6 6.5 5.9 6.4 6.6 MS 5.7 5.4 6.8 5.8 5.8 5.2 6.4 6.7 6.1 6.6 7.1 6.6 7.0 6.6 6.9 6.4 6.2 6.2 5.8 13810 6.6 6.5 6.1 6.7 6.1 MS 5.9 6.1 6.5 5.6 5.6 6.4 5.7 5.9 FD 1 13811 13812 N_P_GNANT 6.2 6.2 6.7 6.2 6.7 6.9 6.4 6.5 67 6.2 6.2 6.3 6.6 6.7 13813 13814 75 75 8.1 60 8.1 7.5 6.7 7.2 69 76 69 6.4 57 59 59 58 6.2 5.4 5.4 5.8 62 53 61 5.8 48 5.4 5.5 5.5 4.0 13815 57 59 60 54 5.6 6.1 5.9 5.7 62 53 55 5.3 56 5.9 5.4 13816 65 64 69 62 6.7 6.3 6.3 6.0 58 62 64 5.8 63 6.0 6.2 13817 72 70 69 68 6.6 7.1 6.9 6.0 64 63 71 5.7 65 6.0 6.5 13818 59 61 63 56 6.4 6.4 6.4 6.2 55 58 55 5.1 51 5.5 5.8 5.4 13819 6.0 62 63 6 6 MD 1 5.6 5.5 5.3 5.4 57 57 5.9 49 13820 6.2 7.2 64 71 6.5 6.1 5.7 6.3 6.2 57 6.6 6.4 61 6.4 13821 5.9 5.7 54 60 6.0 5.6 5.4 5.3 5.2 5.6 5.5 4.9 58 5.0 5.4 5.3 5.0 13822 7.1 7.5 7,1 66 7.2 6.9 6.5 6.7 6.4 6.7 6.6 6.5 13823 7.5 6.9 6.7 7.0 7.0 6.7 6.4 7.0 7.2 13824 7.0 6.6 6.3 7.0 6.6 6.9 6.3 6.4 6.3 6.2 5.9 6.8 5.6 5.4 6.1 6.5 13825 6.2 6.5 6.3 6.7 6.2 6.0 6.6 5.7 5.7 6,6 6.1 7.0 6.1 6.1 6.5 13826 7.3 6.2 6.2 6.4 6.7 6.7 7.4 7.2 6.3 6.4 6.86.2 6.0 5.8 6.3 5.9 13827 6.9 6.1 6.5 6.4 6.3 6.2 6.5 5.8 7.1 6.5 6.0 6,3 3.4 6.5 5.5 6.1 13828 7.1 6.3 6.5 6.8 6.5 6.6 6.3 6.5 6.7 5.6 6.6 6.1 5.9 6.5 > 13829 6.7 6.7 6.3 6.7 6.5 7.3 6.5 6.7 6.0 5.9 6.6 6.3 6.5 13830 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 _L _IG_S _ _CO_ED IN GRAMS (G) . ME_ LITER _IG_S INCL_E ONLY WEIGHTS OF LI_ PUPS. FIRST LETER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECO_ LETTER--A-_I_, S-STILLBO_, U-_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIBALIZED), i X-SACRIFICED D_ TO SACRIFICE OF DAM NUMBERFOL_WING"SECO_ LETER"I_I_TES_EDAYPOSTP_TUM_EEVE_ OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) _O-GE_TION (APFO) IN RATS (SPONSOR'S (0_ LITER STUDY NUMBER: PER GE_TION) T-6889.6) REPRODUCTION STUDY OF AMMONI_ PERFLUOROO_OATE T_LE C37 (PAGE 2): PUP BODY _IG_S FROM BIRTH TO DAY 22 POSTP_TUM - I_IVIDUAL DATA - F1 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 .................................................................................................................................... _T/ LITER # _TE_ DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 5.9 6.3 6.6 6.5 5.9 6.9 6.3 6.4 6.1 7.0 6.6 7.0 6.6 7.5 7.1 6.6 6.8 6.2 6.3 5.8 5.8 6.1 5.2 5.2 5.5 5.6 6.1 6.4 6.6 6.7 5.6 6.2 6.4 5.2 5.5 6.8 5.7 6.5 6.0 5.8 6.0 6.1 4.2 5.8 5.5 MORIBUND SACRIFICED ON DAY 59 OF STaY 6.2 5.6 6.3 6.3 6.4 5.1 5.6 5.8 6.2 6.2 6.4 6.5 6.6 7.1 6.3 6.4 5.7 6.1 6.9 6.3 6.6 6.3 7.0 6.5 6.4 5.8 6.6 i0 6.7 6.7 5.8 5.6 5.7 6.2 5.6 6.5 ii 6.3 6.8 4.9 6.0 5.6 5.3 5.9 6.8 12 6.1 6.2 5.6 5.8 6.0 FS 5.0 6.1 13 14 15 16 POSTP_TUM DAY 1 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 17 5.4 5.6 5.9 18 5.4 5.6 13840 13841 N_ P_GNANT 5.9 5.8 5.5 6.5 5.9 58 5.9 5.6 5.7 4.9 FD 13842 5.8 6.7 6.1 5.8 6.2 60 6.7 5.7 5.7 5.5 5.7 6.0 5.8 13843 13844 6.5 6.8 6.4 6.6 7.0 57 6.4 5.8 6.0 6.2 6.0 58 5.2 6.1 5.8 6.5 5.3 5.7 5.5 5.7 5.5 5.8 6.1 6.3 5.5 5.5 5.7 13845 68 6.9 6.9 6.9 6.3 68 6.6 6.5 6.7 6.5 6.1 7.1 13846 59 6.3 6.0 6.4 5.8 62 6.3 5.i 5.8 5.9 5.8 3.5 5.9 6.1 13847 64 6.0 5.3 MS MS MS MS 5.2 5.7 6.1 5.9 6.0 FS FS FS 13848 68 6.6 6.9 6.3 6.6 6.7 7.0 6.4 6.3 6.6 7.3 7.1 6.1 6.4 6.4 5.9 13849 67 6.1 6.1 5.4 6.5 6.4 5.8 6.8 5.6 6.3 6.3 6.1 5.9 6.0 5.6 6.1 13850 59 5.9 5.9 6.0 6.1 5.8 5.0 5.4 5.5 6.0 5.5 5.7 FS 13851 N_ P_GNANT 13852 6.5 5.5 7.0 6.2 6.5 6.2 6.7 6.1 6.0 6.6 6.2 5.8 13853 4.9 5.2 5.2 5.3 5.1 4.8 5.4 5.5 5.1 5.1 4.7 4.9 37 45 5.0 4.9 4.9 13854 6.3 6.8 5.9 6.2 5.9 6.4 6.3 6.1 6.4 5.9 5.4 5.4 66 63 5.9 5.6 6.1 13855 5.8 4.8 5.8 5.7 6.2 6.0 5.6 5.9 5.9 5.1 5.4 5.6 55 54 6.1 FD 1 13856 5.8 5.8 6.0 5.7 5.5 5.4 5.2 6.3 5.4 4.7 5.0 5.5 50 44 5.4 5.5 13857 6.7 6.8 6.6 7.2 5.9 6.7 5.8 6.0 6.5 6.4 5.7 6.5 65 67 FS 13858 5.7 5.0 5.5 5.5 5.6 5.6 5.1 5.2 6.2 5.3 5.2 5.1 51 50 5.0 5.6 5.0 > 13859 6.0 6.3 5.8 6.3 6.0 6.3 5.5 5.8 5.3 5.7 6.0 5.8 57 55 5.9 13860 5.4 6.2 5.5 5.7 5.7 6.0 5.8 5.8 5.4 5.7 5.4 5.7 59 .................................................................................................................................... _L _IG_S _ _CO_ED IN GRAMS (G}. ME_ LITER _IGHTS INCL_E ONLY WEIGHTS OF LI_ PUPS. FIRST LE_ER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECO_ LE_ER -- A-_I_, S-STILLBO_, U-_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIBALIZED), X-SACRIFICED D_ TO SACRIFICE OF D_ NUMBERFOL_WING"SECO_ LE_ER"I_I_TES_EDAYPOSTP_T_ _EEVE_ OCCURRED. O PR_OL418-020: ORAL(GAVAGE) (APFO) IN _TS _O-GE_TION(O_ (S_NSOR'S STUDY LITERPERGE_TION) NUMBER: T-6889.6) REPRODU_IONSTUDYOFAMMONI_ PERFLUOR_CT_OATE T_LE C37 (PAGE 3): PUP BODY _IG_S FR_ BIRTH TO DAY 22 _STP_TUM - I_IVIDUAL DATA - F1 GE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITER # _TE_ _SAGE GRO_ III 3 MG/KG/DAY .................................................................................................................................... POSTP_TUM DAY 1 13861 13862 13863 13864 13865 13866 13867 13868 13869 6.3 5.7 5.8 6.2 6.2 6.0 6.0 6.2 5.1 5.9 P_GNANT; DID NOT DELI_R A LITER 5.7 6.5 6.0 5.7 6.3 5.8 6.1 5.9 3.5 5.3 5.5 5.6 5.8 5.7 5.7 5.5 7.1 6.8 5.9 5.8 6.4 6.4 FS 5.3 5.6 4.3 5.6 5.7 5.1 5.9 MD 1 4.9 5.4 5.7 5.8 5.4 5.6 5.5 5.1 4.8 6.2 6.1 6.5 6.3 6.7 6.8 7.4 6.5 6.1 6.2 6.1 6.2 6.2 6.4 6.1 6.1 6.2 5.9 6.5 5.7 6.1 6.2 5.8 5.1 6.3 5.6 6.5 MS 5.6 6.0 5.8 5.8 5.7 6.3 5.5 5.6 6.1 5.7 5.5 5.5 5.8 5.7 5.5 5.7 5.3 5.1 5.0 5.7 5.6 5.5 6.4 6.2 7.0 6.2 6.2 6.1 7.1 6.4 6.7 6.1 5.7 6.0 6.1 6.0 6.1 6.1 13870 7.0 7.5 7.2 6.6 6.2 6.16.5 7.0 13871 13872 13873 13874 13875 13876 13877 6.4 5.9 6.3 6.6 6.2 5.7 6.0 6.2 6.3 6.0 6.3 6.0 6.0 4.7 6.3 5.1 5.7 5.8 5.6 6.3 56 6.0 5.7 5.7 6.4 5.6 6.0 5.0 4.7 5.0 5.2 5.7 6.0 5.9 7.1 6.0 4.7 66 6.5 6.5 6.1 5.5 6.0 6.3 5.5 5.7 5.6 6.2 6.2 7.4 7.8 7.4 6.9 7.2 66 6.4 6.4 6.5 6.4 6.9 5.8 7.0 6.7 6.7 6.2 4.5 6.5 6.6 6.3 5.0 6.1 57 6.1 6.5 6.3 5.9 5.7 5.6 5.5 6.2 6.3 6.4 6.5 6.6 6.1 6.8 6.9 66 65 6.2 6.7 6.1 5.6 6.1 6.5 FS FD 1 7.3 7.1 7.2 7.3 6.5 70 71 6.0 6.1 6.5 6.7 6.7 6.2 FS 13878 13879 77 7.3 7.5 7.3 7.7 66 73 7.4 7.4 70 7.4 6.7 6.7 7.5 75 68 6.1 62 7.2 7.0 13880 66 7.4 7.4 6._ 6.6 72 67 6.9 55 6.3 6.8 6.0 6.3 13881 53 6.9 7.1 6.4 6.6 67 60 5.9 54 6.1 6.4 13882 53 5.6 6.1 5.9 5.9 6.0 55 6.1 55 5.7 4.8 5.0 6.3 5.3 5.6 4.4 13883 67 6.3 7.5 6.9 6.1 6.6 7.3 6.3 59 7.2 7.2 6.1 6.6 6.7 FD 1 13884 72 6.6 6.5 5.4 7.0 6.4 6.6 5.0 62 6.4 6.3 13885 69 8.0 7.4 13886 6.3 5.9 6.7 6.3 6.1 6.5 6.4 5.8 6.6 6.0 6.2 6.4 13887 6.4 6.4 6.5 5.9 6.8 6.1 5.9 6.3 5.7 6.0 6.1 13888 7.0 6.1 6.0 5.7 6.1 6.0 6.1 6.1 6.1 6.6 6.4 6.1 6.6 5.7 FS > 13889 5.7 5.7 5.7 5.4 5.9 5.7 5.7 5.0 5.3 5.7 5.3 5.3 5.7 5.2 4.9 5.2 13890 6.5 6.1 5.6 6.0 5.4 5.9 6.1 5.2 6.0 6.7 6.0 5.7 6.3 6.0 5.5" ........................................................................... ' _L _IG_S _ _CO_ED IN GRAMS (G). ME_ LITER _IG_S INCL_E ONLY nIGHTS OF LI_ PUPS. FIRST LETER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE _ SECO_ LETTER -- A-_I_, S-STILtOn, U'_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIBALIZED), X-SA_IFICED D_ TO SACRIFICE OF D_ NUMBER FOL_WING "SECO_ LETER" I_I_TE8 _E DAY _STP_TUM _E EVENT OCCURRED. PROTOCOL418-020: ORAL(GAVAGE) [APFO) IN _TS _O-GE_TION(O_ (SPONSOR'S STaY LITERPERGE_TION) NUMBER: T-6889.6) REPRODU_IONST_YOFAMMONI_ PERFLUOR_OATE T_LE C37 (PAGE 4): PUP BODY _IG_S FROM BIRTH TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F1 GE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 .................................................................................................................................... _T/ LITER # _TE_ _SAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... POSTP_TUM DAY 1 13891 13892 13893 13894 13895 13896 13897 13898 13899 6.7 6.9 6.9 7.2 MS 7.2 6.8 6.5 6.7 6.8 7.0 6.1 5.8 5.9 5.8 5.8 5.6 5.6 5.7 6.1 5.5 5.4 5.4 5.3 6.1 5.1 FS 7.0 6.5 6.8 6.2 6.7 6.5 7.3 5.5 5.6 5.6 6.0 6.2 6.6 6.9 6.6 6.5 7,2 5.8 6.9 6.3 6.4 7.7 5.9 4.4 6.0 6.5 6.3 6.2 6.0 5.7 6.2 5.4 5.1 5.6 4.2 5.5 5.8 6.3 5.2 5.9 5.3 5.3 5.6 5.2 5.9 7.0 7.1 6.9 7.3 6.5 6.9 6.7 6.1 6.0 6.3 5.9 7.4 7.3 7.0 6.6 6.8 6.7 7.2 6.5 5.8 6.3 6.2 6.9 6.3 6.8 6.8 6.3 6.8 6.0 5.6 6.5 5.7 6.3 5.8 5.4 6.2 5.5 5.7 6.0 6.3 6.4 6.4 6.3 6.4 6.0 6.6 6.3 6.0 5.9 5.6 5.9 13900 13901 N_ P_GNANT; _TINGN_CONFI_ED 6.4 6.0 6.4 6.4 6.5 6.7 5.7 5.7 6.2 5.6 5.3 6.2 6.2 5.9 5.9 6.3 13902 6.5 6.6 7.1 6.7 6.6 7.4 6.1 7.4 6.4 6.2 6.9 6.5 6.4 6.9 6.6 13903 6.3 6.5 6.7 7.3 6.8 7.0 6.7 7.4 7.0 6.3 5.3 6.5 7.3 6.7 13904 13905 7.4 7.1 5.9 6.8 7.2 71 65 71 6.4 6.1 6.5 6.2 6.2 6.3 . 6.7 6.0 4.6 7.3 6.0 5.1 5.6 5.0 4.8 5.7 5.3 5.1 4.9 5.3 6.3 5.6 13906 5.7 6.7 5.8 6.7 6.0 6.7 MS MS 6,3 5.6 6.2 6.0 6.5 5.3 6.4 5.8 13907 59 5.8 5.9 5.8 5.5 6.1 5.1 5.5 5.5 5.6 5.7 4.8 5.3 5.6 5.5 5.3 13908 75 69 59 8.1 13909 56 59 58 5.1 5.4 5.2 5.8 5.5 5.4 5.9 5.9 5.5 5.5 5.0 13910 53 62 63 6.7 6.7 5.5 5.7 6.0 55 6.0 6.0 5.7 5.7 6.1 5.5 13911 65 65 65 6.7 6.6 6.5 6.3 6.7 63 6.4 5.8 6.4 13912 59 67 57 51 6.0 6.5 5.7 5.5 52 5.4 5.3 5.4 5.4 5.5 13913 62 63 60 61 5.9 6.0 6.2 6.4 53 5.9 5.9 5.4 5.3 13914 60 56 53 61 5.9 5.9 6.7 5.6 63 6.0 6.2 5.5 6.0 5.4 5.7 5.2 5.3 5.7 13915 63 65 61 55 6.6 5.8 5.8 6.8 60 5.4 5.9 5.9 5.9 6.1 5.9 6.2 6,3 13916 65 6.1 6,8 64 6.1 5.6 6.1 5.8 5.7 5.9 5.8 5.9 5.4 6.3 6.1 5.8 13917 6.3 7.0 6,6 60 6.1 6.9 6.1 13918 6.6 6.3 6.4 61 6.5 6.6 5.5 6.7 6.4 6.3 5.8 6.1 5.6 5.7 13919 6.2 6.0 6.5 63 5.6 6.0 6.3 5.9 5.8 4.9 6.6 5.4 5.8 6.6 13920 7.1 6.5 6.6 6.6 4.9 6.4 6.2 5.9 5.7 .................................................................................................................................... 6.4 6.0 6.1 5.7 6.1 6.6 - 6.1 _L _IG_S _ _CO_ED IN GRAMS (G). MEW LITER _IGHTS INCL_E ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECO_ LETER -- A-_I_, S-STILtOn, U-_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIB_IZED), X-SACRIFICED D_ TO SA_IFICE OF D_ NUMBERFOL_WING"SECO_ LETER"I_ICATES_EDAY _STP_TUM_EEVE_ OCCURRED. O PROTOCOL418-020: ORAL(GAVAGE) (APFO) IN _TS _O-GE_TION(O_ (SPONSOR'S STUDY LITTERPERGENE_TION) NUMBER: T-6889.6) REPRODU_IONST_YOF _MONI_ PERFLUOR_CT_OATE T_LE C37 (PAGE 5): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F1 GE_TION PUPS .................................................................................................................................... P_ # 1 2 3 4 5 6 7 8 9 i0 II 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITER # _TE_ DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... POSTP_TUM DAY 1 13921 13922 13923 13924 13925 13926 13927 13928 13929 6.5 6.0 6.0 6.5 6.1 5.8 7.5 6.5 6.2 5.5 6.2 6.2 5.0 5.6 5.4 3.9 4.1 4.4 4.7 4.5 MD 1 MD 1 4.3 3.8 5.3 6.0 6.3 6.5 5.9 6.3 5.8 5.3 6.2 5.8 5.5 5.3 5.6 5.9 6.0 6.1 6.1 5.2 5.9 5.4 5.5 5.9 6.0 6.4 6.3 5.7 5.8 6.1 5.8 5.4 5.2 6.8 6.3 6.3 4.7 5.5 6.4 5.6 4.9 6.0 5.3 5.8 5.5 5.5 5.4 5.8 5.7 5.5 5.0 5.0 5.5 5.8 MS 4.8 5.2 5.0 5.3 5.3 5.7 6.1 5.3 5.7 6.0 5.4 6.1 5.6 5.9 5.7 5.5 4.4 5.5 5.1 6.0 5.6 5.4 6.9 6.8 6.6 7.3 6.5 7.1 6.4 6.8 6.0 7.2 6.0 5.9 6.1 6.7 6.0 6.6 NOTP_GNANT 139301 5.42 55..56 55..05 5.87 5.63 64.19 65.04 64.04 54.97 5.31 5.52 4.95 45.42 5.21 5.41 5.7 5.1 5.1 13932 6.4 5.6 6.6 6.2 6.3 6.0 5.9 5.9 5.3 5.6 5.6 5.7 5.9 5.6 13933 13934 6.6 6.2 6.6 6.9 6.7 6.5 66 6.2 5.8 5.4 5.6 5.6 6.4 5.7 5.1 5.1 5.2 5.9 5.3 54 5.4 4.8 5.5 5.2 5.4 5.6 5.4 4._ 13935 5.6 57 5.9 5.4 5.6 5.4 58 5.7 5.7 5.3 4.9 5.3 5.1 5.3 5.9 13936 6.2 59 6.1 6.4 6.0 6.4 53 61 6.1 5.4 4.2 5.4 5.8 4.9 13937 75 78 6.9 7.2 7.4 6.9 73 67 7.2 7.4 7.1 6.4 6.6 6.2 6.7 13938 58 60 5.3 5.6 5.6 5.4 52 55 5.4 5.0 5.7 5.3 5.6 5.3 5.3 5.3 13939 56 60 5.9 5.1 5.8 5.3 52 59 5.4 5.7 4.7 5.3 5.9 5.5 FS 13940 57 52 56 6.0 5.9 5.6 6.2 52 4.8 5.4 5.7 5.3 5.8 5.2 5.5 13941 52 67 56 6.3 6.2 6.3 7.0 61 6.6 6.3 5.9 6.0 5.4 FS 13942 13943 60 58 56 5.0 6.2 6.2 5.7 61 5.2 5.6 6.1 5.4 5.4 5.3 5.6 5.3 77 66 61 7.0 7.0 5.9 7.7 13944 13945 58 56 60 6.0 5.5 5.5 5.4 5.6 6.1 5.5 5.2 5.5 55 56 58 5.5 5.5 5.4 5.3 5.6 5.4 5.4 5.8 5.8 5.7 5.6 13946 13947 67 66 64 6.4 6.2 6.0 5.9 6.1 6,1 8.4 6.2 SA_IFICED D_ TO NO S_VIVING PUPS ON DAY 1 OF _ATION 13948 13949 6.6 5.2 6.1 6.1 5.6 6.3 5.7 5.3 5,7 5.4 5.6 5.3 5.5 5.4 5.2 5.5 6.3 5.8 5.4 5.2 6.0 5.3 5.3 5.4 5.6 13950 5.8 6.2 6.2 6.0 5.8 5.7 MS 5.3 5.5 5.2 6.0 5.6 FS FS .................................................................................................................................... _L _IG_S _ _CO_ED IN GRAMS (G). MEW LITER NIGHTS INCL_E ONLY WEIGHTS OF LIVE PUPS. FIRST LE_ER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECO_ LE_ER -- A-_I_, S-STILLBO_, U-_CERTAIN, D-DIED, M-MISSING (PRESSED CANNIBALIZED), X-SACRIFICED D_ TO SACRIFICE OF D_ NUMBERFOLLOWING"SECO_ LE_ER"I_ICATES_EDAYPOSTP_TIR4THEE_ OCCURRED. t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 6): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 5 13801 13802 13803 13804 13805 13806 13807 13808 13809 13810 9.5 8.1 9.2 8.4 7.9 8.5 9.2 8.2 8.5 12.0 12.4 12.5 12.2 12.2 12.2 11.4 11.6 11.9 10.7 11.9 11.6 10.9 10.1 11.3 9.6 9.4 11.8 11.4 14.1 10.7 12.1 7.1 10.7 12.1 12.0 9.3 11.8 11.8 10.5 MORIBUND SACRIFICED ON DAY 68 OF STUDY 10.2 10.3 11.7 10.1 10.6 10.8 9.8 i0.0 10.1 9.9 11.1 9.0 10.1 7.7 8.7 8.2 8.7 8.3 MM 3 8.6 8.4 8.1 8.4 7.7 8.4 7.6 8.0 8.4 8.2 8.5 9.5 9.4 9.2 9.0 9.3 9.0 9.2 8.5 9.6 8.6 8.4 7.9 8.9 8.1 9.8 8.6 9.2 10.7 10.5 9.4 10.4 10.6 9.3 MS 9.8 10.7 9.6 10.1 9.0 10.1 9.7 10.2 9.8 10.6 9.6 10.4 10.2 9.0 9.6 9.3 8.6 9.3 9.6 10.3 10.3 9.9 8.9 MD 3 MS 8.4 9.7 9.2 9.2 10.5 9.6 9.6 9.0 FD 1 13811 13812 13813 NOT 10.6 12.6 PREGNANT 9.6 9.1 12.4 11.5 10.7 11.7 10.7 9.6 i0.i 10.4 10.6 10.9 11.2 11.6 11.6 12.7 10.6 11.3 13814 7.8 8.3 7.6 8.4 7.9 8.2 8.1 9.0 8.0 8.7 13815 8.7 8.4 8.6 7.9 7.6 8.3 7.6 8.3 8.4 8.2 13816 9.0 9.1 8.5 9.4 8.6 8.9 8.5 8.0 8.9 8.1 13817 9.3 9.2 9.3 9.7 9.4 8.4 9.7 9.3 8.6 9.0 13818 7.3 7.8 7.3 7.9 7.8 7.6 6.4 7.3 7.1 7.2 13819 10.4 9.4 9.1 9.9 MD 1 8.8 9.2 9.2 7.5 8.3 13820 9.3 8.6 9.9 8.4 8.7 9.5 8.5 8.4 7.5 9.7 13821 10.7 9.7 9.6 8.9 8.8 8.9 9.9 9.5 9.0 8.9 13822 11.6 12.1 12.5 11.7 11.4 11.3 11.1 11.6 11.8 10.6 13823 13.1 13 3 12.0 12.6 13.3 12,4 12.8 12.7 12.8 13824 10.2 96 9.8 9.9 9.5 9,2 8.5 11.0 8.9 90 13825 8.3 79 9.0 7.6 8.2 9.0 8.6 7.3 8.3 76 13826 9.9 8 5 10.6 10.2 10.2 10,1 9.8 9.8 9.2 89 13827 9.8 89 9.7 9.5 10.4 9.4 9.4 9.7 MM 2 94 13828 9.1 80 8.7 8.9 8.6 9.1 8.5 8,4 7.9 83 13829 10.1 89 9.7 10.3 9.8 10.2 9.9 10.8 9.0 91 13830 8.4 7.7 7.9 8.3 7.4 8.3 7.8 MS 8.3 7.7 .................................................................................................................................... 10.4 11.7 6.6 7.7 8.2 8.6 6.2 6.8 8.3 9.5 11.2 86 66 84 91 85 91 79 9.9 12.3 7.2 8.3 8.2 8,8 6.8 8.0 8,8 8.6 10.9 9.2 79 90 91 72 10 3 72 i0.i 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 10.9 7.2 _.5 8.9 8.0 7.2 8.3 8.8 9.0 8.6 9.5 9.3 8.7 8.0 7.7 7.4 8.2 FD 2 FM 4 8.6 9.2 9.1 9.4 8.8 6.7 FM 2 UU FD 2 9.7 8.5 7.8 8.4 8.9 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O0 X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 7) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 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 MORIBUND SACRIFICED ON 8.5 9.2 8.5 8.0 9.9 9.5 8.8 8.3 10.4 10.3 9.3 8.7 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 DAY 59 OF STUDY 8.1 8.0 8.0 8.9 8.9 9.4 10.0 7.4 9.0 8.8 9.2 9.1 9.2 8.5 8.0 8.2 10.0 9.2 10.4 9.3 8.7 8.3 7.0 8.5 10.2 10 9.8 9.6 8.1 9.2 6.9 7.2 8.8 9.9 13840 NOT PREGNANT 11 9.6 9.3 9.1 9.8 8.0 8.9 8.7 10.8 12 10.5 10.7 7.6 9.8 8.3 FS 8.4 10.8 13 14 15 16 POSTPARTUM DAY 5 8.6 10.1 9.1 9.1 9.1 9.4 9.0 7.5 9.1 8.3 FM 3 8.0 8.1 8.0 6.0 9.0 8.0 8.2 17 18 8.6 FD 3 FD 2 8.7 FD 4 138412 13843 13844 8.7 107..49 96.9 9.17 89..98 97.79 97.57 98.04 78.84 97,.4 F7D.8 U7U.7 9.1 7.9 7.6 8.3 8.0 8.4 7.2 6.5 6.8 7,4 8.1 7.3 7.9 6.9 7.3 8.7 8.5 8.3 8.2 7.0 7.3 8.0 6.2 5.9 7.0 6,7 7.0 8.0 13845 13846 13847 13848 13849 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 10.6 9.6 9.2 8.5 10.2 9.9 10.0 i0.0 9.1 10.1 9.9 9.8 8.9 10.1 8.9 8.3 9.5 9.6 9.5 9.3 8.5 8.7 8.5 8.3 8.5 FM 2 10.6 9.9 10.7 MS MS MS MS 10.7 10,1 11.1 9.6 9,6 FS FS FS 9.8 10.2 9.5 8.5 8.6 8.8 10.2 8.6 9.2 9.1 10.2 10.4 9.1 8.8 9.0 9.3 8.9 8.2 8.4 7.7 7.8 8.3 8.3 8.9 8.3 8.5 7.3 7.5 7.9 8.1 7.6 7.5 8.9 8.1 8.4 8.5 8.7 8.6 7.6 8.4 7.6 8.1 8.1 9,1 FS NOT PREGNANT 8.5 9.4 9.3 9.8 10.2 10.0 8.3 9,0 9.7 9.4 9,4 8.4 7.8 8.5 7.7 8.1 7.2 7.0 85 8.5 8.0 7.1 8.2 7.3 7.9 7.9 7.2 7.2 7.4 8.5 9.0 9.4 8.7 9.5 9.4 10 1 9.3 10.1 9,2 9.7 9.8 9.1 9.6 8.8 8.0 8.7 10.0 9.5 10.2 9.7 10.1 7.6 9 1 10.5 10.2 9.7 9.2 9.7 8.4 9.9 FD 5 FD 1 8.7 8.6 9.0 9.7 9.3 9.7 8 9 10.0 8.7 9.1 7.3 8.7 7.0 8.5 7.5 8.9 9.7 10.7 10.3 10.3 10.0 9.4 9 8 10.0 9.3 i0.0 I0.0 9.9 10.2 9.2 FS 7.4 7.9 7.5 8.6 8.3 _.0 80 7.0 7.3 8.3 7.8 7.6 7.6 7.8 7.4 6,9 6,8 9.0 8.2 8.8 8.8 8.1 8.4 86 8.3 7.2 8.5 7.7 8.9 8.4 8.2 8,7 8.9 9.1 8.0 8.2 8.3 8.7 77 9.0 8.7 8.0 8.7 8.5 8.5 ............................................................................................ '-....................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS, FIRST SECOND NUMBER LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, X-SACRIFICED DUE TO SACRIFICE OF DAM FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM M-MISSING (PRESUMED THE EVENT OCCURRED. CANNIBALIZED), [J_ _._4h" O0 _,_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 8): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 5 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 13871 13872 10.5 10.2 10.6 10.4 8.3 9.4 8.7 10.3 7.7 10.4 PREGNANT; DID NOT DELIVER A LITTER 9.4 9.0 9.2 9.1 10.0 9.7 8.8 9.5 9.4 9.0 8.4 8.8 9.5 8.1 9.5 FM 3 10.7 12.4 12.2 10.4 12.1 10.5 FS 9.2 9.2 7.9 8.6 6.5 8.7 8.6 MD 1 9.4 8.8 9.3 8.2 8.8 8.1 8.8 7.7 7.3 10.2 8.1 8.1 9.3 9.2 9.0 8.8 8.4 8.9 8.7 8.6 8.1 8.3 8.4 8.1 8.3 8.9 8.8 6.1 7.4 6.9 7.1 7.3 6.9 7.1 4.5 5.6 MS 7.1 6.5 6.5 7.2 7.3 6.5 9.9 8.3 8.9 9.8 9.3 8.6 i0.I 8.9 8.5 8.7 8.4 8.4 8.4 8.5 8.4 9.3 7.6 8.7 8.5 8.7 9.3 7.3 8.3 8.3 8.6 7.7 8.5 8.2 8.6 7.5 7.5 FD 4 9.3 9.2 8.4 8.5 7.5 10.4 10.0 10.0 8.8 7.5 7.4 8.0 MD 3 8.6 79 8.0 7.9 7.2 7.7 7.3 4.8 7.8 FD 4 7.6 7.6 7.9 7.4 8.0 76 77 8.0 7.6 8.7 7.9 7.4 7.6 7.7 6.9 6.8 6.7 13873 13874 8.9 10.8 5.7 12.4 9.4 11.5 9.1 11.9 10.2 11.7 90 i0 3 13875 i0.I 8.9 8.7 9.0 9.3 96 13876 I0.0 10.4 i0.i 10.3 10.0 10 6 13877 9.6 9.3 10.6 9.8 10.3 94 13878 10.5 9.3 II.i 11.3 10.4 ii 3 13879 11.2 11.5 12.2 11 9 11.5 11.6 13880 12.1 12 3 9.7 13 0 12.2 12.5 13881 11.6 11 5 11.4 8 9 i0.4 11.9 13882 9.1 86 9.8 99 9.2 9.5 13883 9.6 11 5 10.6 11 2 9.9 9.3 13884 10.3 10 3 9.8 10 6 9.9 7.9 13885 14.3 13 5 13.7 13886 10.0 9.0 9.1 9.4 8.8 9.5 13887 11.0 11.0 10.7 11.5 11.1 11.2 13888 13889 9.0 9.5 9.0 9.5 8.5 8.6 7.8 8.9 9.3 8.7 8.6 8.1 13890 9.5 10.1 8.4 9.7 9.0 9.5 ........................................................................................... 73 85 90 10 3 93 92 11.3 11.7 10.5 10.0 10.2 9.1 8.8 10.4 6.7 9.6 8.3 10.5 11.8 11.1 9.9 9.9 9.8 10.0 9.7 10.9 8.3 8.7 8.8 9.5 11.8 9.2 9.1 9.0 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 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 8.7 i0.i 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 8.6 11.1 9.3 9.8 7.4 11.2 8.1 10.9 9.9 8.7 7.9 9.9 8.4 9.9 7.1 10.0 8.6 12.8 10.2 8.9 8.3 7.8 5.9 9.1 10.5 9.2 FS FS 9.4 10.8 8.5 FD 1 9.5 10.3 7.5 FM 4 FD 2 7.3 8.1 FD 3 9.9 FD 1 8.8 FS 7.2 7.6 8.3 9.7 9.1 . _"........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [J_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE _t_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O_ X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. [Q_) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 9) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 I0.0 9.4 10.8 10.8 9.4 10.6 11.3 8.8 10.1 NOT 11.5 11.2 11.6 MS 10.9 8.8 8.6 9.2 9.4 9.1 10.4 9,4 9.9 11.1 11.2 7.6 8.9 8.0 8.0 8.6 9.3 7.9 6.9 6.6 8.7 9.6 10.7 10.6 11.1 9.2 9.4 10.2 9.8 9.2 10.9 9.2 9.8 9.9 8.4 7.6 9.6 10.6 10.1 10.1 9.4 PREGNANT; MATING NOT CONFIRMED 10.8 8.7 9.8 MM 4 7.5 9.5 10.1 8.7 8.7 11.3 9.0 9.6 8.2 8.1 9.2 10.2 8.5 9.3 10.2 9.3 9.9 8.6 9.8 10.3 9.3 8.8 8.8 10.2 8.4 9.6 7.4 5.1 10.5 10.1 8.9 10.8 11 11.2 8.9 9.1 8.5 7.2 9.7 8.6 8.1 9.4 12 8.5 11.1 8.2 8.0 10.4 8.5 7.7 13 14 15 16 17 18 POSTPARTUM DAY 5 8.2 7.9 8.6 FS 9.1 9.0 10.9 7.5 4.9 8.0 7.2 8.6 8.6 7.7 8.9 8.2 FD 3 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 7.8 10.1 10.3 i0 0 11 3 10 8 91 11 7 87 85 93 82 9.6 7.9 8.1 9.7 11.3 9.2 i0 1 10 2 88 10 7 87 10 8 93 7.8 10.2 8.8 8.0 9.1 11.6 i0 5 66 93 85 12 4 82 10 2 9.9 9.3 10.0 8.2 7.8 10.5 10.4 i0.0 9.7 10.7 8.3 10.0 9.0 10.6 9.7 8.8 10.8 9.0 8.0 9.7 10.6 10,7 11.0 8.8 9.2 7.7 9.7 11.8 9.6 8.5 MD 3 9.0 7.1 10.5 11.2 9.0 9.7 MS 8.5 9.0 9,3 9.7 9.5 10.9 8.8 8.9 10.7 10.0 8.2 10.5 8.8 8.4 8.5 10.2 9.1 10.5 9.8 7.5 8.7 8.2 I0.0 9.2 MS 6.9 8.1 10.4 9.6 7.8 11.6 9.0 7.1 9.0 10.8 9.6 8.4 9.9 8.1 7.9 9.8 9.5 8.3 10.6 8.1 7.2 9.5 11.4 9.1 11.0 10.8 9.2 6.8 9.5 11.7 9.2 8.1 9.5 7.7 6.0 9.5 10.6 9.2 9.1 10.0 8.6 7.5 9.8 10.4 9.6 8.6 9.3 8.6 91 99 96 85 10 3 84 86 10 3 96 86 87 83 89 10 7 91 75 86 92 8.8 10.4 6.8 8.7 8.9 6.3 9.2 10.3 8.6 7.7 7.9 8.2 8.9 11.2 8.3 8.1 7.4 6.9 8.6 9.0 9.7 8.6 10.2 8.6 7.7 9.2 8.9 7.9 8.8 FM 3 13915 13916 9.6 8.3 9.0 9.2 9.2 8.2 9.2 9.5 8.2 9.1 8.8 84 9.1 8.6 9.1 8.6 8.4 9.4 8.3 8.9 7.9 9.4 9.3 8.7 8.2 8.3 8.5 7.4 8.1 7.4 7.6 7.4 8.7 13917 9.7 10.2 10.0 9.5 10.2 8.2 8.8 13918 9.6 10.3 11.3 9.6 10.6 10.3 10.3 9.9 8.8 9.7 9.3 8.7 i0.i 9.7 13919 9.3 9.7 9.5 9.9 9.2 10.3 9.4 9.4 9.1 7.9 8.2 7.5 8.9 8.8 13920 7.3 9.2 9.0 8.3 8.9 8.9 9.7 8.7 8.2 8.8 8.6 8.2 8.8 7,0 8.0 .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 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O0 X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 5 13921 13922 8.4 71 92 93 9.6 9.7 9.0 8.9 7.3 7.3 8.5 7.9 5.4 8.2 8.3 70 58 68 7 3 MM 2 MD 1 MD 1 FM 2 FM 2 13923 13924 13925 13926 13927 13928 88 76 82 81 8.4 9.2 8.8 7.6 8.0 86 7.5 8.2 8.7 9.1 89 90 90 87 7.7 7.4 7.9 9.0 8.4 87 8.6 8.1 8.5 6.4 7.8 7.8 8.8 87 67 87 71 7.7 8.7 7.3 7.6 7.1 69 8.1 7.1 8.1 74 69 76 73 7.7 6.3 8.0 7.4 MS 74 6.4 8.0 6.9 7.1 7.2 91 94 86 91 8.7 8.2 9.0 8.6 8.4 92 8.9 5.4 8.0 7.7 7.8 9.0 85 9 1 i0 4 90 8.3 MD 3 8.6 9.3 9.0 80 7.6 7.5 9.4 8.9 7.6 8.7 13929 NOT PREGNANT 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 7.1 6.1 6.9 7.1 8.3 8.7 9.3 10.1 6.2 6.8 8.7 8.8 10.6 8.5 10.9 11.5 7.0 6.5 7.4 8.5 8.8 10,3 9.4 10.6 9.0 12,1 9.5 13.1 6.9 6.6 9,1 9.5 11.2 9.6 SACRIFICED 6.7 7.2 6.6 4.8 6.6 6.1 8.2 8.9 8.5 9.8 8.2 9.6 MM 4 7.4 7.0 9.3 8.9 8.9 10.2 10.0 10.1 11.4 11.1 11.2 7.6 7.4 6.7 8.9 8.9 8.4 8.8 8.9 8.9 10.6 8.6 9.9 9.7 11.7 9.8 13.8 10.1 9.2 7.6 MM 5 5.3 9.8 9.3 9.5 i0.0 9.9 10.4 DUE TO NO SURVIVING 8.0 5.3 8.7 9.3 6.5 9.2 9.9 11.1 7.0 8.6 9.7 9.7 9.8 11.9 6.6 9.4 9.4 PUPS 6.5 5.2 6.5 3.9 6.5 6.7 5.9 6.3 9.2 8.8 7.6 7.9 8.2 8.3 8.7 9.8 7.2 6.2 7.5 5.4 8.4 6.6 8.2 8.4 10.3 10.0 10.7 7.5 9.6 10.7 11.5 11.6 7.6 MD 2 6.8 7.6 9.5 7.8 9.0 8.3 9.5 9.1 8.0 8.1 9.7 9.7 8.5 7.9 9.4 6.8 10.1 9.0 10.3 6.3 5.7 7.5 6.2 9.2 9.6 9.6 9.8 9.6 9.0 9.2 9.5 ON DAY 1 OF LACTATION 6.7 6.1 8.1 9.1 7.2 8.7 8.4 10.4 6.7 8.2 9.1 9.5 8.9 7.5 9.2 9.6 6.5 5.9 61 5.7 6.8 6.1 6.6 5.9 FM 2 79 8.1 8.4 91 9.3 62 7.6 7.5 7.3 88 9.0 8.3 9.3 79 9.5 i0,i 9.7 10.6 10.6 11.0 7.0 7.7 6.8 7.1 7.0 8.9 6.8 9.2 FS 7.0 8.3 8.9 8.1 9.4 9.6 FS 8.6 8.5 9.6 9.1 8.7 7.2 9.3 9.7 9.8 6.1 FM 5 13948 9.6 8.3 8.5 8.7 9.6 9.2 8.1 7.6 8.3 7.7 8.7 FM 3 13949 9.0 I0.0 9.6 8.9 8.6 9.1 9.3 9.1 9.6 8.6 8.8 9.1 8.8 13950 10.2 8.2 9.5 9.6 8.9 8.7 MS i0.0 8.6 8.7 8.8 FD 2 FS FS _'_ ............................................................................................ '........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [/) FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O0 X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 11) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 8 13801 13802 13803 13804 13805 13806 13807 13808 13809 13.1 13.4 12.9 13.2 17.2 18.1 18.2 17.8 16.3 15.3 16.0 19.9 MORIBUND SACRIFICED ON 16.5 16.0 14.9 14.7 12.6 11.3 10.6 11.7 13.0 12.6 10.9 13.0 14.2 15.2 15.0 15.7 15.1 13.9 14.0 14.2 13.2 12.3 12.8 17.5 16.1 17.1 13.3 13.9 17.2 DAY 68 OF STUDY 14.7 15.4 13.7 13.1 MM 3 12.3 11.6 11.6 12.9 13.4 13.4 MS 13.2 12.4 14.8 14.2 17.7 16.8 13.2 12.2 12.0 14.7 14.6 13.3 17.6 12.8 16.1 FM 7 17.7 14.9 13 8 12 3 11 7 13 4 13 3 12.8 11.8 13.8 13.9 13.8 14.4 12.0 13.3 14.0 12.9 18.0 17.0 15.0 11.7 10.8 15.0 11.7 15.3 16.0 15.1 11.6 11.8 14.7 13.4 16.2 14.2 11.8 10.6 14.1 12.0 12.6 16.0 13.7 11.2 12.7 12.7 13810 14.2 15.3 13.7 15.5 MD 3 MS 14.8 12.3 14 2 13.7 14.4 15.4 14.0 13.0 FD 1 13811 13812 13813 NOT 16.0 17.5 PREGNANT 15 9 14.6 18 1 17.4 15.4 14.6 15.8 18.5 14.6 17.0 14.1 16.9 16.5 15.2 15 1 16 5 15.0 18.4 15.5 17.0 14.8 18.0 14.3 UU 15.6 13814 13815 11.3 12.0 i0 8 i0 0 i0 9 ii 6 11.5 11.4 9.1 11.5 12.1 10.9 10.5 11.3 12.2 10.4 i0 8 i0 4 11.2 12 1 11.7 11.4 11.2 9.2 11.7 10.3 8.0 10.3 10.6 11.3 ii.0 FM 2 13816 13817 12.6 11 9 11 2 11.2 10.8 10.6 11.7 10.0 10 1 11 3 11 3 10.6 11.8 11.0 10.7 UU 12.6 12 9 13 1 12.5 13.0 12.9 11.8 12.0 12 5 i0 8 12 6 12.3 11.9 12.0 FD 2 13818 10.6 11 2 9 1 11.3 12.0 11.4 10.9 11.2 9 0 10 5 11 4 8.6 9.6 9.7 FM 4 FD 2 13819 13.1 14 2 14 0 13.2 MD 1 12.0 12.9 10.7 13 4 13 8 i0 4 13.4 12.0 13820 14.5 13 4 11 9 13.4 14.1 13.0 13.8 13.1 11 2 12 0 12 3 11.5 11.5 10.3 13821 13.0 13 8 14 4 15.5 14.2 12.9 15.2 12.9 13 9 12 8 12 1 13.9 13.6 12.8 12.8 12.0 13.4 13822 MX 8 MX 8 MX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 13823 18.4 19.3 19.3 18.0 18.8 18.6 18.4 19.9 18.0 13824 12.9 14.2 14.9 13.7 13.2 10.8 13.5 12.2 13.1 12.3 12.9 13.1 13.4 11.4 13.6 12.6 13825 12.0 11.9 12.6 11.8 12.0 12.1 11.8 12.3 13.1 11.6 11.4 13.1 10.8 9.9 12.5 13826 13.3 13.6 9.7 13.8 14.6 13.4 13.3 11.6 11.2 12.9 13.4 12.2 12.5 12.2 11.4 12.0 13827 14.5 13.3 13.7 13.9 14.6 15.2 13.6 13.5 MM 2 12.7 14.1 12.7 13.1 12.6 13.6 13.5 13828 13829 13.0 11.8 12.8 10.3 13.0 11.8 12.9 12.0 Ii.0 12.2 12.8 12.6 12.7 11.5 9.4 12.7 10.5 10.7 12.3 10.9 12.0 10.6 13.5 12.1 12.6 11.1 12.3 13830 11.6 12.1 ii.i 12.5 10.4 10.4 11.9 MS 12.2 11.7 ii.I ii.i ii.i 12.1 _'_ ........................................................................................... '-........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE _t_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED}, OO X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. bJ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 12): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 .... _T/ ............................................................................................................................ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13.2 13.8 12.9 12.9 13.4 13.2 13.1 14.5 13.8 15,2 14.0 14,5 12.7 14.6 12.0 14.2 14.0 13.5 12.9 13.6 14.1 13.0 11.8 13.1 12.5 15.1 11.6 14.1 12.3 14,3 12.7 12.5 15.2 14.7 13.0 13.6 14.4 14.4 13.2 14.1 13835 13836 12.6 12.7 12.9 13.4 13.2 12.5 11.6 MORIBUND SACRIFICED ON DAY 59 OF STUDY 12.8 12.8 11.7 13837 13.4 11.8 13.1 12.2 12.6 11.8 10.7 12.0 10.9 13.1 13838 13839 14.8 13.9 11.9 16.2 13,0 16,4 13.6 15.0 12.8 15.7 13,2 15.9 13.9 14.7 12.5 15.4 12.6 14.4 12.4 12.0 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 13850 13851 NOT 12 7 14 1 11 1 13 8 14 0 12 4 16 1 14 7 12 4 12 4 NOT PREGNANT 13 7 14.1 12 6 12.0 11 7 10,4 i0 9 14 5 12 3 11.9 13 2 12.3 16 0 15.0 14 8 13.4 11 6 12.0 11 8 12.1 PREGNANT 11.8 14.3 11.0 I0 " 5 13.9 12.1 MS 14.0 11.2 11.7 11.4 11.7 11.9 10.7 13.1 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 13.1 12.3 10.8 13 2 13 3 I0 3 i0 I 14 4 13 3 16 1 12 2 12 6 11 1 13 1 11 1 87 Ii 5 14 3 12 7 15 5 13 7 I0 1 11 0 13.0 12 1 i0 0 97 14 6 12 5 15 9 12 9 11 0 11 9 13852 13853 13854 13855 13856 13857 13 8 12 5 13 5 14 9 12 8 13 9 13 6 11 3 14 4 14 6 13 1 15 1 13.6 10.8 13.2 15.6 14.6 14,8 13.2 10.6 14.7 12.1 12.5 15.7 13.2 10.8 13.5 14.0 14.6 13.3 14.7 11.5 13,5 14,5 12,7 13.9 12.2 11.2 13.2 14.8 13.3 13.6 12.4 9.9 13.3 14.9 12.3 14.4 12.9 9.7 11.3 13.7 12.7 14.1 13 5 12 4 14 8 15 8 10 2 15 4 11.1 13.1 12.3 14.7 13.7 11.9 11.8 15.5 FD 10.5 10.2 14.3 11.2 14.0 14.0 11.0 9.6 14.1 10.1 12.8 15.2 12.4 16.3 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 POSTPARTUM DAY 8 12.1 14.3 11.4 13.7 11.4 13.8 11.7 13.0 12.8 13.0 11.2 FM 3 12.2 12.7 11.1 FD 3 FD 2 12.0 12.1 11.8 13.0 11.1 FD 4 12.2 9.7 12.0 FS 12.5 11.2 FS 12.4 11.3 FM 2 FS 13.6 10.5 FS 13.4 11.5 8.6 13.6 10.1 FD 8 10.3 12.9 12.7 10.5 14.0 9.9 10.5 13.9 12.4 13.7 10.5 11.7 12.2 12.3 14,2 12.0 " FD 5 FD 1 10.7 12.5 FS 13858 i0 2 11 7 10,4 11.0 9.5 11.7 11.1 13.4 11.2 11 2 12.3 11.1 10.5 10.9 ii.0 11.8 10.8 _> 13859 13 3 13 2 12,6 11.6 12.4 12,7 11.7 12.7 12.1 9 6 12.6 12.2 9.6 13.3 12.7 13860 12 3 12 0 12.0 11.9 11.9 12,3 12.2 Ii,i 11.7 13 2 ii.i 12.6 12.0 _'_ ............................................................................................ . ...................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G}. MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [29 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM _D NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APPO) _I_ RATS ISPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C20 (PAGE 2): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - P GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 i0 30 DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 27 29 29 29 SURVIVING PUPS/LITTER a DAY 1b MEANS.D. 14.2 _ 2.2 14.2 + 2.6 13.4 + 3,6 13.8 3.0 13.4 3.3 DAY 5 MEAN+S.D. 13.8 _ 2.1 13.9 + 2.5 13.0 f 3.4 13.6 + 2.8 12.9 3.7 DAY 8 DAY 15 _'D DAY 22 MEANS.D. MEANS.D. MEANS.D. 13.9 _ 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 12.9 3.4 12.8 3.3 12.8 + 3.4 13.6 2.8 13.4 _ 2.8 13.4 + 2.8 12.6 + 3.6 12.5 + 3.6 12.5 + 3.6 O0 PERCENT MALE PUPS PER NUMBER OF PUPS SEXED DAY 1 b MEANiS.D. 46.9 f 13.2 52.2 + 13.6 48.6 + 17.5 47.1 + 10.2 49.9 16.9 DAY 5 DAY 8 DAY 15 DAY 22 MEANfS.D. MEAN+S.D. MEANS.D. MEANS.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 47.1 10.2 47.3 + 10.1 47.4 i0.i 47.4 10.1 52.4 17.2 [ 28]d 52.4 17.3 [ 28] d 52.2 + 17.8 [ 28]d 52.2 17.8 [ 28]d .................................................................................................................................... DAY = DAY POSTPARTUM ] = NUMBER OF VALUES AVERAGED a. Average number of llve pups per litter, including litters with no surviving pups. b. Includes C. Excludes pups born alive, litters in which found dead on day 1 postpartum. the dam was sacrificed. d. Excludes litter 13947, which had no surviving pups on day 1 of lactation. O_ _0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 13} : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 8 .................................................................................................................................... 13861 15.3 12.1 12.2 15.7 14.0 15.4 14.4 14.8 15.2 10.6 13862 PREGNANT; DID NOT DELIVER A LITTER 13863 13864 14.5 16.8 12.8 19.8 13.7 17.3 14.2 19.4 14.0 19.3 13.4 17.7 13.3 FS 14.0 13.8 14.6 12.0 13.4 12.7 14.7 13.8 FM 3 13865 13866 13867 13868 13869 13870 9.5 9.7 11.1 13.8 10.4 13.3 11.8 10.6 10.7 14.3 11.1 13.0 11.8 9.9 10.1 13.8 11.8 14.6 12.4 12.7 8.0 14.6 11.1 12.4 12.2 10.8 9.4 11.9 11.0 15.1 12.3 11.7 9.1 12.3 9.8 14 5 10.6 i0 0 90 14 0 i0 7 11 5 MD 1 11.3 MD 7 13.4 10.2 10.6 11.7 11.1 MD 6 12.5 10.8 10.9 11.9 MS 13.3 10.8 12.5 10.6 10.4 12.1 9.8 13.0 10.8 9.9 13.1 10.8 11.9 8.8 9.9 12.9 11.3 11.7 9.2 9.3 12.8 10.6 9.6 11.1 8.7 12.9 10.7 13.0 11.2 FD 6 12.2 FD 4 10.5 9.3 FD 8 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 13.1 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 11.4 I0.0 11.5 17.5 12.3 15.0 12.9 15.6 18.0 16.6 15.8 14.4 15.9 12.7 18.7 13.8 16.0 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 11.9 Ii.I 9.9 16.3 14.4 15.3 15.3 15.4 16.1 16.2 16.7 15.1 14.2 12.8 MD 3 11.5 13.5 18.0 12.6 15.9 12.9 15.0 15.3 16.2 14.7 15.1 12.3 12.5 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 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 11.5 ii.i 8.8 ii " 9 8.9 14.7 13.1 16.4 15.6 15.1 14.9 12.7 14.4 12.3 Ii.i 11.6 11.3 15.9 13.0 14.7 11.6 15.0 16.1 14.3 14.4 14.9 12.9 12.6 14.7 15.3 13.9 15.6 13.9 16.0 13.4 15.7 13.2 16.9 14.4 16.3 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 12.0 9.1 13.5 13.4 11.0 16.4 10.8 12.0 10.7 15.1 15.7 14.1 15.5 12.5 16.8 15.0 14.7 11.8 16.0 6.9 15.2 15.9 16.1 14.2 14.6 11.1 11.7 10.6 12.8 15.4 11.2 14.8 13.0 14.9 15.1 14.8 FM 7 11.2 13.1 14.3 13.9 FS FS FD 4 11.3 13.6 14.6 11.8 FD 1 11.1 13.5 14.8 11.0 8.7 FM 4 FD 2 12.1 14.1 10.7 FD 1 FD 3 13888 10.9 11.6 11.1 10.7 11.5 10.7 10.9 10.6 10.3 10.5 11.2 10.8 10.7 10.7 FS > 13889 12.3 13.4 13.2 11.3 12.5 11.5 12.5 13.3 12.1 12.7 11.6 12.0 11.1 11.7 12.5 11.8 13890 13.6 13.4 13.5 10.9 12.7 12.9 14.0 12.3 13.2 12.5 13.1 13.8 13.2 13.6 7.4 - .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [2D FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND L_-I_iER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O0 X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. h.) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 14): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 15.2 13.8 16.3 16.3 MS 15.4 15.9 14.3 16.1 14.5 13892 12.8 13.1 12.3 13.9 13.0 13.7 12.2 11.7 11.9 11.1 13893 14.5 15.5 15.4 16.5 14.3 15.1 13.0 13.9 13.2 13.1 13894 15.1 12.5 11.1 13.0 11.5 12.5 MM 4 11.1 10.9 11.9 13895 13896 12.8 13.3 10.2 15.6 14.6 14.5 8.3 15.4 11.7 15.4 13.7 13.1 13.9 15.2 11.3 14.1 12.4 14.6 9.2 14.3 13897 15.6 14.1 14.7 14.3 14.4 12.9 13.2 13.2 13.7 15.0 13898 13899 12.1 13.5 13.7 14.3 10.3 13.4 11.8 13.5 11.8 13.6 13.4 12.6 11.0 13.4 11.8 12.1 11.8 12.6 9.9 12.7 15.5 13.6 15.7 12.1 13.9 14.0 14.6 11.0 12.6 12.7 13.3 11.8 12.3 14.4 15.1 11.6 POSTPARTUM DAY 8 12.0 13.9 12.5 FS 15.0 12.5 14.5 12.8 7.1 13.4 12.1 11.9 10.1 9.8 10.7 11.4 FD 3 13900 NOT PREGNANT; MATING NOT CONFIRMED 13901 13902 13903 13904 13905 13906 13907 13908 10.7 13.6 15.2 12.5 16.1 14.3 10.8 16.4 9.9 13.6 16.0 Ii.0 9.8 16.4 11.8 17.0 10.7 12.7 14.9 10.2 16.8 15.0 13.6 14.5 10.3 14.4 12.3 12.6 13.3 15.8 12.2 18.2 10.3 14.6 15.3 11.3 15.5 14.0 13.4 11.3 14.0 11.1 7.9 12.5 MD 3 13.1 10.2 13.2 12.8 12.4 11.6 MS 11.8 10.6 14.4 15.2 12.1 16.5 MS 13.4 I0.0 12.8 15.4 14.1 14.2 15.8 12.2 9.1 13.0 14.4 8.8 11.2 15.2 12.1 8.0 12.5 15.4 i0.0 15.1 14.6 12.2 9.6 10.7 14.2 11.9 12.8 15.0 11.8 9.1 13.2 14.6 9.7 13.8 13.3 11.6 9.1 11.8 16.1 9.7 13.3 15.6 13.3 9.1 13.4 13.2 14.4 11.0 10.6 11.3 FD 8 12.7 13909 13910 13911 13912 13913 13914 13915 13916 13917 12.9 15.8 12.3 13.1 15.0 12.2 11.3 13.5 13.4 13.1 15.8 12.7 11.9 15.7 13.1 13.3 14.4 12.9 13.5 15.3 12.2 12.6 13.7 13.0 10.8 12.0 14.7 12.5 15.4 11.8 13.4 15.6 11.3 11.3 14.6 13.2 11.9 13.7 13.2 11.0 15.6 11.8 12.0 12.9 14.6 11.7 13.2 13.4 13.8 15.3 13.2 12.3 12.1 13.1 13.2 14.0 12.7 12.4 15.1 11.4 11.7 12.9 11.4 12.8 14.0 11.9 11.5 12.5 10.1 13.0 12.5 13.2 14.5 12.1 10.2 15.2 12.3 12.2 11.9 12.7 14.4 11.6 12.4 16.3 12.6 11.7 12.1 11.5 15.6 12.1 11.5 16.3 12.5 12.8 12.5 12.7 16.2 12.3 11.5 13.1 12.5 11.3 13.0 12.7 15.5 11.9 12.6 11.4 12.6 12.1 12.3 14.8 11.4 i0.0 12.0 11.1 15.0 10.9 10.8 12.6 12.3 11.5 10.8 10.7 11.5 FM 3 13918 13919 16.7 11.3 14.5 12.4 15.0 12.4 16.1 11.5 16.1 11.7 15.1 12.2 14.5 11.7 14.4 11.6 12.8 11.1 14.0 9.9 15.9 8.4 15.1 9.9 14.4 11.1 14.9 11.1 13920 9.3 10.9 10.3 11.1 11.2 8.7 10.5 10.7 8.1 ........................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 10.2 i0.0 INCLUDE ONLY 10.6 WEIGHTS 9.7 OF 10.7 10.0 .FD 3 _ ........................................ LIVE PUPS. C/_ 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 15) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... 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 8 13921 13922 13923 13924 13925 13926 13927 13928 13929 13.4 9.7 10.7 13.6 13.2 9.2 11.3 12.5 NOT 8.3 12.7 9.4 7.2 10.2 10.8 12.6 ii.0 9.7 9.0 11.3 11.3 10.3 12.1 12.9 14.1 PREGNANT 8.0 9.5 11.4 12.8 9.4 11.2 12.5 12.9 13.3 MM 2 ii.0 13.0 12.9 12.1 11.9 MD 8 13.5 MD 1 11.2 11.3 8.3 10.0 11.7 MD 3 12.7 MD 1 12.2 12.6 10.9 11.4 10.8 13.4 12.9 FM 2 10.7 10.4 12.2 11.9 10.8 11.7 MM 6 FM 2 11.5 12.4 7.8 MS 10.7 10.5 12.8 10.8 12.9 12.5 10.4 11.7 11.6 12.1 I0.I 13.0 8.1 12.2 11.4 11.7 10.9 ii.0 11.9 10.3 11.0 11.7 12.6 12.7 10.8 11.8 11.8 ii.0 10.5 10.7 5.5 10.5 11.3 9.3 12.0 11.5 6.9 10.2 10.7 11.3 12.0 8.3 11.1 FD 7 9.8 13930 9.8 10.8 10.6 9.7 9.8 i0.0 7.2 10.4 MD 8 8.5 9.0 8.7 9.0 8.4 9.9 9.9 FD 6 FM 5 1133993321 127..92 126 94 115..63 137..87 127..25 128..10 M1D2.18 M1D2.66 116..84 116..48 126..09 117..80 F1D1.26 F1D0.86 FM 2 13933 12.0 i0 7 12.0 13.0 12 1 12.1 12.3 12.0 12.3 11.2 i0 8 11.5 10.4 13934 7.8 8 0 MM 4 9.9 i0 3 7.3 11.0 8.2 11.1 10.2 8 9 10.4 8.1 11.7 FM 6 13935 11.7 12 0 13.4 12.3 11 6 12.8 13.3 12.9 12.0 10.5 12 5 12.4 11.7 8.7 11.5 13936 11.5 14 3 14.6 15.0 12 3 11.5 14.5 13.0 14.7 14.1 14 6 13.7 12.0 14.2 13937 15.4 16 2 15.4 15.3 14 7 14.7 15.5 15.2 15.1 13.5 14 5 14.1 13.5 14.0 13.9 13938 11.1 10.3 9.6 9.5 10 1 9.0 II.0 MD 2 9.8 9.8 i0 5 11.2 9.7 10.1 i0.i 10.9 13939 13.3 13.7 13.7 13.4 12 1 12.3 12.6 12.7 12.9 12.4 12.4 11.0 13.5 12.2 FS 13940 13.3 11.8 12.4 12.3 11.6 12.7 10.5 12.5 11.6 12.0 10.1 12.6 10.5 11.2 10.6 13941 14.1 12.1 12.3 13.7 14.3 14.1 14.5 14.1 13.4 13.5 13.5 11.6 13.3 FS 13942 12.0 14.1 14.8 14.0 13.1 9.0 14.3 13.3 14.5 14.5 13.4 12.4 11.8 13.9 13.6 13.1 13943 17.4 20.0 18.0 17.4 15.2 13.7 17.8 13944 10.3 11.1 9.1 MM 5 11.3 9.2 11.0 6.0 9.4 7.7 9.4 9.6 13945 14.3 13.9 13.4 13.5 13.6 14.3 14.1 14.4 13.6 14.7 13.4 13.5 14.4 14.1 13946 14.2 15.3 14.7 16.2 14.5 14.1 13.1 14.1 14.2 13.9 14.4 13947 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY 1 OF LACTATION 13948 13.6 11.4 13.6 13.9 12.0 11.6 13.9 11.4 10.4 11.8 12.0 FM 3 > 13949 12.6 14.5 13.0 13.4 13.6 13.0 12.7 13.0 14.0 12.5 12.9 12.7 12.2 13950 13.3 13.0 14.8 12.9 14.3 12.4 MS 13.0 14.8 12.4 12.9 FD 2 FS FS ............................................................................................ '........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 2,_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. t_ %.J PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 16): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 28.6 30.0 29.2 29.0 27.6 30.3 29.1 28.0 28.6 13802 31.6 30.8 31.4 29.8 31.4 33.1 30.6 28.1 31.0 27.7 13803 13804 27.0 23.0 23.6 21.3 21.1 23.1 22.6 MORIBUND SACRIFICED ON DAY 68 OF STUDY 24.4 23.2 FM 7 13805 28.3 29.4 28.5 27.5 28.9 29.9 26.8 26.0 29.6 25.5 13806 26.1 23.1 23.3 25.3 24.3 MM 3 23.6 22.8 27.1 25.4 13807 24.7 24.3 24.3 25.1 22.8 22.4 23.2 17.7 25.2 23.1 13808 30.5 30.6 29.2 27.4 31.1 29.3 MS 30.6 29.2 30.9 13809 27.8 29.2 26.1 30.0 29.0 28.2 27.2 28.7 29.1 26.3 13810 31.7 29.6 32.1 31.2 MD 3 MS 29.2 31.8 29.1 29.9 32.3 21.4 27.8 25.6 23.2 29.1 25.0 31.3 29.0 22.8 25.0 23.9 23.1 28.0 27.8 27.1 POSTPARTUM DAY 15 29.3 23.2 24.5 24.6 25.3 27.9 27.0 29.5 31.3 24.8 25.2 21.8 30.9 21.9 22.8 23.6 22.1 24.7 23.3 FD 1 23.9 20.4 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 NOT 28.2 33.9 22.6 21.6 21.6 25.5 20.8 22.1 26.9 28.7 MX 8 32.3 25.8 24.8 22.3 27.9 PREGNANT 28.6 26.0 31.4 32.7 23.8 23.3 20.6 21.3 20.6 19.2 23.3 23.9 17.6 20.4 22.3 20.4 26.1 26.3 26.0 MX 8 27.5 MX 8 32.4 34.3 27.0 28.9 24.7 23.8 21.5 20.5 23.9 25.7 26.6 33.2 25.3 20.8 19.5 22.0 18.8 19.1 28.2 22.6 FX 8 33.6 20.3 24.1 16.4 27.4 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 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 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 27.1 30.5 23.1 21.6 19.6 23.6 17.0 20.5 25.5 26.1 FX 8 32.9 28.7 20.8 14.9 28.2 26.2 30.7 18.3 19.9 16.2 21.8 16.6 20.3 24.9 23.1 FX 8 33.0 25.1 24.8 16.0 MM 2 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 25.7 32.6 20.7 22.6 16.8 23.1 17.8 20.1 26.7 27.1 FX 8 26.9 31.2 22 5 19.1 15.6 23.1 16.1 20.8 22.0 22.9 FX 8 23.3 21.7 16.9 25.8 26.8 24.8 18.9 25.6 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 26.9 18 8 16.5 19.6 22.5 18.4 26.5 25.6 25.3 25.8 20.1 23.9 23 3 21.5 14.7 FD 2 FM 4 23.9 24.6 23.3 17.9 25.4 20 4 UU FD 2 25.3 24.2 20.6 25.1 FM 2 25.4 13828 25.6 21.8 25.3 28.0 26.5 20.0 24.4 26.0 22.3 24.6 27.3 24.4 26.0 25.5 > 13829 25.2 25.0 23.3 23.8 23.0 23.6 24.3 22.4 20.5 23.3 20.0 18.6 24.8 13830 23.1 23.2 22.7 24.2 21.6 22.8 21.4 MS 23.0 24.3 22.8 21.7 22.6 21.7 _'_ ........................................................................................... 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 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O0 NUMBER FOLLOWING X-SACRIFICED DUE TO SACRIFICE OF DAM "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 17): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 26.3 25.9 25.4 24.1 23.0 26.0 27.1 26.4 24.8 22.6 26.5 25.8 26.2 24.9 26.4 27.2 26.6 24.0 26.1 27.0 13833 13834 26.5 27.6 25.8 26.4 25.7 25.6 25.0 26.9 26.2 25.8 27.9 25.5 25.9 26.1 26.6 26.6 24.2 24.6 25.1 26.8 13835 13836 24.6 24.0 27.4 26.4 26.2 24.1 25.6 MORIBUND SACRIFICED ON DAY 59 OF STUDY 23.5 25.7 24.7 13837 27.2 25.7 27.3 25.1 26.6 27.7 25.8 24.0 24.2 25.6 13838 13839 13840 25.4 24.5 NOT 24.3 24.8 26.4 24.7 PREGNANT 23.8 24.3 28.1 24.2 25.7 24.2 25.1 23.6 24.9 23.2 24.8 24.8 23.7 17.4 ii 22.0 27.0 22.4 24.6 20.2 25.2 24.3 23.6 12 23.4 23.5 26.7 26.3 25.4 FS 13.9 25.0 13 14 15 16 POSTPARTUM DAY 15 23.1 23.1 24.9 24.5 22.5 22.6 22.0 24.8 22.0 24.6 21.9 FM 3 26.2 22.0 25.9 24.2 24.6 23.2 17 18 27.7 FD 3 FD 2 23.9 FD 4 13841 13842 13843 23.9 25.8 24.4 26.1 23.8 22.7 20.1 29.6 23.7 24.7 26.5 24.0 23.5 29.5 23.9 25.1 MD 7 22.1 17 5 23 0 25 0 25 6 22 6 22 0 20.8 24.4 21.3 23.4 24.4 23.1 FD 25.0 UD 27.3 25.9 13844 13845 13846 19 ..6.... 25 6 29.6 27.5 23.4 22.8 22 9 30.0 23.9 20.2 27.9 23.4 22.0 28.7 25.2 20 0 22.7 24.1 21 6 28 3 20 7 20 4 28 6 23 1 19 5 30.1 21.3 18 9 28.8 22.2 22.0 27.3 20.5 19.7 29.3 23.1 17.1 23.0 22.7 18.3 FM 2 17.6 FD 8 13847 13848 13849 13850 13851 13852 29.9 24.1 22.6 24.9 NOT MX11 32.2 33.0 24.0 25.6 20.8 20.2 25.9 25.1 PREGNANT MX11 MXll MS 24.9 21.5 25.2 MXll MS 29,4 20.5 24.9 MS 27.8 21.2 25.0 MS 25.6 19.7 23.6 MXll MXll MX11 32 6 28 8 22 6 24 2 31.6 24.3 22.5 22.8 MX11 FXll 29.7 25.7 21.7 24.9 FX11 32.1 26.2 20.4 25.5 FX11 31.7 25.7 21.0 23.5 FX11 FS 24.4 22.1 FS FS 23.3 19.0 FS 27.9 21.1 25.8 19.2 13853 13854 13855 13856 13857 21 1 21 3 29 2 22 9 27 4 22 6 19 6 30 8 20 1 27 3 24 5 21 0 29 1 23 0 26 7 24.5 20.7 28.8 21.0 28.2 18.9 19.2 28.6 20.6 26.5 23.3 20.9 27.3 19.4 24.4 21.2 18.6 28.5 20.5 27.4 19.9 17.9 27.6 21.4 25.3 21.4 22.2 25 6 19 9 26 1 21.5 19.6 30.4 16.5 27.7 24.1 18.9 26.1 20.2 26.6 19.1 16.5 27.0 22.5 29.6 19.8 18.8 29.9 19.4 26.7 22.4 17.5 26.5 15.5 26.2 19.0 18.7 FD 5 20.2 FS 18.7 18.5 FD 1 17.3 18.7 19.0 13858 13859 13860 25 5 22 0 24 2 21 7 23 6 24 0 24 5 23 7 22 2 23.6 22.4 24.8 24.9 22.3 23.5 24.2 22.2 23.7 21.8 19.5 22.7 19.8 21.9 22.9 21 2 22 2 22 3 21.6 23.0 22.2 23.3 22.9 24.1 19.1 22.0 21.0 22.9 22.8 23.9 23.9 22.6 21.3 FDII 24.7 23.7 ............................................................................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE WEIGHTS INCLUDE ONLY WEIGHTS _ ....................................... OF LIVE PUPS. [2) 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O_ X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 18): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 13862 13863 13864 13865 13866 13867 13868 13869 13870 28.3 28.0 PREGNANT; 21.7 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 24.8 26.9 25.6 DID NOT DELIVER A 22.2 21.7 21.6 36.3 38.2 38.1 17.2 19.6 18.9 21.0 24.7 21.5 21.8 22.2 17.9 25.1 27.7 29.5 19.6 22.1 19.5 25.4 30.8 25.7 24.5 LITTER 19.8 38.2 19.5 14 4 20 2 20 5 21 1 31 1 28.6 22.1 FS 19.7 23 9 21 3 24 1 21 3 30 3 28.1 22.5 MD 1 MDI5 MD 7 26.4 20.8 24 4 28.0 23.1 17.5 25.9 MD 6 26.0 21.0 24.0 20.6 18.9 23.3 MS 26.4 15.2 11 22.5 20.0 19.1 21.7 26.4 15.4 12 22.1 15.3 10.4 21.1 27.2 18.6 13 14 15 16 17 POSTPARTUM DAY 15 23.6 18.8 19.7 20.0 24.7 15.1 22.3 18.8 22.7 20.8 26.3 18.6 21.7 19.8 26.7 22.3 23.1 19.5 FM 3 20.2 24.5 FD 6 26.9 FD 4 17.7 20.3 18 FD 8 138712 13873 1292 19 19 9 1282.54 23.9 210.03 29.6 20.23 20.1 M2D2.6 3 25.8 203 2 26 3 1280 81 24 4 1281 42 16 3 2109.3 5 20 6 20.31 26.0 2109..15 24.1 1272.06 25.2 1271.02 24.9 F1M9.97 24.5 F2D1.94 26.2 19.3 24.7 17.2 FM 4 13874 13875 13876 13877 13878 13879 13880 31 8 24 4 31 2 29 8 30.4 32.6 30.7 31.8 24.4 31.8 29.9 32.0 32.5 29.8 32 2 25 9 30 8 29 8 33 8 32 0 32 0 32.3 27.5 28.7 32.5 32.8 31.6 29.7 32.4 28.9 29.2 30.0 31.7 28.8 30.2 25 9 18 9 28.8 29.1 32.6 33.0 32.4 29.9 28.9 30.1 28.9 30.0 31.0 28.0 29 0 24 4 29.7 27.3 31.7 31.2 24.8 28 2 22 5 29 7 28 0 31.8 31.4 28.4 27.1 22.4 28.8 27.3 33.1 30.0 26.7 26.9 25.5 26.6 28.6 19.8 29.9 26.2 29 3 29 2 31.3 30.3 26.5 30.4 26.7 30.1 27.8 22.3 FS FS 28.0 25.6 FD 1 28.9 25.7 FD 2 13881 13882 29.8 27.8 31.1 27.5 30.1 25.1 28.6 27.2 27.9 25.9 28.5 29.4 28.4 24.6 29.5 28.0 28.2 28.3 30.8 28.7 29 6 22 8 23.7 30.2 25.0 29.1 FD 3 13883 13884 13885 13886 28.1 32.3 33.1 25.5 23.6 29.1 34.6 27.5 30.6 30.8 32.0 25.7 24.7 26.1 26.0 28.3 23.1 25.2 29.6 28.0 25.4 25.2 30.2 25.4 26.5 27.5 24.7 26.2 28.5 25.3 30.5 28.5 21.9 29 2 17 2 29.4 25.3 25.0 27.4 23.4 FD 1 13887 13888 13889 13890 31.4 25.3 25.8 26.9 31.7 24.9 25.7 25.6 31.8 22.0 24.8 25.4 31.2 21.7 24.9 24.3 34.0 23.8 25.8 26.5 33.8 21.7 28.7 12.8 32.6 21.4 27.0 22.4 31.5 22.1 27.7 24.0 29.3 24.0 26.8 27.7 32.3 24.1 25.6 26.8 29.0 19.8 24.9 25.6 22.9 25.1 25.6 20.5 26.8 27.0 23.8 22.7 2.6.6 FS 24.6 26.6 24.3 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE "_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO,O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 19): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 ........................................................................... _ ........................................................ RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 13892 13893 13894 31 0 27 8 27 5 26 3 32 3 26 1 26 5 26 1 30.0 24 0 28 6 24 0 28.7 26.8 25.3 25.0 MS 23.0 29.1 28.6 29.3 24.6 25.7 24.0 29.7 25.3 25.9 MM 4 29,0 23,6 27,0 23,8 28.0 24.4 24.4 24.3 30.2 24.0 23.3 24.3 13895 13896 28 6 27 9 28 3 23 9 12 7 25 8 22,4 27.5 28.2 27.5 28.6 23.6 24.1 24.4 25.4 25.5 19.2 25.6 28.0 26.0 13897 13898 13899 30 2 22 1 22 7 30 8 18 2 22 4 27 9 21 6 21,8 30.0 25.3 22,6 32.2 21.1 20.8 28.0 23.5 20.0 26.9 24.4 19.1 30.5 19.2 19.3 29.0 22.6 20.4 27.1 20.2 19.9 28.7 25.0 27.8 25.1 28.3 21.2 27.8 20.8 21.9 23.0 23.7 17.6 26.7 26.9 28.6 21.6 POSTPARTUM DAY 15 25.8 25.4 25.0 FS 26.3 24.3 27.6 23.3 23.4 25.7 26.2 25.4 21.1 19.1 18.4 23.0 FD 3 13900 NOT PREGNANT; MATING NOT CONFIRMED 13901 13902 13903 21.9 26.9 27.8 23.1 27.8 26,4 20.0 26.6 26,8 23.8 24.9 22.8 23.1 26.1 21.8 21,9 28.6 25.6 21.7 25.7 28.0 19.4 23.7 26.1 15.6 25.4 25.8 18.8 23.4 26.4 22.6 25.6 24.3 22.6 24.5 26.8 20.3 23.8 28.8 19.0 24.4 22.9 20.0 20.3 FD 7 13904 20.8 20.2 21.5 15,2 22.1 20.4 17.8 20.7 18.2 17.2 20.3 13.6 16.7 18.5 13905 23.9 28.2 27.5 27.1 19.7 21.7 23.7 23.0 26.2 23.6 21.4 22.5 22.7 25.2 27.0 25,9 13906 32.2 31.2 30.1 28.4 30.6 MD 3 MS MS 27.3 29.8 30.9 29.9 30.4 31.6 32.2 FD 8 13907 18.7 17.7 18.0 16.0 20.7 18,3 19.5 18.1 19.1 20.2 17.9 19.0 16.9 18.6 17.0 19.9 13908 35.1 37.5 33.1 38.8 13909 25.0 24.7 23.3 23.1 24.9 25,2 23.3 25.1 24.1 21.6 22.7 22.7 21.8 24,8 13910 23.6 20.0 23.8 22,0 22.1 21,0 22.1 24.0 24.3 25.0 22.3 24.4 22.4 22.5 24.1 13911 28.9 27.7 25.6 27.3 27.0 26.0 24.2 25.7 25.4 26.5 25.5 25.0 13912 25.9 26.1 24.2 25.6 24.2 25.9 29.0 24.5 23.3 21.8 25.1 25.1 25.7 25.5 13913 30.7 29.3 28.4 27,7 29.9 28.3 29.6 32.2 26.0 30.8 25.9 26.5 30.0 13914 22.1 25.2 20.1 25.1 22.5 21.8 25 7 25.5 21.8 22.2 21.9 20.2 25.8 23.8 22.8 24.3 23.2 FM 3 13915 22.5 19.3 24.8 21.6 22.4 22.6 22 7 18.6 24.6 21.3 20.2 21.8 21.0 22.2 20.9 21.3 21,9 13916 29.3 24.7 26.3 25.4 27.5 30.4 29 5 26.0 23.7 21.2 26.1 22.1 25.6 23.4 25.8 24.9 13917 28.2 25,8 30.2 28.2 25.8 30.0 25 1 13918 31.9 30.3 26.5 27.2 29.2 26.4 28 4 28.4 26.9 28.0 27.3 26.7 27.2 24.3 13919 22.8 24.4 24.9 23.1 23.4 25.2 22 3 20.0 18.1 24.7 18.8 22.3 23.6 24.7 13920 17.3 17,9 17.4 14.1 17.5 17.4 MD 9 11.9 16.8 16.4 16.1 15.0 15.1 FD 9 FD 9 .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 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), O0 X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. t_) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 20): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 13921 26.3 16.4 28.0 26.7 25.6 26.4 26.9 13.7 MM 6 24.7 13922 23.0 23.8 23.8 18.3 MM 2 MD 1 MD 1 FM 2 FM 2 13923 21.3 20.8 21.1 21.9 20.7 21.0 20.0 19.5 20.0 20.7 13924 22.8 23.9 21.1 24.5 20.6 25.3 17.8 20.9 23.5 23.2 13925 18.3 21.1 18.8 25.3 13.9 24.5 14.7 15.2 21.0 22.5 13926 24.9 23.9 23.8 23.8 24.1 22.3 23.8 19.9 MS 22.9 13927 15.9 15.6 15.1 13.8 17.1 14.5 15.0 15.3 14.3 16.5 13928 13929 26.7 26.8 27.7 NOT PREGNANT 26.4 MD 8 MD 3 26.8 25.8 24.6 24.7 23.8 19.7 21.3 23.2 23.5 14.6 23.8 25.6 20.1 22.6 23.7 23.1 14.7 23.6 POSTPARTUM DAY 15 10.0 13.1 25.5 19.1 24.4 22.4 24.6 13.7 27.6 17.1 19.0 21.1 12.8 21.7 19.3 23.0 12.6 25.0 15.5 23.1 FD 7 26.1 13930 20.6 19.4 20.4 13.9 19.6 20.8 19.1 20.2 MD 8 19.3 19 6 16 5 19.0 19.6 18.4 19.6 FD 6 FM 5 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 13947 18.2 23.4 19.9 22.0 18.2 18.5 15.4 MMI2 22.0 20.7 26.5 27.1 26.8 26.6 17.5 16.9 27.0 24.1 22.8 23.6 25.7 25.7 23.2 37.1 22.8 35.9 20.4 24.1 25.2 31.8 25.3 30.4 SACRIFICED 15.9 23.6 11.9 22.7 19.8 22.8 16.1 15.4 18.0 MM 4 24.2 20.9 24.1 19.7 22 1 27.0 22.9 26 2 26.2 24.9 25 3 14.3 18.8 17 5 26.1 26.5 24 5 25.8 22.8 21 9 24.2 25.8 23 4 26.2 36.8 28.1 40.5 25 0 36 6 22.1 MM 5 21 6 25.3 29.8 26.3 29.3 26.4 28.6 DUE TO NO SURVIVING 17.2 23.9 MD 8 MD 6 17.2 22.9 22.4 21.2 16.7 22.8 15.5 16.7 17.6 16.3 16.8 23.1 25.4 15.1 21.0 14.5 22.8 22.6 20.2 14.9 21.8 25.6 23.0 26.2 26.2 22.6 26.0 26.9 22.9 24.5 21.8 17.9 16.3 MD 2 16.8 17.0 24.0 26.7 23.6 24.6 25.6 23.7 23.0 21.6 21.1 19.8 24.0 24.9 22.9 25.4 19.9 24.5 31.0 25.9 34.3 26.5 25.8 20.8 24.3 20.7 24.9 20.9 16.5 25.4 28.4 25.0 28.2 25.9 27.7 26.4 27.9 24.1 27.6 PUPS ON DAY 1 OF LACTATION 14 9 20 8 19 3 13 0 19 4 23 2 24 7 17 2 23 4 22 2 23 5 16 4 17 5 23 3 17 7 18 1 22 5 22 9 22 7 17 7 24 9 22 7 24 2 23 6 FD 6 23.0 18.1 20.3 23.0 23.4 24.0 17.6 22.3 18.4 23.4 22.8 FD 6 22.2 24.6 21 8 25 3 24 9 17 7 24 7 20 7 FS 27.2 FM 2 FM 6 22.1 25.8 16.7 FS 22.4 20.3 15.9 23.0 21.4 25.5 26.8 FMI0 24.3 25.3 27.1 13948 13949 27.1 27.0 28.1 28.2 27.9 27.0 27.6 28.2 24.6 27.4 25.5 27.1 24.4 27.8 25.4 28.4 24.9 29.4 27.1 27.5 13950 28.9 28.6 28.4 30.3 25.7 27.5 MS 26.9 26.1 27.0 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE FIRST LE"ITER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 23.1 27.3 29.0 ONLY FM 3 27.3 26.7 FD 2 FS FS WEIGHTS OF LIVE PUPS. > _'_ 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM _D NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. I_) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 21): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 45.0 44.6 47.5 45.2 40.6 42.5 44.3 46.3 44.1 13802 44.3 45.4 43.0 43.1 46.5 40.5 44.7 43.5 37.3 41.3 13803 13804 43.9 40.0 40.7 40.6 48.3 38.8 42.1 MORIBUND SACRIFICED ON DAY 68 OF STUDY 36.9 44.5 FM 7 44.9 42.5 42.1 42.0 POSTPARTUM DAY 22 44.4 41.9 41.6 39.7 38.9 38.4 13805 13806 13807 13808 13809 48.1 32.7 27.4 40.9 32.2 44.9 35.4 26.4 41.1 38.5 46.6 32.1 26.8 42.8 36.9 46.3 35.0 20.1 36.6 35.9 45.3 34.4 25.4 39.5 34.6 43.2 MM 3 26.5 44.4 36.5 41.0 34.2 26.2 MS 37.3 43.0 32.4 26.1 39.8 35.3 38.3 33.4 24.8 42.2 37.3 45.2 36.4 23.5 36.4 34.5 39.0 32.8 26.0 37.7 36.2 40.0 35.5 24.8 43.2 32.4 43.4 31.4 23.4 41.8 33.8 33.7 27.3 35.3 25.2 36.2 22.3 36.6 25.8 13810 48.3 45.4 43.4 45.1 MD 3 MS 43.5 41.2 45.3 41.4 43.1 41.7 41.6 43.5 FD 1 138112 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 43N.O2T 43.9 37.1 36.2 32.8 36.0 31.9 31.7 27.2 36.4 MX 8 57.2 PR4E2G.N0ANT 40.1 31.8 33.4 32.2 36.2 24.3 29.1 25.0 43.0 MX 8 53.3 41.4 44.2 36.4 32.8 31.8 39.9 27.1 30.6 26.1 48.9 MX 8 52.0 44.7 45.2 35.3 33.8 34.4 37.9 31.8 30.6 27.8 40.6 FX 8 53.4 41.9 45.8 38.8 32.2 34.4 41.0 28.1 MD 1 27.7 35.0 FX 8 52.9 42 5 44 0 35 5 33 5 25 6 37 5 31.2 30.0 20.8 36.9 FX 8 53.0 44.9 39 5 32 7 31 7 32 5 36 7 28 9 29 8 23 4 44 7 FX 8 54 I 40.7 46.4 33.2 31.6 27.9 40.7 25.8 27.8 21.8 38.7 FX 8 55.1 48.6 43.1 31.9 30.8 30.9 33.3 28.5 27.8 25.7 35.1 FX 8 51.3 39.6 40.6 34.1 32.4 27.3 39.7 26.0 29.9 36.4 40.6 FX 8 41.5 42.9 26.9 34.9 29.1 36.7 27.3 26.4 32.1 43.1 FX 8 42.4 46.6 36.5 28.4 27.1 38.2 26.5 29.6 34.2 39.2 FX 8 40.1 UU 32.9 34.0 32.4 37.1 24.6 29.8 33.4 39.6 42.4 32.5 31.3 30.4 36.8 26.6 32.8 35.7 34.5 26.5 29.9 FD 2 FM 4 26.6 UU FD 2 FM 2 39.7 37.5 36.4 13824 13825 13826 13827 31.7 36.1 26.4 42.5 49.1 34.9 34.9 40.3 40.5 29.1 32.0 39.8 43.7 35.9 27.7 45.0 40.7 34.6 31.8 37.9 41.7 32.7 33.3 42.4 37 0 36 1 35 2 42 9 38.4 34.3 35.1 43.7 37.0 32.9 23.6 MM 2 33.3 31.1 28.8 41.1 37.6 41.1 37.4 35.6 27.833.9 42.1 37.5 41.2 36.4 27.2 40.6 40.2 33.4 29.9 41.2 38.8 34.6 30.1 38.3 43.7 28.0 39.7 13828 13829 13830 39.3 42.8 38.5 35.8 42.0 34.6 47.0 45.5 35.3 42.2 40.6 36.7 42.0 39.0 35.0 40.8 38.2 33.2 41 1 40 8 35.4 35.8 40.6 MS 40.7 32.8 32.9 32.5 42.4 35.8 40.2 42.5 36.9 42.7 33.5 38.0 39.6 36.5 34.2 40.2 32.7 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS [G). MEAN LITTER WEIGHTS INCLUDE FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE ONLY WEIGHTS OF LIVE PUPS. [29 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACI_IFICE OF DAM _D NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. t,_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 22}: PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 13839 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 MORIBUND SACRIFICED ON 37.8 39.4 41.1 38.5 36.0 41.6 37.8 33.3 37.0 36.1 32.6 37.5 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 DAY 59 OF STUDY 41.1 36.1 41.6 37.6 32.8 38.0 34.0 39.3 40.0 33.6 35.3 38.8 37.7 30.4 37.6 36.6 39.0 30.6 40.1 40.7 32.4 35.6 37.6 21.7 22.0 32.6 43.4 39.9 41.2 30.5 38.1 35.0 32.7 35.6 39.8 43.7 34.3 33.5 34.9 35.8 31.9 33.1 44.0 36.0 36.7 31.1 FS 34.7 33.0 POSTPARTUM DAY 22 36.5 37.0 40.0 37.7 37.3 32.6 35.5 41.8 28.7 32.6 28.7 FM 3 35.7 31.0 33.0 34.9 36.0 34.6 36.7 FD 3 37.7 13840 NOT PREGNANT 1133884412 13843 13844 13845 13846 13847 13848 13849 13850 4367 52 35 1 42 9 45 3 36 2 55.0 39.3 27.5 37.4 4453..24 33.2 32.0 33.8 37.2 51.4 43.8 26.5 37.7 3369 30 35 3 33 6 45 1 35 7 55 4 43 3 23 7 38 4 3483..84 34.6 34.5 42.7 31.2 MS 40.9 25.3 39.0 4319..44 34.3 37.3 42.7 35.1 MS 43.2 26.3 37.3 3M7D.0 7 33.7 32.0 48.4 35.3 MS 43.1 28.1 38.5 3334..02 30.1 30.1 43.6 36.3 MS 42.7 25.5 33.8 4343..37 34.0 30.5 44.5 31.0 56.6 39.2 24.3 35.6 3397..52 30.6 26.9 43.3 35.8 50.4 49.5 25.6 38.0 4327..21 33.5 26.5 40.4 28.8 52.7 45.0 28.4 34.6 39F.D2 29,7 45.6 32.9 53.5 37.9 27.6 33.4 37U.U7 34.8 42.8 33.7 52.5 43.1 29.6 33.8 37.2 28.4 34.1 FS 40.6 26.7 FS 27.6 27.8 FM 2 FS 41.1 23.6 FS 38.4 24.9 28.4 38.6 25.3 FD 8 13851 13852 NOT PREGNANT MXII MXI1 MX11 MX11 MXll MX11 MX11 MX11 FX11 FX11 FX11 FX11 13853 33.4 37.8 32.2 32.9 31.4 35.0 13854 30.1 26.5 35.2 28.8 29.6 29.5 13855 40.2 38.9 34.0 42.0 39.5 38.8 13856 32.9 31.6 29.8 38.6 32.7 33.6 13857 39.6 44.1 43.9 44.2 42.7 41.2 13858 30.5 35.3 33.8 33.2 35.2 32.7 13859 37.4 40.3 39.6 40.1 43.4 41.5 13860 33.9 36.6 39.5 37.3 37.5 35.4 ........................................................................................... 33.7 29.6 39.3 33.0 38.6 31.3 40.1 36.1 28.3 25.9 39.4 35.5 42.3 34.6 35.9 39.0 29.7 30.8 40.4 34.0 41.4 32.1 39.0 35.4 32.4 29.2 37.0 22.7 41.5 33.6 42.7 38.7 32.8 29.7 36.7 31.1 39.8 30.6 38.5 38.3 34.1 30.3 39.9 25.6 38.4 30.7 38.3 35.9 29.8 23.8 39.6 29.9 41.8 33.2 38.6 37.0 28.1 29.0 40.8 36.0 38.3 35.7 40.7 27.5 25.4 FD 5 31.8 FS 36.4 FDII 27.1 27.3 FD 1 23.6 36.2 30.0 27.1 32.3 '......................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST SECOND NUMBER LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, X-SACRIFICED DUE TO SACRIFICE OF DAM FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM M-MISSING (PRESUMED THE EVENT OCCURRED CANNIBALIZED}, 18 FD 2 FD 4 _> [/9 ___t_ O0 h_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 23) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS PUP # 1 ........................ RAT/ 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1 ........................................................................................................... LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY POSTPARTUM DAY 22 .................................................................................................................................... 13861 32.8 33.1 32.0 36.5 36.2 36.8 36.0 33.8 32.0 35.2 13862 PREGNANT; DID NOT DELIVER A LITTER 13863 13864 32.2 57.8 30.8 60.2 32.5 61.1 32.1 59.3 33.0 61.5 30.3 59.8 33.9 FS 34.3 30.5 28.6 30.2 27.3 34.6 33.0 31.5 FM 3 13865 13866 13867 13868 13869 13870 26.9 18.1 26.2 37.6 27.0 41.6 29.5 35.8 30.2 33.8 33.3 37.7 30.9 36.3 28.0 26.6 29.7 36.3 30.4 39.3 29.4 37.4 31.7 44.6 28.5 33.8 29.9 34.5 33.7 37.7 31.9 43.5 31.2 35.6 33.0 44.4 31.4 39.1 30.9 34.3 34.8 42.3 MD 1 MD15 MD 7 35.2 23.2 35.5 26.2 10.4 MD 6 33.0 29.8 27.7 38.6 MS 32.8 24.1 30.3 27.6 30.0 33.3 27.2 28,6 30.3 27.7 34,9 29.0 25.3 37.9 28.2 34.5 31.6 30.7 34.0 28.2 32.1 33.9 30.8 38.3 31.6 35.6 22.7 31.5 32.4 FD 6 35.0 FD 4 29.8 35.8 FD 8 13871 13872 13873 13874 13875 13876 13877 13878 13879 13880 13881 13882 13883 13884 13885 13886 13887 26.9 30.7 39.1 49.1 41.2 49.0 48.5 48.9 48.7 45.0 41.4 37.6 43.6 36.4 55.5 43.9 47.7 26.1 34.1 24.5 50.0 33.0 50.3 47.2 48.8 50.2 40.0 40.1 44.0 47.3 51.3 51.5 38.8 49.9 32.3 27.8 29.8 48.5 35.3 47.2 43.9 52.3 48.0 44.8 39.1 37.4 48.0 42.3 53.5 40.3 52.4 26.8 29.5 35.3 51.3 28.9 50.2 45.8 51.8 46.1 47.6 39.1 39.3 41.9 43.5 44.3 51.7 MD 3 29.8 31.0 54.7 38.1 47.0 46.7 42.4 48.8 49.9 37.7 42.2 45.9 39.9 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 42.4 53.8 47.9 50.4 23.6 32.2 41.9 43.4 44.4 48.1 46.0 52.3 51.6 47.1 40.8 46.3 52.9 27.4 42.6 50.0 29.9 33.7 39.4 42.5 40.1 41.1 42.2 46.7 47.9 52.8 37.2 43.3 48.0 43.1 40.6 50.7 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 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 29.4 27.0 36.8 50.1 39.9 48.7 42.5 29,1 27,6 28.3 46.1 40,7 46,4 43.7 47.4 42.9 38.8 34.1 51.4 40.9 47.4 34.8 51,4 41.4 46.3 33.9 FD20 27.7 36.8 46.0 44.4 47.2 47.4 49.3 44.5 42.3 FM 7 30.1 34.0 42.2 33.5 FS FS FD 4 30.0 34.3 42.6 42.9 FD 1 26.7 37.2 45.1 35.0 27.1 FM 4 FD 2 37.3 47.6 45.1 FD 1 FD 3 13888 36.3 36.5 31.4 30.7 29.7 29.6 30.2 31.3 25.9 34.2 32.7 30.7 29.7 32.5 FS > 13889 35.4 34.4 32.2 34.1 35.8 34.1 36.9 38.9 35.0 39.1 32.1 35.1 31.7 32.3 32.4 29.6 13890 43.1 39.0 20.4 31.1 42.3 40.5 42.5 38.8 42.0 38.2 35.6 38.6 42.0 38.9 44.0 . ........................................................................................... _ ........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [/_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED, _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 24): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 11 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 13891 13892 13893 13894 47.8 36.8 44.1 40.2 51.6 38.7 39.1 36.9 49.0 35.3 46.4 35.9 46.0 41.1 46.1 46.0 MS 44.3 42.2 34.9 47.2 39.5 42.5 36.9 44.1 38.5 40.9 MM 4 46.1 37.9 41.2 26.9 45.5 37.8 38.7 37.0 47.8 36.3 44.0 37.3 13895 13896 13897 40.1 44.5 44.9 30.3 41.7 48.6 33.0 39.8 48.5 22.7 44.3 48.8 41.0 40.7 44.4 42.2 37.6 45.6 43.6 40.6 41.0 39.2 39.0 42.2 43.8 37.1 45.5 45.5 33.9 42.3 13898 13899 23.7 32.4 33.2 35.1 27.9 34.4 28.9 32.8 32.9 37.1 29.0 36.9 33.6 32.5 25.1 32.2 24.0 30.5 28.5 35.8 43.8 37.8 37.8 35.7 41.3 37.4 43.1 25.4 31.7 POSTPARTUM DAY 22 35.7 42.0 38.9 39.9 41.0 44 .I 28.1 37.4 43.4 34.2 39.6 29.9 36.5 37.0 34.5 40.0 29.6 36,7 43.5 37.3 28.1 FS 29.0 FD 3 13900 NOT PREGNANT; MATING NOT CONFIRMED 13901 13902 13903 13904 13905 13906 13907 13908 13909 13910 13911 13912 13913 13914 13915 13916 13917 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 30.6 43.3 40.4 31.3 29.2 47.4 30.9 59.5 42.5 39.5 43.4 35.7 44.8 35.9 39.5 47.2 44.3 35.5 42.2 38.8 38.9 44.2 50.3 23.2 59.5 37.3 36.0 43.4 39.7 46.2 29.8 31.8 43.2 46.2 29.3 44.3 42.3 35.6 42.3 48.1 26.4 50.5 41.4 36.2 40.3 43.6 44.1 34.4 36.6 39.7 40.8 30.7 41.9 42.0 36.9 36.1 45.9 30.4 34.7 41.5 40.9 36.2 44.8 MD 3 28.3 32.7 43.7 36.4 34.0 36.6 MS 25.7 39.8 35.8 42.5 40.0 46.9 29.3 37.0 49.3 48.0 38.4 40.9 46.3 38.4 47 0 33 3 34 9 46 0 41 5 39.1 36.6 41.3 39.9 45.9 33.4 41.6 44.9 43.6 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 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 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 25.9 40.2 44.1 36.3 33.5 48.3 26.9 37.1 36.1 43.0 37.4 41.0 28.9 37.8 40.2 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 29.5 39.6 38.4 31.5 41.0 46.5 31.6 35.6 38.0 37.1 42.6 26.5 35.8 39.6 32.8 42.3 32.4 32.3 37.0 52.1 28.5 38.7 41.2 38.9 37.0 35.0 37.4 27.6 37.9 41.0 50.5 25.9 39.0 32.2 34.9 38.9 FD 7 41.6 FD 8 23.4 32.7 29.3 41.6 32.1 33.3 FM 3 13918 13919 46.7 38.2 40.0 39.6 45.3 40.0 46.3 39.6 44.8 38.1 40 5 38.4 37.1 30.2 43.1 29.7 41.7 32.9 43.5 40.2 38.4 41.9 42.7 36.1 39.1 37.3 41.3 37.4 13920 26.9 32.5 32.3 33.6 32.6 33.1 MD 9 32.2 23.7 29.9 30.9 31.7 31.5 FD 9 FD 9- FD 3 _'_ .................................................................................. ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE ................................... PUPS. [_0 FIRST LK'_'i"KR -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), OO X-SACRIFICED DUE TO SACRIFICE OF DAM _D NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 50 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C37 (PAGE 25): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/XG/DAY .................................................................................................................................... 13921 13922 13923 13924 13925 13926 13927 13928 13929 41 8 42 0 31 5 33 5 32 9 34 6 25.3 42.1 NOT 27.6 40.9 33.4 32.3 31.0 33.2 27.1 40.7 PREGNANT 23.2 40.4 33.5 30.2 40.8 33.3 23.9 40.3 46 1 32 8 33 0 29 8 40 8 30 0 22 3 43.1 47.0 MM 2 31.9 28.6 31.0 32.3 24.0 MD 8 45.6 MD 1 31.6 34.5 23.0 34.4 25.4 MD 3 46.5 MD 1 33.6 34.3 24.0 30.9 25.7 43.2 42.1 FM 2 29.6 34.3 36.7 34.0 18.9 36.8 MM 6 FM 2 28.4 37.2 26.2 MS 20.6 34.7 40.7 29.4 35.4 37.2 32.3 24.7 38.2 13930 19.3 24.2 25.6 26.4 27.3 25.2 25.1 25.3 MD 8 25.2 11 13.6 30.7 25.2 38.2 34.9 27.6 38.4 21.4 12 19.5 30.7 30.7 32.8 28.7 22.5 40.7 21.3 13 14 15 16 17 18 POSTPARTUM DAY 22 40.6 41.7 43.9 30.3 32.3 34.7 31.9 22.5 36.6 32.5 26.1 31.2 23.4 37.7 34.3 32.8 25.3 38.8 32.6 27.9 FD 7 37.6 25.2 24.9 20.5 24.3 FD 6 FM 5 139312 13933 1391.93 27.9 2383.34 26.7 234.9 25.5 2396.35 29.6 2361.35 32.6 2373..71 27.5 M3D3.68 26.7 M3D2.76 27.6 2351.20 24.6 2362.27 29.8 13934 29.4 MMI2 MM 4 24.9 27.3 35.7 26.8 33.3 33.9 35.2 13935 31.6 30.7 36.1 34.3 36.3 33.4 32.9 30.4 21.5 33.4 13936 38.2 45.2 38.0 37.6 44.1 38.5 44.3 42.4 42.6 39.4 13937 40.0 41.2 44.9 43.5 41.5 39.0 40.0 42.8 38.6 40.4 13938 21.7 28.0 29.2 25.3 28.9 30.0 26.1 MD 2 31.4 25.9 13939 42.1 42.4 38.4 40.1 38.1 44.3 44.3 41.1 37.6 41.6 13940 35.7 34.0 30.0 30.2 31.0 32.0 26.8 28.7 26.2 27.3 13941 42.1 38.5 36.8 38.5 39.8 42.4 41.4 39.6 35.9 31.9 13942 40.7 24.3 35.7 32.6 38.9 39.3 38.0 35.5 34.3 40.0 13943 57.5 57.2 46.9 61.7 51.9 53.6 56.4 13944 35.1 39.7 37.2 MM 5 27.9 34.1 36.5 34.7 37.3 38.3 13945 37.6 38.7 41.5 38.7 39.0 39.7 39.5 39.3 40.0 40.0 13946 43.2 44.1 46.2 44.5 45.8 40.9 43.1 41.7 43.1 42.3 13947 SACRIFICED DUE TO NO SURVIVING PUPS ON DAY i OF LACTATION 13948 48.4 40.2 46.1 43.4 44.8 39.9 39.9 41.7 37.1 41.9 13949 44.2 40.8 40.9 42.9 43.0 42.3 41.5 43.6 40.9 42.2 13950 44.1 40.7 47.3 44.2 47.5 47.4 MS 45.4 44.7 42.0 ........................................................................................... 2361.42 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 2343.97 30.0 38.5 35.6 35.2 40.4 27.3 39.6 30.7 35.2 30.4 FM10 37.0 F3D3.16 27.6 33.7 33.5 40.4 38.1 26.0 38.5 31.0 37.1 36.1 F3D3.96 38.1 35.7 36.4 41.3 28.1 42.0 27.2 FS 35.5 FM 2 FM 6 34.7 39.9 26.0 FS 32.1 40.1 29.5 35.4 42.8 38.0 FM 3 39.9 FD 2 38.3 FS FS --........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED DUE TO SACRIFICE OF DAM NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PUPS. _> "_ O0 t,O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C38 (PAGE i) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 ii 12 13 14 15 16 17 18 19 20 21 22 23 ................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 13801 MA MA M A MA FA FA FA FA FA 13802 M A M A M A M A M A M A MA M A F A FA FA FA 13803 13804 MA MA MA M A MORIBUND SACRIFICED M A MA FA FA ON DAY 68 OF STUDY F A FM 7 FA FA 13805 M A M A M A M A M A M A FA F A F A FA FA FA 13806 M A M A M A M A M A MM 3 F A F A F A F A F A F A 13807 13808 MA MA MA MA MA MA MA MA MA MA MA MA MA MS MA FA FA FA FA FA FA FA FA FA 13809 MA MA M A M A M A MA MA M A MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA 13810 M A M A M A M A MD 3 M S F A F A F A F A F A F A F A F A FD 1 13811 13812 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 NOT PREGNANT MA MA M A MA MA MA MA MA MA FA FA FA M A M A M A MA MA FA FA F A F A FA FA FA MA MA MA M A M A MA MA M A M A MA MA FA MA MA MA M A M A MA MA MA MA MA FA FA MA MA MA M A M A F A FA F A F A FA FA FA MA MA MA M A M A MA MA MA F A FA FA FA MA MA MA MA MA MA MA MA M A MD 1 MA FA MA FA MA FA FA FA FA FA FA FA FA FA M A M A M A M A M A FA F A F A F A F A F A F A MA MA MA M A M A MA MA MA FA FA FA FA MX 8 MX 8 MX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 FX 8 M A M A M A M A F A FA F A F A F A MA MA MA M A M A MA MA MA FA FA FA FA M A M A F A F A F A FA F A F A F A F A F A F A MA MA MA M A M A MA MA MA FA FA FA FA M A M A M A M A M A M A M A M A MM 2 M A F A F A FA UU FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A F A FM 2 FA FA FA FA U U 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 13828 13829 13830 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA FA MA MA FA MA MS FA FA FA FA FA FA .......................................................................................... FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, X-SACRIFICED DUE TO SACRIFICE OF DAM FA FA FA FA FA FA M-MISSING FA FA FA FA FA (PRESUMED , CANNIBALIZED), ...................................... _> _'_ [2_ 4_ OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C38 (PAGE 2): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 i0 Ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY ...... - ............................................................................................................................. 13831 13832 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 FA FA FA FA FA FA 13833 13834 MA MA MA MA MA MA MA MA MA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FM 3 13835 13836 13837 MA MA MORIBUND MA MA MA MA SACRIFICED MA MA M A MA ON DAY 59 M A FA FA FA OF STUDY FA FA FA FA FA FA FA FA FA FS FA FA FA F A FD 3 FD 2 13838 13839 13840 MA M A MA MA M A M A NOT PREGNANT MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 4 138412 13843 MA MA MA MA MA MA MA MA MM A MDF A7 M A FA FA FA FF A FA FA FA FA FA F DA UF UA FA 13844 13845 13846 13847 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MS MA MA MA MS MA MA MA MS FA MA MA MS FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FM 2 FS FS FA FS F A FD 8 13848 13849 13850 13851 MA MA MA MA MA MA MA MA MA NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA FA MA MA FA MA MA FA MA MA FA MA MA FA MA FA FA FA FA FS FA FA FA FA FA FA 13852 13853 13854 13855 13856 13857 MXll MA MA MA MA MA MXll MA MA MA MA MA MX11 MA MA MA MA MA MX11 MA MA MA MA MA MX11 MA MA MA MA FA MX11 MA MA MA MA FA MX11 MA MA MA MA FA MX11 MA MA MA MA FA FX11 MA MA MA MA FA FX11 MA MA FA FA FA FX11 FA MA FA FA FA FXll 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 F S FA FA 13858 M A M A M A M A M A M A MA M A M A F A F A F A F A FA F A F A F A _> 13859 M A M A M A M A M A M A F A F A F A F A F A F A F A F A FDII 13860 M A M A M A M A M A M A MA M A M A F A F A F A FA ........................................................................................... FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE ........................................ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), 4_ X-SACRIFICED DUE TO SACRIFICE OF DAM OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. hO O PROTOCOL 418-020. ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C38 (PAGE 3) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 13861 13862 13863 13864 13865 13866 13867 13868 13869 MA MA PREGNANT; MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA DID MA MA MA MA MA MA MA MA MA NOT DELIVER MA MA M A FA MA M A MA M A MA M A MA MA MA M A M A MA M A FA A LITTER F A FA F A F A FA FS M A M A MD 1 F A M A M A MD15 FA M A M A MD 7 MD 6 MA MA M A FA M A M A FA FA FA FA FA FA MS 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 FM 3 FA FA FA FA F A FD 6 FA FA F A FD 4 FA F A FD 8 13870 MA MA FA FA FA FA FA FA 1133887712 13873 13874 13875 13876 13877 13878 13879 13880 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA M AA MA MA MA MA MA FA MA MA M A MDM A3 MA MA MA MA M A MA MA MA MA MA FA FA MA MA MA MA FM A MA FA MA MA MA FA MA MA MF A MA FA MA MA MA FA FA MA MF A MA FA MA FA FA FA FA MA MF A FA FA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F AA FDF20A FMF A7 FDF A4 F A FA FA FA FA F A FA FA F A FA FA FA F A F A F S FD 1 FA FA FS FA F A FA FA F A FM 4 F A FD 2 FA 13881 13882 13883 13884 13885 13886 13887 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 MA MA MA MA MA MA MA MA MA MA FA MA MA FA FA MA FA FA MA MA FA MA FA MA FA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A FD 3 F A FD 1 13888 M A MA FA FA FA FA FA FA FA F A FA FA FA FA FS 13889 MA MA MA MA M A M A M A M A M A M A FA FA FA FA FA FA 13890 MA FA FA FA FA FA FA FA FA FA F A FA FA FA FA _'_ ............................. ' FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), 4_ X-SACRIFICED DUE TO SACRIFICE OF DAM O0 NDMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C38 (PAGE 4) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 i0 Ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... 13891 M A M A M A M A M S F A FA FA FA FA FA 13892 13893 13894 13895 13896 13897 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA M A MA M A MA M A MM 4 M A MA F A FA M A FA FA FA FA MA FA FA FA FA FA MA 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 FS 13898 13899 MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD 3 13900 NOT PREGNANT; MATING NOT CONFIRMED 13901 13902 13903 13904 13905 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 FA MA FA MA MA FA MA FA FA FA FA MA 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 F A FD 7 FA FA FA 13906 13907 13908 13909 13910 13911 13912 13913 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 FA MA MA MA MA MA M A MD 3 MA MA MS MA MS MA MA MA MA MA MA FA MA MA MA MA FA FA MA MA MA FA FA MA FA FA FA MA 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 F A FD 8 FA FA FA 13914 13915 13916 13917 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA MA FA MA MA MA FA MA MA MA FA MA MA 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 F A FM 3 FA 13918 13919 MA MA MA MA MA MA MA MA MA MA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA 13920 M A M A M A M A M A M A MD 9 F A F A F A F A F A F A FD 9 FD 9 FD 3 .................................................................................................................................... FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), 4_ X-SACRIFICED DUE TO SACRIFICE OF DAM OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C38 (PAGE 5) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 II 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY ...... .............................................................................................................................. 13921 13922 13923 13924 13925 13926 13927 13928 13929 MA MA MA MA MA MA MA MA NOT M A MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA PREGNANT M A M A M A M A M A MM 6 M A MM 2 MD 1 MD 1 FM 2 FM 2 MA M A M A MA F A F A MA MA M A MA M A M A M A M A M A FA F A F A MA MA MA MA M A M S MA MA MA MA FA FA M A MD 8 MD 3 F A F A F A 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 F A FD 7 FA FA FA 13930 M A M A M A M A M A M A M A M A MD 8 F A F A F A F A F A F A F A FD 6 FM 5 1133993312 MM AA MM AA MM AA MM AA MM AA MM AA MDM 8A MDM A6 13933 M A M A M A M A M A F A FA FA 13934 M A MMI2 MM 4 F A F A F A F A F A 13935 MA MA MA MA M A M A MA FA 13936 MA MA MA MA M A M A MA M A 13937 M A M A M A M A M A M A FA F A 13938 M A M A M A M A M A M A M A MD 2 13939 MA M A M A MA MA M A MA FA 13940 M A M A M A M A M A M A FA F A 13941 M A M A M A M A M A M A MA M A 13942 M A M A M A M A M A M A MA M A 13943 M A M A FA FA FA FA FA 13944 M A M A M A MM 5 F A F A F A F A 13945 M A M A MA M A M A MA MA MA 13946 M A M A M A M A M A F A FA F A 13947 FD 1 13948 MA MA MA MA M A M A MA FA 13949 MA MA MA MA M A M A MA M A 13950 MA MA MA MA MA M A MS FA .......................................................................................... FF AA FA FA FA MA FA FA FA FA MA MA FA MA FA FA MA FA FF AA FA FA FA MA FA FA FA FA FA MA FA FA FA FA FA FA FF AA FA FA FA MA FA FA FA FA FA MA FF AA FDF 6A FDF 6A FM 2 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 F A FA FA FA F A FMI0 FA FA FA FA FA F A FM 3 FA FA F A FD 2 FA FS FS FA FA ' ........................................ FIRST SECOND NUMBER LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, X-SACRIFICED DUE TO SACRIFICE OF DAM FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM M-MISSING (PRESUMED THE EVENT OCCURRED. CANNIBALIZED}, _> _'_ _._4_ OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C39 (PAGE i): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY (S) MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... I 0 13807 5 OBSERVATIONS a 3/17 PUPS: COLD TO TOUCH; NOT NESTING; NOT NURSING. 13817 1 1/15 PUPS: COLD TO TOUCH; NO MILK IN STOMACH. 13820 5 1/14 PUPS: COLD TO TOUCH. 13824 2 16/16 PUPS: COLD TO TOUCH. II 1 (_ t_ _-_ "/ 13827 13833 13837 13839 1 8, 9 1 1-22 4 1/16 PUPS: COLD TO TOUCH. 1/14 PUPS: 1/12 PUPS: 1/12 1/12 PUPS: PUPS: UMBILICAL HERNIA. COLD TO TOUCH. NO TAIL PRESENT COLD TO TOUCH, b; NINDLIMBS ROTATED INWARD. 13849 3 1/16 PUPS: COLD TO TOUCH. 13850 1 5-22 2/13 1/12 PUPS: PUPS: COLD TO TOUCH. TIP OF TAIL MISSING. 13852 5- 6 .................................................................................................................................... 1/12 PUPS: NIPPLE EXAMINATIONS FORALLMALE PUPS APPEARED NORMAL. a. Tabulation restricted to adverse observations; all other pups appeared normal. b. Observation confirmed at necropsy. LEFT FORELIMB, MASS (0.3 CM IN DIAMETER). > C _n 4_ o0 to o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C39 (PAGE 2}: CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY (S) MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... III 3 13868 1 OBSERVATIONS a 16/16 PUPS: COLD TO TOUCH. PUPS 13873 7 1/16 PUPS: COLD TO TOUCH. 13877 3 1/13 PUPS: COLD TO TOUCH. 13878 1 9/ 9 PUPS: COLD TO TOUCH. 13887 1-20 21,22 1/11 1/11 PUPS: PUPS: TIP OF TAIL TIP OF TAIL BLACK. MISSING.b t_ _-_ IV OO i0 13888 13889 13894 12 7 1- 4 5-22 1/14 PUPS: 2/16 PUPS: RED PERIANAL SUBSTANCE. COLD TO TOUCH. 1/14 1/13 PUPS: PUPS: TIP OF TAIL TIP OF TAIL MISSING. MISSING. 13895 1- 6 1/15 PUPS: BRUISE, BACK (DID NOT EXCEED 2.0 CM X 1.0 CM). 13898 5 1/16 PUPS: COLD TO TOUCH. 13905 21,22 1/16 PUPS: LEFT EYE, TRAUMATIZED CORNEA.b 13906 7 1/13 PUPS: PALE; NO MILK IN STOMACH; NOT NESTING. 13912 5 1/14 PUPS: SCAB, BACK (0.2 CM IN DIAMETER). 12 1/14 PUPS: UMBILICAL HERNIA. 13914 1,2 .................................................................................................................................... 1/18 PUPS: NIPPLE EXAMINATIONS FOR ALLMALE PUPS APPEARED NORMAL. a. Tabulation b. Observation restricted confirmed to adverse observations; at necropsy. all other pups appeared normal. COLD TO TOUCH; NO MILK IN STOMACH. > [2_ _-4_ O t_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C39 (PAGE 3}: CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY (S) MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... V 30 13921 12-22 OBSERVATIONS a 1/14 PUPS: MOUTH, MASS 0.I CM). (DID NOT EXCEED 0.2 CM X 0.3 CM X 13922 1 15-19 i/ 9 PUPS: 1/ 9 PUPS: COLD TO TOUCH. UMBILICAL HERNIA. 13927 4- 7 8- 9 1/16 1/15 PUPS: PUPS: BACK, BACK, BRUISE BRUISE (DID (0.2 NOT EXCEED 1.0 CM UM IN DIAMETER). X 0.5 CM). 13930 1, 2 3 18/18 3/18 PUPS: PUPS: COLD COLD TO TOUCH. TO TOUCH. 4 18/18 PUPS: COLD TO TOUCH. 5 12-20 1/18 PUPS: 1/15 PUPS: BACK, BRUISE (0.5 CM IN DIAMETER). UMBILICAL HERNIA. t_ _" 13931 1 1/15 PUPS: NO MILK IN STOMACH. k_ 4,5 1/14 PUPS: BACK, BRUISE (i.0 CM X 0.5 UM). 13934 1,2 1/15 PUPS: HEAD, BRUISE (0.5 UM IN DIAMETER), BACK, BRUISE (2.0 CM X 1.0 CM). 3 1/15 PUPS: HEAD AND BACK, BRUISE (1.0 CM IN DIAMETER), CHEST AND LOWER MIDLINE, BRUISE (2.5 CM X 1.5 UM); COLD TO TOUCH. 13944 9 1/11 PUPS: PALE; NO MILK IN STOMACH. 13948 3 4 .................................................................................................................................... 11/12 11/11 PUPS: PUPS: NIPPLE EXAMINATIONS FOR a. Tabulation restricted ALL MALE PUPS APPEARED NORMAL. to adverse observations; all other pups appeared normal. COLD TO TOUCH. COLD TO TOUCH. > c _b "3 t_ tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE I): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... I 0 13801 22 13802 22 13803 22 13805 22 13806 22 13807 22 OBSERVATIONS a ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. PUPS 13808 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13809 22 ALL PUPS EXAMINED APPEARED NORMAL. 13810 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 3 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13812 13813 13814 13815 13816 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13817 2 22 .................................................................................................................................... 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. C O_ bJ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 2): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - Pl GENERATION PUPS -_ .................................................................................................................................. MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... I (Cont.) 0 13818 2 22 OBSERVATIONS a 1 PUP: POUND DEAD. AUTOLYSIS PRECLUDED EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. FURTHER 13819 1 1 PUP: POUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13820 13821 13822 22 22 8b ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 13823 22 ALL PUPS EXAMINED APPEARED NORMAL. 1133882245 2222 AALLLL PPUUPPSS EEXXAAMMIINNEEDD AAPPPPEEAARREEDD NNOORRMMAALL.. %0 13826 22 ALL PUPS EXAMINED APPEARED NORMAL. 13827 22 ALL PUPS EXAMINED APPEARED NORMAL. 13828 22 ALL PUPS EXAMINED APPEARED NORMAL. 13829 22 ALL PUPS EXAMINED APPEARED NORMAL. ...... a. b. 13830 1 22 .............................................................................................................................. 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. > O _9 4= O0 d:, t,.,I 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 3): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - Pl GENERATION .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... II 1 13831 22 13832 22 13833 22 13834 22 OBSERVATIONS a ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. PUPS 13835 2 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 3 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13837 1 1 PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. t_ 13838 4 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. b_ 22 ALL PUPS EXAMINED APPEARED NORMAL. 13839 22 ALL PUPS EXAMINED APPEARED NORMAL. 13841 1 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13842 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13843 22 ALL PUPS EXAMINED APPEARED NORMAL. 13844 8 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13845 13846 22 ALL PUPS EXAMINED 'APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. -_ .................................................................................................................................. a. Complete necropsles were not performed on pups in which autolysis individual pup clinical observations table (Table C39) for external or cannibalization precluded evaluation. Refer clinical observations confirmed at necropsy. to the _19 w-- O0 bo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 4): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... II (Cont.) 1 13847 1 22 OBSERVATIONS a 7 PUPS: STILLBORN. EVALUATION. ALL PUPS EXAMINED AUTOLYSIS PRECLUDED APPEARED NORMAL. FURTHER 13848 13849 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13850 1 i PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13852 llb ALL PUPS EXAMINED APPEARED NORMAL. 13853 22 ALL PUPS EXAMINED APPEARED NORMAL. t_ 13854 22 ALL PUPS EXAMINED APPEARED NORMAL. _O t_ 13855 1 i PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 5 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13856 22 ALL PUPS EXAMINED APPEARED NORMAL. 13857 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13858 22 ALL PUPS EXAMINED APPEARED NORMAL. 13859 11 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13860 22 ALL PUPS EXAMINED APPEARED NQRMAL. C a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. b. The litters from dams 13822 in Group I and 13852 in Group II were mixed together. Both dams and litters were sacrificed because it was not possible to identify to which litter the pups belonged. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITI'ER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 5) : NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... III 3 13861 22 13863 22 OBSERVATIONS a ALL PUPS ALL PUPS EXAMINED EXAMINED APPEARED APPEARED NORMAL. NORMAL, 13864 1 1 PUP: STILLBORN, ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13865 1 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL, 13866 8 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 15 1 PUP: FOUND DEAD. NO MILK IN STOMACH. (_ AUTOLYSIS PRECLUDED FURTHER EVALUATION. t_ 22 ALL PUPS EXAMINED APPEARED NORMAL. tO 4_ 13867 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 6 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL, 13868 13869 22 ALL PUPS EXAMINED APPEARED NORMAL. 4 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13870 22 ALL PUPS EXAMINED APPEARED NORMAL. 13871 3 4 20 22 .................................................................................................................................... 1 PUP: 1 PUP: FOUND DEAD. ALL TISSUES APPEARED FOUND DEAD. NO MILK IN STOMACH. PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. NO MILK IN STOMACH. PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. NORMAL. AUTOLYSIS AUTOLYSIS _J9 4_ w.- OO _.) a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the O individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 6): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM ........................................................................................................................... III (Cont.) 3 13872 22 13873 22 OBSERVATIONS a ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED NORMAL. NORMAL. ' ........ 13874 2 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13875 22 ALL PUPS EXAMINED APPEARED NORMAL. 13876 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13877 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. t_ 22 ALL PUPS EXAMINED APPEARED NORMAL. b_ tJl 13878 22 ALL PUPS EXAMINED APPEARED NORMAL. 13879 22 ALL PUPS EXAMINED APPEARED NORMAL. 13880 22 ALL PUPS EXAMINED APPEARED NORMAL. 13881 22 ALL PUPS EXAMINED APPEARED NORMAL. 13882 3 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13883 1 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13884 13886 13887 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13888 1 1 PUP: STILLBORN.' ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. [/] 4_ 13889 22 ALL PUPS EXAMINED APPEARED NORMAL. O0 13890 22 ALL PUPS EXAMINED APPEARED NORMAL. tO .................................................................................................................................... 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 (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 7): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... IV I0 13891 1 22 OBSERVATIONS a 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 13892 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13893 13894 13895 13896 13897 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13898 223 A1LLPUPP:UPS FOEUXNADMINEDDEAD. APPEALRLED TISNSOUREMSAL. APPEARED NORMAL. t_ b.) 13899 22 ALL PUPS EXAMINED APPEARED NORMAL. O% 13901 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13902 13903 13904 13905 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13906 1 3 8 22 13907 22 __ .................................................................................................................................. 2 PUPS: 1 PUP: STILLBORN. ALL TISSUES APPEARED FOUND DEAD. NO MILK IN STOMACH. PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. NORMAL. AUTOLYSIS FURTHER ALL PUPS EXAMINED APPEARED NORMAL. C [/9 -_ a. Complete necropsles were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the Oo individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 8): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS -_ .................................................................................................................................. MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... IV (Cont.) i0 13909 22 13910 22 13911 22 13912 22 13913 22 13914 22 13915 22 13916 22 13917 22 13918 22 13919 22 OBSERVATIONS a ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 13920 3 9 t_ _O "_ 22 .................................................................................................................................... 1 PUP: 2 PUPS: 1 PUP: ALL PUPS FOUND DEAD. ALL TISSUES APPEARED FOUND DEAD. AUTOLYSIS PRECLUDED EVALUATION. FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. EXAMINED APPEARED NORMAL. NORMAL. FURTHER 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 cllnical observations confirmed at necropsy. > OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 9}: NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... V 30 13921 22 OBSERVATIONS a ALL PUPS EXAMINED APPEARED NORMAL. 13922 1 2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13923 13924 13925 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13926 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13927 7 1 PUP: FOUND DEAD. NO MILK IN STOMACH. (_ ALL OTHER TISSUES APPEARED NORMAL. t_ 22 ALL PUPS EXAMINED APPEARED NORMAL. OO 13928 3 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 8 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13930 6 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 8 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13931 6 2 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH. AUTOLYSIS > PRECLUDED FURTHER EVALUATION. 8 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED 'APPEARED NORMAL. 13932 22 ALL PUPS EXAMINED APPEARED NORMAL. 4_ 13933 22 ALL PUPS EXAMINED APPEARED NORMAL. OO .................................................................................................................................... a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the _OO individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C40 (PAGE 10): NECROPSY OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER DAY MATERNAL DOSAGE (MG/KG/DAY) NUMBER POSTPARTUM .................................................................................................................................... V (Cont.) 30 13934 22 13935 22 13936 22 13937 22 OBSERVATIONS a ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 13938 2 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13939 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13940 22 ALL PUPS EXAMINED APPEARED NORMAL. 13941 1 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. t_ 22 ALL PUPS EXAMINED APPEARED NORMAL. %0 13942 22 ALL PUPS EXAMINED APPEARED NORMAL. 13943 22 ALL PUPS EXAMINED APPEARED NORMAL. 13944 22 ALL PUPS EXAMINED APPEARED NORMAL. 13945 22 ALL PUPS EXAMINED APPEARED NORMAL. 13946 22 1 PUP: KIDNEYS, RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL. 13947 1 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 13948 13949 22 ALL PUPS EXAMINED APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 13950 1 2 22 __ .................................................................................................................................. 3 PUPS: STILLBORN. ALL TISSUES APPEARED 1 PUP: FOUND DEAD'. ALL TISSUES APPEARED ALL PUPS EXAMINED APPEARED NORMAL. NORMAL. NORMAL. [/) a. Complete necropsles were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the O0 individual pup clinical observations table (Table C39) for external clinical observations confirmed at necropsy. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C41 (PAGE 1): PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F1 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT/ LITTER NUMBER BRAIN M F T SPLEEN M F T THYMUS M F T .................................................................................................................................... 13801 13802 13803 13804 1.67 1.53 1.60 1.58 1.48 1.53 1.35 1.43 1.39 MORIBUND SACRIFICED 0.27 0.i0 0.ii ON 0.21 0.15 0.13 DAY 68 0.24 0.12 0.12 OF STUDY 0.21 0.19 0.17 0.23 0.16 0.21 0.22 0.18 0.19 TERMINAL M BODY F WEIGHT T 44.6 43.0 a 42.5 41.3 a 43.6 42.2 a 13805 13806 13807 13808 1.31 1.45 1.27 1.45 1.20 1.41 1.23 1.63 1.26 1.43 1.25 1.54 0.19 0.12 0.09 0.18 0.ii 0.14 0.06 0.21 0 15 0 13 0 08 0 20 0.26 0.13 0.07 0.22 0.16 0.14 0.07 0.28 0.21 0.14 0.07 0.25 46.6 32.1 a 40.9 41.0 31.4 a 39.8 43.8 31.8 a 40.4 13809 13810 13811 1.40 1.41 1.47 1.40 NOT PREGNANT 1.40 1.44 0.14 0.17 0.12 0.17 0 13 0 17 0.ii 0.21 0.13 0.25 0.12 0.23 35.9 43.4 33.8 43.1 34.8 43.2 13812 13813 13814 13815 1381G 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 1.36 1.29 1.38 1.48 1.38 1.33 1.36 1.34 1.20 1.16 1.59 1.54 1.30 1.38 1.25 1.35 1.43 1.26 1.45 1.41 SACRIFICED 1.51 1.49 1.48 1.41 .... 1.37 1.36 1.25 1.32 1.43 1.36 1.35 1.18 1.56 1.28 1.36 1.34 1.43 ON DAY 1.50 1.44 1.37 1.30 0.ii 0.10 0 i0 0.13 0.14 0 14 0.13 0.08 0 i0 0.05 0.05 0 05 0.17 0.14 0 16 0.14 0.13 0 14 0.08 0.20 0.06 0.12 0 07 0 16 0.12 0.08 0 i0 0.07 0.17 0 12 8 OF LACTATION 0.34 0.22 0 28 0.14 0.11 0 12 .... 0.07 0 07 0.14 0.14 0 14 0.08 0.14 0.15 0.13 0.13 0.12 0.09 0.18 0.18 0.11 0.28 0.16 .... 0.13 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.ii 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 43.2 43.9 38.8 33.8 32.8 37.9 25.8 30.6 26.1 35.0 52.0 38.4 .... 31.8 40.1 44.0 32.5 28.4 27.3 36.7 26.5 27.8 21.8 39.6 51.3 38.8 32.7 23.6 41.6 44.0 35.6 31.1 30.0 37.3 26.2 29.2 24.0 37.3 51.6 38.6 32.7 27.7 13827 1.57 1.56 1.56 0.17 0.20 0 18 0.15 0.13 0.14 42.5 37.5 40.0 > 13828 1.39 1.45 1.42 0.25 0.16 0 20 0.18 0.12 0.15 42.2 39.6 40.9 13829 1.51 1.27 1.39 0.15 0.13 0 14 0.17 0.15 0.16 42.0 32.8 37.4 13830 1.38 1.44 1.41 0.11 0.I0 0 10 0.14 0.20 0.17 35.0 36.9 36_0 .................................................................................................................................... _#_ MALE F = FEMALE T = TOTAL WEIGHTS WERE RECORDED IN GRAMS (G) " _O-0- Pup's identification was not recorded; therefore, terminal body weight could not be determined. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C41 (PAGE 2): PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT/ LITTER BRAIN SPLEEN THYMUS NUMBER M F T M F T M F T .................................................................................................................................... 13831 13832 13833 13834 13835 13836 13837 13838 1,47 1.47 1.47 1.65 1.49 1.57 1.51 1,49 1.50 1.52 1.47 1,50 1.52 1.44 1.48 MORIBUND SACRIFICED 1.66 1.49 1.58 1.45 1.40 1.42 0.ii 0.14 0.15 0.12 0.12 0.12 0.07 0.08 0.10 0.14 ON DAY 59 0.19 0.17 0,11 0.09 0.12 0.14 0.12 0,08 0.12 OF STUDY 0.18 0.10 0.12 0.14 0.17 0.18 0.11 0.26 0.16 0.13 0.17 0.19 0.12 0.17 0.22 0.12 0.12 0.16 0.18 0.15 0,14 0.24 0.14 TERMINAL M BODY F 33.1 45.2 a 36.2 36.7 36,7 35.5 a 37.7 37.3 a 36.0 a 36.0 13839 13840 1.42 1.45 1.44 NOT PREGNANT 0.14 0.13 0.14 0.17 0.i0 0.14 36.1 32.7 13841 13842 1.34 1.49 1.33 1.40 1.34 1.44 0,15 0.17 0.15 0.12 0.15 0.14 0.15 0.14 0 15 0 19 0.15 0 16 13843 1.33 1.29 1.31 0,Ii 0.ii 0.ii 0.13 0 13 0 13 13844 1 39 1.29 1.34 0,12 0.06 0.09 0,15 0 12 0 14 13845 1 43 1.49 1.46 0,11 0.16 0.14 0.13 0 16 0 14 13846 1 41 1.45 1.43 0.16 0.08 0.12 0.17 0 17 0 17 13847 1 53 1.49 1.51 0,21 0.21 0.21 0.21 0 24 0 22 13848 1 32 1.34 1.33 0.11 0.04 0.08 0.15 0 15 0 15 13849 1 30 1.28 1.29 0.06 0.07 0.06 0.08 0 07 0 08 13850 1.56 1.42 1.49 0.13 0.14 0.14 0.17 0 16 0 16 13851 NOT PREGNANT 13852 SACRIFICED ON DAY 11 OF LACTATION 13853 1.53 1.40 1.46 0.13 0.14 0,14 0.17 0.14 0.16 13854 1.11 1.10 1.10 0.15 0.04 0 10 0.18 0.05 0.12 13855 1.53 1.53 1.53 0.08 0.08 0 08 0.20 0.18 0.19 13856 1.40 1.30 1.35 0.I0 0.07 0 08 0.10 0.07 0.08 13857 1.45 1.54 1.50 0.06 0.15 0 i0 0.22 0.25 0.24 13858 1.36 1.36 1.36 0,ii 0.ii 0 Ii 0.ii 0.12 0,12 13859 1.52 1.50 1.51 0.18 0.17 0 18 0.16 0,20 0.18 13860 1.44 1.37 1.40 0.i0 0.i0 0 I0 0.19 0.18 0.19 .................................................................................................................................... 36.3 43.4 34.3 33.6 a 36.3 51.4 a 27.5 37.3 37.0 37.7 30,1 27.8 a 31,0 50.4 a 23,6 33,8 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 -- MALE F = FEMALE ALL WEIGHTS WERE RECORDED Pup's identification determined, T = TOTAL IN GRAMS (G). was not recorded or appeared incorrectly recorded; therefore, WEIGHT T 34.9 40.4 a 37.0 37.0 a 36.0 34.4 36.6 40.6 32.2 30.7 a 33.6 50.9 a 25.6 35,6 32.6 27.0 38.6 29.2 40.7 32.0 39.0 37.D terminal body weight could not be _'_ 00 _t_ O0 t_) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE C41 (PAGE 3): PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F1 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT/ LITTER BRAIN SPLEEN THYMUS NUMBER M F T M F T M F T .................................................................................................................................... 13861 13862 13863 13864 13865 13866 13867 13868 1.34 .... 1.34 PREGNANT; DID NOT 1.36 1.43 1.40 1.50 .... 1.50 1.48 1.42 1.45 1.28 1.13 1.20 1.34 1.28 1.31 1.41 1.45 1.43 0.08 DELIVER 0 11 0 28 0 12 0 12 0 05 0 08 .... 0.08 A LITTER 0.11 0.11 .... 0,28 0.14 0.13 0.06 0,09 0.12 0.08 0.11 0,10 0.04 0.11 0.23 0.08 0.11 0.i0 0.13 .... 0.04 0.11 .... 0.14 0.11 0.12 0.15 0.ii 0.23 0.11 0.11 0.11 0.14 TERMINAL M BODY F WEIGHT T 36.2 .... 36.2 32.5 59.3 30.4 a 29.9 a 34.6 .... 28,6 a 28.2 a 33.6 59.3 29.5 a 29.0 a 13869 1,23 1,35 1.29 0 09 0 I0 0,I0 0.07 0.i0 0.08 33.7 29.8 31.8 13870 13871 .... 1.12 1.25 1.25 1.25 1.18 .... 0 I0 0,i0 0 02 0 08 0,05 .... 0.15 0.15 0 08 0 08 0.08 .... 26.8 36.3 29.1 36.3 28.0 13872 1.44 1.41 1.42 0 09 0 10 0.i0 0 i0 0 15 0.12 29.8 30.0 29.9 13873 1.40 1.40 1.40 0 I0 0 12 0.ii 0 15 0 15 0.15 35.3 35.6 35.4 13874 1.63 1.40 1.52 0 22 0 16 0.19 0 15 0 18 0.16 49.1 43.4 46.2 13875 1.48 1.43 1.46 0 13 0 13 0.13 0 14 0 08 0.11 40.1 42.9 41.5 13876 1.59 1.62 1.60 0 11 0 23 0.17 0 15 0 06 0.10 45.3 47.0 46.2 13877 1.51 1 55 1.53 0.16 0 14 0.15 0 22 0 18 0.20 45.8 42.5 44,2 13878 .... 1 54 1.54 .... 0 23 0.23 .... 0 20 0.20 .... 51.8 51,8 13879 1.64 1 53 1.58 0.10 0 19 0.14 0 16 0 24 0.20 46.1 47.7 46.9 13880 1.58 1 39 1.48 0.19 0 16 0.18 0 21 0 15 0.18 52.8 42.9 47.8 13881 1.45 1 39 1.42 0.06 0 07 0.06 0 11 0 08 0.10 37.7 37.2 37.4 13882 1.45 1 50 1.48 0.10 0 13 0.12 0 11 0 12 0.12 37.6 44.5 41.0 13883 1.47 1.39 1.43 0.19 0.13 0.16 0 22 0.18 0.20 43.6 48.0 45.8 13884 1.51 1.31 1.41 0.21 0.08 0.14 0 18 0.15 0.16 42.3 27.4 34.8 13885 b 13886 1.47 1.45 1,46 0,12 0,12 0,12 0,15 0.15 0.15 40.3 40.6 40.4 13887 1.62 1.55 1.58 0.18 0.18 0.18 0.24 0.20 0.22 49.9 45.3 47.6 13888 .... 1,31 1.31 .... 0.15 0.15 .... 0.09 0.09 .... 25.9 25.9 13889 1.53 1.32 1.42 0.15 0.i0 0.12 0,16 0.13 0.14 35.8 32.1 34.0 _'_ 13890 .... 1.37 1.37 .... 0.06 0.06 .... 0.17 0.17 .................................................................................................................................... .... 38.8 38.'8 = MALE F = FEMALE T = TOTAL ALL WEIGHTS WERE RECORDED IN GRAMS (G). O_ Pup's identification was not recorded; therefore, terminal body weight could not be determined. All pups were selected for continued observation, tO_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NI_4BER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C41 (PAGE 4) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F1 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT/ LITTER NUMBER BRAIN M F T SPLEEN M F T THYMUS M F T .................................................................................................................................... 13891 13892 1.60 1.44 1 53 1 51 1,56 1.48 0.17 0.19 0.26 0.13 0.22 0.16 0.17 0.19 0.22 0.15 0 20 0 17 13893 13894 13895 13896 13897 13898 1.52 1.40 1.54 1.52 1.44 1.37 1 37 1 41 1 39 1 46 1 36 1 28 1.44 1.40 1.46 1.49 1.40 1.32 0,17 0.10 0.16 0.12 0.16 0.10 0.13 0.16 0.19 0.13 0.14 0.06 0.15 0.13 0.18 0.12 0.15 0.08 0.22 0.17 0.22 0.13 0.27 0.11 0.16 0.20 0.14 0.14 0.26 0.10 0 19 0 18 0 18 0 14 0 26 0 10 13899 1.33 1 30 1.32 0.07 0.ii 0.09 0.20 0.15 0 18 TERMINAL M BODY F WEIGHT 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 31,7 46.0 37.7 41.6 34.7 40.6 a 43.3 31.3 32.0 139001 13902 13903 13904 13905 13906 13907 13908 N1OT36 PRE1G.N2A8NT; 1 60 1.49 1 43 1 27 1 38 1.30 1 32 1.13 1 53 1.41 1 20 b 1.29 1.3M2ATING 0.0N7OT 1 54 0.19 1 40 0.15 1 28 0.11 1 22 0.05 1 47 0.18 1 24 0.12 C0O.N0F7IRME0D.07 0.17 0.18 0.13 0.14 0.13 0.12 0.07 0.06 0.23 0.20 0.10 0.11 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 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 13909 13910 13911 13912 13913 13914 13915 13916 1.50 1.42 1.44 1.49 1.44 1.43 1 30 1 32 1 43 1 39 1 47 1 41 1 25 1 41 1 31 1 54 1.46 1.40 1.46 1 45 1 34 1 42 1 30 1 43 0.12 0.17 0.10 0.13 0.20 0.09 0.08 0.18 0.I0 0.14 0.14 0.16 0.19 0.10 0.10 0.20 0.11 0.16 0.12 0.14 0.20 0.10 0.09 0.19 0.14 0.18 0.23 0.18 0.27 0.18 0.13 0.22 0.11 0.16 0.23 0,15 0.23 0.13 0.15 0.20 0.12 0.17 0.23 0.16 0.25 0.16 0.14 0.21 39.8 39,5 43,3 a 43.2 a 31.8 43.2 38,4 38.0 40,7 a 37,2 a 349 40.2 39.1 38.8 42.0 a 40.2 a 33.4 41.7 13917 1 42 1 40 1 41 0.12 0.13 0.12 0.16 0.17 0.16 41.3 40.8 41.0 > 13918 1 62 1 37 1 50 0.26 0.16 0.21 0.19 0.15 0.17 45.3 39.1 42.2 13919 1 48 1.49 1 48 0.08 0.12 0.10 0.11 0.09 0.i0 38,4 37.4 37.9 13920 1 12 1.38 1 25 0.12 0.12 0.12 0.23 0.19 0.21 .................................................................................................................................... 26,9 23.7 25,3 MALE F = FEMALE T = TOTAL 4_ WEIGHTS WERE RECORDED IN GRAMS (G) _O-O- Pup's identification determined. was not recorded or appeared incorrectly recorded; therefore, terminal body weight could not be All pups were selected for continued observation. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE C41 (PAGE 5): PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F1 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT/ LITTER NUMBER BRAIN M F T SPLEEN M F T THYMUS M F T .................................................................................................................................... 13921 1.53 1.49 1.51 0 16 0.14 0.15 0.18 0.i0 0.14 13922 1.29 .... 1.29 0 12 .... 0.12 0.10 .... 0.10 13923 1.52 1.41 1.46 0 10 0.09 0.10 0.15 0.13 0.14 13924 1.49 1.43 1.46 0 09 0.08 0.08 0.14 0.15 0.14 13925 1.35 1.40 1.38 0 11 0.13 0.12 0.16 0.17 0.16 13926 1.39 1.35 1.37 0 11 0.12 0.12 0.16 0.16 0.16 13927 1.19 1.16 1.18 0 06 0.07 0.06 0.07 0.06 0.06 13928 1.46 1.39 1.42 0 16 0.18 0.17 0.20 0.18 0.19 TERMINAL M BODY F WEIGHT T 46.1 32.8 a 34.5 32.9 34.0 23.9 a 40.6 .... a 34.3 38.2 31.2 22.5 a 43.4 32.8 a 34.4 35.6 32.6 23.2 a 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 13940 13941 13942 13943 13944 13945 13946 NOT PREGNANT 1.28 1.13 1.32 1.17 .... 1.33 1.42 1.43 1.32 1.51 1.29 1.59 1.58 .... 1.39 1.41 1.35 1.33 1.15 1.30 1.19 1.26 1.30 1.48 1.40 1.21 1.46 1.22 1.52 1.41 1.56 1.35 1.35 1.26 1.30 1.14 1.31 1.18 1.26 1.32 1.45 1.42 1.26 1.48 1.26 1.56 1.50 1.56 1.37 1.38 1.30 0.08 0.07 0.ii 0.06 .... 0 05 0 15 0 11 0 09 0 16 0 04 0 19 0 18 .... 0.13 0.09 0.ii 0.I0 0.07 0.14 0.i0 0.12 0.07 0.15 0.13 0.06 0.15 0.06 0.13 0.15 0.24 0.12 0.11 0.14 0.09 0.07 0.12 0.08 0.12 0.06 0.15 0.12 0.08 0.16 0.05 0.16 0.16 0.24 0.12 0.10 0.12 0.06 0.09 0.05 0.06 .... 0.11 0.13 0.12 0.14 0.14 0.04 0.18 0.14 .... 0.16 0.12 0.16 0.06 0.10 0.12 0.08 0.15 0.08 0.19 0.11 0.11 0.23 0.07 0.13 0.12 0.20 0.18 0.14 0.17 0.06 0.10 0.08 0.07 0.15 0.10 0.16 0.12 0.12 0.18 0.06 0.16 0.13 0.20 0.17 0.13 0.16 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 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 22.9 24.9 32.1 a 30.6 27.9 36.6 38.8 27.8 40.2 28.4 36.6 a a 34.9 a 42.8 13947 13948 SACRIFICED 1.46 1.38 DUE TO NO SURVIVING 1.42 0.14 0.14 PUPS 0.14 ON DAY 0.18 1 OF LACTATION 0.15 0.16 43.4 42.4 42.9 13949 1.52 1.45 1.48 0.12 0.12 0.12 0.19 0.18 0.18 40.9 38.3 39.6 13950 1.64 1.48 1.56 0.18 0.17 0.18 0.28 0.21 0.24 47.4 42.0 44.7 .................................................................................................................................... _#_ MALE F = FEMALE T = TOTAL WEIGHTS WERE RECORDED IN GRAMS (G). O_ Pup's identification was not recorded or appeared incorrectly recorded; therefore, terminal body weight could not be determined. [_ O ARGUS 418-020 APPENDIX D REPORT TABLES - F1 GENERATION MALE RATS Page 335 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.G) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D1 (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... MAXIMUM POSSIBLE INCIDENCE 4563/ 60 4547/ 60 MORTALITY FOUND DEAD a MORIBUND SACRIFICED a 3 3 2 3 1 0 III 3 4576/ 60 3 3 0 IV 10 4602/ 60 2 1 1 V 30 4473/ 60 7 6 1 ANNULAR CONSTRICTION CHROMORHINORRHEA ABDOMINAL DISTENTION OF THE TAIL 44/ 4 12/ 9 25/ 4 122/ ii* 18/ 9 41/ 4 69/ 7 22/ ii 11/ 1 122/ Ii* i0/ 4 73/ 5 214/ 21,* 26/ 12 124/ 10.* URINE-STAINEDABDOMINAL FUR 11/ 1 2/ 2 13/ 1 6/ 1 40/ 9** t_ EMACIATION UO (3_ CHROMODACRYORRHEA 0/ 0 22/ 3 i/ i 53/ 5 2/ 2 244/ 9 15/ 3* 55/ 4 22/ 7** 171/ 6 DECREASED MOTOR ACTIVITY 1/ 1 i/ 1 0/ 0 i/ 1 12/ 5** COLD TO TOUCH i/ 1 i/ 1 i/ 1 13/ 2 11/ 5 INCISORS: TOTAL MISALIGNED MISSING/BROKEN 47/ 5 12/ 3 36/ 4 62/ 3 62/ 3 0/ 0 258/ 9 194/ 7 66/ 4 171/ 5 123/ 3 48/ 2 188/ 4 181/ 4 25/ 2 SCAB h 89/ 4 30/ 2 55/ 5 18/ 3 7/ 3 SOFT OR LIQUID FECES 22/ II 14/ Ii 6/ 5 7/ 7 3/ 3 .................................................................................................................................... MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/_BER N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS a. Refer to the individual clinical observations sacrificed. OF RATS EXAMINED WITH OBSERVATION. table (Table DI4) PER GROUP. for observations for ra_s that were found dead or moribund b. Located on neck, head, back, mouth, and behind left ear. 4_ * Significantly different from the Group I value (p_0.05). O0 ** Significantly different from the Group I value (p_0.01). PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION TABLE D1 (PAGE 2): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE -_ .................................................................................................................................. DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 10 .................................................................................................................................... MAXIMUM POSSIBLE INCIDENCE 4563/ 60 4547/ 60 4576/ 60 4602/ 60 MORTALITY FOUND DEAD a MORIBUND SACRIFICED a 3 3 3 2 2 3 3 1 1 0 0 1 V 30 4473/ 60 7 6 1 LOCALIZED ALOPECIA: TOTAL LIMBS BACK HEAD RIGHT OR BOTH EYE(S): CORNEAL BALES OPACITY 30/ 1 30/ 1 0/ 0 01 0 01 0 11 I 56/ 1 56/ 1 0/ 0 01 0 141 1 01 0 36/ 3 31/ 1 3/ 1 21 i 01 0 01 0 i0/ 1 0/ 0 I0/ i 01 0 01 0 01 0 7/ 2 7/ 2 0/ 0 01 0 21 2 21 2 t_ DEHYDRATION t_ "] LACRIMATION 01 0 0/ 0 01 0 0/ 0 01 0 34/ 1 191 2 0/ 0 14/ 1 6/ 1 RIGHT EYE: SWOLLEN 0/ 0 0/ 0 0/ 0 0/ 0 6/ 1 SNOUT: SWOLLEN 3/ 1 2/ i 32/ 2 6/ 1 4/ 1 PENIS: RED SUBSTANCE 0/ 0 0/ 0 0/ 0 i/ 1 4/ 1 EXCESS SALIVATION 4/ 4 2/" 2 3/ 3 i/ 1 i/ 1 RED, DRIED, SLIGHT PERINASAL SUBSTANCE 0/ 0 0/ 0 3/ 2 1/ 1 i/ 1 VOCALIZATION BOTH EARS: SWOLLEN I/ I i/ I 0/ 0 0/ 0 1/ 1 > 0/ 0 0/ 0 8/ 3 2/ 2 0/ 0 .................................................................................................................................... MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. [29 a. Refer to the individual clinical observations table (Table DI4) for observations for rats that were found dead or moribund 4_ sacrificed. O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D1 (PAGE 3): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... M/_IMUM POSSIBLE INCIDENCE 4563/ 60 4547/ 60 MORTIuLITY FOUND DEAD a MORIBUND SACRIFICED a 3 3 2 3 1 0 III 3 4576/ 60 3 3 0 IV 10 4602/ 60 2 1 1 V 30 4473/ 60 7 6 1 TIP OF TAIL MISSING 0/ 0 0/ 0 0/ 0 21/ 1 0/ 0 TIP OF TAIL BLACK 0/ 0 0/ 0 0/ 0 9/ i 0/ 0 BACK: ULCERATION 0/ 0 0/ 0 0/ 0 I/ 1 0/ 0 RED, SLIGHT PERIORAL SUBSTANCE PTOSIS OO ENOPHTH_J240S HEAD: ABRASION 0/ 0 01 0 0/ 0 18/ 2 0/ 0 201 1 2/ 1 0/ 0 i/ 1 ol 0 0/ 0 0/ 0 0/ 0 01 0 0/ 0 0/ 0 0/ 0 ol 0 0/ 0 0/ 0 RIGHT EYE: ENLARGED 102/ 1 0/ 0 .................................................................................................................................... 0/ 0 MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS a. Refer to the individual clinical observations sacrificed. OF RATS EXAMINED PER GROUP. WITH OBSERVATION. table (Table D14) for observations for rats that 0/ 0 were found dead 0/ 0 or moribund > c 4_ oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D2 (PAGE I): BODY WEIGHTS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V I0 30 60 60 BODY WEIGHT (G) DAY 1 MEANS.D. 42.7 6.9 41.0 6.8 43.8 + 9.7 44.6 + 6 6 40.4 + 8.4 DAY 8 DAY 15 DAY 22 MEAN+S.D. MEAN+S.D. MEANS.D. 75.2 11.7 59]a 124.1 15.9 59]a 183.9 + 20.4 59]a 72.3 [ 118.8 [ 175.6 + 9.8 58]a f 13.3 58]a + 17.9 [ 58]a 77.3 [ 126.9 [ 186.6 + 15.2 58]a 20.7 57|a + 26.0 [ 57]a 76.4 + 10 9 [ 59]a 122.6 15 8 [ 59]a 181.4 + 21 8 [ 59]a 69.6 [ 109.2 [ 162.7 + 12.7" 55]a 17.6.* 55]a + 20.4** [ 55]a DAY 29 MEAN+S.D. 241.0 58]a23.1 231.6[ 58]a21.0 t_ DAY 36 MEANS.D. 297.9 27.7 288.2 + 28.3 t_ 47]a [ 54]a %0 DAY 43 MEANS.D. 342.4 28.8 327.8 25.9 30]a [ 30]a DAY 50 MEANiS.D. 383.2 33.7 359.7 26.8* 30]a [ 29]a .................................................................................................................................... 243.2[ 299.7 [ 335.7 [ 369.7 [ 57]a29.4 + 29.7 51]a 30.1 31]a 31.9 31]a 233.0[ 280.1 [ 323.6 [ 355.3 [ 59+]a27 6 40 0* 49]a f 34 0* 30]a 40.2** 30]a 211.1[ 250.8 [ 291.3 [ 318.3 [ 55]a 25.2** 33.4** 48]a 32.5** 30]a 35.3** 30]a DAY [] a. * ** = DAY POSTWEANING = NUMBER OF VALUES AVERAGED Excludes values for rats that were sacrificed Significantly different from the Group I value Significantly different from the Group I value following (p<_0.05). (p<_0.01). sexual maturation, found dead or moribund sacrificed. > C O"9 W-d O0 tO PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D2 (PAGE 2): BODY WEIGHTS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 30a 29a 30a 30a 30a BODY WEIGHT (G) DAY 57 MEANS.D. 412.5 36.4 387.8 28.8* 398.7 33.0 380.1 43 8** 338.5 _ 36.7** DAY 64 MEANS.D. 443.9 40.9 416.4 32.8* 424.1 34.8 404.5 49 3** 360.2 39.4** DAY 70b MEANS.D. 463.7 44.2 434.6 39.2* 442.2 36.6 420.9 51 i** 372.7 f 40.7** PRECOHABITATION c MEANiS.D. 488.1 46.5 463.3 46.4 468.2 39.9 443.8 53 9** 391.0 f 42.0** t_ DAY 99d 4_ O DAY 106 MEANS.D. MEANfS.D. 521.9 54.0 539.0 55.5 493.0 49.4* 504.6 52.0* 497.4 40.9 506.9 45.4* 469.5 57 5** 481.8 60 8** 409.8 41.1"* 416.1 48.0** DAY 113 MEANS.D. 554.8 57.6 [ 28] a 513.4 53.6* 512.3 49.0* 488.7 61 0"* 428.0 40.1"* [ 29] a .................................................................................................................................... DAY = DAY POSTWEANING [ ] = NUMBER a. Excludes OF VALUES AVERAGED values for rats that were sacrificed following sexual maturation, found dead or moribund sacrificed. b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. c. Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. d. First weekly value recorded after cohabitation. * Significantly different from the Group I value (p_0.05). > ** Significantly different from the Group I value (p_0.01). C%_ c OC t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D3 (PAGE 1): BODY WEIGHT CHANGES - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY| 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 59a 58a 58a 59a 55a BODY WEIGHT CHANGE (G) DAYS 1- 8 MEAN+S.D. +32.3 f 7.0 +30.9 + 5.4 +33.0 + 7.1 +31.8 + 5.9 +27.9 + 6.4** DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 MEAN+S.D. MEAN+S.D. MEANS.D. +48.9 f 7.6 +59.8 f 6.0 +56.5 + 6.1 [ 58] a +46.5 5.0 +56.8 + 7.0* +55.9 + 5.2 +49.2 + 6 9 57]a +59.7 + 7 1 57] a +56.6 + 5 6 57] a +46.2 + 6.6* +58.8 + 8.2 +51.7 + I0.i** +39.6 + 6.6** +53.5 + 5.3** +48.4 12.6-* t_ DAYS 29 - 36 MEAN+S.D. +56.8 i 6.8 +57.0 + 17.0 +56.5 i 6 5 +47.9 + 20.9** +40.7 + 13.2"* 4_ [ 47]a [ 54]a 51]a [ 49]a [ 48]a DAYS 36 - 43 MEAN+S.D. +42.7 _ 9.5 [ 30]a +39.8 + 19.1 [ 30]a +39.1 + 8 3 31]a +38.1 + 8.3 [ 30]a +35.4 + 7.7** [ 30]a DAYS 43 - 50 MEAN+S.D. +40.8 f 9.8 +33.0 + 6.3** +34.0 + 8 1"* +31.7 9.2** +27.0 9.6** [ 30]a [ 29]a .................................................................................................................................... 31]a [ 30]a [ 30]a DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that * Significantly different from ** Significantly different from were sacrificed the Group I value the Group I value following (p<0.05). (p_<0.01). sexual maturation, found dead or moribund sacrificed. > C OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D3 (PAGE 2): BODY WEIGHT CHANGES - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 30a 29a 30a 30a 30a BODY WEIGHT CHANGE (G) DAYS 50 - 57 MEAN+S.D. +29.3 f 8.0 +28.1 6.2 +27.3 13.1 +24.8 + 7.3* +20.2 9.1"* DAYS 57 - 64 MEAN+S.D. +31.4 _ 8.3 +28.6 + 6.8 +25.3 6.4* +24.4 + 12.3 +21.7 + 6.6** DAYS 64 - 70b MEAN+S.D. +19.8 6.2 +18.3 9.1 +18.2 5.3 +16.4 8.2 +12.5 + 6.8** DAY 1- PRECOHABITATION MEAN+S.D. +445,1 + 44.1 +422.3 44.5 +423.5 f 38.9 +399.7 i 50.8** +350.5 + 39.1"* t_ 4_ DAYS 99c-106 MEANS.D. +17.1 f 33.5 +11.6 + 8.3 +9.6 + 12.4 +12.2 + 9.4 +6.3 + 26.5 _O DAYS 106- 113 MEAN+S.D. +10.1 _ 37.3 [ 28] a +8.8 10.0 DAYS 1 -113 MEANS.D. +511.6f 55.0 +472.5+ 52.3** [ 28] a .................................................................................................................................... +5.4 + 15.6 +467.6 49.6** +7.0 + 8.1 +444.6+ 58.3** DAY(S) = DAY(S) POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed b. Precohabitation body weights were recorded on rats were 92 to 106 days of age. c. First weekly value recorded after cohabitation. * Significantly different from the Group I value following sexual maturation, found the day cohabitation was begun for (p<0.05). dead or moribund the F1 generation sacrificed. rats; at ** Significantly different from the Group I value (p<0.01). +7.3 + 10.8 [ 29) a +387.8+ 37.4** [ 29] a that time these _9 4_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D4 (PAGE 1): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V I0 30 60 60 INCLUDED IN ANALYSES N 59a 58a 58a 59a 55a FEED CONSUMPTION (G/DAY) DAYS 1- 8 MEAN+S.D. 10.5 1.5 10.4 + 1.3 10.8 2.4 10.6 1.6 9.3 1.7,* DAYS 8 - 15 DAYS 15 - 22 MEANS.D. MEANfS.D. 18.1 2.0 [ 58]b 22.4 2.1 17.4 1.8 21.6 2.0 18.2 2.9 [ 57]a 22.3 2.7 [ 57] a 17.6 2.8 21.6 + 2.4 16.0 + 20.2 3.0** 3.2** DAYS 22 - 29 MEANiS.D. 25.[6 58]a 3.4 24.7 2.2* 25.3[ 56]a,b 3.6 t_ DAYS 29 - 36 MEANiS.D. 28.1 2.4 26.8 2.1" 27.8 + 2.9 4_ [ 47]a [ 54]a [ 50]a,b t_ DAYS 36 - 43 MEAN+S.D. 29.0 2.5 27.9 2.0 28.7 2.5 [ 30]a [ 29]a,b [ 31]a DAYS 43 - 50 MEANiS.D. 29.2 3.2 [ 29]a,b 27.0 2.1"* [ 29]a,b 28.8 2.9 [ 29]a,b DAYS 50 - 57 MEAN+S.D. 29.9 2.8 28.3 2.4 29.9 3.2 [ 28]a,b [ 26]a,b [ 29]a,b DAYS 57 - 64 MEANS.D. 30.0 + 3.8 28.2 2.7 28.9 3.5 [ 26]a,b [ 27]a,b [ 28]a,b DAYS 64 - 70c MEAN+S.D. 29.2 3.8 27.6 3.3 28.5 2.6 [ 30]a [ 28]a,b [ 29]a,b DAYS 1 - 70c MEANS.D. 25.1 1.8 23.7 1.7"* 24.7 2.3 [ 30]a [ 28]a,b .................................................................................................................................... [ 29]a,b 25 7 58]b 2.5 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. 2.4 30]a 24.5 + 3.1" 26.5 3.1"* [ 47]a,b 27.9 3.8 [ 30]a 27.2 3.0* [ 28]a,b 27.6 3.3* [ 28]a,b 27.4 3.4 [ 30]a 26.8 + 3.8 [ 30]a 23.2 + 2.6** [ 30]a DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund sacrificed. b. Excludes values that were associated with spillage, wet or soiled feed. c. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was _l] the last interval in which a feed consumption value was recorded for the youngest rats in this group. _4_ * Significantly different from the Group I value (p_0.05). OO ** Significantly different from the Group I value (p<0.01). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D4 (PAGE 2): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 30a 28a,b 29a,b 30a 29a,b FEED CONSUMPTION (G/DAY) DAYS 99 -i06 MEANIS.D. 28.7 f 2.9 27.7 i 3.1 27.8 + 3.1 28.5 i 3.3 26.9 + 3.6 DAYS106 -113 DAYS 99 -113 .................... MEANIS.D. 28.8 f 3.0 27.6 + 3.2 [ 24]b,c MEANfS.D. 28.8 + 3.0 27.6 + 2.9 [ 24]b,c i ............................................................................................................... 27.2 27.5 4.1 3,3 28.2 f 3.1 [ 28]b 28.2 f 3.0 [ 28]b 26.9 3.4 [ 28]a,b 27.2 + 3.1 [ 28]a,b DAYS = DAYS POSTWEANING L_ [ ] = NUMBER OF VALUES AVERAGED ab.. EExxcclluuddeess vvaalluueess ftohrat rawtesre thaastsocwiearteed sacwriitfhicsepdillfaoglel,owiwnegt soerxusaolilemdatufreaetdi.on, found dead or moribund sacrificed. c. Excludes values for rats that were sacrificed before day 113 postweaning. _n 4_ OO t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D5 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 59a 58a 58a 59a 55a FEED CONSUMPTION (G/KG/DAY) DAYS 1- 8 MEAN+S.D. 179.2 23.9 183.8 + 19.4 177.8 25.7 176.6 t 19.9 168.3 25.0* DAYS 8 - 15 DAYS 15 - 22 MEANiS.D. MEANS.D. 182.9 t [ 58]b 146.3 19.5 12.2 182.6 t 15.9 147.3 10.4 179.6 [ 143.3 57]a + 22.2 10.9 177.3 + 22.4 142.6 + 12.9 181.0 25.6 149.4 17.7 (_ t_) 4_ t2_ DAYS 22 - 29 MEANS.D. 121.0 15.8 121.7 8.8 [ 58]a DAYS 29 - 36 MEANS.D. 104.6 7.6 103 8 7.6 47]a 54]a DAYS 36 - 43 MEANiS.D. 90.7 68 91.3 7.7 30]a 29]a,b DAYS 43 - 50 MEANiS.D. 81.0 90 78.7 5.6 29]a,b 29]a,b DAYS 50 - 57 MEAN+S.D. 75.6 + 66 75.8 5.4 28]a,b 26]a,b DAYS 57 - 64 MEANS.D. 70.1 62 70.0 + 5.2 26]a,b 27]a,b DAYS 64 - 70c MEANS.D. 64.4 66 64.8 5.5 30]a 28]a,b DAYS 1 - 70c MEANiS.D. 91.8 48 91.8 4.5 30]a 28]a,b .................................................................................................................................... [ 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 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 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 DAYS = DAYS POSTWEANING > [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund .sacrificed. b. Excludes values that were associated with spillage, wet or soiled feed. c. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. _t_ * Significantly different from the Group I value (p<0.05). O0 ** Significantly different from the Group I value (p<_0.01). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D5 (PAGE 2): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 30a 28a,b 29a,b 30a 29a,b FEED CONSUMPTION (G/KG/DAY) DAYS 99 -106 MEANS.D. 54.4 4.6 55.7 5.0 55.3 5.5 60.4 8.8** 65.6 8.1"* DAYS106 -113 DAYS 99 -113 MEANS.D. MEANS.D. 52.8 4.8 [ 24]b,c 53.7 4.4 [ 24]b,c 54.7 f 5.6 55.1 4.9 53.5 6.7 54.5 5.3 58.0 [ 28]b 58.6 t 5.0** 5.0** [ 28]b 63.3 6.5** [ 28]a,b 64.8 6.6** [ 28_a,b DAYS = DAYS POSTWEANING t_ [ ] _ NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation, found dead or moribund sacrificed. 0% b. Excludes values that were associated with spillage, wet or soiled feed. c. Excludes values for rats that were sacrificed before day 113 postweaning. ** Significantly different from the Group I value (p<0.01) . oo 50 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D6 (PAGE 1): SEXUAL MATURATION _ SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 10 30 MALE RATS N 60 60 60 60 60 INCLUDED IN ANA/_YSES N 52a-d 58a 57a 58a 54a PREPUTIAL SEPAP3%TION e MEAMS.D. 48.5 2.0 49.5 f 2.7 49.4 3.4 49.7 3.1 ...................................................... a. Excludes values for rats that were found dead _ ............................................................................. or.morlbund sacrificed. b. Excludes values for rats in which testing was discontinued before the rat became sexually c. Excludes values for rats that were not observed. d. Excludes values for rat 6555, which did not have preputial separation recorded on one day e. Average day postpartum that the prepuce was observed to be separated. ** Significantly different from the Group I value (p50.01). mature. and was separated 52.2 3.1.* the following day. t_ > C C <D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D7 (PAGE 1): MATING AND FERTILITY - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS IN COHABITATION N 30 29 III 3 30 IV V 10 30 30 30 DAYS IN COHABITATION a MEAN+S.D. 3.0 + 2.4 3.0 + 1.1 2.4 + 1.2 2.7 + 1.6 2.5 + 1.2 RATS THAT MATED b N(%) 29(96.7) 29(100.0) 30(100.0) 30(100.0) 30(I00.0) FERTILITY INDEX c RATS WITH CONFIRMED MATING DATES N/N (%) N 28/ 29 (96.6) 29 28/ 29 (96.6) 29 28/ 30 (93.3) 30 28/ 30 (93.3) 30 29/ 30 (96.7) 30 MATED WITH FEMALE d DAYS 1-7 N(%) 291100.0) 29(100.0) 30(100.0) 4_ RATS PREGNANT/RATS IN O0 COHABITATION N/N 28/ 30 28/ 29 (%} (93.3) (96.6) .................................................................................................................................... 28/ 30 (93.3) [ ] = NUMBER OF VALUES AVERAGED a. Restricted to rats with a confirmed mating date and rats that did not mate. b. Includes only one mating for each male rat. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date. 30(100.0) 28/ 30 (93.3) 30(100.0) 29/ 30 (96.7) > 4_ OO t,_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D8 (PAGE I): NECROPSY OBSERVATIONS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS EXAMINED a N 60 60 III 3 60 MORTALITY a N 3 3 3 FOUND DEAD N 2 3 3 MORIBUND SACRIFICED N 1 0 0 APPEARED NORMAL N 59 58 53 LUNGS : ALL LOBES, MOTTLED DARK RED N 1 0 0 STUDY OF AMMONIUM PERFLUOROOCTANOATE IV i0 60 2 1 1 44** 0 V 30 60 7 6 1 49** 0 PROSTATE : SMALL N 0 i 0 0 0 t_ TESTES : LEFT, FLACCID, SMALL N 0 1 0 0 0 LEFT, LARGE N 0 0 1 0 0 EPIDIDYMIDES : LEFT, SMALL N 0 1 0 0 0 LIVER: LEFT LATERAL AND/OR MEDIAN LOBES, TAN AND/OR BLACK OR WHITE AREA(S) N 0 0 6* 10"* 9** LARGE N 0 0 0 0 1 KIDNEYS : RIGHT, PELVIS, MODERATE OR SLIGHT DILATION N 0 ............................................................................................ a. Refer to the individual clinical observations table (Table rats that were found dead or moribund sacrificed. * significantly ** Significantly different different from the Group from the Group I value I value (p_0.05). (p<0.01). 0 D14) for external 0 observations A** '-....................................... confirmed at necropsy 1 and for [/_ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D8 (PAGE 2): NECROPSY OBSERVATIONS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS EXAMINED a N 60 60 III 3 60 IV V 10 30 60 60 MORTALI _"/ a N 3 3 3 2 7 FOUND DE/d) N 2 3 3 1 6 MORIBUND SACRIFICED N 1 0 0 1 1 INTESTINES : DISTENDED WITH GAS N 0 0 0 1 0 THYMUS : SMALL N 0 0 0 1 0 STOMACH : L_ CARDIAC REGION, ULCERATIONS N 0 La 0 0 1 0 O SPLEEN : TAN AREA EXTENDED INTO THE PARENCHYMA N 0 0 0 1 0 SMALL N 0 0 .................................................................................................................................... a. Refer to the individual clinical observations table (Table D14) rats that were found dead or moribund sacrificed. ** Significantly different from the Group I value (p<0.01). for external 0 observations 0 1 confirmed at necropsy and for > oo to C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE D9 (PAGE 1): TERMINAL BODY WEIGHTS A_ ORGAN WEIGHTS - SUMMARY - F1 GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 30 29 30 30 29 TERMINAL BODY WEIGHT MEANS.D. 559.9 59.8 527.2 54.8* 523.9 48.2* 499.3 63.5** 437.6 41.6"* EPIDIDYMIS LEFT MEANS.D. 0.6854 0.0589 0.6626 0.0821 0.6749 0.0573 0.6720 0.0589 0.6503 0.0488 CAUDA EPIDIDYMIS LEFT MEANS.D. 0.3333 0.0363 0.3177 0.0499 0.3287 0.0301 0.3288 0.0395 0.3169 0.0290 TESTIS LEFT LEFT TESTIS MINUS TUNICA ALBUGINEA SEMINAL VESICLES t_ WITH FLUID tm SEMINAL VESICLES WITHOI)T FLUID MEANS.D. MEANtS.D. MEANtS.D. MEANtS.D. 1.7456 0.1501 1.6129 0.1426 1.8978 0.3480 0.9878 0.1781 1.7058 t0.1844 1.5455 0.2513 2.0708 0.2430 1.0380 0.1480 1.8278 0.2751 1.6826 0.2590 1.9677 0.2768 1.0194 0.1240 1.7732 0.1254 1.6259 0.1201 2.0598 0.3113 1.0701 0.1428 1.7284 0.1618 1.5914 0.1483 1.8930 0.3026 0.9493 0.1712 EPIDIDYMIS RIGHT MEANtS.D. 0.6982 0.0609 0.6870 0.0446 0.6831 0.0458 0.6881 0.0455 0.6693 0.0503 TESTIS RIGHT MEANtS.D. 1.7324 0.1389 1.7227 0.1363 1.7860 0.1539 1.7677 0.1195 1.7432 0.1783 PROSTATE MEANS.D. 1.0374 0.2849 1.0825 0.2897 1.0265 0.2336 1.0455 0.2343 0.8724 0.1759" PITUITARY MEANS.D. 0.015 0.003 0.017 0.006 BRAIN MEANtS.D. 2.34 0.13 2.28 .................................................................................................................................... 0.16 0.016 0.006 2.31 0.12 0.014 0.005 2.28 0.I0 0.013 0.006 [ 28]a 2.18 0.14"* ALL WEIGHTS WERE RECORDED IN GRAMS [G). > a. Excludes values for rats that had organs damaged (weight affected * Significantly different from the Group I value (p_0.05). ** Significantly different from the Group I value (p_0.01). O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D9 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 30 29 30 30 29 TERMINAL BODY WEIGHT MEAN+S.D. 559,9 + 59,8 527.2 + 54.8* 523.9 f 48.2* 499.3 63.5 *_ 437.6 41.6"* LIVER MEAM+S.D. 21.65 3.22 24.57 4.04** 28.24 4.22** 29.28 4.09 *_ 29.74 3.97** KIDNEY LEFT MEANS.D. 2.21 + 0.20 2.35 0.26* 2.46 0.20** 2.30 0.22 2.03 0.22** KIDNEY RIGHT MEANS.D. 2.24 + 0.21 2.34 0.28 2.48 0.24** 2.33 0.25 2.04 0.21"* ADRENAL LEFT MEANS.D. 0.032 0.006 0.032 + 0.008 0.031 0.005 0.029 _ 0.006 0.028 0.006* ADRENAL RIGHT MEA_iS.D. 0.030 0.007 0.029 + 0.007 0.029 0.005 0.028 0.006 0.026 + 0.006 t_ SPLEEN ta MEANiS.D. [ 29] a 0.94 0.14 0.83 0.15" THYMUS MEAMfS.D. 0.51 0.12 0.46 .................................................................................................................................... 0.12 0.85 0.14" 0.44 0.15 0.81 0.23** 0.38 0,11"* 0.74 0.13"* 0.39 0.15"* ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes values for rats that had organs damaged (weight * Significantly different from the Group I value (p_<0.05). ** Significantly different from the Group I value (p_0.01}. affected). > O0 t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D10 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 30 29 30 30 29 TERMINAL BODY WEIGHT MEANtS.D. 559.9 59.8 527.2 54.8* 523.9 48.2* 499.3 f 63.5** 437.6 41.6"* EPIDIDYMIS LEFT ME_NS.D. 0.123 0.014 0.127 0.018 0.130 0.016 0.136 _ 0.017"* 0.149 0.017"* CAUDA EPIDIDYMIS LEFT MEANtS.D. 0.060 0.007 0.060 0.011 0.063 0.008 0.066 0.010" 0.072 0.010"* TESTIS LEFT LEFT TESTIS MINUS TUNICA A L_UGINEA SEMINAL VESICLES t_ WITH FLUID tn L_ SEMINAL VESICLES WITHOUT FLUID MEANfS.D. MEAN_S.D. MF2%N_S.D. MEAN_S.D. 0.314 0.036 0.290 0.034 0.339 0.061 0.176 0.033 0.327 0.050 0.296 0.057 0.396 0.052** 0.198 0.034* 0.351 0.061"* 0.324 0.057* 0.377 0.049* 0.196 0.028* 0.360 0.048** 0.330 0.047** 0.416 f 0.064** 0.217 0.032** 0.396 0.044** 0.366 0.041"* 0.436 f 0.082** 0.218 0.046** EPIDIDYMIS RIGHT MEAN_S.D. 0.126 0.014 0.131 0.011 0.130 0.013 0.140 f 0.017"* 0.152 t 0.018"* TESTIS RIGHT ME_LNS.D. 0.312 t 0.036 0.329 0.040 0.343 0.044* 0.358 t 0.049** 0.401 0.050** PROSTATE MEANS.D. 0.185 0.052 0.203 0.050 0.197 0.046 0.210 0.043 0.199 0.039 PITUITARY a MEANfS.D. 2.621 0.589 3.181 1.203 3.071 1.054 2.809 1.064 3.041 f 1.421 [ 28]b BRAIN MEANS.D. 0.421 0.045 0.435 0.040 .................................................................................................................................... 0.443 0.041 0.461 0.055** 0.502 f 0.043** ALL WEIGHTS WERE RECORDED IN GRAMS (G). RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. > a. Value was multiplied by I000. b. Excludes values for rats that had organs damaged (weight affected). * Significantly different from the Group I value (p_O.05). 50 ** Significantly different from the Group I value (p_O.Ol). Oo t_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO} IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI0 (PAGE 2) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 10 30 RATS TESTED N 30 29 30 30 29 TERMINAL BODY WEIGHT LIVER KIDNEY LEFT KIDNEY RIGHT MEANS.D. MEANS.D. MEAN+S.D. MEAN+S.D. 559.9 59.8 3.860 + 0.324 0.396 + 0.031 0.402 + 0.034 527.2 + 54.8* 4.648 + 0.510"* 0.446 + 0.042** 0.446 0.041"* 523.9 + 48.2* 5.408 + 0.754** 0.472 + 0.045** 0.474 + 0.041"* 499.3 + 63.5** 5.895 + 0.697** 0.464 + 0.046** 0.469 + 0.050** 437.6 + 41.6"* 6.787 + 0.550** 0.465 + 0.038** 0.467 0.036** ADRENAL LEFT a MEANS.D. 5.693 + 1.124 6.016 + 1.402 5.999 1.124 5.837 + 1.282 6.332 + 1.366 ADRENAL RIGHT a MEANfS.D. 5.355 + 1.242 [ 29]h 5.517 + 1.251 t_ SPLEEN tn MEANfS.D. 0.169 0.024 0.157 f 0.023 4_ THYMUS MEANS.D. 0.091 0.022 0.088 0.023 .................................................................................................................................... 5.494 + 1.007 0.161 + 0.021 0.082 + 0.024 5.697 + 1.076 0.166 + 0.063 0.077 0.025 5.899 1.426 0.171 0.027 0.088 0.033 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was multiplied by 1000. b. Excludes values for rats that had organs damaged (weight affected). * Significantl 7 different from the Group I value (p__0.05). ** Significantly different from the Group I value (p_<0.01). RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. > C U_ 4= 0o to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE Dll (PAGE I) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 29 REPRODUCTION STUDY OF AMMONIUM - F1 GENERATION MALE RATS III IV 3 10 30 30 PERFLUOROOCTANOATE V 30 29 BRAIN WEIGHT MEANS.D. 2.34 0.13 2.28 0.16 2.31 _ 0.12 2.28 0.10 2.18 _ 0.14"* EPIDIDYMIS LEFT MEANiS.D. 29.33 2.23 29.11 3.84 29.28 2.70 29.57 2.64 29.91 2.74 CAUDA EPIDIDYMIS LEFT MEANS.D. 14.26 f 1.41 13.94 2.20 14.28 1.53 14.46 1.71 14.60 1.74 TESTIS LEFT MEANS.D. 74.71 5.90 74.92 8.24 79.23 11.56 78.03 6.10 79.31 6.62* LEFT TESTIS MINUS .3 TUNICA ALBUGINEA SEMINAL VESICLES t_ WITH FLUID t_ L_ SEMINAL VESICLES WITHOUT FLUID MEANIS.D. MEANtS.D. MEANS.D. 69.03 5.56 81.16 13.80 42.24 7.07 67.86 11.31 90.84 9.80* 45.56 6.31 72.93 10.86 85.37 f 12.40 44.20 5.44 71.56 5.80 90.50 12.96" 47.06 6.27 73.09 6.81 87.40 16.74 43.78 8.89 EPIDIDYMIS RIGHT MEANS.D. 29.88 2.19 30.20 2.42 29.63 2.13 30.27 f 2.06 30.80 3.04 TESTIS RIGHT MEANS.D. 74.15 5.37 75,66 f 6.05 77.43 6.43 77.76 5.38* 80.05 8.12"* PROSTATE MEANS.D. 44.37 11.95 47.19 11.80 44.54 10.14 45,93 10.09 40.10 8.42 PITUITARY MEANS.D. 0.62 0.14 0.73 0.25 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes values for rats that had organs damaged (weight * Significantly different from the Group I value (p50.05). affected). 0.70 0.24 0.60 0.20 RATIOS {%) = (ORGAN WEIGHT/BRAIN WEIGHT) 0.61 0.29 [ 28] a X 100. ** Significantly different from the Group I value (p_0.01). _n 4_ OO 0 PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE Dll (PAGE 2) : RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 30 29 30 30 29 BRAIN WEIGHT MEAN+S.D. 2.34 + 0.13 2.28 + 0.16 2.31 + 0.12 2.28 + 0.10 2.18 + 0.14"* LIVER MEAN+S.D. 927.17 +135.62 1074.98 f149.66"* 1224.30 +178.78"* 1285.40 +159.24"* 1363.79 +165.99"* KIDNEY LEFT MEAN+S.D. 94.77 7.87 102.81 _ 7.56** 106.56 + 9.07** 100.98 7.93* 93.27 + 9.95 KIDNEY RIGHT MEAN+S.D. 95.87 + 9.05 102.62 f 7.68** 107.40 10.20"* 102.29 + 9.81" 93.60 7.88 ADRENAL LEFT MEANS.D. 1.35 + 0.24 1.39 + 0.36 1.35 + 0.23 1.27 + 0.26 1.26 + 0.25 _D ADRENAL RIGHT MEAN+S.D. 1.28 + 0.28 [ 29] a 1.28 0.31 1.24 + 0.22 1.24 + 0.24 1.17 + 0.26 SPLEEN tm MEAN+S.D. 40.39 + 5.51 36.24 4.69* 0% THYMUS MEAN+S.D. 21.84 5.64 20.35 + 5.61 .................................................................................................................................... 36.73 + 6.06* 19.15 + 6.53 35.91 10.99"* 16.77 + 4.95** 34.21 + 5.76** 17.78 6.93* ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes values for rats that had organs damaged (weight * Significantly different from the Group I value (p<0.05). ** Significantly different from the Group I value (p<0.01). affected). RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. > O 4_ OO <D PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI2 (PAGE i): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - F1 GENERATION MALE RATS ..............................................................................................................._._._...................................................................,....... DOSAGE GROUP I II III IV V ..9_9_..(_9/_/_.A.t.................._................................!...........................l...........................}._..........................)._....................... RATS TESTED N 30 29 30 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 STATIC COUNT (NONMOTILE) MEANS.D. MEANiS.D. 83.1 8.8 51.2 30.5 83.7 6.8 51.9 27.0 83,9 6.9 52.8 27.0 82.6 7.0 56.3 28.4 80.1 10.9 64.6 40.4 TOTAL COUNT b MEANS.D. 301.3 77.8 318.4 108.6 324.4 87.4 315.2 88.9 321.8 104.1 SPERM COUNT c MEANS.D. 135.6 67.8 162.0 _ 110.4 144.6 t 79.0 136.3 62.0 115.7 57.5 t_) SPERM DENSITY d MEANS.D. 1194.3 632.1 1423.7 922.5 1248.5 686.5 1206.8 565.8 1052.7 487.7 u. ._:-_:_:_7_:q::_7;:_:_:%_:_[:_-:_:_7_7_)_;_;7_?_:7i57: .............................................................. 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 I0 -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 epldidymis (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 _unalysls 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. > C _n 4_ oo PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI2 (PAGE 2}: CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - SUMMARY - FI GENERATION MALE RATS DOSAGE GROUP I II III IV V ..Pg_99_..I._g_Y..!.g.Y...D...9._.............!................................!............................_..........................._...........................l._............. RATS TESTED N 30 29 30 30 29 INCLUDED IN ANALYSES N 30 SPERMATIDCOUMTb MEANS.D. 4S.3 _ _3._ 28a 40.4 IS.1 30 39.3 _S.4 30 40.2 _ _S.7 29 42.7 _ 16.2 .._.._.._AD..PA_.9._..._...M._-._!_-.._.9._._.A..._.._...._.=_......Z._......_.....Z._:!....._.L.A..._....!._A .....!._.....A...3..L......Z.L._.....A.__LI...... 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 I0 -6 mL), multiplying by 2 (dilution factor) and multiplying by I0 "_ to obtain the spermatid concentration. The calculated spermatid concentration value (rounded to I decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis minus tunlca albuglnea (see Table D20 for the weight of the left testis minus tunica albuglnea) 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 fleld causing a slight underestimate of the actual volume and an t_ overestimate of the concentration. tn OO > O C _n oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE D13 (PAGE 1): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - SUMMARY - F1 GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 30 29 30 30 29 INCLUDED IN ANALYSES N 30 28a 30 30 29 NORMAL MEANS.D. 195.3 + 1.9 195.2 2.6 194.9 + 2.0 195.3 f 2.1 194.1 + 2.6 DETACHED HEAD MEAN+S.D. 2.7 + 1.6 3.2 + 1.8 3.0 + 1.7 3.0 + 1.8 3.1 + 1.4 NO HEAD MEANfS.D. 1.4 + 1.0 1.4 + 1.2 1.7 + 1.1 1.2 + 1.2 2.0 + 1.6 BROKEN FLAGELLUM MEAN+S.D, 0.5 + 0.7 0.0 + 0.2" 0.3 + 0.5 0.3 0.6 0.6 + 0.8 NO HOOK t_ COILED FLAGELLUM t_ kO BENT FLAGELLUM MEAN+S.D, MEANfS.D. MEANfS.D. 0.0 + 0.0 0.0 + 0.2 0.0 + 0.0 0.1 + 0.3 0.0 + 0.0 0.0 + 0.0 0.0 + 0.2 0.i 0.3 0.0 + 0.0 BENT FLAGELLUM TIP MEANfS.D. 0.0 + 0.0 0.0 + 0.0 0.0 0.0 PERCENT ABNORMAL MEAN+S.D. 2.4 + 0.9 2.4 i .................................................................................................................................... 1.3 a. Excludes values for rat 1082, which had less than 200 sperm per 20 * Significantly different from the Group I value (p<0.05). fields. 2.6 + 1.0 0.0 + 0.2 0.0 + 0,2 0.0 0.2 0.0 0.0 2.4 + 1.0 0o0 + 0.0 0.0 + 0.2 0.0 + 0.2 0.0 + 0.2 2.9 + 1.3 OO C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE D14 (PAGE 1): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1001 1002 1003 1004 1005 1006 1007 DP( 93- 94) DP( 93- 94) DP( 93- 97) DP (112 -113 ) DP (114-118) NO ADVERSE FINDINGS CHROMORHINORRHEA SNOUT: SWOLLEN CHROMODACRYORRBEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS : MI SALIGNED INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1008 1009 NO ADVERSE NO ADVERSE FINDINGS FINDINGS i010 1011 1012 DP( 76 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES 1013 1014 DP( 24 ) ANNULAR CONSTRICTION NO ADVERSE FINDINGS OF THE TAIL 1015 NO ADVERSE FINDINGS 1016 NO ADVERSE FINDINGS 1017 DP( 3) SOFT OR LIQUID FECES 6553 DP( 4- 7} SOFT OR LIQUID FECES DP( 4- 14) URINE-STAINED ABDOMINAL FUR DP( 22- 32) ANNULAR CONSTRICTION OF THE TAIL 6554 DP( 22- 32) NECK AND HEAD: SCAB (0.4 CM IN DIAMETER) DP( 31- 35) ABDOMINAL DISTENTION a 6555 NO ADVERSE FINDINGS 1021 DP( 35- 37) SNOUT: SWOLLEN DP( 35- 37) INCISORS: MISSING/BROKEN DP( 37- 59) NECK: SCAB (0.3 CM IN DIAMETER) > 1022 DP( 27- 34} HEAD: SCAB (0.5 CM IN DIAMETER) 1023 DP( 35- 37) HEAD: ABRASION (1.0 CM IN DIAMETER}a NO ADVERSE FINDINGS 1024 DP( 25 ) FOUND DEAD 1025 DP( 36 } CMROMORHINORRHEA 1026 DP(17-118) RIGHT EYE: ENLARGED a O_ DP( 36 ) EXCESS SALIVATION .................................................................................................................................... _) DAY POSTWEANING O Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION D14 (PAGE 2): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1027 1028 1029 1030 1031 DP( 8- 9) DP( 2) DP( 8- 16) DP( 23- 43) DP( 2- 4) DP( 4) DP( 4) DP( 4) ABDOMINAL DISTENTION SOFT OR LIQUID FECES ABDOMINAL DISTENTION ANNULAR CONSTRICTION OF THE CHROMORHINORRHEA a DECREASED MOTOR ACTIVITY COLD TO TOUCH MORIBUND SACRIFICED NO ADVERSE FINDINGS NO ADVERSE FINDINGS TAIL 1032 NO ADVERSE FINDINGS 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 DDPP(( 8-35 16)) DP( 74 ) DP( 2) DP( 35 ) DP( 34 ) DP( 34 ) DP( 42 ) DP( 77- 85) DPI 8) DP 15- 24) DPI 30- 31) DPI 32- 46) DPq 33- 34) DPI 33- 40) DPq 47- 54) DP_ 59- 85) DP I 89-118) AEBXDCOEMSISNAL SALIDVIASTTIEONNTION SOFT OR LIQUID FECES CHROMORHINORRHEA EXCESS SALIVATION NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA VOCALIZATION FOUND DEAD INCISORS: NO ADVERSE MISALIGNED FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES BACK: SCAB (DID NOT EXCEED 0.5 CM HEAD: SCAB (0.4 CM IN DIAMETER) HEAD: ABRASION (I.0 CM IN DIAMETER) CHROMODACRYORRHEA INCISORS: MISSING/BROKEN HEAD: SCAB (0.8 CM IN DIAMETER) BACK: SCAB (DID NOT EXCEED 1.0 CM LOCALIZED ALOPECIA: LIMBS a IN DIAMETER) X 0.5 CM) DAY POSTWEANING O0 Observation confirmed at necropsy. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE D14 (PAGE 3): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1044 1045 1046 1047 NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE FINDINGS FINDINGS FINDINGS FINDINGS 1048 1049 1050 DP 33- 34) DP' 34 ) DP 34 ) DP 34 ) SOFT OR LIQUID FECES CHROMORHINORRHEA SOFT OR LIQUID FECES EXCESS SALIVATION 1051 1052 1053 DP 2) DP 9- 13) DP 42 ) DP 93- 94) DP 20 ) CHROMORHINORRHEA SOFT OR LIQUID SOFT OR LIQUID SOFT OR LIQUID SOFT OR LIQUID FECES FECES FECES FECES 1054 1055 NOADVERSE NO ADVERSE FINDINGS FINDINGS 1056 DP( 29 ) SOFT OR LIQUID FECES 1057 DP( 4) CHROMORHINORRHEA 1058 DP( 18- 28) ANNULAR CONSTRICTION OF THE TAIL 1059 DP( 90 ) CHROMORHINORRHEA DP( 90 ) RALES DP( 90- 97) CHROMODACRYORRHEA DP(90-109) INCISORS: MISSING/BROKEN a DP(103-109) CHROMODACRYORRHEA a DP ( 109 ) INCISORS : MISALIGNED a 1060 NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING Observation confirmed at necropsy. > 5_ 0 PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION CONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE D14 (PAGE 4): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1061 1062 1063 1064 1065 1066 1067 1068 DP( 28- 36) DP(104-105) DP( 5) DP( 5) DP( 6) DP ( DP ( 3) 38 ) NO ADVERSE FINDINGS ANNULAR CONSTRICTION OF THE TAIL CHROMODACRYORRHEA CHROMORHINORRHEA a URINE-STAINED ABDOMINAL FUR FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA 1069 1070 DP( 26- 36) DP( 25- 35) ANNULAR ANNULAR CONSTRICTION CONSTRICTION OF THE TAIL OF THE TAIL 1071 DP( 29 ) DP( 44- 45) SOFT SOFT OR LIQUID OR LIQUID FECES FECES 1072 1073 1074 DP( 27 ) SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1075 1076 DP( 25- 35) ANNULAR CONSTRICTION NO ADVERSE FINDINGS OF THE TAIL 1077 1078 DP( 37 ) VOCALIZATION NO ADVERSE FINDINGS 1079 1080 1081 1082 1083 1084 DP( 25- 35) DP( 37 ) DP( 37 ) ANNULAR CONSTRICTION NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS EXCESS SALIVATION OF THE TAIL 1085 DP( 25- 35) ANNULAR CONSTRICTION OF THE TAIL DP( 28- 37) HEAD: SCAB (0.2 CM IN DIAMETER) .................................................................................................................................... DAY POSTWEANING Observation confirmed at necropsy. 00 4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D14 (PAGE 5): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1086 DP( 10- 17) DP( 80 ) DP( 80- 81) DP(80-115) DP(80-119) ABDOMINAL DISTENTION CHROMORHINORRHEA SNOUT: SWOLLEN INCISORS: MISALIGNED CNROMODACRYORRHEA a 1087 1088 DP(102-103) DP( 45 ) CHROMORHINORP/qEA FOUND DEAD NO ADVERSE FINDINGS 1089 DP( 25- 38) DP( 37 ) RIGHT EYE: CORNEAL OPACITY SOFT OR LIQUID FECES 1090 1091 DP( 37 ) EXCESS SALIVATION NO ADVERSE FINDINGS 1092 NO ADVERSE FINDINGS t_ 1093 DP( 20 ) SOFT OR LIQUID FECES 1094 DP( 32- 51} DP( 42- 51) PTOSIS ANNULAR CONSTRICTION OF THE TAIL DP( 50- 52) CHROMODACRYORRHEA 1095 NO ADVERSE FINDINGS 1096 DP( 3- 6) CHROMODACRYORRHEA DP( 24- 25) ENOPHTHALMOS DP( 35- 36) CHROMORHINORRHEA DP( 50- 51) CHROMORHINORRHEA 1097 NO ADVERSE FINDINGS 1098 NO ADVERSE FINDINGS 1099 DP ( 34 ) SNOUT: SWOLLEN DP( 34 ) URINE-STAINED ABDOMINAL FUR DP( 34- 36) CHROMORHINORRHEA DP( 34- 37) CHROMODACRYORRHEA a DP( 34- 37) INCISORS: MISALIGNED a > ................................................................................. -................................................... DP = DAY POSTWEANING a. Observation confirmed at necropsy. 4_ O0 bJ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION DI4 (PAGE 6): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1100 NO ADVERSE FINDINGS 1101 1102 1103 1104 DP( 36 ) DP( DP( DP ( 1) 1) 1) SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS DECREASED MOTOR ACTIVITY COLD TO TOUCH EMACIATION 1105 DP ( 2) DP( 8- 18) DP( 23- 35) FOUND DEAD ABDOMINAL DISTENTION ANNULAR CONSTRICTION OF THE TAIL 1106 DP( 8- 18) DP{100-101) ABDOMINAL DISTENTION SOFT OR LIQUID FECES 1107 1108 1109 1110 DP( 23- 33) DP(100-101} DP( 23- 33) ANNULAR CONSTRICTION CHROMORMINORRHEA ANNULAR CONSTRICTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS OF THE TAIL OF THE TAIL iiii 1112 1113 1114 DP( 5) DP( 35 ) DP( 34 ) DP( 7- 17) DP( 22- 41) CHROMOR/4INORRHEA CHROMORHINORRHEA CHROMOREINORRHEA ABDOMINAL DISTENTION HEAD AND NECK: SCAB (DID NOT EXCEED 0.5 CM IN DIAMETER) DP( 34 ) DP(64-119) SOFT OR LIQUID FECES LOCALIZED ALOPECIA: LIMBS a 1115 1116 1117 DP( 22- 34) ANNULAR CONSTRICTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS OF THE TAIL 1118 DP( 34 } SOFT OR LIQUID FECES DP( i00 ) SOFT OR LIQUID FECES 1119 DP( 34 ) SOFT OR LIQUID FECES 1120 DP( 64- 85) INCISORS: MISALIGNED ............................................................................................ _ ....................................... DAY POSTWEANING Observation confirmed at necropsy. 4_ Oo t_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI4 (PAGE 7): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III ........................................................... 3 MG/KG/DAY _ ........................................................................ RAT # DESCRIPTION .................................................................................................................................... 1121 1122 1123 1124 DP 5) DP 38 ) DP 45 ) DP 62- 67) DP 97- 98) DP 97-110) DP 97-118) DP 100-118) DP 118 ) FOUND DEAD SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS BACK: SCAB (DID NOT CHROMORHINORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED SNOUT: SWOLLEN a CHROMODACRYORRHEA a NO ADVERSE FINDINGS OF THE TAIL EXCEED 0.5 CM a IN DIAMETER) 1125 DP 5- 9) CHROMORHINORRHEA 1126 DP 257- 358) AHNENAUDL:AR SCAOBNSTRI(CDTIDONSNOT OEFXCETEHDE T0A.I5L CM IN DIAMETER)a t_ DP 35- 38) NECK: SCAB (2.0 CM X 0.5 CM)a (D% 1127 DPl 25- 28) BACK: SCAB (0.4 CM IN DIAMETER) DP( 27- 54) BEHIND LEFT EAR: SCAB (DID NOT EXCEED 0.5 CM IN DIAMETER) 1128 DPI 25- 35) ANNULAR CONSTRICTIONS OF THE TAIL 1129 DPq 25- 35) ANNULAR CONSTRICTIONS OF THE TAIL DPd 64- 69) INCISORS: MISSING/BROKEN 1130 DPq 2) FOUND DEAD 1131 DP_ 4- 5) CHROMORHINORRHEA DPq 50 ) RED, DRIED, SLIGHT PERINASAL SUBSTANCE 1132 DP, 30- 81) INCISORS: MISALIGNED DP_ 30-118) CHROMODACRYORRHEA a DP, 37 } CHROMORHINORRHEA DP 44- 77) DP 82-118) LACRIMATION INCISORS: MISSING/BROKEN a 1133 DP 37 ) CHROMORHINORRI4EA 1134 DP 25- 35) ANNULAR CONSTRICTIONS OF THE TAIL > 1135 NO ADVERSE FINDINGS ...................................................................................................... _ ............................. DP = DAY POSTWEANING ,_ a. Observation confirmed at necropsy. _ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE D14 (PAGE 8): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1136 1137 1138 1139 1140 1141 1142 DP(107-119) DP(107-119) DP(107-119) DP(109-110) DP( 3) DP( 9) CHROMODACRYORRHEA a SNOUT: SWOLLEN a INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA EMACIATION FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1143 NO ADVERSE FINDINGS 1144 1145 1146 DDPP(( 22 )) DP( 3) DP( 3- 15) DP( 9- 19) ECMOALCDIATTIOON TOUCH CHROMORHINORRHEA URINE-STAINED ABDOMINAL ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1147 1148 DP(101-I03) CHROMODACRYORRHEA NO ADVERSE FINDINGS 1149 1150 DP( 36 ) EXCESS SALIVATION NO ADVERSE FINDINGS 1151 1152 1153 DP( 36 ) DP(76-103) DP(91-103) DP(I05-110) DP(119-120) DP( 24- 36) SOFT OR LIQUID FECES INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA CHROMODACRYORRHEA a NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS ................................................................................ DAY POSTWEANING FUR OF THE Observation confirmed at necropsy. TAIL - ................................................... _'_ _[_ O0 b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE DI4 (PAGE 9): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1154 1155 1156 1157 1158 1159 DP( 35 ) DP( 59- 62) DP( 63- 65) DP( 35 ) DP( 59 ) DP( 59- 65) DP( 92 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED, SLIGHT PERIORAL BACK: ScAB (0.5 CM LOCALIZED ALOPECIA: CHROMORHINORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA SUBSTANCE IN DIAMETER) BACK 1160 DP(102-119) CHROMODACRYORRHEA a NO ADVERSE FINDINGS 1161 1162 1163 DP( 35 ) DP( 23- 33) DP( 43- 44) DP( 43- 54) SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS CHROMODACRYORRHEA INCISORS: MISALIGNED NO ADVERSE FINDINGS OF THE TAIL 1164 1165 1166 1167 DP( 63- 93) DP( 35 ) DP( i- 4) LOCALIZED ALOPECIA: SOFT OR LIQUID FECES CHROMORHINORRHEA NO ADVERSE FINDINGS LIMBS 1168 1169 DP( 38- 39) DP( 24 ) RED, SOFT DRIED, SLIGHT PERINASAL OR LIQUID FECES SUBSTANCE 1170 1171 1172 1173 DP( 34 ) SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1174 NO ADVERSE FINDINGS _ .................................................................................................................................... _U DAY POSTWEANING Observation confirmed at necropsy. _n 4_ Oo 6 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION tONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D14 (PAGE i0): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1175 1176 DP( 34 ) DP( 56- 57) DP( 56- 61) DP(56-108) DP(56-119) DP(109-118) DP(117-119) DP( 103 ) DP(103-119) DP(103-119} EXCESS SALIVATION CHROMORHINORRHEA SNOUT: SWOLLEN INCISORS: MISALIGNED CHROMODACRYORRHEA a INCISORS: MISSING/BROKEN INCISORS: MISALIGNED a CHROMORHINORRHEA CHROMODACRYORRHEA a INCISORS: MISALIGNED a 1177 1178 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1179 NO ADVERSE FINDINGS t_ 1180 DP( 18- 20) HEAD: SCAB (0.3 CM IN DIAMETER) (_ DP( 21- 22) LOCALIZED ALOPECIA: HEAD DP( 30 ) EXCESS SALIVATION .................................................................................................................................... DP = DAY POSTWEANING a. Observation confirmed at necropsy. > C _n o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE D14 (PAGE 11): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1181 1182 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1183 1184 1185 1186 1187 DP( 10- 20) DP ( 5) DP( 10- 20} DP( 25- 44) DP( 25- 33) ABDOMINAL DISTENTION CHROMORH INORRHEA ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS ANNULAR CONSTRICTIONS NO ADVERSE FINDINGS NO ADVERSE FINDINGS OF THE OF THE TAIL TAIL 1188 DP( 82- 83) CHROMODACRYORRHEA DP( 82- 98) INCISORS: MISALIGNED 1189 DP( 481-02 55}) SIONFCTISOROSR: LIQUMIIDSSINFGE/CBERSOKEN 1190 DP( 81- 86) INCISORS: NO ADVERSE MISSING/BROKEN FINDINGS 1191 NO ADVERSE FINDINGS 1192 DP(84-117) INCISORS: MISSING/BROKEN a 1193 DP( 24- 26) MOUTH: SCAB (DID NOT EXCEED 0.5 CM X 0.5 CM) 1194 DP( 60 } BACK: ULCERATION (1.0 CM X 0.5 CM) DP( 61- 65) BACK: SCAB (i.0 CM X 0.5 CM) DP( 66- 75) LOCALIZED ALOPECIA: BACK 1195 DP ( 87 ) PENIS : RED SUBSTANCE NO ADVERSE FINDINGS 1196 NO ADVERSE FINDINGS 1197 DP( 8- 16) TIP OF TAIL BLACK DP( 17- 37) TIP OF TAIL MISSING a 1198 1199 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1200 DP ( 24 ) CHROMODACRYORRHEA > DP( 24- 40) DEHYDRATION a DP( 25- 40) ABDOMINAL DISTENTION a DP( 29- 32) URINE-STAINED ABDOMINAL FUR DP( 29- 40) EMACIATION a _0 DP( 29- 40) COLD TO TOUCH 4_ DP( 39- 40} URINE-STAINED ABDOMINAL FUR O0 DP ( 40 ) MORIBUND SACRIFICED .................................................................................................................................... _ DAY POSTWEANING CD Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION D14 (PAGE 12): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1201 1202 1203 1204 1205 1206 1207 1208 1209 DP( 36 ) DP(69-118) DP( 23- 33) DP( 41- 42) DP( 35 ) DP{ 47 ) SOFT OR LIQUID FECES NO ADVERSE FINDINGS INCISORS: MISALIGNED a ANNULAR CONSTRICTIONS OF THE NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE NO ADVERSE FINDINGS EXCESS SALIVATION RED, DRIED, SLIGHT PERINASAL TAIL TAIL SUBSTANCE 1210 DP( 3) DP( 3) DP( 3) DECREASED MOTOR EMACIATION a COLD TO TOUCH ACTIVITY 1211 1212 DP ( DP( DP( 4) 23- 32) 64 ) FOUND HEAD: DEAD SCAB (DID NOT SOFT OR LIQUID FECES NO ADVERSE FINDINGS EXCEED 0.4 CM 1213 1214 1215 DP( 35- 36) DEHYDRATION NO ADVERSE NO ADVERSE a FINDINGS FINDINGS 1216 1217 DP( 35 ) DP( 35 ) CHROMORHINORRHEA SOFT OR LIQUID FECES NO ADVERSE FINDINGS 1218 1219 1220 1221 DP( 31 ) DP( 34 ) SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA DP( 34 ) DP( 63- 64) SOFT OR LIQUID CHROMORHINORRHEA FECES DP( 63- 68) DP( 63- 68) CHROMODACRYORRHEA SNOUT: SWOLLEN DP( 63- 68) INCISORS: MISALIGNED DP(69-118) INCISORS: MISALIGNED a DP(74-118) CHROMODACRYORRHEA a .................................................................................................................................... DAY POSTWEANING Observation confirmed at necropsy, IN DIAMETER) STUDY OF AMMONIUM PERFLUOROOCTANOATE > [29 4_ tO_) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION DI4 (PAGE 13): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1222 1223 1224 1225 1226 1227 DP( 22- 32) DP( 2- 6} DPI 4- 5} DPI 7- 24) DPq 7- 23) DPq 22- 34) DPI 22- 32) DPq 48- 49) DPq 22- 32) ANNULAR CONSTRICTIONS NO ADVERSE FINDINGS CHROMORHINORRHEA EMACIATION ABDOMINAL DISTENTION ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS ANNULAR CONSTRICTIONS SOFT OR LIQUID FECES ANNULAR CONSTRICTIONS OF THE TAIL OF THE OF THE TAIL TAIL OF THE TAIL 1228 1229 DP' 22- 32) DP_ 8) ANNULAR CONSTRICTIONS SOFT OR LIQUID FECES OF THE TAIL DP 22- 34) ANNULAR CONSTRICTIONS OF THE TAIL 1230 DP 61-119) BOTH EARS: SWOLLEN a NO ADVERSE FINDINGS 1231 NO ADVERSE FINDINGS 1232 NO ADVERSE FINDINGS 1233 NO ADVERSE FINDINGS 1234 1235 DP( 22- 31) ANNULAR CONSTRICTIONS NO ADVERSE FINDINGS OF THE TAIL 1236 DP( 80 ) CHROMODACRYORR/4EA 1237 NO ADVERSE FINDINGS 1238 NO ADVERSE FINDINGS 1239 NO ADVERSE FINDINGS 1240 NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE 6 O t_ "-_ t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D14 (PAGE 14) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1241 1242 1243 1244 1245 1246 1247 DP( 26- 36) DP( 26- 34) DP( 38- 39) DP 25- 26) DP 25- 35) DP 5- 7) DP i0- 18) DP 37 ) ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL HEAD: SCAB (0.2 CM IN DIAMETER)a NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL ANNULAR CONSTRICTIONS OF THE TAIL URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION CHROMORHINORRHEA 1248 1249 DP i0- 20) DP 25- 34) DP I0- 20) ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS ABDOMINAL DISTENTION OF THE TAIL 125 0 DP 29- 42) DP 37 ) DP 5- 6) DP 25- 38 ANNULAR CONSTRICTIONS EXCESS SALIVATION CHROMORHINORRHEA ANNULAR CONSTRICTIONS OF THE TAIL OF THE TAIL a 1251 DP 37 CHROMORH INORRHEA 1252 DP ( 37 VOCALIZATION DP( 37 ANNULAR CONSTRICTIONS OF THE TAIL 1253 DP( 37 ANNULAR CONSTRICTIONS OF THE TAIL DP ( 37 PALES DP ( 38 EMACIATION 1254 DP ( 4 CHROMORHINORRHEA DP( 10- 20) ABDOMINAL DISTENTION DP( 25- 35) ANNULAR CONSTRICTIONS OF THE TAIL .................................................................................................................................... DP = DAY POSTWEANING a. Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE _n 4_ Oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI4 (PAGE 15): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1255 1256 1257 1258 DP 36 ) DP 36 ) DP 67 ) DP 83- 91) DP 84 ) DP 87 ) DP 92- 96) DP 93 ) DP 3- 4) NO ADVERSE FINDINGS SOFT OR LIQUID FECES SOFT OR LIQUID FECES PENIS : RED SUBSTANCE URINE-STAINED ABDOMINAL FUR PENIS : RED SUBSTANCE PENIS: RED SUBSTANCE UNGROOMED COAT PENIS : RED SUBSTANCE CHROMORHINORRHEA _I_ DP 8- 9 ) CHROMORH INORRHEA DP 24- 34) ANNULAR CONSTRICTIONS OF THE TAIL 1259 DP 6) CHROMORHINORRBEA L_ DP 9- 19) ABDOMINAL DISTENTION -_ 1260 DP 3) DECREASED MOTOR ACTIVITY 4_ DP 3) COLD TO TOUCH DP 3) URINE-STAINED ABDOMINAL FUR DP 4) FOUND DEAD 1261 NO ADVERSE FINDINGS 1262 1263 1264 DP 24- 37} DPi 1 DP 1 DP _ 1 DP4 1 DP q 2 DPi 1 DPI 1 DP 1 ANNULAR CONSTRICTIONS OF THE TAIL a DECREASED MOTOR ACTIVITY BOTH EYES: CORNEAL OPACITY a EMACIATION a COLD TO TOUCH FOUND DEAD DECREASED MOTOR ACTIVITY BOTH EYES: CORNEAL OPACITY a EMACIATION DP 1 DP 2 COLD TO TOUCH FOUND DEAD .................................................................................................................................... DP = DAY POSTWEANING a. Observation confirmed at necropsy. 4= O_ b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI4 (PAGE 16): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1265 1266 1267 1268 1269 1270 1271 1272 DP( 24- 34) DP( 36- 39) DP( 36 ) DP( 11- 16) DP( 11- 16) DP( 36- 37) _ CONSTRICTIONS AN_ CONSTRICTIONS ANNULAR CONSTRICTIONS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LACRIMATION RIGHT EYE: SWOLLEN ;u_ CONSTRICTIONS NO ADVERSE FINDINGS NO ADVERSE FINDINGS OF THE OF THE OF THE TAIL TAIL TAIL OF THE TAIL a 1273 NO ADVERSE FINDINGS 1274 DDpPiI 76-49 77)) RCEHDR,OMODDARCIREYDO,RRHESALIGHT PERINASAL SUBSTANCE 1275 DP 26- 33) CHROMORHINORRHEA "-_ DP 26 - 39) DEHYDRATED a t_ DP 29- 39} EMACIATION a DP 32- 39) DECRE_ED MOTOR ACTIVITY DP 32- 39) URINE-STAINED ABDOMINAL FUR a DP 33- 39) COLD TO TOUCH a DP 39 ) CHROMODACRYORRHEA a DP 39 ) MORIBUND SACRIFICED 1276 DP 5) URINE-STAINED ABDOMINAL FUR 1277 DP 2- 3) CHROMORHINORRBEA a DP 3) DECRY_ED MOTOR ACTIVITY DP 3) EMACIATION a DP 3) COLD TO TOUCH DP 3} URINE-STAINED ABDOMINAL FUR a DP 4) FOUND DEAD 1278 DP 3- 15) URINE-STAINED ABDOMINAL FUR > DP 5- 7) EMACIATION DP 8- 16) ABDOMINAL DISTENTION DP_ 23- 70) ANNULAR CONSTRICTIONS OF THE TAIL .................................................................................................................................... DP = DAY POSI_EANING 4_ a. Observation confirmed at necropsy. O0 t,J 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION DI4 (PAGE 17): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 DP 8- 18) DP 28- 35) DP 2) DP 3) DPq 16 ) DP{ 18- 21) DP( 61- 69) DPi 89 ) DPq 89 } DP_ 89- 91) DP, 89-119) DP(102-104) DP(IIT-II9) DP(I18-119) DP(118-I19) DP 22- 32) DP 7- 23) DP 7- 23) DP 9- i0) DP 59- 61) DP 7- 23) DP 61- 64) DP 61-119) DP 61-119) DP 22- 23) DP( 15 ) ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL CHROMORHINORRHEA FOUND DEAD LOCALIZEDALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS INCISORS: MISALIGNED CHROMORHINORRHEA SOFT OR LIQUID FECES CHROMODACRYORRHEA INCISORS: MISALIGNED a CHROMODACRYORRBEA CHROMODACRYORRHEA a INCISORS: MISSING/BROKEN a LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS OF THE TAIL ABDOMINAL DISTENTION ABDOMINAL DISTENTION CHROMORHINORPd4EA BACK: SCAB (0.3 CM IN DIAMETER) ABDOMINAL DISTENTION SNOUT: SWOLLEN CHROMODACRYORRHEA a INCISORS: MISALIGNED a NECK: SCAB (0.5 CM IN DIAMETER) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS NO ADVERSE FINDINGS ................................................................................................................................. DAY POSTING Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE _'_ [2_ _._ OO O t_ --_ "_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D14 (PAGE 18): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1296 1297 1298 1299 DP( 100 ) DP(100-101) DP(100-106) DP(100-106) DP(I03-106) DP(104-106) DP( 107 ) DP( 20- 29) RALES CHROMORHINORRHEA CHROMODACRYORRHEA a INCISORS: MISALIGNED EMACIATION a URINE-STAINED ABDOMINAL FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS ANNULAR CONSTRICTIONS a FUR a OF THE TAIL 1300 DP( 20- 29) DP( 25- 99) ANNULAR CONSTRICTIONS INCISORS: MISALIGNED OF THE TAIL DP(25-117) CHROMODACRYORRHEA a DP( 67 ) DP( 72- 84) INCISORS: INCISORS: MISSING/BROKEN MISSING/BROKEN DP( 91- 92) INCISORS: MISSING/BROKEN DP(111-117) INCISORS: MISSING/BROKEN a .................................................................................................................................... DP = DAY POSTWEANING a. Observation confirmed at necropsy. STUDY OF AMMONIUM PERFLUOROOCTANOATE > C O_ IO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DIS (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP I .................................................................................................................................... 0 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 57 64 70a PRECOHABITATION b ............................................................................................................................... i001 36 ...5.4.. 105. 159. 218. 281. 1002 1003 1004 39 69. 118. 176. 233. 289. 337, 387. 424. 461. 487. 524. 45 81, 133. 198. 264. 323. 368. 407. 439. 469. 489. 523. 45 75. 122. 178. 231. 292. 1005 1006 1007 1008 1009 1010 38 74. 133. 192, 254. 319. 364. 408. 433. 465. 487. 525. 38 67. 116. 173. 227. 286. 42 78. 124. 181. 240. 293. 334. 372. 407. 434. 452. 487. 44 83. 138. 194. 250. 304. 50 87. 148. 212. 270. 338. 41 69. 116. 169. 225. 279. I011 42 79. 132. 188. 252. 307. 350. 394. 417. 441. 473. 508. 1012 1013 1014 1015 1016 49 84, 123. 175. 230. 282. 320. 387. 422. 460. 485. 537. 48 77. 116. 176. 236. 300. 354. 401. 432. 471, 500. 542. 46 88, 147. 209. 274. 328. 359. 398. 416. 445. 459. 497, 47 91. 148. 222. 290. 350. 48 90, 137 201. 262. 322, 1017 6553 6554 6555 44 80. 129 192. 250. 300. 336. 365. 387. 421. 435. 472. 35 57. 97 152. 200. 45 80. 131 185. 227. 47 80, 128 189. 238. 1021 1022 1023 1024 1025 1026 1027 53 85. 131 201. 259. 318. 367. 411. 449. 491, 520, 559. 48 56. 135 201. 268. 338. 31 57. 104 164, 215. 269. 319. 368, 412. 451. 483. 524. 30 62. 97 153. FOUND DEAD ON DAY 25 POSTWEANING 35 66. 101 163. 220. 271. 37 69. 115 174. 235. 286. 331. 368. 403. 446. 466. 500. 38 57. 106 158. 210. 261. 1028 38 62, 107 161. 208. 260. 1029 1030 31 MORIBUND SACRIFICED ON DAY 4 POSTWEANING 44 76. 130. 198. 255. 317. .................................................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G), 298, 329. 343. 379. 398. 420. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning /_ was the last day on which the youngest rats (in this group) had a body weight value recorded. OO Precohabitatlon body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE 2): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP I .................................................................................................................................... 0 MG/KG/DAY DAY 1 8 15 22 29 36 43 .................................................................................................................................... 50 57 64 70a PRECOHABITATION b 1031 1032 1033 46. 79. 132. 192. 253. 315. 364. 407. 445. 474. 491. 518. 45. 77. 126. 184. 240. 291. 31. 55. 92. 144. 198. 249. 1034 1035 1036 1037 1038 1039 1040 28. 52. 89. 150. 198. 246. 289. 319. 345. 371. 385. 395. 40. 65. 110. 161. 219. 267. 299. 313. 349. 372. 385. 406. 40. 71. 124. 186. 240. 296. 39. 63. 108. 161. 211. 262. 48. 81. 129. 188. 245. 44. 76. 121. 182. 232. 275. FOUND DEAD ON DAY 42 POSTWEANING 40. 70. 112 163. 215. 256. 320. 365. 388. 415. 434. 457. 1041 37. 61. I01 150 198. 257. 297. 332. 351. 379. 396. 421. 1042 1043 1044 42. 77. 112 166 50. 84. 138 199 62. 102. 155 215 221. 252. 261. 305. 348. 392. 423. 448. 464. 496. 1045 1046 58. 90. 141 201 256. 307. 348. 379. 406. 422. 432. 458. 58. 97. 150 217 272. 1047 1048 1049 55. 92. 147 214 275. 346. 411. 458. 496. 540. 569. 598. 43. 77. 126 191 256. 322. 368. 420. 456. 504. 520. 548. 39. 67. 107 162 219. 1050 1051 1052 1053 1054 1055 1056 1057 1058 39. 70. 108 161 213. 276. 313. 347. 372. 395. 405. 428. 46. 85. 139 205 270. 333. 373. 427, 461. 491. 512. 545. 44. 87. 144 217 270. 335. 365. 408. 443. 483. 500. 510. 46. 82. 133 194 247. 50. 89. 139. 202 267. 331. 365. 412. 429. 451. 477. 505. 45. 85. 138. 209 270. 329. 365. 407. 419. 454. 470. 490. 41. 90. 144. 220 272. 36. 66. 118. 177 240. 37. 70. 122. 178 248. 306. 365. 392. 424. 462. 480. 493. 1059 1060 39. 76. 128. 187 246. 306. 340. 378. 407. 426. 441. 441. 39. 68. 123. 183 231. 279. 304. 344. 376. 395. 415. 415. ...................................................................................................... = DAY POSTWEANING n ............................. WEIGHTS WERE RECORDED IN GRAMS (G). [/_ Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE 3): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP I ...... _ ............................................................................................................................. DAY 78 85 92 99a .................................................................................................... 106 113 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 507. 509. 510. 474. 504. 523. 523, 480. 537. 542. 547. 503. 530. 554. 558. 508. 547. 580. 576. 525. 556. 592. 567. 532. 491. 504, 525. 536. 552. 565. 0 MG/KG/DAY 120 -................................ 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 518. 528. 488. 456. 541. 533. 498. 473. 560. 564. 510. 490. 577. 574. 509. 489. 595. 585. 535. 500. 621. 605. 540. 518. 534. 555. 573. 576. 607. 506. FOUND 518. DEAD ON DAY 540. 559. 25 POSTWEANING 577. 491, 503. 531. 534. 562. 410. MORIBUND 422. SACRIFICED 432. ON DAY 441. 568. 4 POSTWEANING 612. 593. 573. 452. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). First weekly value recorded after cohabitation. 4_ oO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DIS (PAGE 4): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS - .............................................................................................................................. RAT # DOSAGE GROUP I ............................................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 1031 510. 533. 546. 547. 444. 581. 1032 1033 1034 1035 1036 1037 389. 402. 413. 404. 418. 423. 425. 432. 447. 509. 465. 456. 1038 1039 1040 FOUND 450. DEAD ON DAY 464. 42 POSTWEANING 489. 496. 507. 516. i041 1042 416. 433. 448. 454. 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 492. 453. 596. 542. 421. 523. 512. 495. 483. 486. 461. 593. 545. 427. 551. 513. 514. 503. 506. 476. 621. 582. 450. 573. 525. 523. 510. 525. 487. 641. 594. 462. 595. 540. 540. 532. 1057 1058 497. 506. 526. 537. 1059 1060 455. 436. 470. 439. 436. 451. 449. 455. ...................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). First weekly value recorded after cohabitation. 473. 529. 484. 667. 603. 473. 615. 560. 545. 546. 541. 440. 478. 477. 540. 496. 682. 624. 489. 642. 576. 555. 562. 548. 0 MG/KG/DAY 120 STUDY OF AMMONIUM PERFLUOROOCTANOATE _ ............................. > _..4_ oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE 5) : BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP II .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1061 1062 43. 69. 112. 166. 223. 264. 44. 73. 118, 170. 225. 281. 1063 1064 1065 1066 1067 1068 1069 1070 41. 71. 122. 159. 220. 273. 37. FOUND DEAD ON DAY 6 POSTWEANING 35. 59 97. 140. 185. 239 35. 59 101. 150. 203. 254 31. 51 95. 145. 204. 260 40. 65 109. 161. 211. 273 37. 59 99. 146. 201. 253 46. 78 125. 187. 245. 321 1071 40. 69 112. 163. 221. 279 1 MG/KG/DAY 43 50 301. 332. 317. 358. 299. 311. 296. 318. 335. 544. 321. 353. 57 360. 394. 357. 367. 343. 378. 64 385. 422. 379. 400. 355. 406. 70a PRECOHABITATION b 400. 436. 438. 465. 394. 397. 356. 438. 422. 439. 380. 477. 10723 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 4510.. 7846 12347. 12806. 24614. 31205 365. 390. 419. 446. 464. 494. 40. 71 116. 181. 239. 300 42. 74 128. 190. 242. 312 47. 83 132. 195. 258. 322 44. 80 131. 195. 252. 313 347, 382. 408. 443. 467. 490. 48. 86 148. 206. 264. 332 372. 404. 439. 474. 496. 538. 33. 60 97. 150. 205. 254 48. 78 128. 193. 245. 296 48. 79 130. 193. 254. 313 350. 381. 397. 425. 453. 481. 41. 72 116. 172. 228. 286 328. 366, 404, 436. 462. 512. 37 66. 113. 165. 220. 280 322. 347. 387. 416. 442. 477. 37 67. 112. 165. 216 268 32 55. 95. 146. 190 245 33 60. 101. 152. 196 245 282. 306. 328. 345. 357. 329. 43 83. 132. 194. 258 322 361. FOUND DEAD ON DAY 45 POSTWEANING 42 81. 134. 196. 254 315. 349. 378. 410. 446. 465. 494. 1089 1090 35 80. 127. 181. 36 64. iii. 152. ...................................................................................................... DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 238 201 300. 246. 288. 323. 355. 387. 400. 452. _ ............................. [2_ Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. OO Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D15 (PAGE 6) : BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP II .................................................................................................................................... 1 MG/KG/DAY DAY 1 8 15 22 29 36 43 50 57 64 .................................................................................................................................... 70a PRECOHABITATION b 1091 1092 1093 39. 70. 117 178 233. 293. 334. 372. 395. 419. 435. 464. 44. 78. 126 186 246. 303. 40. 73. 125 179 242. 294. 1094 1095 36. 71. 111 168 226. 278. 330. 370. 402, 440. 470. 509. 40. 73. 123 184 244. 310. 1096 1097 39. 69. 118 178 234. 293. 336. 386. 422. 459. 491. 521. 42. 66. 108 165 224. 272. 1098 1099 37. 75. 123 178 239. 293. 332. 366. 390. 412. 424. 445. 39. 76. 125 187 254. 271. Ii00 1101 56 94. 142 196 248. 295. 335. 359. 379. 402. 414. 440. 63 92. 142 193 249. 310. 1102 1103 1104 1105 45 78. 135 195 257. 313. 33 71. 128 190 245. 302. 345. 388. 418. 450. 469. 501. 23 FOUND DEAD ON DAY 2 POSTWEANING 32 57. i01 151 210. 275. 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 30 52. 92 136 184. 229. 276. 311. 348. 387. 404. 438. 44 75. 118 172 220. 268. 307. 337. 360. 381. 393. 409. 48 79. 125 184 231, 281. 45 72. 120 170 223. 284. 40 62. 107 161 212. 262. 298. 325. 343. 368. 373 392 38 59. 106 173 230. 286. 50 87. 137 201 266. 324. 364. 396. 426. 453. 487 520 49. 86. 131 202 265. 48 84. 134 194 257. 307. 353. 382. 409. 451. 479 496 35 65. 102 165. 220. 1116 1117 35 67. 108 165. 224. 381. 330. 369. 399. 424. 445 471 47 75. 118 177. 231. 1118 52 84. 126 188. 242. 265. 346. 372. 402. 432. 444 477 1119 1120 43 77. 120 184. 43 74. 121 182. ...................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 232. 239. 291. 342. 378. 408. 432. 448 467 r ............................. [/) Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. bJ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D15 (PAGE 7): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP II .................................................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 1061 1062 421. 438. 449. 459. 468. 478. 1063 1064 1065 455. FOUND 465. 478. 490. DEAD ON DAY 6 POSTWEANING 511. 509. 1066 1067 1068 406. 419. 423. 428. 428. 448. 438. 451. 455. 475. 466. 464. 1069 1070 369. 370. 389. 399. 416. 413. 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 465. 484. 473. 495. 491. 505. 512. 518. 511. 520. 525. 525. 480. 518. 485. 555. 506. 562. 511. 579. 469. 492. 462. 476. 503. 462. 489. 530. 479. 501. 557. 492. 375. FOUND 480. 323. 364. 386. DEAD ON DAY 45 POSTWEANING 497. 505. 526. 538. 595. 517. 569. 507. 372. 533. 542. 625. 528. 558. 521. 402. 556. 1089 1090 433. 459. 478. 496. 496. 516. .................................................................................................................................... = DAY POSTWEANING WEIGHTS WERE First weekly RECORDED IN GRAMS (G). value recorded after cohabitation. 1 MG/KG/DAY 120 [/_ 4_ OO 6 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DIS (PAGE 8): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # ........................ DOSAGE GROUP II 1 MG/KG/DAY _ ........................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 120 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 452. 500. 506. 438. 429. 460. 509. 519. 440. 434. 474. 533. 543. 458. 454. 489. 554. 566. 465. 471. 494. 573. 582. 475. 479. 504. 573. 603. 474. 485. 512. 594. 632. 498. 494. 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 490. FOUND 503. 521. 535. 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. ............................................................................................ = DAY POSTWEANING 551. 492. 434. 425. 559. 543. 527. 511. 506. 562. 503. 440. 429. 571. 549. 541. 517. 511. 446. 437. ........... _ ............................. WEIGHTS WERE RECORDED IN GRAMS (G). 4_ First weekly value recorded after cohabitation. __ O_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLED15 {PAGE 9): BODY WEIGHTS - INDIVIDUAL DATA - Pl GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 35 FOUND DEAD ON DAY 5 POSTWEANING 39 74. 120. 186 247. 300. 39 78. 132. 195 249. 309. 31 64. 112. 178 239. 297. 33 56. 99. 154 208. 274. 34 60. 103. 152 205. 269. 35. 58. 102. 153 205. 258. 39. 72. 125. 191 248. 312. 36. 62. 102. 167 228. 288. 24. FOUND DEAD ON DAY 2 POSTg_EANING 3 MG/KG/DAY 43 50 337. 345. 376. 379. 303. 325. 339. 360. 57 407. 419. 354. 390. 64 431. 452. 375. 422. 70a PRECOHABITATION b 448. 472. 480. 517. 389. 436. 407. 473. 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 32. 56 102. 160. 226. 287 344. 392. 427. 457. 469. 495. 42. 72 117. 179. 233. 283 318. 354. 390. 419. 441. 474. 45. 77 116. 173. 225. 280 53. 88 142. 213. 270. 340 367. 406. 438. 467. 483. 520. 51. 87 140. 204. 266. 317 338. 362, 380. 398. 421. 450, 40. 76 129. 184. 233. 288 326. 360. 386. 406. 418. 439. 40. 80 131. 197. 252. 306 46. 85 140. 204. 273. 328 47. 78 128. 192. 252, 305. 327. 352. 377. 395. 400. 417. 37. 55. FOUND DEAD ON DAY 9 POSTWEANING 35. 63. 109. 164. 222. 2_i. 322. 364. 398. 426. 451. 494. 32. 58. 99. 151. 203. 256. 298. 331. 352. 383. 402. 433. 35. 67. 110. 168. 225. 283. 34 52. 92. 146. 191. 248. 42 68. 110. 163. 211. 245. 276. 297. 315. 339. 354. 376. 56 85. 136. 196. 257. 313. 53 85. 141. 194. 250. 304. 335. 381. 413. 441. 469. 485. 56 94. 144. 198. 251. 299, 54 96, 145. 201. 249. 304. 338. 371. 391. 417. 432, 458. 1150 46 77. 124. 182. ................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 234. 2..7.7.................... Because body was the last Precohabitation weight values were recorded at weekly intervals, based on day on which the youngest rats (in this group) had a body body weights were recorded on the day cohabitation was rats were 92 to 106 days of age. each rat's day postweaning, weight value recorded, begun for the F1 generation ............ day 70 postweaning rats; at that time these 2u [/_ _.,4_ oo CD PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D15 (PAGE 10): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 57 64 .................................................................................................................................... 1151 1152 54 i00, 158. 226. 293. 338. 384. 418. 455. 488. 52 92. 145. 207. 269 328. 70a PRECOHABITATION b 514. 544. 1153 1154 1155 1156 1157 1158 1159 1160 49 86. 145. 207. 261 317. 355. 390. 428. 453. 474. 495. 63 99. 160. 228. 292 346. 389. 429. 456, 482. 499. 514. 59 98. 151. 216. 282 345. 36 66. 121. 189. 253 327. 36 73. 122. 186. 242 300. 36 70. 124. 183. 238 291. 328. 343. 391. 422. 445. 473. 50 94. 152. 226. 291 345. 385. 419. 448. 471. 489. 525. 48 93. 147. 215. 277 339. 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 53 96. 148. 216. 277 46 79. 126. 177. 238 46 77. 120. 171. 231 50 93. 152. 222. 274 49 87. 148. 211. 272 30 46. 82. 120. 172 30 49. 86. 137. 189 36 63. 102. 159. 215 34 59. 95. 144. 193 36 64. 104. 155. 202 36 66. 108. 164. 214 55 95. 144. 204. 261 46 87. 137. 190. 241 58 96. 161. 231. 293 58 98. 149. 213. 275 47 80. 125. 177. 225 64 103. 156. 220. 275 65 101. 155. 220. 274 339. 291. 288. 326. 336. 228. 248. 274. 265, 300. 340. 279. 330. 332. 359. 280. 298. 325. 294. 342. 385. 324. 371. 377. 392. 319, 338. 368. 313. 370. 414. 360. 392. 399. 417. 381. 399. 332. 407. 390. 391. 401. 421. 446. ' 438. 458. 416. 427. 435. 452. 353. 439. 396. 416. 416. 368. 451. 413. 434. 437. 462. 477. 467. 483. 384. 477. 432. 461. 443. 1179 42 72. 126. 184. 239 1180 45 80. 135. 196. 255 312. 356. ....................................................................................................... = DAY POSTWEANING 395. 430. 448. 475. 490. .............................. WEIGHTS WERE RECORDED IN GRAMS (G). _O Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweanlng _t_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE Ii) : BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III .................................................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 1121 FOUND DEAD ON DAY 5 POSTWEANING 1122 1123 1124 1125 1126 462. 505. 471. 508. 491. 535. 497. 504. 513. 498. 509. 503. 1127 1128 399. 408. 414. 425. 437. 447. 1129 1130 450. FOUND 480. DEAD ON DAY 505. 517. 2 POSTWEANING 536. 557. 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 476. 465. 507. 440. 430. 492. 476. 512. 445 " 431. 512. 490. 530. 465. 451. 517. 507. 542. 482 " 456. 405. FOUND 476. 423. 412. DEAD ON DAY 485. 422. 428. 436. 9 POSTWEANING 510. 526. 443. 460. 372. 483. 377. 477. 383. 512. 394. 520. 538. 524. 561. 489. 472. 443. 545. 475. 405. S30. 556. 540. 580. 505 " 419. 453. 562. 489. 411. 494. 1149 nso 445. 457. 474. 487. 497. 501. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). First weekly value recorded after cohabitation. 3 MG/KG/DAY 120 STUDY OF AMMONIUM PERFLUOROOCTANOATE ;_ _2_ 4_ 0 cb PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D15 (PAGE 12): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP III .................................................................................................................................... 3 MG/KG/DAY DAY 78 85 92 99a 106 113 .................................................................................................................................... 120 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 530. 486. 504. 532. 500. 511. 556. 505. 527. 560. 516. 542. 579, 516. 561. 576. 528. 567. 588. 539. 580. 456. 515. 456. 475. 524. 455 490. 536. 482. 512. 551. 496. 514. 566. 512. 523. 573. 531 1163 1164 477. 478. 491. 502. 1165 1166 1167 1168 459. 478. 486, 486, 507. 516. 526. 529. 1169 1170 1171 377. 388. 405. 417. 1172 1173 472. 481. 496. 512. 1174 1175 432. 436. 451. 472. 1176 453. 465. 480. 491. 1177 442. 450. 463. 480. 1178 1179 1180 480. 518. 541. 545. ....................................................................................................... 498. 541. 548. 427. 518. 478. 460. 457. 570, 509. 555. 554. 432. 524. 469. 471. 466, 565. .............................. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). First weekly value recorded after cohabitation. OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D15 (PAGE 13): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV .................................................................................................................................... i0 MG/KG/DAY DAY 1 8 15 22 29 36 43 .................................................................................................................................... 50 57 64 70a PRECOHABITATION b 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 47. 76. 121. 183. 231. 283 46. 77. 123. 189. 243. 292 324. 353. 370. 400. 410. 434. 34. 58. 102. 158. 214. 255 35. 60 101. 161. 221. 269 308. 346. 374. 401. 426. 472. 33. 54 90. 134. 181. 227 31. 54 92. 143. 199. 245 292. 330. 354. 381. 407. 430. 46. 80 131. 190. 247. 296 48. 82 142. 204. 244. 293 323. 346. 371. 383. 386. 401. 43. 78 130. 202. 266. 338 391. 435. 454. 467. 490. 521. 47. 88 149. 218. 288. 361 45. 77 124. 182. 236. 282 45. 79 120. 183. 238. 290 322. 364. 390. 418. 443. 462. 1193 1194 50. 90. 135. 201. 254 48. 84. 132. 198. 262 1195 47. 83. 125. 183. 233 1196 48. 78. 120. 179. 233 1197 55. 83. 125. 178. 230 1198 61. 100. 151. 218. 282 1199 43. 70. 109. 161. 207 1200 41 71. 117. 144. 134 1201 45 95. 127. 183. 235 1202 46 76. 126. 187. 242 1203 35 70. 116. 178. 238 1204 44 76. 116. 186. 240 1205 43 70. 112. 176. 227 1206 36 66. 109. 168. 215. 1207 40 66. 102. 158. 207. 1208 53 82. 137. 198. 252. 1209 1210 49 83. 135. 198. 246. 41 FOUND DEAD ON DAY 4 POSTWEANING ...................................................................................................... 303 311. 283. 282. 280. 348. 245. 116. 285. 297. 282. 291. 288. 277. 263. 315. 306. 354. 320. 385. 351. 415. 377. 440. 399. 463. 415. 490. 441. 404. 450. 497. 541. 573. MORIBUND SACRIFICED ON DAY 40 POSTWEANING 607. 314. 334. 346. 354. 372. 383. 397. 406. 402. 413. 422. 433. 306. 351. 339. 381. 361. 414. 393. 413. 444. 447. 463. 478. r ............................. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning _t_ was the last day on which the youngest rats (in this group) had a body weight value recorded. ,00 Precohahitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE 14): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP IV .................................................................................................................................... 10 MG/KG/DAY DAY 1 8 15 22 29 36 43 .................................................................................................................................... 50 57 64 70a PRECOHABITATION b 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 38. 61 102. 161. 204. 254 287. 320. 336. 358. 372. 400. 51. 89 149. 222. 280. 330 373. 416. 440. 473. 483. 497. 52. 90 143. 204. 260. 193 47. 83 136. 200. 255. 306 43, 82 135. 204. 260. 315 351. 390. 413. 439. 455. 476. 42. 76 122. 186. 236. 291 334. 370. 404. 439. 449. 476. 42. 77 128. 183. 24 296 336. 372. 401. 428. 436. 459. 36. 63 108. 166. 214 269. 35. 62 104. 150. 188 238. 274. 297, 309. 326. 338. 364. 55. 84 135. 190. 242 52. 83 126. 177, 233 273. 303. 334. 363. 335. 373. 386. 52. 88 134. 197. 246 302. 333. 362. 384. 404. 414. 432. 1223 1224 50 85. 132. 198. 256 35 52. 80. 123. 177 221. 274. 301. 332. 364. 389. 424. 1225 1226 1227 1228 1229 1230 35 54. 92. 139. 196 251. 291. 310. 342. 370. 387. 399. 48 82. 132. 199. 256 305. 345. 369. 387. 406. 422. 451. 48 80. 130. 188. 232 42 70. 111 157. 204 39 68. 110 159. 202 253. 276. 306. 324. 346. 365. 390. 38 65. 108 155. 203 1231 1232 1233 1234 1235 1236 1237 1238 35 77. 127 190 242 48 84. 128 184 226. 259. 290. 298. 312. 329. 336. 346, 55 89. 140 205 259. 319. 354. 400. 421, 462. 484. 508. 54 93. 149 212 267. 47 78. 125 179 236. 46. 77. 129 196 245. 301. 343. 383. 403. 432. 442, 454. 39. 66. 104 158 207. 253. 273. 288. 305. 326. 338. 353. 44. 75. 126 191 246. 1239 49. 83. 132 193 246. > 1240 51. 85. 136. 194 246. 293. 328. 362. 394. 424. 440. 463. ...................................................................................................... _ ............................. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). [29 Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning _t_ was the last day on which the youngest rats (in this group) had a body weight value recorded. Oo Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these _D rats were 92 to 106 days of age. to O PROTOCOL 418-020: ORAL (GARAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DIS (PAGE 15): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV .................................................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 1181 1182 1183 427. 424. 440. 438. 445. 460. 1184 1185 i186 1187 1188 1189 1190 450. 423. 415. 506. 462. 440. 391. 510. 485. 453. 425. 532. 501. 454. 446. 547. 509. 479. 457. 574. 533. 488. 470. 582. il9i 1192 452. 450. 466. 476. 492. 488. 1193 1194 477. 494. 507. 513. 523. 1195 435. 446. 466. 480. 495. 1196 1197 1198 595. 607. 633. 638. 679. 1199 1200 MORIBUND SACRIFICED ON DAY 40 POSTWEANING 1201 1202 1203 411. 428. 441. 455. 469. 1204 430. 430. 444. 451. 473. 1205 12o6 1207 432. 447. 461. 473. 483. 1208 1209 472. 481. 494. 504. 517. 1210 FOUND DEAD ON DAY 4 POSTWEANING ...................................................................................................... I DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G}. First weekly value recorded after cohabitation. 534. 498. 661. 483. 473. 489. 526. 10 MG/KG/DAY 120 STUDY OF AMMONIUM PERFLUOROOCTANOATE _ ............................. _> O0 _--4_ OQ b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE 16): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP IV .................................................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 388. 491. 471. 471. 458. 357. 382. 427. 396. 497. 470. 468. 452. 346. 372. 446. 412. 510. 480. 484. 472. 373. 403. 457. 428. 538. 492. 500. 480. 382. 404. 480. 447. 542. 501. 507. 498. 400. 413. 492. 455. 561. 512. 522. 503. 402. 414. 502. i0 MG/KG/DAY 120 1223 1224 414. 424. 450. 466. 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 393. 443. 386. 338. 503. 452. 350. 454. 396. 455. 392. 348. 509. 455. 341. 458. 414. 471. 392. 352. 526. 454. 357. 468. 429. 484. 402. 360. 545. 464. 367. 489. ...................................................................................................... = DAY POSTWEANING 486. 424. 489. 407. 365. 544. 465. 386. 492. 490. 429. 500. 411. 366. 556. 480. 381. 493. > r ............................. WEIGHTS WERE RECORDED IN GRAMS (G). 4_ First weekly value recorded after cohabitation. __ Oo b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D15 (PAGE 17} : BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP V .................................................................................................................................... 30 MG/KG/DAY DAY 1 8 15 22 29 36 .................................................................................................................................... 1241 1242 1243 35. 60, I00. 157 216. 269 34. 61. 102. 158 216. 260 34. 51. 91. 147 202. 235 1244 36. 68. 113. 176 237. 289 1245 1246 41. 70. 119. 180 244. 311 36. 65. 100 156 216. 262 1247 1248 1249 1250 32. 54. 85 136 190. 235 28. 48. 80 129 179. 222 30. 46. 82 132 177. 229 43. 64. 101 148 183. 211 1251 38. 77. 126 172 213. 248 43 330. 329, 354. 278. 254. 268. 50 369. 359. 397. 310. 278. 300. 57 397. 374. 407. 339. 305. 330. 64 432. 402. 421. 365. 317. 346. 70a PRECOHABITATION b 448. 465. 422. 428. 382. 324. 348. 446. 457. 399. 336. 360. 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 41. 71. i18 170 209. 243 272. 281. 304. 323. 340. 359. 45. 70. 107 160 204. 247 39. 58. 92 145 194. 229 258. 278. 288. 311. 328. 350. 48. 85. 133 187 241. 289 330. 365. 381. 401. 410. 441. 48. 86. 132 186 240. 290 43. 71. 112 168 231. 274 309. 351. 381. 406. 416. 420. 41. 61. 97 146 182. 204 26. 47. 69 118 171. 214 253. 290. 312. 337. 353. 371. 24. FOUND DEAD ON DAY 4 POSTWEANING 43. 68. 103. 151. 199. 232. 260. 286. 322. 349. 359. 377. 45. 71. 109. 162. 208. 248. 25. FOUND DEAD ON DAY 2 POSTWEANING 24. FOUND DEAD ON DAY 2 POSTWEANING 40. 66. 99. 150. 198. 242 42. 71. 107. 157. 213. 255 282. 306. 321. 340. 352. 369. 42. 73. 113. 165. 219. 269 47. 83. 120. 181. 235. 272 1269 47. 86. 128. 197. 255. 288 331. 356. 391. 417. 418. 442. > 1270 59. 99. 142, 191. 242. 269 ...................................................................................................... = DAY POSTWEANING T ............................. WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning ,t_ was the last day on which the youngest rats (in this group) had a body weight value recorded, O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. IV <D PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI5 (PAGE 18): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE RAT # DOSAGE GROUP V .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1271 1272 60 100. 152 205 256. 298. 42 66. 102 155 201. 238. 1273 1274 1275 1276 1277 39 63. 100 147 199. 239. 47 77. 127 184 242. 285. 42 69. 117 162 145. 116. 45 72. 111 169 199. 244. 25 FOUND DEAD ON DAY 4 POSTWEANING 1278 1279 1280 27 40. 67. 108. 144. 172. 33 52. 83. 130. 187. 234. 34 FOUND DEAD ON DAY 3 POSTWEANING 30 MG/KG/DAY 43 50 57 64 70a PRECOHABITATION b 330. 362. 388. 410. 436. 469. 265. 323. MORIBUND 282. 299. 348. 376. SACRIFICED ON DAY 320. 334. 412. 440. 39 POSTWEANING 355. 456. 205. 243. 261. 289. 301. 324. 1281 36 70. 113 167. 214. 261. 294. 320. 354. 374. 388. 414. 1282 1283 1284 1285 1286 50 79. 122 175. 51 81. 124 171. 46 71. 108 164. 45 70. iii 170. 32 55. 85 138. 1287 1288 1289 1290 1291 1292 1293 36 56. 88 137. 29 52. 85 130. 48 77. 119 180. 47 80. 125 185. 45 76. 124 178. 50 87. 134 185. 49 84. 114 167 1294 1295 49 81. 112 172 52 79. 123 182 1296 1297 49 76. 119 180 38 67. 114 167 1298 36 65. 106 158 1299 1300 44 75. 122 182 42 76. 120 177 ...................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 223. 232. 210. 188. 187. 181. 182. 234. 239. 224. 232. 224. 229. 237. 218. 220. 203. 239. 210. 260. 276. 256. 238. 226. 278. 284. 259. 270. 261. 242. 267. 287. 283. 278. 264. 316. 318. 289. 310. 304. 264. 300. 293. 302. 316. 286. 331. 336. 303. 344. 329. 294. 334. 298. 322. 338. 311. 350. 354. 312. 350. 349. 300. 341. 307. 346. 323. 359. 346. 389. 359. 323. 376. 374. 329. 372. 338. 386. 390. 336. 376. 350. 388. 392. 353. 367. 388. 401. 370. 376. 394. 312. 318. 341. 371. 368. 391. _ ............................. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. _0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6} REPRODUCTION TABLE DI5 (PAGE 19): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP V .................................................................................................................................... ...... DAY 78 85 92 99a 106 113 ,.............................................................................................................................. 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 456. 432. 435. 394. 332. 355. 457. 436. 449. 398. 338. 353. 461. 466. 472. 413. 356. 364. 477. 469. 477. 418. 358. 372. 476. 486. 480. 427. 368. 383. 441. 492. 490. 439. 377. 378. 30 MG/KG/DAY 120 1251 1252 354. 352. 365. 382. 396. 403. 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 343. 429. 346, 433. 361. 443. 366. 448. 416, 378, 415, 427. 365. FOUND 370. 378. 384. 397. DEAD ON DAY 4 POSTWEANING 357. 378. 367. FOUND FOUND DEAD DEAD ON DAY ON DAY 2 POSTWEANING 2 POSTWEANING 366. 367. 380. 390. 380. 462. 444. 411. 384. 403. 401. 476. 446. 422. 376. 423. 1267 1268 1269 437. 445. 467. 477. 495. 498. > ..........1..2.7..0...................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). First weekly value recorded after cohabitation. _ .............................. OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D15 (PAGE 20): BODY WEIGHTS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP V .................................................................................................................................... DAY 78 85 92 99a 106 113 .................................................................................................................................... 30 MG/KG/DAY 120 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 452. 457. 465. 465. 478. 350. 450. MORIBUND 341. 356, 359. 372. 448. 469. 475, 486. SACRIFICED ON DAY 39 POSTWEANING FOUND 323. DEAD ON DAY 4 POSTWEANING 326. 334. 345. 369. FOUND 407. 334. DEAD ON DAY 412. 350. 3 POSTWEANING 423. 437. 355. 363. 450. 362. 491. 378. 490. 382. 466. 383. 510. 394. 507. 1283 1284 1285 1286 1287 1288 1289 384. 378. 341. 385. 396. 373. 355. 388. 406. 388. 360. 391. 423. 405. 371. 412. 434. 413. 382. 422. 435. 420, 397. 428. 1290 1291 391. 350. 388. 359. 393. 372. 403. 386. 415. 396. 427, 397. 1292 1293 1294 1295 1296 1297 1298 1299 1300 405. 391. 338. 391. 408. 394. 344. 386. 417. 402. 352. 394. 433. 414, 378. 401, 435. 284. 372. 419. 440. FOUND DEAD ON DAY 107 POSTWEANING 383. 434. ...................................................................................................... _ ............................. = DAY POSTWEANING O0 WEIGHTS WERE RECORDED IN GRAMS (G). First weekly value recorded after cohabitation. 4_ 00 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE DI6 (PAGE I) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS PERFLUOROOCTANOATE RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1001 60. 116. 163. 188. 199 43 - 50 1002 1003 1004 72. 124. 165. 202. 195 88. 144. 191. 215. 231 76. 135. 164. 181. 200 197. 233. 183. 207. 1005 1006 81. 140. 178. 205. 212 74. 130. 161. 173. 177 222. 204. 1007 1008 1009 i010 78. 117. 151. 172. 180 87. 130. 165. 183. 193 82. 143. 191. 197. 219 69. 114. 145. 165. 178 195. 188. I011 78 129. 156. 172. 189 203. 208. 50 - 57 194. 223. 210. 194. 209. 57 - 64 194. 229. 203. 197. 211. 64 - 70a 99b-106 106 -113 159. 173. 175. 170. 159. 218. 206. 197. 178. 213. 191. 188. 192. 206. 219. 10123 1014 1015 7638 15367. 16550. 16791. 210833 220061.. 211886.. 20223. 20295. 17931. 2118. c 96 143. 171. 193. 211 199. 189. 199. 197. 164. 195. 202. 97 169. 194. 209. 234 1016 86 147. 158. 176. 195 1017 6553 6554 6555 70 142. 162. 181. 192 182. 186. 193. c 167. 186. c 50 107. 131. 144. 85 143. 155. 260. 80 135. 151. 166. 1021 1022 76 132. 149. 169. 178. 193. 204. 224. 225. 186. 223. 220. 82 151. 167. 191. 205. 1023 1024 1025 68 116. 147. 174. 193. 205. 203. 205. 212. 185. 208. c 76 129. 149. FOUND DEAD ON DAY 25 POSTWEANING 69 118. 143. 179. 195. 1026 1027 66 125. 140. 166. 181. 186. 182. 200. 200. 173. 205. 214. 78 111. 123. 137. 156. 1028 66 108. 139. 158. 176. 177. 168. 173. 165. 143. 173. 147. 1029 1030 MORIBUND 71. SACRIFICED ON DAY 4 POSTWEANING 134. 168. 196. 205. ....................................................................................................... = DAY POSTWEANING > . ............................ WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 First value recorded after cohabitation. Spilled feed precluded the calculation of this value, tJ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D16 (PAGE 2): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64 64 - 70a 99b-106 .................................................................................................................................... 106 -113 1031 76. 115. 165. 196. 200. 207. 203. 1032 62. 109. 158 191. 199. 1033 1034 62. 106. 147 53. 110. 142 180. 174. 189. 187. 194. 185, 1035 1036 1037 60. d 140 171 191. 181. 160. 76. 122. 163 190 188. 55. 100. 136 155 162. 1038 80. 112. 154 180 1039 75. 112. 157 181 207. FOUND DEAD ON DAY 1040 75. 121, 147 165 188. 183. 192. 1041 46. 103. 131 147 179, 181. 199. 1042 78. 118 136 157 1043 66. 128 170. 186 183. 218. 224. 1044 87. 143 162. 173 1045 74. 124 151. 177. 190. 198. 221. 1046 82. 136 158. 175. 1047 69. 135 161. 175. 212. 211. 228. 1048 74. 124 159. 182. 212. 221. 244. 1049 65. 119 145. 172. 1050 70. 117. 138. 174. 199. 206, 263. 1051 71 128. 166. 199. 237. 254. C 1052 70 143. 177. 189. 210. 210. 232. 1053 71 115. 149. 193. 1054 81 129. 153. 206. 215. 200. 196. 1055 81 136. 172. 201. 216. 201. 200. 1056 87 141. 170. 191. 1057 72 126. 161. 72. 1058 77 133. 168. 192. 214. 209. 209. 1059 82 118, 163. 191. 208. 237. 237. 1060 57. 111. 163. 183. 187. 192. 207. ...................................................................................................... 213. 194. 182. c 188. 173. 42 POSTWEANING 177. 179. 198. 185. 249. 267. 227. 214. 228. 243. 240. 246. 240. c 242, c c 264. 204, 204. 190. 196. 201. c 206, 219. 241. 193. 174. 156. 133, 204. 193. 162. 212. 200. 166. 144. 149. 196. 156. 191. 185. 163. 215. 185. 176. 246. 187. 190. 232. 187. 220. 216. 198. 259. 218. 188. 206. 180. 195. 213. 189. 224. 212. 194. 246. 217. 192. 207. 181, 207. 213, 201, 180. 153, 190. , ............................. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which First value recorded after a feed consumption cohabitation. value was recorded for the youngest rats in this group. Spilled Soiled feed precluded feed precluded the calculation the calculation of this value. of this value. > [2_ _-4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D16 (PAGE 3): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DA .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 57 57 - 64 64 - 70a 99b-106 .................................................................................................................................... 106 -113 1061 1062 67. 120. 77. 125. 159. 151. 168. 169. 178. 185. 175. 170. 180. 169. 140. 165. 168. 1063 1064 1065 69. FOUND 66. 123. DEAD ON 106 128. 164. DAY 6 POSTWEANING 134. 160. 187, 180. 207. 180. 183. 180. 152. 191. 187. 1066 1067 1068 64. 106 54. 99 69. 119 139. 145. 155. 155. 174. 176. 169. 190. 196. 171. 200. 168. 177. 182. 186. 167. 185. 142. 139, 176. 186. 182. 165. 1069 1070 62. 108 79. 121 138. 159. 162, 176. 192. 203. 200. 209. 204. 204. 158. 195. 189. 1071 1072 72. 117 65. 130 141. 159. 161. 181, 179. 201. 190. 174. 174. 176. c 184. 181, 1073 1074 86. 146 72. 123 177. 169. 189. 191. 201. 207. 199. 181. 188. 189. 162. 177. 171. 1075 1076 72. 145 80. 132 179. 165. 200. 185. 213. 187. 1077 1078 1079 1080 68. 132 84. 151 70. 114 84. 128 160. 182. 146. 150. 173. 192. 164. 171. 191. 208, 172. 184. 191. 231. 190. 208. 195. 243. 204. 239. 169. 207. 222. 241. 189. 240. 1081 1082 1083 1084 1085 74. 124 74. 135 61. 121 72. 119 69. 110 154. 144. 152. 140. 140. 168. 167. 173. 158. 156. 181. 177. 192. 176. 178. 192. 193. 195. 195. 180. 175. 211. 184. 188. 215. 183. 183. 177. 159. 157. 204. 193. 184. 200. 182. 183. 1086 1087 1088 72. 117 87. 122 90. 121 135. 172. 167. 147. 191. 173. 158. 203. 188. 211. 213. 198. 161. FOUND 190. DEAD c c 130. ON DAY 45 POSTWEANING c c 174. 131. 204. 171. 256. 1089 92, 136 158. 175. 191. 1090 78. 124 136. 154. 159. 191, 179. ....................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 191. 179. 145. c 174. .............................. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 First value recorded after cohabitation. Spilled feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE DI6 (PAGE 4) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1091 1092 1093 70. 115. 75. 120. 65. 108. 145. 150. 149. 171. 170. 181. 189. 189. 193. 195. 43 - 50 198. 1094 1095 74. 115. 157. 180. 199. 215. 214. 80. 125. 167. 203. 228. 1096 1097 66. 118. 66. 128. 147. 143. 167. 167. 184. 187. 199. 222. 1098 1099 70. 129. 153. 183. 195. 198. 200. 84. 151. 170. 218. 175. ii00 1101 96. 134. 90. 162. 160. 154. 180. 170. 203. 183. 202. 184. 50 - 57 200. 223. 238. 210. 197. 57 - 64 195. 222. 236. 198. 200. 64 - 70a 99b-106 106 -113 159. 185. 194. 193. 207. 187. 156. 221. 218. 193. 181. c 238. 191. 187. 11023 1104 1105 6754. FOUND 65. 12392. DEAD ON 115. 116780.. 210809. DAY 2 POSTWEANING 141. 174. 210957.. 188. 201. 199. 207. 204. 175. 198. 194. 1106 1107 1108 1109 59. i00. 120. 137. 151. 162. 172. 186. 188. 165. 194. 190. 75. 111. 135. 159. 167. 178. 188. 184. 204. 183. 214. 210. 75. 115 149. 172. 197. 67. 118 139. 168 176. 1110 1111 72. 109 59. 109 124. 164 148. 164 173. 182. 180. 192. 179. 147. 165. 167 173. 1112 1113 77. 120 82. 120 154. 186 165. 196 206. c 206. 208. 223. 184. 206. 207 1114 1115 1116 1117 1118 80. 128 62. 108 68. 101 72. 112 71. 117 161. 183 136. 162 136. 148 137. 146 149. 167 200. 197. 188. 201. 207. 177. 209. 198 178. 193. 203. 205. 205. 171. 212. 209 193. 183. 188. 198. 199. 154. 182. 197 1119 1120 60. 112 66. 117 157. 157. 175 185. 202. 199. 198. c 203. 165. 202. 194 ...................................................................................................... = DAY POSTWEANING _ ............................. WEIGHTS WERE RECORDED IN GRAMS (G). O_ Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 First value recorded after cohabitation. Spilled feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI6 (PAGE 5): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS ...... _.............................................................................................................................. RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1121 FOUND DEAD ON DAY 5 POSTWEANING 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 89. 90. 68. 58. 68. 56. 64. 51. FOUND 59 131. 137. 114. 114. 104. 101. 117. 112. DEAD ON 122. 169. 61. 171. 184. 153. 175. 146. 173. 137. 166. 131. 154. 165. 187. 157. 185. DAY 2 POSTWEANING 145. 170. 198 203 189 181 175 175 c 199. 178. 200. 213. 195. 198. 211. 1132 81 128. 164. 179. 161. 189. 43 - 50 192. 199. 188. 202. 219. 183. 50 - 57 189. 216. 192. 212. 233. 196. 57 - 64 181. 211. 190. 207. 226. 196. 64 - 70a 99b-106 106 -113 157. 178. 176. 121. 183. 136. 160. 185. 183. 164. 193. 229. 215. 200. 184. 231. 229. 202. 1133 1134 86 138. 154. 167. 178. 83 149. 176 198 210. 222. 213. 218. 212. c 199. 197. 1135 1136 1137 1138 82 143. 180 205 217. 207. 189. 189. 189. 169. 210. 210. 42 99. 153 165 179. 190. 190. 203. 201. 164. 192. 113. 73. 123. 164 181 185. 92. 147. 175 191 208. 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 82. 129. 170 208 195. 63. FOUND DEAD ON DAY 9 POSTWEANING 72. 119. 146. 165. 176. 50. 102. 131. c 170. 69. 138. 143. 170. 190. 56. 109 139. 157. 180. 62. 160 137. 157. 171. 68. 177 147. 175. 194. 89. 159 180. 173. 195. 91. 149 144. 160. 173. 87. 135 161. 169. 195. 81. 126 155. 182. 198. 203. 198. 181. 165. 214. 213. 192. 189. 178. 172. 212. c 197. 194. 176. 172. 211. 207. 199. 190. 177. 164. 209. 210. 165. 162. 156. 144. 185. 164. c 199. 182. 167. 203. 191. 183. 204. 191. 164. 162. 190. ...................................................................................................... _ ............................. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. First value recorded after cohabitation. Spilled feed precluded the calculation of this value, 50 _--4_ O0 t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE D16 (PAGE 6): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 1151 1152 101. 151 82. 162 181. 176. 210. 197. 225. 213. 228. 227. 1153 1154 1155 1156 1157 88. 149 96. 146 98. 147 74. 124 75. 119 176. 179. 181. 162. 150. 185. 205. 203. 195. 178. 202. 219. 224. 218. 195. 217. 217. c 213. 1158 1159 1160 79. 123 122. 146 98. 142 160. 185. 176. 182. 208. 193. 204. 233. 220. 212. 222. 202. 262. 50 - 57 235. 236. 225. 256. 269. 57 - 64 223. c 224. 254. 235. 64 - 70a 99b-106 106 -113 194. 199. 211. 193. 182. 205. 209. c 210. 198. 202. 207. 216. 228. 210. 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 92. 129 66. iii 70. 112 89. 144 83. 138 33. 69 42. 90 48. 99 56. 99 71. 113 68. 105 75. 133 85. 133 85. 142 90. 136 73. 113 81. 139 87. 131 164. 129. 132. 181. 177. 101. 121. 135. 125. 137. 129. 159. 152. 182. 175. 137. 166. 170. 188. 170. 165. 195. 214. 128. 148. 159. 142. 154. 147. 205. 180. 213. 206. 149. 181. 183. 199. 190. 179. 216. 230. 149. 167. 187. 166. 195. 230. 165. 204. 179. 209. 173. 185. 203. 164. 189. 227. 182. 206. 183. 209. 186. 218. 216. 167. 200. 228. 198. 206. 186. 220. 217. 218. c 209. 176. 203. 208. 180. 212. 225. 216. c 211. 123. 202. 203. 151. 177. 176. 177. 139. 167. 151. 167. 180. 190. 194. 224. 218. 168. 193. 199. 157. 186. 200. 204. 220. 201 168 186 155. 145. 213. 1179 1180 78. 122 81. 117 168. 155. 190. 184. ...................................................................................................... = DAY POSTWEANING 218. 212. 229. 206. 194. 168. 206. 200. _ ............................. WEIGHTS WERE RECORDED IN GRAMS (G). 0_ Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweanlng was the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 First value recorded after cohabitation. Spilled feed precluded the calculation of this value, tJ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI6 (PAGE 7): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 76 137. 156. 190. 205 75 119. 163. 199. 211 212. 198. 58 i01. 134. 159. 176 63 103. 147 174. 189 195. 169. 56 110. 127 174. 206 64 107. 135 169. 179 162. 178. 78 136. 160 178. 197 84 134. 174 184. 200 201. 187. 80 160. 164 201. 241 231. 243. 88 194. 180 238 265. 1191 84 138. 157 176 189. 11119923 8975.. 113450. 115656 117939 220233.. 199. 195. 50 - 57 206. 181. 182. c 230. 200. 57 - 64 213. 176. 182. 199. 218. 193. 64 - 70a 99b-i06 106 -113 172. 159. 154. 155. 193. 195. 196. 190. 208. 239. 194. 204. 188. 207. 239. 167. 198. 191. 1195 1194 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 85. 143 85. 138 81. 129 59. 117 91. 152 72. 142 75. 143 86. 140 83. 126 75. 155 84. 123 80. 127 79. 123 73. 112 85. 137. 84. 122. 155 164 137 131. 169. 142. 170. 162. 148. 168. 161. 157. 146. 132. 156. 154. 195 190 165 155 192 177 d 178. 174. 205. 208. 203. 168. 161. 183. 184. 218. 219. 184. 183. 223. 198. 181. 208. 199. 216. 225. 239. 194. 179. 206. 211. 213. 218. 196. 213. 206. 221. 192. 220. 163. 194. 238. MORIBUND 241. 260. 257. 213. SACRIFICED ON DAY 40 POSTWEANING 197. 211. 179. 198. 190. 219. 178. 213. 141. 178. 189. 206. 187. 212. 189. 212. 182. 215. 157. 184. 199. 205. 233. 183. 240. 185. 209. 200. 226. 236. 187. 229. 180. 211. 1210 FOUND DEAD ON DAY 4 POSTWEANING ..................................................................................................... _ .............................. = DAY POSTWEANING ' WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweanlng was the last interval in which First value recorded after a feed consumption cohabitation. value was recorded for the youngest rats in this group. Spilled feed precluded Wet feed precluded the the calculation of this value. calculation of this value. _> UJ _.,4_ O_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D16 (PAGE 8): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV I0 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 64 106. 130 154. 90 145. 185 212 86 132. 165 198 79 125. 161 193 76 121. 188 204 76 116. 114 155 86 125. 165 181 62 105. 132 162 59. 80. 125 152 75. 121. 145 165 67. 112 129. 155 77. 123 149. 183 167. 220. 99. 201. 211. 170. 194. 179. 177. 164. 193. 174. 224. 206. 184. 197. 186. 166. 191. 183. 230. 200. 194. 217. 184. 183. 186. 50 - 57 189. 229. 203. 212. 232. 190. 189. 188. 57 - 64 183. 221. 190. 216. 226. 176. 165. 185. 64 - 70a 99b-106 106 -113 159. 188. 197. 209. 200. 220. 164. 181. 191. 157. 109. 141. 178. 203. 203. 184. 192. 188, 181. c 193. 181. 206. 199. 1223 1224 1225 1226 1227 1228 75. 117 39. 76 39. 83 80. 122 70. 113 71. 110 156. 112. 119. 159. 142. 136. 179. 150. 174. 176. 161. 161. 169. 190. 197. 174. 192. 209. 178. 202. 212. 177. 207. 212. 183. 220. 210. 149. 173. 180. 187. 189. 206. 177. 187. 199. 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 66. 109 64. 112 76. 121 76. 114 76. 122 83 130. 69 107. 69 107. 65 104, 72 120. 75 119. 74 118. 147. 145. 161. 135. 166. 166. 145. 148. 140. 169. 152. 151. 177. 171. 193. 161. 191. 193. 177. 165. 173. 202. 179. 194. 198. 166. 211. 178. 281. 217. c 161. 208. 183. 177. 204. 184. 153. 222. 199. 188. 227. 184. 146. 228. 197. 192. 228. 165. 145. 232. 204. 203. 226. 143. 124. 202. 168. 165. 158. 154. 151. 221. 186. 260. 193. 152. 145. 214. 191. c 190. ...................................................................................................... = DAY POSTWEANING _ ............................. WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4= the last interval in which a feed consumption value was recorded for the youngest rats in this group. Oi 0 First value recorded after cohabitation. Spilled feed precluded the calculation of this value, b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE DI6 (PAGE 9): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 1241 1242 1243 52. 99. 137. 166. 185. 210. 193. 60. 107. 143. 180. 187. 47. 94. 147. 180. 176. 1244 1245 1246 70. 123. 75. 127. 68. 108. 177. 168. 144. 217. 211. 171. 237. 248. 188. 250. 259. 232. c 1247 1248 1249 1250 55. 92. 118. 150. 168. 182. 172. 74. 92. 117. 142. 168. 174. 159. 49. 93. 113. 149. 176. 190. 167. 61. 100. 136. 152. 158. 1251 1252 1253 81. 132. 73. 129. 69. 114. 143. 147. 139. 167. 161. 170. 184. 188. 184. 196. 185. 50 - 57 188. c 246. 184. 169. 176. 200. 57 - 64 210. 215. 239. 177. 158. 159. 189. 64 - 70a 99b-106 106 -113 165. 178. 142. 193. 179. 159. 135. 118. c 230. 173. 156. 152. 217. 236. 174. 164. 147. 168. 203. 185. 11225545 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 5893.. 83. 70. 58. 50. FOUND 66. 74. FOUND FOUND 69. 75. 72. 69. 110266.. 123. 125. 120. 88. DEAD ON 133. 146. DEAD ON DEAD ON 126. 123. 149. 197. 113438.. 142. 117744.. 165. 137. 128. 162. 140. 118. 151. DAY 4 POSTWEANING 129. 134. 155. 169. DAY 2 POSTWEANING DAY 2 POSTWEANING 139. 171. 135. 143. 172. 157. 174. 205. 118924.. 178. 185. 148. 167. 161. c 188. 176. 200. 215. 119957.. 191. 178. 165. 180. 117949.. 203. 176. 172. 170. 117956.. 218. 170. 180. 170. 118857.. 216. 166. 181. 167. 116519.. 180. 140. 144. 144. 213841.. 197. 171. 179. 190. 119919.. 198. 176. 162. 192. 1269 81. 138. 187. 222. 229. 261. 230. 239. 231. 182. 222. 226. > 1270 91. 135. 242. 172. 194. ....................................................................................................... = DAY POSTWEANING . ............................. WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O_ First value recorded after cohabitation. Spilled feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LIXTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI6 (PAGE i0): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 50 - 57 57 - 64 64 - 70a 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 92. 63. 67. 79. 70. 49. FOUND 29. 44. FOUND 136. 95. 101. 116. 113. 107. DEAD ON 68. 81. DEAD ON 99. 202 128. 157 128. 165 168. 200 164. 235 146. 145 DAY 4 POSTWEANING 105. 128. 119. 159. DAY 3 POSTWEANING 206. 163. 186. 213. 173. 169. 134. 177. 221. 179. 210. MORIBUND 227. 231. 215. 190. 166. 168. 192. 199. SACRIFICED ON DAY 167. 142. 214. 178. 39 POSTWEANING 141. 157. 161. 165. 142. 1281 70. 113 134. 165. 189. 181. 197. 216. 201. 164. 1282 1283 67. II0 65. 111 136. 131. 163. 180. 173. 188. 183. 182. 171. 174. 149. 99b-106 203. 169. 178. 180. 204. 163. 106 -113 221. 162. 181. 177. 206. 183. 11228845 5599.. 110121 115559.. 128025.. 198. 187. 180. 186. 173. 153. 203. 194. 1286 55. 88 118. 148. 1287 56. 82 121. 161. 185. 184. c c 226. 228. 218. 216. 1288 55. 91. 117. 147. 182. 190. 183. 189. 178. 168. 189. 191. 1289 68 112. 146. 187. 203. 205. 204. 216. 215. 172. 212. 196. 1290 73 113. 150. 195. 218. 209. 200. 212. 207. 173 202. 199. 1291 60 117. 144. 167. 169. 166. 211. 168. 173. 125 167. 160. 1292 74 136. 168. 194. 1293 70 107. 128. 177. 1294 57 82. 141. 188. 205. 211. 213. 197. 194. 162 194. 170. 1295 67 119. 154. 185. 1296 59 109. 141. 151. 167. 179. 182. 185. 182. 142. 124. d 1297 55 108. 134. 157. 1298 55 I00. 132. 159. 175. 177. 189. 185. 167. 137. 174. e 1299 63 109. 144. 171. 1300 63 102. 148. 164. 203. 210. 221. 222. 230. 165. 213. 218. ...................................................................................................... ............................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweanlng was the last interval in which a feed consumption value was recorded for the youngest rats in this group. First value recorded after cohabitation. Spilled feed precluded the calculation of this value. Rat 1296 was found dead on day 107 postweaning. Wet feed precluded the calculation of this value. _.,4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D17 (PAGE 1): SEXUAL MATURATION - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONI[_4 PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP - MG/KG/DAY .................................................................................................................................... I II III 0 1 3 .................................................................................................................................... PREPUTIAL PREPUTIAL PREPUTIAL RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) RAT # SEPARATION .................................................................................................................................... 1001 52 1002 49 1003 49 1004 49 1005 48 1006 49 1007 47 1008 _7 1009 46 1061 46 1062 47 1063 51 1064 a 1065 51 1066 47 1067 48 1068 48 1069 51 1121 a 1122 51 1123 50 1124 52 1125 50 1126 52 1127 51 1128 45 1129 48 1010 47 1011 45 1012 51 1013 48 1014 46 1015 47 1016 49 1017 48 6553 b 6554 46 6555 52c 1021 52 1022 49 1023 52 1024 d 1070 51 1071 55 1072 51 1073 49 1074 53 1075 51 1076 47 1077 49 1078 47 1079 50 1080 49 1081 47 1082 50 1083 52 1084 50 1130 a 1131 55 1132 53 1133 55 1134 47 1135 47 1136 45 1137 47 1138 48 1139 47 1140 a 1141 55 1142 52 1143 54 1144 58 IV 10 (DAY) RAT # PREPUTIAL SEPARATION 1181 47 1182 46 1183 52 1184 52 1185 58 1186 53 1187 48 1188 46 1189 50 49 1190 1191 48 1192 49 1193 49 1194 49 1195 49 1196 46 1197 49 1198 51 1199 52 1200 d 1201 50 1202 49 1203 48 1204 48 (DAY) V 30 RAT # PREPUTIAL SEPARATION 1241 56 1242 57 1243 59 1244 52 1245 55 1246 56 1247 58 1248 53 1249 55 1250 50 1251 50 1252 53 1253 49 1254 53 1255 49 1256 54 1257 49 1258 54 1259 58 1260 a 1261 51 1262 49 1263 a 1264 a (DAY) 1025 52 1026 53 1027 49 1085 55 1086 50 1087 47 1145 52 1146 46 1147 47 1028 48 1029 a 1088 50 1089 50 1148 46 1149 50 1030 50 1090 47 1150 46 ................................................................................................................................. 1205 56 1206 51 1207 50 1208 50. 1209 48 1210 a = DAY POSTPARTUM Rat was found dead or moribund sacrificed before the start of sexual maturation Sexual maturation testing was discontinued before rat became sexually mature. Rat did not have preputial separation recorded on one day and was separated the averages Rat was and statistical analyses. found dead or moribund sacrificed. evaluation, following day; value 1265 1266 1267 1268 1269 1270 excluded 49 49 50 49 46 54 from group [2_ 4_ w-_ t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D17 (PAGE 2): SEXUAL MATURATION - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP - MG/KG/DAY .................................................................................................................................... I II III 0 1 3 .................................................................................................................................... PREPUTIAL PREPUTIAL PREPUTIAL RAT # SEPARATION (DAY) RAT # SEPARATION (DAY) RAT # SEPARATION .................................................................................................................................... 1031 48 1032 50 1033 48 1034 51 1035 48 1036 48 1037 51 1038 49 1039 49 1091 49 1092 52 1093 55 1094 52 1095 51 1096 48 1097 49 1098 46 1099 49 1151 44 1152 49 1153 49 1154 46 1155 49 1156 50 1157 46 1158 50 1159 44 (DAY) IV 10 RAT # PREPUTIAL SEPARATION 1211 51 1212 48 1213 48 1214 48 1215 48 1216 49 1217 50 1218 53 1219 53 1040 c 1041 49 1042 47 1043 44 1044 47 1045 50 1046 47 1047 49 1048 50 1049 50 1050 47 1051 47 1052 c 1053 49 1054 48 1055 48 1056 44 1057 48 1058 49 1059 d 1060 d ii00 45 1101 49 1102 50 1103 51 1104 b 1105 56 1106 53 1107 48 1108 45 1109 48 1110 48 1111 50 1112 48 1113 50 1114 47 1115 55 1116 52 1117 48 1118 47 1119 47 1120 44 1160 46 1161 46 1162 47 1163 51 1164 48 1165 46 1166 58 1167 53 1168 50 1169 52 1170 53 1171 52 1172 52 1173 52 1174 45 1175 45 1176 50 1177 46 1178 46 1179 49 1180 49 .................................................................................................................................... = DAY POSTPARTUM Rat was found Rat was found dead dead or moribund or moribund sacrificed. sacrificed before the start of sexual Sexual Sexual maturation maturation testing was discontinued before rat became was not observed on rats 1059 and 1060. sexually 1220 47 1221 44 1222 54 1223 47 1224 58 1225 59 1226 48 1227 45 1228 50 1229 52 1230 52 1231 49 1232 49 1233 48 1234 49 1255 50 1236 45 1237 53 1238 50' 1239 47 1240 47 maturation mature. evaluation. (DAY) V 30 RAT # PREPUTIAL SEPARATION 1271 49 1272 53 1273 54 1274 5D 1275 a 1276 50 1277 b 1278 56 1279 54 1280 b 1281 54 1282 54 1283 48 1284 52 1285 52 1286 55 1287 58 1288 56 1289 53 1290 53 1291 49 1292 52 1293 49 1294 47 1295 52 1296 52 1297 52 1298 52 1299 49 1300 50 (DAY) _'_ O0 "_ --I_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NL_BER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D18 (PAGE 1): MATING AND FERTILITY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAYS IN FEMALE PREGNANCY RAT # COHABITATION MATING STATUS MATING DATE STATUS .................................................................................................................................... 1002 2 1003 4 1005 3 1007 2 i011 2 1012 14 1013 2 1014 2 1017 1 M C M C M C M C M C DID NOT MATE - M C M C M C P(1341) P(1302) P(1335) P(1318) P(1308) -(1358} P(1334) P(1304) P(1346) 1021 4 M C 1023 2 M C 1026 3 M C 1028 3 M C 1031 1034 1035 2 M C 4 M C 4 M C 1040 1 M C 1041 3 M C 1043 5 M C 1045 1 M C 1047 5 M C 1048 2 M C 1050 4 M C 1051 2 M C 1052 4 M C 1054 2 M C 1055 1 M C 1058 3 M C 1059 3 M C 1060 1 M C ........................................................................................... M = MATED C = CONFIRMED p = PREGNANT ( ) = FEMALE NP = NOT RAT NUMBER PREGNANT P(1359) P(1350) P(1355) P(1336) P(1342) P(1328) P(1344) NP(1316) P(1330) P(1353) P(1348) P(1340) P 1338) P 1331) P 1345) P 1306) P 1313) P 1312) P 1321) P 1310) P 1325) 1 ........................................ [/_ 4_ O_ tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI8 (PAGE 2) : MATING AND FERTILITY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... DATE 1061 1 M C 1063 3 M C 1066 3 M C 1067 4 M C 1069 3 M C 1071 4 M C 1073 3 M C 1077 3 M C 1078 4 M C 1081 3 M C 1082 2 M C 1083 4 M C 1086 6 M C 1088 2 M C 1090 4 M C 1091 4 M C 1094 2 M C 1096 2 M C 1098 3 M C 1100 4 M C 1103 2 M C 1106 3 M C 1107 2 M C Iii0 3 M C 1112 4 M C 1114 2 M C 1116 i M c 1118 2 M C 1120 4 M C ....................................................................................................... M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED p. = pREGNANT NP = NOT PREGNANT FEMALE PREGNANCY STATUS P(1415) P(1410) P(1364) P(1362) P(1387) P(1392} P(1363) NP(1378) P(1371) P(1368) P(1418) P(1367) P(1409) P(1389) P(1404) P(1413) P(1375) P(1397) P(1407) P(1376) P(1383) P(1399) P(1401) P(1382) P(1379) P(1384) P(1416) P(1393) P(1381) .............................. > ._ _-, OO 6 b,J O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D18 (PAGE 3): MATING AND FERTILITY - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... DATE 1122 1 M C 1123 2 M C 1127 4 M C 1129 3 M C 1131 2 M C 1132 4 M C 1134 4 M C 1135 2 M C 1136 2 M C 1139 2 M C 1141 3 M C 1142 4 M C 1145 1 M C 1147 4 M C 1149 1 M C 1151 3 M C 1153 1 M C 1154 4 M C 1158 1 M C 1159 2 M C 1162 4 M C 1164 2 M C 1167 1 M C 1168 3 M C 1171 2 M C 1173 3 M C 1175 2 M C 1176 4 M C 1177 1 S C 1180 1 M C ............................................................................................ M = MATED C = CONFIRMED p = PREGNANT ( ) = FEMALE NP I NOT RAT NUMBER PREGNANT FEMALE PREGNANCY STATUS P(1456) P(1443) P(1476) P(1461) P(1474) P(1472} P(1455) P(1448) P(1430) P(1424) P(1450) NP(1446) P(1480) P(1437) P(1426) P(1439) P(1431) P(1477) P(1469) P(1452) P(1436) P(1459) NP(1458) P(1428) P(1465) P(1433) P(1463) P(1468) P(1421) P(1442) ........................................ > _'_ _n 4_ _.. O0 _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D18 (PAGE 4): MATING AND FERTILITY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... DATE 1182 3 M C 1184 4 M C 1186 4 M C 1188 2 M C 1189 4 M C 1192 7 M C 1194 1 M C 1195 1 M C 1198 2 M C 1203 2 M C 1204 3 M C 1207 1 M C 1209 1 M C 1211 3 M C 1212 4 M C 1215 4 M C 1216 3 M C 1217 4 M C 1219 4 M C 1221 4 M C 1222 1 M C 1224 5 M C 1225 1 M C 1226 1 M C 1229 1 M C 1232 2 M C 1233 1 M C 1236 3 M C 1237 4 M C 1240 1 M C ............................................................................................ M = MATED C = CONFIRMED ( ) = FEMALE RAT NUMBER P = PREGNANT NP = NOT PREGNANT FEMALE PREGNANCY STATUS P(1528) P(1523) P(1516) P(1513) P(1527) NP(1511) P(1519) P(1502) P(1496) P(1491) P(1533) NP(1483) P(1488) P(1500) P(1521) P(1531) P(1505| P(1508) P(1497) P(1494) P(1486) P(1539) P(1534) P(1517) P(1524) P(1514) P(1482) P(1537) P(1507) P(1490) L ....................................... _u C_ /_ T C.2 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE D18 (PAGE 5): MATING AND FERTILITY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAYS IN RAT # COHABITATION MATING STATUS MATING .................................................................................................................................... DATE 1241 3 M C 1244 2 M C 1245 2 M C 1247 1 M C 1248 4 M C 1249 4 M C 1252 4 M C 1254 3 M C 1255 2 M C 1257 4 M C 1259 2 M C 1261 4 M C 1266 3 M C 1269 1 M C 1271 4 M C 1273 3 M C 1274 3 M C 1278 3 M C 1281 3 M C 1282 3 M C 1284 2 M C 1287 5 M C 1288 1 M C 1289 1 M C 1290 1 M C 1291 1 M C 1294 1 M C 1296 2 M C 1298 1 M C 1300 3 M C .................................................................................................................................... M = MATED C _ CONFIRMED ( ) = FEMALE RAT NUMBER p = PREGNANT NP s NOT PREGNANT FEMALE PREGNANCY STATUS P(1588) P(1565) P(1557) P(1560) P(1566) P(1555) P(1546) P(1548) P(1573) P(1586) P(1541) P(1598) P(1568) P(1558) P(1600) P(1589) P(1571) NP(1578) P(1545) P(1552) P(1591) P(1544) P(1584) P(1583) P(1593) P(1550) P(1576) P(1579) P(1587) P(1564) PERFLUOROOCTANOATE _'_ C/_ T O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI9 (PAGE I): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE 4_ t_a'_ DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... I 0 1001 DP 39 38 ALL TISSUES 1002 DP 119 118 ALL TISSUES 1003 1004 DP 119 118 DP 39 38 ALL TISSUES ALL TISSUES 1005 DP 118 117 ALL TISSUES 1006 DP 38 37 ALL TISSUES 1007 DP 118 117 ALL TISSUES 1008 DP 38 37 ALL TISSUES 1009 DP 38 37 ALL TISSUES 1010 DP 38 37 ALL TISSUES i011 DP 118 117 ALL TISSUES 1012 1013 1014 1015 1016 1017 6553 6554 6555 1021 1022 1023 DP 117 DP 117 DP 117 DP 37 DP 37 DP 118 DP 35 DP 35 DP 35 DP 118 DP 37 DP 118 116 116 116 36 36 117 34 34 34 117 36 117 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1024 DP 25 25 1025 1026 DP 37 DP 118 ............................................................................................ DP = DAY POSTWEANING 36 117 FOUND AFTER DEAD ON DAY 25 POSTWEANING DOSAGE ADMINISTRATION). (DEATH LUNGS: ALL LOBES, MOTTLED, ALL OTHER TISSUES APPEARED DARK RED. NORMAL. OCCURRED 56 MINUTES ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. _ ....................................... > [29 a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. 4_ O_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI9 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY} NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... I 0 CONT. 1027 1028 DP 37 DP 117 36 116 ALL TISSUES ALL TISSUES a APPEARED APPEARED NORMAL. NORMAL. 1029 DP 4 4 MORIBUND SACRIFICED ON DAY 4 POSTWEANING. ALL TISSUES APPEARED NORMAL. 1030 1031 1032 1033 DP 36 35 DP 117 116 DP 36 35 DP 3G 35 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 1034 1035 DP 117 116 DP 119 118 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1036 DP 36 35 ALL TISSUES APPEARED NORMAL. 1037 DP 36 35 ALL TISSUES APPEARED NORMAL. _-_ 1038 DP 35 34 ALL TISSUES APPEARED NORMAL. C_ 1039 DP 42 42 FOUND DEAD ON DAY 42 POSTWEANING AFTER DOSAGE ADMINISTRATION}. ALL TISSUES APPEARED NORMAL. (DEATH OCCURRED 33 MINUTES 1040 1041 1042 DP 118 DP 118 DP 35 117 117 34 ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1043 DP 118 117 ALL TISSUES APPEARED NORMAL. 1044 DP 35 34 ALL TISSUES APPEARED NORMAL. 1045 DP 118 117 ALL TISSUES APPEARED NORMAL. 1046 DP 35 34 ALL TISSUES APPEARED NORMAL. 1047 1048 DP 118 117 DP 118 117 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1049 DP 35 34 ALL TISSUES APPEARED NORMAL. 1050 DP 118 117 ALL TISSUES APPEARED NORMAL. 1051 DP 119 118 ALL .................................................................................................................................... TISSUES APPEARED NORMAL.' DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. Cn 4_ _.. OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... I 0 1052 DP 119 118 ALL CONT. 1053 DP 34 33 ALL 1054 DP 118 117 ALL 1055 DP 118 117 ALL 1056 DP 34 33 ALL 1057 DP 31 30 ALL 1058 DP 115 114 ALL 1059 DP 109 108 ALL 1060 DP 109 108 ALL .................................................................................................................................... TISSUES TISSUES TISSUES TISSUES TISSUES TISSUES TISSUES TISSUES TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. > C oo to O PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI9 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... II 1 1061 DP 119 118 ALL TISSUES 1062 DP 39 38 ALL TISSUES 1063 DP 119 118 ALL TISSUES a APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. PERFLUOROOCTANOATE 1064 DP 6 5 FOUND DEAD ON DAY 6 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1065 DP 39 38 ALL TISSUES APPEARED NORMAL. 1066 DP 119 118 PROSTATE: ALL OTHER SMALL TISSUES (0.2716 G). APPEARED NORMAL. 1067 DP 119 118 ALL TISSUES APPEARED NORMAL. 4_ 1068 DP 39 38 ALL TISSUES APPEARED NORMAL. _'_ 1069 DP 119 118 b OO 1070 DP 38 37 ALL TISSUES APPEARED NORMAL. 1071 1072 DP 118 DP 38 117 37 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1073 DP 118 117 ALL TISSUES APPEARED NORMAL. 1074 DP 38 37 ALL TISSUES APPEARED NORMAL. 1075 DP 38 37 ALL TISSUES APPEARED NORMAL. 1076 DP 38 37 ALL TISSUES APPEARED NORMAL. 1077 DP 118 117 ALL TISSUES APPEARED NORMAL. 1078 DP 119 118 ALL TISSUES APPEARED NORMAL. 1079 DP 38 37 ALL TISSUES APPEARED NORMAL. 1080 DP 38 37 ALL TISSUES APPEARED NORMAL. 1081 DP 119 118 ALL TISSUES APPEARED NORMAL. 1082 DP 119 118 TESTES: LEFT, FLACCID, SMALL (1.0590 G) . > EPIDIDYMIDES: LEFT, SMALL (0.3393 G). ALL OTHER TISSUES APPEARED NORMAL. 1083 1084 DP 119 118 ALL DP 38 37 ALL 1085 DP 38 37 ALL 1086 DP 119 118 ALL .................................................................................................................................... DP = DAY POSTWEANING TISSUES TISSUES TISSUES TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. a. Refer to the individual clinical observations b. Necropsy observations were not recorded. table (Table D14) for external observations confirmed at necropsy. [/) 4_ OO _) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI9 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY} NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... II 1 CONT. 1087 DP 45 44 FOUND DEAD ON DAY 45 ADMINISTRATION). ALL TISSUES APPEARED POSTWEANING NORMAL. (DEATH OCCURRED PRIOR TO DOSAGE 1088 DP 119 118 ALL TISSUES APPEARED NORMAL. 1089 1090 1091 1092 1093 DP 38 37 DP 119 118 DP 120 119 DP 37 36 DP 37 36 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. _I_ 1094 DP 120 119 ALL TISSUES APPEARED NORMAL. 10956 DP 12307 11396 ALL TISSUES APPEARED NORMAL. 4_ 1097 DP 37 36 ALL TISSUES APPEARED NORMAL. _'_ 1098 DP 120 119 ALL TISSUES APPEARED NORMAL. 1099 DP 37 36 ALL TISSUES APPEARED NORMAL. 1100 DP 120 119 ALL TISSUES APPEARED NORMAL. 1101 DP 37 36 ALL TISSUES APPEARED NORMAL. 1102 DP 36 35 ALL TISSUES APPEARED NORMAL. 1103 DP 119 118 ALL TISSUES APPEARED NORMAL. 1104 DP 2 1 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1105 1106 1107 1108 DP 36 35 DP 119 118 DP 120 119 DP 36 35 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 1109 IIi0 DP 36 35 DP 120 119 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. ...................................................................................................... DP - DAY POSTWEANING _ ............................. a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. O0 4_ OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... II 1 CONT. 1111 1112 1113 1114 1115 1116 1117 DP 36 35 DP 119 118 DP 35 34 DP 119 118 DP 35 34 DP 119 118 DP 35 34 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES 1118 1119 1120 DP 119 118 DP 35 34 DP 119 118 ALL TISSUES ALL TISSUES ALL TISSUES .................................................................................................................................... a APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. DaP. = ReDfAeYr PtOoSTWtEhAeNINiGndividual clinical observations table (Table D14) for external observations confirmed at necropsy. O Cn O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION} T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 7): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... III 3 1121 DP 5 4 FOUND DEAD ALL TISSUES a ON DAY 5 POSTWEANING APPEARED NORMAL. (DEATH OCCURRED OVERNIGHT). 1122 1123 DP 119 118 DP 118 117 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1124 DP 38 37 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED NUMEROUS NORMAL. TAN AREAS, (PINPOINT TO 0.3 CM). 1125 DP 38 37 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED FOUR TAN NORMAL. AREAS (PINPOINT TO 0.I CM). 1126 DP 38 37 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.2 CM). 4_ ALL OTHER TISSUES APPEARED NORMAL. _O _'_ 1127 DP 118 117 ALL TISSUES APPEARED NORMAL. 1128 DP 38 37 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED TAN AREA NORMAL. (0.4 CM X 0.2 CM). 1129 1130 DP 118 DP 2 117 1 ALL TISSUES APPEARED NORMAL. FOUND DEAD ALL TISSUES ON DAY 2 POSTWEANING APPEARED NORMAL. (DEATH OCCURRED OVERNIGHT). 1131 1132 1133 DP 118 DP 118 DP 38 117 117 37 ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1134 1135 1136 1137 1138 1139 DP 118 117 DP 119 118 DP 119 118 DP 38 37 DP 38 37 DP 119 118 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL.' NORMAL. NORMAL. .................................................................................................................................... DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. [2_ _t_ O0 _, PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI9 (PAGE 8): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... III 3 CONT. 1140 DP 9 8 FOUND DEAD ALL TISSUES a ON DAY 9 POSTWEANING APPEARED NORMAL. (DEATH OCCURRED OVERNIGHT). 1141 1142 1143 1144 1145 1146 1147 DP 119 DP 118 DP 37 DP 37 DP 118 DP 37 DP 118 118 117 36 36 117 36 117 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. _I_ 1148 DP 37 36 ALL TISSUES APPEARED NORMAL. 1149 DP 118 117 ALL TISSUES APPEARED NORMAL. 1150 DP 37 36 ALL TISSUES APPEARED NORMAL. 4_ 1151 DP 120 119 ALL TISSUES APPEARED NORMAL. tO 1152 DP 37 36 ALL TISSUES APPEARED NORMAL. tO 1153 DP 120 119 TESTES: LEFT, LARGE (3.0171 G). ALL OTHER TISSUES APPEARED NORMAL. 1154 1155 DP 120 DP 37 119 36 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1156 DP 36 35 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED SIX TAN NORMAL. AREAS (PINPOINT TO 0.3 CM) . 1157 1158 DP 36 35 DP 119 118 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1159 DP 119 118 ALL TISSUES APPEARED NORMAL. 1160 DP 36 35 ALL TISSUES APPEARED NORMAL. 1161 DP 36 35 ALL TISSUES APPEARED NORMAL. 1162 DP 119 118 ALL TISSUES APPEARED NORMAL. _'_ 1163 DP 36 35 ALL TISSUES APPEARED NORMAL.' 1164 DP 119 118 ALL TISSUES APPEARED NORMAL. 4_ __. .................................................................................................................................. ___ DP = DAY POSTWEANING OO a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 9): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... III 3 CONT. 1165 DP 36 35 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED NUMEROUS NORMAL. TAN AREAS, (PINPOINT TO 0.2 CM). 4_ b_ t_ ;;-; 1166 1167 1168 1169 1170 1171 1172 DP 56 DP 119 DP 119 DP 35 DP 35 DP 119 DP 35 55 118 118 34 34 118 34 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1173 DP 119 118 ALL TISSUES APPEARED NORMAL. 1174 1175 1176 1177 1178 1179 1180 DP 35 DP 119 DP 119 DP 118 DP 34 DP 31 DP 115 34 118 118 117 33 30 114 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. ............................................................... a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. > C _n 4_ oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 10}: NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... IV I0 1181 DP 38 37 ALL TISSUES 1182 DP 118 117 ALL TISSUES 1183 DP 38 37 ALL TISSUES 1184 DP 118 117 ALL TISSUES 1185 DP 38 37 ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1186 DP 118 117 KIDNEYS: ALL OTHER RIGHT, TISSUES PELVIS, MODERATE APPEARED NORMAL. DILATION. 1187 DP 38 37 ALL TISSUES APPEARED NORMAL. 1188 1189 DP 118 117 DP 117 116 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 4_ 1190 DP 37 36 LIVER: LEFT LATERAL AND MEDIAN LOBES, NUMEROUS TAN AREAS, tO (PINPOINT TO 0.2 CM}. _t_ ALL OTHER TISSUES APPEARED NORMAL. 1191 DP 37 36 LIVER: LATERAL LOBE, NUMEROUS TAN AREAS, ALL OTHER TISSUES APPEARED NORMAL. (PINPOINT TO 0.1 CM). 1192 DP 117 116 ALL TISSUES APPEARED NORMAL. 1193 DP 37 36 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED FOUR TAN AREAS NORMAL. (PINPOINT TO 0.2 CM). 1194 1195 1196 1197 1198 DP 117 DP 118 DP 37 DP 37 DP 118 1199 DP 37 ............................................................................................ 116 117 36 36 117 36 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. -'....................................... DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. 4_ Oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE II) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... IV i0 CONT. 1200 DP 40 39 MORIBUND SACRIFICED ON DAY 40 POSTWF2hNING. INTESTINES: DISTENDED WITH GAS. THYMUS: SMALL, (0.02 G). STOMACH: TWO REGIONS OF THE CARDIAC REGION, NUMEROUS ULCERATIONS, (PINPOINT TO 0.1 CM IN SECOND REGION, FIVE ULCERATIONS (PINPOINT). ALL OTHER TISSUES APPEARED NORMAL. FIRST REGION, DIAMETER), 1201 1202 DP 37 36 DP 37 36 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1203 1204 DP 118 117 DP 117 116 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 4_ 1205 DP 36 35 LIVER: LEFT LATERAL LOBE, NUMEROUS TAN AREAS, (PINPOINT TO 0.5 CM). _O ALL OTHER TISSUES APPEARED NORMAL. ta 1206 DP 36 35 LIVER: LEFT LATERAL LOBE, (PINPOINT TO 0.5 CM X 0.i ALL OTHER TISSUES APPEARED NUMEROUS CM). NORMAL. TAN AREAS, 1207 1208 1209 DP 117 116 DP 36 35 DP 117 116 ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1210 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1211 1212 1213 1214 1215 1216 1217 DP 117 DP 117 DP 36 DP 36 DP 119 DP 119 DP 119 116 116 35 35 118 118 118 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.' NORMAL. NORMAL. .................................................................................................................................... DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. _'_ 4_ I_) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI9 (PAGE 12) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NL_BER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... IV i0 CONT. 1218 DP 36 35 LIVER: LEFT LATERAL LOBE, TAN AND CAUDATE LOBE, TAN AREA (0.4 CM). ALL OTHER TISSUES APPEARED NORMAL. BLACK AREA (0.2 CM X 0.2 CM); 1219 1220 1221 1222 DP 119 DP 35 DP 118 DP 118 118 34 117 117 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 1223 DP 35 34 LIVER: LEFT LATERAL LOBE, NUMEROUS (PINPOINT TO 0.2 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL. TAN AREAS, 4_ 1224 DP 118 117 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 0% 1225 1226 1227 1228 DP 119 DP 119 DP 35 DP 35 118 118 34 34 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 1229 DP 119 118 SPLEEN: TAN AREA ALL OTHER TISSUES EXTENDED APPEARED INTO THE PARENCHYMA NORMAL. (2.0 CM X 1.5 CM). 1230 DP 35 34 ALL TISSUES APPEARED NORMAL. 1231 DP 35 34 LIVER: LEFT LATERAL LOBE, FIVE TAN AREAS (PINPOINT TO 0.5 CM). ALL OTHER TISSUES APPEARED NORMAL. > 1232 DP 119 118 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. C 1233 DP 119 118 ALL TISSUES APPEARED NORMAL. O0 ............................................................ -_ ...................................................................... _._ DP = DAY POSTWEANING O0 a. Refer to the individual clinical observations table (Table DI4} for external observations confirmed at necropsy. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 13): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... IV I0 CONT. 1234 DP 35 34 LIVER: LEFT LATERAL LOBE, NUMEROUS (PINPOINT TO 0.7 CM); MEDIAN LOBE, ALL OTHER TISSUES APPEARED NORMAL. TAN AREAS, ONE TAN AREA (0.2 CM). 1235 1236 1237 1238 1239 DP 35 DP 119 DP 119 DP 35 DP 35 34 118 118 34 34 LIVER: LEFT LATERAL LOBE, MEDIAN LOBE, NUMEROUS TAN ALL OTHER TISSUES APPEARED 4 TO 5 TAN AREAS, AREAS, (PINPOINT TO NORMAL. (PINPOINT 0.3 CM). TO 0.1 CM); ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 1240 DP 119 118 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. _O ALL OTHER TISSUES APPEARED NORMAL. .................................................................................................................................... DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. > _n oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE D19 (PAGE 14): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS .................................................................................................................................... V 30 1241 DP 119 118 ALL TISSUES 1242 DP 39 38 ALL TISSUES 1243 DP 39 38 ALL TISSUES 1244 DP 118 117 ALL TISSUES 1245 DP 118 117 ALL TISSUES 1246 1247 DP 38 DP 118 37 117 ALL TISSUES ALL TISSUES 1248 DP 118 117 ALL TISSUES 1249 DP 118 117 ALL TISSUES 1250 DP 38 37 ALL TISSUES a APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. PERFLUOROOCTANOATE 1251 DP 38 37 LIVER: LEFT LATERAL AND MEDIAN LOBES, NUMEROUS TAN AREAS, (% (PINPOINT TO 0.3 CM IN DIAMETER). 4_ ALL OTHER TISSUES APPEARED NORMAL. _o O0 1252 DP 118 117 ALL TISSUES APPEARED NORMAL. 1253 DP 38 37 ALL TISSUES APPEARED NORMAL. 1254 DP 119 118 ALL TISSUES APPEARED NORMAL. 1255 DP 118 117 ALL TISSUES APPEARED NORMAL. 1256 DP 37 36 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED TAN AREA NORMAL. (0.8 CM). 1257 1258 1259 DP 118 DP 37 DP 118 117 36 117 ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1260 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. > 1261 DP 118 117 ALL TISSUES APPEARED NORMAL. - ..................................... _'_ DP = DAY POSTWEANING [/_ a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. 4_ Oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D19 (PAGE 15): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... V 30 1262 DP 37 36 LIVER: LEFT LATERAL LOBE, SIX TAN AREAS CONT. MEDIAN LOBE, FIVE TAN AREAS (PINPOINT TO ALL OTHER TISSUES APPEARED NORMAL. (PINPOINT 0.3 CM). TO 1.0 CM) ; 1263 DP 2 1 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1264 DP 2 1 FOUND DEAD ON DAY 2 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1265 DP 37 36 ALL TISSUES APPEARED NORMAL. 1266 DP 118 117 ALL TISSUES APPEARED NORMAL. (_ 1267 DP 37 36 ALL TISSUES APPEARED NORMAL. [_O 1268 DP 37 36 LIVER: MEDIAN LOBE, NUMEROUS TAN AREAS, kC) (PINPOINT TO 0.4 CM X 0.2 CM). ALL OTHER TISSUES APPEARED NORMAL. 1269 1270 1271 1272 1273 1274 DP 118 DP 37 DP 120 DP 37 DP 120 DP 120 117 36 119 36 119 119 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1275 DP 39 38 MORIBUND SACRIFICED ON DAY 39 POSTWEANING. LIVER: MEDIAN LOBE, NUMEROUS TAN AREAS, SPLEEN: SMALL (0.04 G). ALL OTHER TISSUES APPEARED NORMAL. (PINPOINT TO 0.1 CM). 1276 DP 37 36 LIVER: LARGE (26.64 G). ALL OTHER TISSUES APPEARED NORMAL. O0 1277 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT). "_ ALL TISSUES APPEARED NORMAL. OO 1278 DP 119 118 ALL TISSUES APPEARED .......................................................................................................... NORMAL. DP = DAY POSTWEANING a. Refer to the individual cllnical observations table (Table D14) for external observations .......................... confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE DI9 (PAGE 16): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... V 30 CONT. 1279 DP 36 35 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED NUMEROUS NORMAL. TAN AREAS, (PINPOINT TO 0.3 CM). 1280 DP 3 2 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1281 1282 DP 119 118 DP 119 118 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1283 DP 36 35 LIVER: LEFT LATERAL AND MEDIAN LOBES, NUMEROUS TAN AREAS, _I_ (PINPOINT TO 0.3 CM X 0.i CM). ALL OTHER TISSUES APPEARED NORMAL. 4_ 1284 DP 118 117 ALL TISSUES APPEARED NORMAL. L_ 1285 DP 35 34 ALL TISSUES APPEARED NORMAL. O 1286 DP 35 34 ALL TISSUES APPEARED NORMAL. 1287 DP 118 117 ALL TISSUES APPEARED NORMAL. 1288 DP 119 118 ALL TISSUES APPEARED NORMAL. 1289 DP 119 118 ALL TISSUES APPEARED NORMAL. 1290 DP 119 118 ALL TISSUES APPEARED NORMAL. 1291 DP 119 118 ALL TISSUES APPEARED NORMAL. 1292 DP 35 34 ALL TISSUES APPEARED NORMAL. 1293 DP 35 34 LIVER: LEFT LATERAL LOBE, ALL OTHER TISSUES APPEARED NUMEROUS NORMAL. TAN AREAS, (PINPOINT TO 0.5 CM). 1294 DP 119 118 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. > 1295 DP 35 34 LIVER: LEFT LATERAL LOBE, FOUR TAN AND WHITE AREAS (PINPOINT TO 0.3 CM). ALL OTHER TISSUES APPEARED NORMAL. .................................................................................................................................... U9 DP = DAY POSTWEANING 4_ a. Refer to the individual clinical observations table (Table DI4) for external observations confirmed at necropsy. O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE DI9 (PAGE 17): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF DOSAGES DOSAGE (MG/KG/DAY} NUMBER NECROPSY ADMINISTERED OBSERVATIONS a .................................................................................................................................... V 30 1296 DP 107 106 FOUND DEAD ON DAY 107 POSTWEANING ALL TISSUES APPEARED NORMAL. (DEATH OCCURRED OVERNIGHT). 1297 DP 34 33 ALL 1298 DP 118 117 ALL 1299 DP 33 32 ALL 1300 DP 117 116 ALL .................................................................................................................................... TISSUES TISSUES TISSUES TISSUES APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D14) for external observations confirmed at necropsy. 0_ t_ > _n oo t_ o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - F1 GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 1002 1003 1005 1007 1011 1012 1013 567. 602. 572. 546. 580. 633. 607. 0.7752 0.7726 0.6687 0.6686 0.6963 0.7115 0.6641 0.14 0.13 0.12 0.12 0.12 0.11 0.ii 0.3991 0.3611 0.3080 0.3350 0.3387 0.3373 0.3204 0.07 0 06 0 05 0 06 0 06 0 05 0 05 1.9221 1.8125 1.6994 1.5619 1.5902 1.7682 1.6088 0.34 0.30 0.30 0.29 0.27 0.28 0.26 1.7786 1.6880 1.5948 1.4691 1.4829 1.6627 1.5081 0.31 0.28 0.28 0.27 0.26 0.26 0.25 1.6467 2.1281 1.7303 1.8008 1.7689 2.1506 2.2159 0.29 0.35 0.30 0.33 0.30 0.34 0.36 0.8308 1.0361 0.8830 0.9282 0.9602 1.0488 1.2484 0.15 0.17 0.15 0.17 0.16 0.16 0.20 1014 1017 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 557. 528. 623. 604. 581. 464. 585. 465. 461. 537. 496. 537. 509. 700. 642. 503. 645. 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 0.14 0.12 0.11 0.ii 0.13 0.15 0.12 0.15 0.12 0,11 0.12 0.12 0.14 0.10 0.i0 0.14 0.12 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 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 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 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 1.7555 1.6737 1.6868 1.5794 1.8349 1.6188 1.6663 1.4943 1.2926 1.5238 1.4797 1.6406 1.8917 1.6111 1.4321 1.4572 1.8134 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 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 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 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 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 1052 580. 0.7354 0.13 0.3854 0.07 1.9346 0 33 1.7771 0.31 2.0816 0.36 1.1932 0.20 > 1054 568. 0.7518 0.13 0.3819 0.07 1.9560 0 34 1.8014 0.32 2.5943 0.46 1.4246 0,25 1055 574. 0.6775 0.12 0.3243 0.06 1.7734 0 31 1.6231 0.28 2.0127 0.35 1.1275 0.20 1058 565. 0.5881 0.i0 0.2814 0.05 1.6935 0 30 1.5125 0.21 1.8827 0.33 0.9591 0.17 1059 468. 0.6360 0.14 0.2937 0.06 1.7162 0 37 1,6036 0.34 1.1345 0.24 0.7241 0.15 [2_ 1060 498. 0.6379 0.13 0.3128 0.06 1.6027 0 32 1.4347 0.29 1.3529 0.27 0.7172 0.14 4_ .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - F1 GENERATION MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE PITUITARY BRAIN LIVER NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................. REL. % TBW ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. REL. % TBW 1002 1003 1005 1007 1011 1012 1013 567. 602 572 546 580 633 607 0 7585 0 7227 0 6810 0 6742 0 6834 0 6799 0 6817 0.13 0.12 0.12 0.12 0.12 0.ii 0.11 1 8845 1 7920 1 6608 1 5845 1 5867 1 7336 1 6417 0.33 0.30 0.29 0.29 0.27 0.27 0.27 0.4671 0.6059 0.5167 0.5157 0.7725 1.3440 1.0484 0.08 0.i0 0.09 0.09 0.13 0.21 0.17 0.015 0.014 0.011 0.014 0.011 0.014 0.014 2.64 2.32 1.92 2.56 1.90 2.21 2.31 2.27 2.40 2.36 2.23 2.22 2.32 2.29 0.40 0.40 0.41 0.41 0.38 0.37 0.38 21.20 25.00 19.70 21.20 24.75 24.99 21.79 3.74 4.15 3.44 3.88 4.27 3.95 3.59 1014 557 1017 528 1021 623 1023 604 1026 581 1028 464 1031 585 1034 465 1035 461 1040 537 1041 496 1043 537 1045 509 1047 700 1048 642 1050 503 1051 645 0 8172 0 6814 0 7343 0 6593 0 7373 0 6915 0.6714 0 6982 0 _628 0 6359 0 6364 0 6825 0 7169 0 7403 0 6381 0 7014 0 8552 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.i0 0.10 0.14 0.13 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 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 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 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 0.012 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 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 2.51 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 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 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 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 1052 580 0 8026 0.14 1 9853 0.34 1.1700 0.20 0.013 2.24 2.47 0.42 24 34 4.20 _> 1054 568 0 7438 0.13 1 9381 0.34 1.1579 0.20 0.020 3.52 2.46 0.43 20 05 3.53 1055 574 0 7348 0.13 1 8211 0.32 1.1323 0.20 0.021 3.66 2.43. 0.42 21 35 3.72 _'_ 1058 565 0.6267 0.11 1 6947 0.30 1.1133 0.20 0.018 3.18 1.94 0.34 20 17 3.57 1059 468 0.6254 0.13 1 7833 0.38 0.7495 0.16 0.018 3.85 2.44 0.52 16 i0 3.44 [2_ 1060 498 0.6724 0.14 1 7323 0.35 0.8267 0.17 0.012 2.41 2.40 0.48 17 81 3.58 "_ .................................................................................................................................... OO WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00 Value was multiplied by i000. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 3): TERMINAL BODY WEIGHTS _.N'D ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - F1GENERATIONMALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW a ADRENAL RIGHT ABS. WT. REL. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW 1002 1003 1005 1007 1011 1012 567. 602. 572. 546. 580. 633. 2.17 2.38 2.13 2.10 2.19 2.22 0.38 0.40 0.37 0.38 0.38 0.35 2.28 2.20 2.08 2.00 2.18 2.20 0.40 0.36 0.36 0.37 0.38 0.35 0.031 0.029 0.037 0.029 0.038 0.025 5.47 4.82 6.47 5.31 6.55 3.95 0.028 0.023 0.038 0.031 0.032 0.022 4.94 3.82 6.64 5.68 5.52 3.48 0 96 1 02 1 00 1 03 0 95 0 90 0.17 0.17 0.17 0.19 0.16 0.14 0 28 0 42 0 62 0 59 0 71 0 73 0.05 0.07 0.ii 0.ii 0.12 0.12 1013 607. 2.35 0.39 2.28 0.38 0.027 4.45 0.027 4.45 1 02 0.17 0 52 0.08 1014 1017 1021 1023 1026 557. 528. 623. 604. 581. 2.08 2.05 2.41 2.21 2.41 0.37 0.39 0.39 0.36 0.41 2.16 2.04 2.56 2.24 2.39 0.39 0.39 0.41 0.37 0.41 0.026 0.029 0.026 0.035 0.034 4.67 5.49 4.17 5.79 5.85 0.023 0.030 0.036 0.030 0.036 4.13 5.68 5.78 4.97 6.20 0 95 0 72 0 98 0 93 0 97 0.17 0.14 0.16 0.15 0.17 0 32 0 43 0 44 0 50 0 46 0.06 0 08 0 07 0 08 0 08 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 464. 585. 465. 461. 537. 496. 537. 509. 700. 642. 503. 645. 1.85 2.31 1.73 1.98 2.22 2.35 2.07 1.99 2.37 2.58 1.96 2.59 0.40 0.39 0.37 0.43 0.41 0.47 0.38 0.39 0.34 0.40 0.39 0.40 1.93 2.20 1.71 1.95 2.23 2.54 2.22 2.09 2.56 2.63 2.13 2.54 0.42 0.38 0.37 0.42 0.42 0.51 0.41 0.41 0.36 0.41 0.42 0.39 0.036 0.030 0.028 0.028 0.022 0.024 0.023 0.041 0.038 0.039 0.035 0.041 7.76 5.13 6.02 6.07 4.10 4.84 4.28 8.06 5.43 6.07 6.96 6.36 0.037 0.019 0.011b 0.022 0.018 0.024 0.023 0.039 0.036 0.036 0.029 0.041 7.97 3.25 2.36b 4.77 3.35 4.84 4.28 7.66 5.14 5.61 5.76 6.36 0 98 0 93 0 73 0 69 1 34 0 94 0 88 0 79 1 13 1 05 0 83 1 13 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 41 0 44 0 37 0 43 0 45 0 72 0 59 0 61 0 36 0.56 0.59 0.52 0 09 0 08 0 08 0 09 0 08 0 14 0 11 0 12 0 05 0 09 0 12 0 08 1052 580. 2.51 0.43 2.47 0.42 0.033 5.69 0.036 6.21 1 03 0.18 0.70 0 12 1054 568. 2.22 0.39 2.26 0.40 0.028 4.93 0.027 4.75 0 99 0.17 0.54 0 i0 1055 574. 2.31 0.40 2.42 0.42 0.037 6.44 0.037 6.44 0 83 - 0.14 0.55 0 I0 1058 565. 2.21 0.39 2.28 0.40 0.030 5.31 0.030 5.3i 0 86 0.15 0.58 0 i0 1059 468. 2.19 0.47 2.13 0.46 0.039 8.33 0.036 7.69 1 04 0.22 0.33 0 07 O_ 1060 498. 2.30 0.46 2.27 0.46 0.030 6.02 0.023 4.62 0 73 0.15 0.47 0 09 _t_ .................................................................................................................................... O0 WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by I000. _o Damaged during processing (weight affected); values excluded from group averages and statistical analyses. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR's STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 4} : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS L. TESTIS MINUS SEMINAL RAT TERMINAL BODY LEFT LEFT LEFT TUNICA ALBUGINEA WITH NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. % TBW WT. % TBW WT. .................................................................................................................................... VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 1061 1063 1066 1067 1069 1071 486. 522. 480. 485. 424. 545. 0.7660 0.7170 0.6338 0.6124 0.6531 0.6507 0.16 0 14 0 13 0 13 0 15 0 12 0.3553 0.3300 0.2762 0.2886 0.3027 0.3269 0.07 0.06 0.06 0.06 0.07 0.06 1.7863 1.8632 1.7790 1.5556 1.7625 1.6107 0.37 0.36 0.37 0.32 0.42 0 30 1.6295 1.7520 1.6559 1.4453 1.6520 1.5115 0.34 0.34 0.34 0.30 0.39 0.28 1.9084 2.2839 2.2858 1.7391 2.0289 2.2645 0.39 0.44 0.48 0.36 0.48 0.42 1.0157 1.1167 1.3449 0.9152 1.0798 1.1328 0 21 0 21 0 28 0 19 0 25 0 21 1073 541. 0.7059 0 13 0.2707 0.05 1.9881 0 37 1.8542 0.34 2.1775 0.40 1.1732 0 22 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 ii00 1103 1106 1107 iii0 541. 627. 532. 582. 538. 415. 562. 529. 512. 594. 632. 498. 494. 575. 526. 446. 437. 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 14 0 12 0 13 0 06 0 12 0 13 0 13 0 13 0 12 0 ii 0 ii 0 14 0 13 0 12 0 Ii 0 15 0 14 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 0.07 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 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 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 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 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 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 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 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 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 1112 585. 0.6981 0 12 0.3442 0.06 1.8105 0 31 1.6908 0.29 2.1860 0.37 1.2293 0.21 1114 563. 0.6757 0 12 0.3169 0.06 1.9848 0 35 1.8202 0.32 2.3440 0.42 1.2241 0.22 1116 552. 0.6704 0 12 0.2919 0.05 1.5620 0 28 1.4146 0.26 2.0547 0.37 1.0185 0.18 1118 542. 0.6492 0 12 0.2958 0.05 1.6885 0 31 1.5853 0.29 2.1617 0.40 1.0063 0.18 1120 525. 0.7509 0 14 0.3424 0.06 2.0030 0 38 1.8717 0.36 2.3378 0.44 1.0701 0.20 (29 .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. O0 Rat 1082 had a small, left epididymis and cauda epididymls, small, flaccid left testis, and a fluid filled left testis minus tunica albuginea; values included in group averages and statistical analyses. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 5) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE PITUITARY BRAIN LIVER NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. REL. % TBW 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 486. 522. 480. 485. 424. 545. 541. 541. 627. 532. 582. 538. 415. 562. 529. 512. 594. 632. 498. 494. 575. 526. 446. 437. 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 0.15 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 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 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 0.4761 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 0 i0 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 0.011 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 2.26 2.30 2.29 2.47 2.59 2.20 2.96 2.03 2.23 2.63 2.75 2.60 2.89 2.49 3.21 2.73 4.21 2.53 3.01 4.86 2 26 2 47 7 40 3 43 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2.25 2.35 2.17 2.30 2.07 2.33 2.24 2.45 2.28 2.47 2.38 2.33 2.35 2.13 2.15 2.33 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 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 4.27 5.10 4.33 4.32 5.10 4.83 5.16 4.67 4.79 4.29 4.18 4.30 3.74 5.18 4.06 5.29 4.98 5.21 6.10 4.61 4.83 4.31 4.36 4.69 1112 1114 585. 563. 0.6748 0.7494 0 12 0 13 1.8656 1.9312 0.32 0.34 1.4610 1.1564 1116 1118 552. 542. 0.6639 0.6786 0 12 0 12 1.5988 1.7496 0.29 0.32 1.2054 1.0908 1120 525. 0.6911 0 13 1.9723 0.38 1.1517 .................................................................................................................................. 0.25 0.20 0.22 0.20 0.22 0.018 0.023 0.026 0.023 0.028 3 08 4 08 4 71 4 24 5 33 2.64 2.55 2.36. 2.37 2.43 0 45 0 45 0 43 0 44 0.46 28.97 27.29 21.37 22.51 22.49 4.95 4.85 3.87 4.15 4.28 WEIGHTS WERE RECORDED Value was multiplied IN GRAMS by i000. (G). Rat 1066 had a small prostate; values Damaged during processing (weight not ABS. WT. = ORGAN WEIGHT. included in group affected). averages REL. % TBW = (ORGAN WEIGHT/TERMINAL and statistical analyses, BODY WEIGHT) X i00. [2_ OO b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 6): TERMINAL BODY WEIGHTS __N-D ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - F1 GENERATION MALE RATS BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT NUMBER WEIGHT ABS. WT. REL. % TBW ABS. WT. REL. % TBW ABS. WT. REL. % TBW a .................................................................................................................................... ADRENAL RIGHT ABS. REL. WT. % TBW a SPLEEN ABS. WT. REL. % TBW THYMUS ABS. WT. REL. % TBW 1061 1063 1066 1067 1069 1071 486. 522. 480. 485. 424. 545. 2.06 2.50 2.03 1.95 2.10 2.43 0.42 0.48 0.42 0.40 0.50 0.44 1.90 2.46 2.10 2.07 1.98 2.46 0.39 0.47 0.44 0.43 0.47 0.45 0.016 0.041 0.028 0.024 0.020 0.018 1073 541. 2.43 0.45 2.50 0.46 0.037 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 541. 627. 532. 582. 538, 415. 562. 529. 512. 594. 632. 498. 494. 575. 526. 446. 437. 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 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 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 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 0.044 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 1112 1114 585. 563. 2.90 2.80 0 50 0 50 3 01 2 84 0.51 0.50 0.039 0.042 1116 552. 2.33 0 42 2 37 0.43 0.041 1118 1120 542. 525. 2.74 2.46 0 50 0 47 2 73 2 53 0.50 0.48 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 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 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 ii 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 0.60 0.61 0.64 0.46 0.39 0.42 0.22 0.57 0.42 0.37 0.46 0.37 0.29 0.40 0.31 0.55 0.53 0.69 0.61 0.55 0.65 0.58 0.36 0.44 0.35 0.48 0.32 0.41 0.36 0.12 0 12 0 13 0 09 0 09 0 08 0 04 0 i0 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 WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. O0 Value was multiplied by i000. to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 7) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 1122 518. 0.7208 0.14 0.3470 0.07 1.6159 0.31 1.5221 0.29 2 0470 0.40 1.0874 0.21 1123 505. 0.6070 0.12 0.2968 0.06 1.8182 0.36 1.6922 0.34 2 3013 0.46 1.2447 0.25 1127 452. 0.6614 0.15 0.3302 0.07 1.6347 0.36 1.5124 0.33 1 7196 0.38 0.9666 0.21 1129 568. 0.7407 0.13 0.3502 0.06 1.9335 0.34 1.8129 0.32 2 1930 0.39 1.1095 0 20 1131 564. 0.6952 0.12 0.3581 0 06 1.7682 0.31 1.6707 0.30 2 3326 0.41 1.0857 0 19 1132 529. 0.6725 0.13 0.3378 0 06 1.7645 0.33 1.6362 0.31 2 3904 0.45 1.2665 0 24 1134 579. 0.7615 0.13 0.3358 0 06 1.8988 0.33 1,7685 0.30 2 1383 0.37 1.0924 0 19 1135 505. 0.6679 0.13 0.3218 0 06 1.7237 0.34 1.6026 0.32 1 8500 0.37 0.9966 0 20 1136 441. 0.6855 0.16 0.3406 0 08 1.9009 0.43 1.6834 0.38 1.3217 0.30 0.7638 0 17 1139 457. 0.6190 0 14 0.3274 0 07 1.6472 0.36 1.5631 0.34 1.7038 0.37 0.9308 0 20 1141 561. 0.6450 0 II 0.3546 0.06 1.5627 0.28 1.4612 0.26 1.7528 0.31 0.8441 0 15 1142 506. 0.6121 0 12 0.2953 0.06 1.6597 0.33 1.5318 0.30 2.0896 0.41 0.9784 0.19 1145 413. 0.6915 0 17 0.3255 0.08 1.8607 0.45 1.7494 0,42 1.8492 0.45 1.0012 0.24 1147 513 0.7098 0 14 0.3588 0.07 1.6976 0,33 1.6060 0.31 1.7211 0.34 0.9009 0.18 1149 51_ 0.8130 0 16 0.4132 0.08 2.0462 0.40 1.9344 0.38 2.3386 0.46 1.1584 0.23 1151 588 0,6764 0 12 0 3179 0.05 1.8091 0.31 1.5925 0.27 2.2078 0.38 0,9860 0.17 1153 539 0.6843 0.13 0 3349 0.06 3.0171a 0.56 2.7687a 0.51 1,9461 0.36 1.0849 0.20 1154 580 0.5970 0.10 0 2924 0.05 1,7007 0.29 1.4274 0.25 1,8889 0.32 0.8750 0.15 1158 550 0.6503 0.12 0 3024 0.05 1.7179 0.31 1.5439 0.28 2.1813 0.40 1.1530 0.21 1159 587 0 7223 0.12 0 3698 0.06 1.8480 0.31 1.6935 0.29 2,3263 0.40 1 1211 0.19 1162 550 1164 523 0 6669 0 7675 0.12 0.15 0 3101 0.3613 0.06 0.07 1.7050 1.9198 0.31 0.37 1.5581 1.7783 0.28 0.34 2.0033 1 9163 0.36 0.37 0 8661 0 8735 0.16 0.17 1167 566 0 6801 0.12 0.3252 0.06 1.7101 0.30 1.5089 0.27 2 0326 0.36 1 0820 0 19 1168 571 0 6367 0.11 0.2903 0.05 1.8227 0.32 1.6190 0,28 1 5592 0.27 0 9914 0 17 1171 453 0 5776 0.13 0.2903 0.06 1.5240 0.34 1.4063 0.31 1 8020 0.40 1 0915 0 24 1173 530. 0 6524 0.12 0.3273 0.06 1.5741 0.30 1.4256 0.27 2 1183 0.40 1 0216 0 19 _u 1175 498. 0 6272 0.12 0.2745 0.06 1.7498 0.35 1.6409 0.33 1 7132 0.34 1 0295 0 21 _'_ 1176 494. 0.5684 0.12 0.2863 0.06 1.9718 0.40 1.8165 0.37 1 4040 0.28 0.8061 0 16 1177 480. 0.7391 0.15 0.3494 0.07 2.2666 0.47 2.1025 0.44 2 0790 0.43 1.1398 0 24 1180 586. 0.6971 0,12 0.3350 0.06 1.9639 .................................................................................................................................... 0.34 1.8501 0.32 2 1032 0.36 1.0329 0 18 _t_ O_ ALL WEIGHTS WERE RECORDED Rat 1153 had a large, analyses. IN GRAMS (G). left testis and ABS. testis WT. = ORGAN WEIGHT. minus tunica albuginea; REL. values % TBW = (ORGAN WEIGHT/TERMINAL included in group averages BODY WEIGHT) and statistical X i00. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 8) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE PITUITARY BRAIN LIVER NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. REL. % TBW 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 518. 505. 452. 568. 564. 529. 579. 505 441 457 561 506 413 513 512 588 539 580 550 587 550 523 566. 571. 0.6838 0.6106 0.6629 0.7111 0.6877 0 6987 0 7236 0 6703 0 6601 0 6262 0 6701b 0 6442 0 6614 0 6789 0 7538 0 6490 0 7007 0 6741 0 6996 0 7245 0 6761b 0 7592 0 7044 0 6950 0.13 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 1 6035 1 7572 1 6197 1 8049 1 7444 1 7356 1 9533 1 6461 1 8638 1.7137 1.5828 1.6204 1.8248 1.7369 2.0918 1.7336 1.7874 1.7880 1.7801 1.8539 1.6565 1.9644 1.7935 1.9170 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 0.4770 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 0.09 0.08 0.ii 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 0.010 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 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 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 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 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 5.40 5.39 6.19 6.55 5.55 4.62 5.40 5.23 5.57 5.89 4.35 4.93 5.85 5.21 5.55 5.28 2.78 5.42 6.17 4.82 5.70 5.91 5.84 5.53 1171 453. 0 5841 0.13 1.5517 0.34 1 0645 0.23 0 020 4.42 2.31 0.51 25 18 5.56 1173 530. 0 6720 0.13 1.6114 0.30 1.1758 0.22 0 028 5.28 2.41 0.45 27 19 5.13 1175 498. 0 6517 0.13 1.7506 0.35 1.1055 0.22 0 012 2.41 2.53- 0.51 26 00 5.22 1176 494. 0 6153 0.12 1.9358 0.39 0.9663 0.20 0 032 6.48 2.33 0.47 25 54 5.17 1177 480. 0 7824 0.16 2.2229 0.46 1.2319 0.26 0 015 3.12 2.43 0.51 34 48 7.18 [29 1180 586. 0 7608 0.13 1.9351 0.33 1.0538 0.18 0 025 4.27 2.47 0.42 28 35 4.84 _t_ .................................................................................................................................... OO WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. b_ Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 9) : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW a ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. REL. % TBW 1122 1123 1127 1129 1131 1132 1134 518. 505. 452. 568. 564. 529. 579. 2.33 2.40 2.10 2.58 2.81 2,43 2.52 0.45 0.48 0.46 0.45 0.50 0.46 0.44 2.31 2.40 2.11 2.78 2.67 2.49 2.63 0.44 0.48 0.47 0.49 0.47 0.47 0.45 0.024 0.030 0.024 0.036 0.024 0.039 0.037 4 63 5 94 5 31 6 34 4 26 7 37 6 39 0.020 0.032 0.026 0.032 0.028 0.036 0.038 3.86 6 34 5 75 5 63 4 96 6 80 6 56 1.02 0.80 0.75 0.83 0.95 0.59 0.95 0 20 0 16 0 16 0 15 0 17 0 11 0 16 0.49 0.29 0.28 0.72 0.59 0.37 0.66 0.09 0.06 0.06 0.13 0.i0 0.07 0.ii 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 505. 441. 457. 561. 506. 413. 513. 512. 588. 539. 580. 550. 587. 550. 523. 566. 571. 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 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 2.35 2.41 2.48 2.24 2.16 2.02 2.17 2.50 2.78 2.55 2.71 2.57 2.92 2.71 2.62 2.56 2.43 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 0.026 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 5 15 8 84 8 I0 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 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 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 0.75 0.72 0.56 0.94 0.65 0.69 0.86 0.77 0.91 0.93 1.01 0.86 1.08 0.78 0.80 1.17 0.94 0 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 0.33 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 0.06 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 1171 453. 2.09 0.46 1.95 0.43 0.031 6 84 0.032 7 06 0.77 0 17 0.40 0.09 1173 530. 2.28 0.43 2.37 0.45 0.028 5 28 0.033 6 23 0.73 0 14 0.51 0.i0 1175 498. 2.21 0.44 2.45 0.49 0.029 5 82 0.022 4 42 0.94 . 0 19 0.35 0.07 _'_ 1176 494. 2.56 0.52 2.69 0.54 0.036 7 29 0.029 5 8_ 0.76 0 15 0.44 0.09 1177 480. 2.76 0.58 2.79 0.58 0.034 7 08 0.030 6 25 0.89 0 18 0.36 0.08 1180 586. 2.54 0.43 2.51 0.43 0.036 6 14 0.037 6 31 1.05 0 18 0.40 0.07 "_ .................................................................................................................................... _O WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by i000. [0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 10): TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... L. TESTIS MINUS TUNICAALBUGINEA ABS. REL. WT. % TBW 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 458. 547. 498. 474. 591. 500. 549. 510. 682. 488. 0.5873 0.7364 0.6724 0.6851 0.7693 0.6944 0.7103 0.6484 0.7207 0.5748 0.13 0 13 0 14 0 14 0 13 0 14 0 13 0 13 0 I0 0.12 0.2692 0.3508 0.3462 0.3285 0.4167 0.3106 0 3404 0 3165 0 3662 0 2920 0.06 0.06 0.07 0.07 0.07 0.06 0.06 0.06 0.05 0.06 1.6842 1.9148 1.5726 1.7130 1.8304 1.7946 1.7653 1.6721 1.9297 1.5606 0 37 0 35 0 32 0 36 0 31 0 36 0 32 0 33 0 28 0.32 1.5580 1.7769 1.4546 1.5980 1.5499 1.5264 1.6519 1.5753 1.7940 1.4555 0.34 0.32 0.29 0.34 0.26 0.30 0 30 0 31 0 26 0 30 1204 1207 476. 499. 0.7346 0.7013 0.15 0.14 0 3820 0 3523 0.08 0.07 1.7581 1.7531 1209 1211 536. 472. 0 6512 0 6746 0.12 0.14 0.3423 0.3294 0.06 0.07 1.7328 1.7361 1212 572. 0 7302 0.13 0.3596 0.06 1.9206 1215 518. 0 6593 0.13 0.3135 0.06 1.8977 1216 534. 0 6832 0.13 0.3559 0.07 1.7087 1217 515. 0 6969 0.14 0.3209 0.06 1.8089 1219 418. 0.5811 0.14 0.2735 0 06 1.6144 1221 427. 0.5729 0.13 0.2820 0 07 1.7055 1222 520. 0.6980 0.13 0.3349 0 06 2.0374 1224 497. 0.6952 0.14 0.3592 0 07 1.7559 1225 440. 0.6728 0.15 0.3371 0 08 1.6548 1226 514. 0.6327 0.12 0.2997 0 06 1.7194 1229 1232 408. 377. 0.6796 0.6882 0.17 0.18 0.3348 0.3264 0 08 0 09 1.8306 1.9365 1233 585. 0.5594 0.i0 0.2432 0 04 1.7079 1236 491. 0.6243 0.13 0.2962 0.06 1.7320 1237 393. 0.6220 0.16 0.2763 0.07 1.6722 1240 490. 0.8036 0.16 0.4063 0.08 2.0756 ................................................................................................................................. 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 1.6592 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 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 ALL WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 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 2.310A 1.6820 2.0813 2.5458 0.48 0.51 0.33 0.38 0.35 0.45 0 41 0 36 0 33 0 42 0 45 0 41 0.39 0.48 0.45 0.36 0.38 0.34 0.49 0.37 0.41 0.46 0.51 0.34 0.34 0.49 0.39 0.34 0.53 0.52 1.0993 1.3573 0.7547 1.0218 0.9952 1.3117 1.1574 0.9382 1.1818 0.9225 1.0182 1.0792 1.0570 1.2076 1.1246 1.0642 1.0114 0.9204 1.1085 0.9655 1.1960 1.2959 1.0700 0.9698 0.8422 1.0507 1.3382 1.0255 0.9398 1.0793 0.24 0.25 0.15 0.22 0.17 0.26 0.21 0.18 0.17 0.19 0.21 0.22 0.20 0.26 0.20 0.20 0 19 0 18 0 26 0 23 0 23 0 26 0 24 0 19 0 21 0 28 0 23 0.21 0.24 0.22 WEIGHT/TERMINAL BODY WEIGHT) X i00. Q PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 11): TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND MALE RATS RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... 1182 1184 1186 1188 1189 1192 1194 1195 1198 458. 547 498 474 591 500 549 510 682 0.6047 0.7559 0.6982 0.6993 0.7530 0.6947 0.7274 0.6028 0.7218 0.13 0.14 0.14 0.15 0.13 0.14 0.13 0.12 0.I0 1 6680 1 8710 1 6171 1 6425 1 8294 1 7973 1 7765 1 6682 1 8638 0.36 0.34 0.32 0.35 0.31 0.36 0.32 0.33 0.27 0.3623 0.7091 0.8461 1.0337 1.2066 0.8355 1.2309 1.0630 0.9586 REL. % TBW 0.08 0.13 0.17 0.22 0.20 0.17 0.22 0.21 0.14 PITUITARY ABS. WT. REL. % TBW a 0.005 0.015 0.013 0.008 0.014 0.009 0.009 0.012 0.014 1.09 2.74 2.61 1.69 2.37 1.80 1.64 2.35 2.05 BRAIN ABS. WT. REL. % TBW 2.23 2.30 2.16 2.20 2.40 2.22 2.22 2.16 2.36 0.49 0.42 0.43 0.46 0.41 0.44 0.40 0.42 0.35 LIVER ABS. WT. REL. % TBW 25.00 30 64 20 80 27 64 32 61 30 76 29 51 26 56 35 89 5.46 5.60 4.18 5.83 5.52 6.15 5.38 5.21 5.26 1203 488 1204 476 1207 499 1209 536 1211 472 1212 572 1215 518 1216 534 1217 515 1219 418 1221 427 1222 520 0.6076 0.7386 0.7052 0.6614 0.7154 0.7298 0.6595 0.6748 0.7102b 0.6257 0.6549 0.7082 0.12 0.16 0.14 0.12 0.15 0.13 0.13 0.13 0.14 0.15 0.15 0.14 1 6140 1 7777 1 6577 1 6149 1 7180 1 9154 1 9394 1 6544 1 7837 1 6034 1 7229 1 9675 0.33 0.37 0.33 0.30 0.36 0.33 0.37 0.31 0.35 0.38 0.40 0.38 1.2275 1.1547 1.3065 1.2231 1.0513 1.3466 0.9439 1.4602 1.3746 0.9941 0.9705 1.0687 1224 497 1225 440 1226 514 0.7384 0.6937 0.6851 0.15 0.16 0.13 1 8250 1 6822 1 7896 0.37 0.38 0.35 1.0011 1.0253 1.1083 1229 408 0.7064 0.17 1 8647 0.46 0.5994 1232 377 0.6704 0.18 1 8883 0.50 0.9128 1233 585. 0.6843 0.12 1 7895 0.30 1.1748 1236 491. 0.6360 0.13 1 7348 0.35 1.1124 1237 393. 0.6242 0.16 1 6814 0.43 0.8318 1240 490. 0.7558 0.15 2 0720 0.42 1.2324 ................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS Value was multiplied by I000. (G). Damaged during processing (weight not ABS. WT. affected). = ORGAN WEIGHT. 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 0.010 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 2.05 2.73 2.40 2.42 2.54 1.75 2.70 3.18 2.33 4.31 2.81 2.50 5.23 5.91 4.08 3.19 3.98 2.5_ 2.65 2.54 4.08 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 0.45 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 26 54 31 81 24 11 35 57 27 46 34 89 30 79 33 30 30 02 27 85 24 86 31 71 26 90 31 17 32 01 22 60 26 98 38 30 25 35 28 38 28 51 REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) 5.44 6.68 4.83 6.64 5.82 6.10 5.94 6.24 5.83 6.66 5.82 6.10 5.41 7.08 6.23 5.54 7.16 6.55 5.16 7.22 5.82 - X i00. [2_ _t_ O0 CD t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 12): TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND MALE RATS RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT, % TBW WT. % TBW WT. .................................................................................................................................... REL. % TBW a 1182 1184 1186 1188 1189 1192 1194 1195 458. 547. 498. 474. 591. 500. 549. 510. 1.96 2.40 2.00 2.25 2.52 2.16 2.32 2.25 0,43 0.44 0,40 0,47 0.43 0,43 0.42 0,44 2.06 2.30 1.81b 2.21 2.65 2.31 2.72 2.27 0 45 0 42 0 36 0 47 0 45 0 46 0 50 0 44 0.010 0.031 0.033 0.031 0.032 0.032 0,029 0.025 2.18 5.67 6.63 6.54 5.41 6.40 5.28 4.90 1198 1203 682. 488. 2.65 2.32 0.39 0.48 2.61 2.21 0 38 0 45 0.042 0.025 6.16 5.12 ADRENAL RIGHT ABS. REL. WT. % TBW a 0.022 0.033 0.032 0.016 0.037 0.032 0.030 0.028 0.040 0.025 4.80 6.03 6.42 3.38 6.26 6.40 5.46 5.49 5.86 5.12 SPLEEN ABS. WT. REL. % TBW 0.67 0.72 0.69 0.78 0.85 0.92 0.81 0.76 0.81 0.81 0.15 0,13 0.14 0.16 0.14 0,18 0.15 0.15 0.12 0.16 THYMUS ABS. WT. REL. % TBW 0.35 0.39 0.27 0.56 0.35 0.73 0.30 0.37 0.36 0.32 0.08 0.07 0.05 0.12 0.06 0.15 0.05 0.07 0.05 0.06 11220047 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 447969.. 536. 472. 572. 518. 534. 515. 418. 427. 520. 497. 440. 514. 408. 22..5367 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 00,.5447 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 22..4199 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 00 5424 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 00..003225 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 65..7021 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 00..002262 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 45..4416 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 00..7615 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 00,,1153 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 00..4237 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 00..0095 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 1232 1233 377. 585. 2.12 2.77 0,56 0,47 2.07e 2.85 0.55 0.49 0.026 0.036 1236 491. 2.48 0.50 2.44 0.50 0.028 1237 1240 393. 490. 2.00 2.53 0,51 0,52 2.02 2.67 0.51 0.54 0.026 0.039 ................................................................................................................................. 6.90 6.15 5.70 6.62 7.96 0.026 0.038 0.024 0.021 0.039 6.90 6.50 4.89 5.34 7.96 0.82 1.04 0,88 . 0.65 0.70 0.22 0.18 0.18 0.16 0.14 0.39 0.55 0.36 0.27 0.24 0.i0 0.09 0.07 0.07 0.05 _'_ OO ._A WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. O0 Value was multiplied by i000. Rat 1186 had moderate dilation of the pelvis of the right kidney; value included in group averages and statistical analyses, b_ Rat 1224 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. O Rat 1229 had tan areas analysis. on the spleen that extended into the parenchyma; value included in group averages and statistical Rat 1232 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 13) : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT TERMINAL BODY LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW WT. % TBW WT. % TBW .................................................................................................................................... 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 460. 485. 502. 442. 378. 376. 409. 414. 490. 457. 0.6112 0.6273 0.6766 0.6881 0.6792 0.7319 0.6596 0.6469 0 6245 0 7072 0.13 0.13 0.13 0.16 0.18 0.19 0.16 0.16 0.13 0.15 0.2998 0.3142 0.3187 0.3340 0.3129 0.3795 0.3158 0.3557 0.3120 0.3545 0.06 0.06 0.06 0.08 0.08 0.I0 0.08 0.08 0.06 0.08 1.5908 1.7212 1.7176 1.8326 1.6396 1.7786 1.4497 1.7510 1 7416 1 8200 0.34 0.35 0.34 0.41 0.43 0.47 0.35 0.42 0.36 0.40 L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % TBW 1.3979 1.5926 1.6080 1.6988 1.5464 1.6728 1.3774 1.6523 1.6095 1.7299 0.30 0.33 0.32 0.38 0.41 0.44 0.34 0.40 0.33 0.38 SEMINAL WITH ABS. WT. VESICLES FLUID REL. % TBW 1.8364 2.8798 2.1597 1.7738 2.5952 2.0331 1.8891 1.9214 1.6770 2.2625 0.40 0.59 0.43 0.40 0.69 0.54 0.46 0.46 0.34 0.50 SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % TBW 1.0081 1.4614 1.0569 1.0022 1.2934 1.0653 0.9906 0.8235 0.6609 1,0298 0.22 0.30 0.21 0.23 0.34 0.28 0.24 0.20 0.13 0.22 11225691 432868.. 00 65996090 00..1165 00..32593599 00..0088 11 76886438 00..4423 11..65576360 00..3490 21..08326462 00..4487 10..08298533 00..2243 1266 429. 0 6313 0.15 0.3086 0 07 1 6450 0.38 1.5233 0.36 1.9019 0,44 0.7353 0.17 1269 514. 0 6429 0.12 0.3347 0 06 1 7958 0.35 1.6760 0.33 1.8292 0.36 0.8866 0.17 1271 510. 0.6784 0.13 0.2913 0 06 1.9897 0.39 1.7853 0.35 1.8426 0.36 0.9089 0.18 1273 394. 0.5963 0.15 0.2747 0 07 1.5513 0.39 1.4009 0.36 1.9182 0.49 0.9421 0.24 1274 507. 0.6832 0.13 0.3324 0 06 1.8321 0.36 1.6903 0.33 1.6601 0.33 0.8003 0.16 1278 405. 0.6289 0.16 0.2912 0 07 1.6986 0.42 1.6003 0.40 1.7792 0.44 0.8806 0.22 1281 472. 0.6557 0.14 0.3389 0 07 1.5348 0.32 1.3779 0.29 1.8714 0.40 0.9200 0.19 1282 403. 0.6104 0,15 0.2935 0 07 2.0059 0.50 1.8552 0.46 1.4607 0.36 0.7963 0.20 1284 443. 0.6110 0 14 0.3077 0 07 1.7608 0.40 1.6309 0.37 1.6002 0.36 0,8986 0.20 1287 418. 0.5705 0 14 0.2924 0.07 1.5426 0 37 1.4114 0.34 1.5734 0.38 0.7565 0.18 1288 1289 407. 443. 0.5772 0.6419 0 14 0 14 0.2718 0.3011 0.07 0.07 1.4489 1.8533 0 36 0 42 1.3122 1.7185 0.32 0 39 2.0014 1.8222 0.49 0.41 0.9903 1,0444 0.24 0.24 1290 447. 0.6438 0 14 0.2949 0.06 1.8455 0 41 1.6862 0 38 1.6617 0.37 0,8188 0.18 _> 1291 399. 0.7084 0 18 0.3777 0.09 1.8660 0 47 1.5842 0 40 1.8949 0.47 0.9639 0.24 1294 450. 0.7602 0 17 0.3415 0.08 2.0868 0 46 1.8566 0 4,1 1.3983 0.31 0.7453 0.16 1298 385. 0.5738 0 15 0.2755 0.07 1.4615 0 38 1.3341 0 35 1.8111 0.47 0.8992 0.23 1300 438. 0.7065 0 16 0.3154 0.07 1.6906 0 38 1.5934 0 36 1.9824 0.45 1.2279 0.28 4_ .................................................................................................................................... _._ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00 O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 14): TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. .................................................................................................................................... 1241 1244 1245 1247 1248 1249 1252 460. 485. 502. 442. 378. 376. 409. 0.6533 0.6699 0.6880 0.6936 0.7177 0.7145 0.5818 0.14 0.14 0.14 0.16 0.19 0.19 0.14 1.6469 1.6944 1.7335 1.7629 1.7090 1.7860 1.3457 0.36 0.35 0.34 0.40 0.45 0.48 0.33 0.7133 0.4297 0.6958 1.0837 0.8798 0.8470 0.7562 REL. % TBW 0.16 0.09 0.14 0.24 0.23 0.22 0.18 1254 1255 414. 490. 0.6693 0.6530 0.16 0.13 1.8852 1.7597 0.46 0.36 0.9728 1.0766 0.23 0.22 PITUITARY ABS. WT. REL. % TBW a 0 009 0 012 0 013 0 011 0 010 0 011 0 009 0 009 0 010 1.96 2.47 2.59 2.49 2.64 2.92 2.20 2.17 2.04 BRAIN ABS. WT. REL. % TBW 2.21 2.14 2 14 2 19 2 02 2 08 2 16 2 00 2.29 0.48 0.44 0.43 0.50 0.53 0.55 0.53 0.48 0.47 LIVER ABS. WT. REL. % TBW 33.90 37.00 35.80 30.46 23 36 22 66 29 14 24 07 32 45 7.37 7.63 7.13 6.89 6.18 6.03 7 12 5 81 6 62 11225579 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 445276.. 388. 429. 514. 510. 394. 507. 405. 472. 403. 443. 418. 407. 443. 00..77335501 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 00..1167 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 11..88963256 1.7525 1.5782 1.7311 1.9298 1.5443 1.8951 1.7218 1.5678 2.0764 1.8308 1.5509 1.3930 2.0066 00..4414 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 11..01136275 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 00..2226 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 00 001039 0 011 0 014 0 005 0 019 0 021b 0 015 0 024 0 032 0 010 0 012 0 010 0 026 0 010 22..8141 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 21 I9i5 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 00..4466 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 2295 8903 24 08 29 42 32 70 30 75 27 46 34 70 26 59 30 95 29.72 30.21 26.56 25.71 33.07 66 5029 6 21 6 86 6 36 6 03 6 97 6 84 6 56 6 56 7 37 6 82 6 35 6 32 7 46 1290 447. 0.6780 0.15 1.8514 0 41 0.7592 1291 399. 0.7411 0.18 1.8543 0 46 0.7997 1294 450. 0.7335 0.16 1.9582 0 44 0.9946 1298 385. 0.5936 0.15 1.4529 0 38 0.6132 1300 438. 0.7606 0.17 1.7792 0 41 0.9123 .................................................................................................................................. 0.17 0.20 0.22 0.16 0.21 0 014 0 008 0 026 0 011 0 010 3.13 2.00 5.78 2.86 2.28 2 27 2 35 2 372 06 2 18 0.51 0.59 0.53 0.54 0.50 34.68 26.73 33.81 27.51 33.29 7 76 6 70 7 51 7 14 7 60 _'_ [29 ._ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. OO Value was multiplied by i000. Damaged during processing (weight affected); values excluded from group averages and statistical analyses, t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D20 (PAGE 15) : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS MALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT SPLEEN NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. ABS. REL. ABS. WT. % TBW WT. % TBW WT. % TBW a WT. % TBW a WT. .................................................................................................................................... REL. % TBW 1241 1244 1245 1247 1248 1249 460. 485. 502. 442. 378. 376. 2.30 2.60 2.60 1.85 1.90 1.94 0 50 0 54 0 52 0 42 0 50 0 52 2.28 2.41 2.40 1.67 1.94 1.94 0.50 0.50 0.48 0.38 0.51 0.52 0.024 0.035 0.033 0.023 0.031 0.028 5.22 7.22 6.57 5.20 8.20 7.45 0.031 0.030 0.024 0.016 0.029 0.024 6.74 6 18 4 78 3 62 7 67 6 38 0.65 0.64 0.85 0.95 0.60 0.63 0.14 0.13 0.17 0.21 0 16 0 17 1252 409. 1.78 0 44 1.78 0.44 0.027 6.60 0.024 5 87 0.73 0 18 1254 1255 414. 490. 1.91 2.13 0 46 0 43 1.88 2.23 0.45 0.46 0.025 0.023 6 04 4 69 0.022 0.019 5 31 3 88 0.67 0.67 0 16 0 14 THYMUS ABS. WT. REL. % TBW 0.28 0.18 0.73 0.20 0.53 0.28 0.34 0.24 0.31 0.06 0.04 0.14 0.04 0.14 0.07 0.08 0.06 0.06 1257 1259 1261 1266 1269 457. 426. 388. 429. 514. 1.89 1.90 1.75 1.90 1.93 0 41 0 45 0 45 0 44 0 38 1.87 1.79 1.93 2.00 2.12 0.41 0.42 0.50 0.47 0.41 0.028 0.023 0.021 0.030 0.022 6 13 5 40 5 41 6 99 4 28 0.030 0.016 0.025 0.028 0.023 6 56 3 76 6 44 6 53 4 47 0.62 0.69 0.59 0.78 0.89 0 14 0 16 0 15 0 18 0 17 0.26 0.22 0.21 0.30 0.55 0.06 0.05 0.05 0.07 0.11 1271 1273 510. 394. 2.21 1.90 0 43 0 48 2.50 1.86 0.49 0.47 0.038 0.033 7 45 8 38 0.037 0.029 7 25 7 36 0.69 0.75 0 14 0 19 0.51 0.47 0.10 0.12 1274 1278 507. 405. 2.29 1.74 0 45 0 43 2.35 1.81 0.46 0.45 0.020 0.031 3 94 7.65 0.022 0.026 4 34 6 42 0.84 0.84 0 16 0 21 0.68 0.34 0.13 0.08 1281 1282 472. 403. 2.10 1.92 0 44 0 48 2.04 2.01 0.43 0.50 0.030 0.036 6.36 8.93 0.030 0.038 6 36 9 43 0.91 0.78 0 19 0 19 0.52 0.73 0.11 0.18 1284 1287 443. 418. 2.16 2.16 0 49 0 52 1.99 2.06 0.45 0.49 0.034 0.020 7.67 4.78 0.032 0.020 7 22 4 78 0.65 0.67 0 15 0 16 0.46 0.40 0.10 0.10 1288 1289 407. 443. 1.96 2.02 0 48 0 46 2.12 1.97 0.52 0.44 0.028 0.019 6.88 4.29 0.022 0.015 5 40 3 39 0.84 0.71 0 21 0 16 0.31 0.39 0.08 0.09 1290 447. 1.99 0 44 2.08 0.46 0.026 5.82 0.030 6 71 0.81 0 18 0.43 0.i0 1291 399. 2.09 0 52 2.05 0.51 0.023 5.76 0.024 6 02 0.72 0 18 0.27 0.07 1294 450. 2.07 0 46 2.26b 0.50 0.039 8.67 0.035 7 78 1.14 - 0 25 0.44 0.i0 1298 385. 1.85 0 48 1.86 0.48 0.022 5.71 0.019 4 94 0.52 0 14 0.30 0.08 1300 438. 2.06 0 47 1.99 0.45 0.026 5.94 0.024 5 48 0.78 0 18 0.39 0.09 [/_ ................................................................................................................................. WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. OO Value was multiplied by i000. Rat 1294 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. I_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 1) : BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... 1002 1003 1005 1007 1011 1012 2.27 2.40 2.36 2.23 2.22 2.32 0.7752 0.7726 0.6687 0.6686 0.6963 0.7115 34.15 32.19 28.33 29.98 31.36 30.67 0.3991 0.3611 0.3080 0.3350 0.3387 0.3373 17 58 15 04 13 05 15 02 15 26 14 54 1.9221 1.8125 1.6994 1.5619 1.5902 1.7682 84.67 75.52 72.01 70.04 71.63 76.22 1013 2.29 0.6641 29.00 0.3204 13 99 1.6088 70.25 1014 1017 2.51 2.30 0.7869 0.6555 31.35 28.50 0.3583 0.2932 14 27 12 75 1.8831 1.7762 75.02 77.23 L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW 1.7786 1.6880 1.5948 1.4691 1.4829 1.6627 1.5081 1.7555 1.6737 78.35 70.33 67.58 65.88 66.80 71.67 65.86 69.94 72.77 SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW 1.6467 2.1281 1.7303 i_8008 1 7689 2 1506 2 2159 2 5406 1 6431 72.54 88.67 73.32 80.75 79.68 92.70 96.76 101.22 71.44 SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 0.8308 1.0361 0.8830 0.9282 0.9602 1.0488 1.2484 1.3229 0.9578 36.60 43.17 37.42 41.62 43.25 45.21 54 52 52 70 41 64 11002213 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 22..2275 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 00..66958870 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 3209..7284 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 00..33438329 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 1154 3844 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 11..87201284 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 8705..2666 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 11..65876984 1.8349 1.6188 1.6663 1.4943 1.2926 1.5238 1.4797 1.6406 1.8917 1.6111 1.4321 1.4572 1.8134 7740..3210 72.81 74.60 68.01 66.41 57.45 63.76 65.76 68.36 82.97 66.57 59.67 66.24 69.21 11 86363795 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 8704..7191 88.78 73.41 92.07 91.73 75.53 87.65 77.40 60.12 94.62 56.48 84.26 80.05 88.29 10..07047370 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 4343 3092 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 1052 2.47 0.7354 29.77 0.3854 15 60 1.9346 78.32 1.7771 71.95 2 0816 84.28 1.1932 48 31 1054 2.46 0.7518 30.56 0.3819 15 52 1.9560 79.51 1.8014 73.23 2 5943 105.46 1.4246 57 91 1055 2.43 0.6775 27.88 0.3243 13 34 1.7734 72.98 1.6231 66.79 2 0127 82.83 1.1275 46 40 1058 1.94 0.5881 30.31 0.2814 14 50 1.6935 87.29 1.5125 77.9'6 1 8827 97.05 0.9591 49 44 1059 2.44 0.6360 26.06 0.2937 12 04 1.7162 70.34 1.6036 65.72 1 1345 46.50 0.7241 29.68 1060 2.40 0.6379 26.58 0.3128 13 03 1.6027 66.78 1.4347 59.78 1 3529 56.37 0.7172 29.88 _t_ .................................................................................................................................... OO WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. _D b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 2) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... 1002 1003 1005 1007 i011 1012 1013 2.27 2.40 2.36 2.23 2.22 2.32 2.29 0.7585 0.7227 0.6810 0.6742 0.6834 0.6799 0.6817 33.41 30.11 28.86 30.23 30.78 29.31 29.77 1 8845 1 7920 1 6608 1 5845 1 5867 1 7336 1 6417 83.02 74.67 70.37 71.05 71.47 74.72 71.69 0.4671 0.6059 0.5167 0.5157 0.7725 1.3440 1.0484 20.58 25.24 21.89 23.12 34.80 57.93 45.78 1014 1017 2.51 2.30 0.8172 0.6814 32.56 29.63 1 7921 1 7002 71.40 73.92 1.0938 1.3176 43.58 57.29 PITUITARY ABS. WT. REL. % BRW 0.015 0.014 0.011 0.014 0.011 0.014 0.014 0.012 0.013 0.66 0.58 0.47 0.63 0 50 0 60 0 61 0 48 0 56 LIVER ABS. WT. REL. % BRW 21.20 25.00 19.70 21.20 24.75 24.99 21.79 22.01 17.05 933.92 1041.67 834.74 950.67 1114.86 1077.16 951.53 876.89 741.30 KIDNEY LEFT ABS. REL. WT. % BRW 2.17 2.38 2.13 2.10 2.19 2.22 2.35 2.08 2.05 95.59 99.17 90.25 94.17 98.65 95.69 102.62 82.87 89.13 11002213 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 22..2275 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 00..76354933 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 3229..3350 29.26 31.87 27.40 31.03 25.01 26.61 28.28 28.44 31.44 30.59 26.59 31.88 32.64 11 86147357 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 8703..0075 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 01..92022225 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 3594..7343 64.44 58.15 50.11 56.62 36.08 46.93 49.01 35.80 45.86 58.49 43.04 46.87 51.85 00..001135 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 00 5677 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 2253..0689 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 11100542 8849 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 22..4211 2.41 1.85 2.31 1.73 1.98 2.22 2.35 2.07 1.99 2.37 2.58 1.96 2.59 10968..1272 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 1052 2.47 0.8026 32.49 1.9853 80.38 1 1700 47.37 0.013 0 53 24.34 985.42 2.51 101.62 _> 1054 2.46 0.7438 30.24 1.9381 78.78 1 1579 47.07 0..020 0 81 20.05 815.04 2.22 90.24 1055 2.43 0.7348 30.24 1.8211 74.94 1 1323 46.60 0.021 0 86 21.35 - 878.60 2.31 95.06 1058 1.94 0.6267 32.30 1.6947 87.36 1 1133 57.39 0.018 0 93 20.17 1039.69 2.21 113.92 1059 2.44 0.6254 25.63 1.7833 73.09 0 7495 30.72 0.018 0 74 16.10 659.84 2.19 89.75 [/_ 1060 2.40 0.6724 28.02 1.7323 72.18 0.8267 34.44 0.012 0 50 17.81 742.08 2.30 95.83 4_ .................................................................................................................................... O_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 3) : BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT BRAIN KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW 1002 1003 1005 1007 i011 1012 1013 1014 1017 2 27 2 40 2 36 2 23 2 22 2 32 2 29 2 51 2 30 2.28 2 20 2 08 2 00 2 18 2 20 2 28 2 16 2 04 100.44 91.67 88.14 89.69 98.20 94.83 99.56 86.06 88.70 0.031 0.029 0.037 0.029 0.038 0.025 0.027 0.026 0.029 1.36 1.21 1.57 1.30 1.71 1.08 1.18 1.04 1.26 0 028 0 023 0 038 0 031 0 032 0 022 0 027 0 023 0 030 1.23 0.96 1.61 1.39 1.44 0.95 1.18 0.92 1.30 SPLEEN ABS. WT. REL. % BRW 0.96 1.02 1.00 1.03 0 95 0 90 1 02 0 95 0 72 42.29 42.50 42.37 46.19 42.79 38.79 44.54 37.85 31.30 THYMUS ABS. WT. REL. % BRW 0.28 0.42 0.62 0.59 0.71 0.73 0.52 0.32 0.43 12.33 17.50 26.27 26.46 31.98 31.46 22.71 12.75 18.70 1021 1023 1026 1028 1031 1034 1035 1040 1041 1043 1045 1047 1048 1050 1051 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 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 54 112.78 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 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 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 0 036 0 030 0 036 0 037 0 019 0 011a 0 022 0 018 0 024 0 023 0 039 0 036 0 036 0 029 0 041 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 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 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 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 19.38 22.22 18.25 18.89 17.96 16 44 19 11 18 83 32 00 24 58 26 75 14 88 23 33 26.82 19.85 1052 2.47 2.47 I00.00 0.033 1.34 0 036 1.46 1.03 41.70 0.70 28.34 _> 1054 2.46 2.26 91.87 0.028 1.14 0 027 i. I0 0.99 40.24 0.54 21.95 1055 2.43 2.42 99.59 0.037 1.52 0 037 1.52 0.83 34.16 0.55 - 22.63 1058 1.94 2.28 117.52 0.030 1.55 0 030 1.55 0.86 44.33 0.58 29.90 1059 2.44 2.13 87.30 0.039 1.60 0 036 1.48 1.04 42.62 0.33 13.52 1060 2.40 2.27 94.58 0.030 1.25 0 023 0.96 0.73 30.42 0.47 19.58 4_ .................................................................................................................................... O_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Damaged during processing (weight affected); values excluded from group averages and statistical analyses, t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 4) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT NUMBER BRAIN WEIGHT LEFT ABS. REL. LEFT ABS. REL. LEFT ABS. REL. HT. % BRW WT. % BRW WT. .................................................................................................................................... % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. HT. VESICLES FLUID REL. % BRW 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 1088 1090 1091 1094 1096 1098 ii00 1103 1106 1107 1110 2.16 2.26 2.10 1.98 2.04 2.37 2.26 2.08 2 .25 2.35 2.17 2.30 2.07 2.33 2.24 2.45 2 28 2 47 2 38 2 33 2 35 2 13 2 15 2 33 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 35.46 31.72 30.18 30.93 32.01 27.46 31.23 37.81 33.77 30.13 15.64 27.98 26.66 31.14 30.29 25.04 28.19 27.98 29.67 27.23 28.46 28.15 30.70 26.69 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 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 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 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 1.6295 1.7520 1.6559 1.4453 1.6520 1.5115 1.8542 1.6513 1 6647 1 6044 0 4551a 1 3716 I 5186 1 5413 1 5236 1 3518 1 4565 1 5653 1 7580 1 5379 1.5524 1 4213 1 4424 1 5194 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 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 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 1.0157 1 1167 1 3449 0 9152 1 0798 1 1328 1 1732 1 0133 0 9239 0 9701 0 9927 0 9679 0 9166 0 9295 0 8012 1 3115 1 0829 1 0369 1 3095 0 9989 0 7884 1 0277 0 8120 0 8915 47.02 49.41 64.04 46.22 52.93 47.80 51.91 48.72 41 .06 41.28 45.75 42.08 44.28 39.89 35.77 53.53 47.50 41.98 55.02 42.87 33.55 48.25 37 77 38 26 1112 1114 1116 2 64 2 55 2 36 0.6981 0.6757 0.6704 26.44 26.50 28.41 0.3442 0.3169 0.2919 13.04 12.43 12.37 1.8105 1.9848 1.5620 68.58 77.84 66.19 1 6908 1 8202 1 4146 64.04 71.38 59.94 2 1860 2 3440 2 0547 82.80 91.92 87.06 1.2293 1.2241 1.0185 46 56 48 00 43 16 1118 2 37 0.6492 27.39 0.2958 12.48 1.6885 71.24 1 5853 66.89 2 1617 91.21 1.0063 42 46 1120 2 43 0.7509 30.90 0.3424 14.09 2.0030 82.43 1 8717 77.02 2 3378 96.20 1.0701 44 04 [_ ................................................................................................................................ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. O0 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, to PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 5) : BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... 1061 1063 1066 1067 1069 1071 1073 2.16 2.26 2.10 1.98 2.04 2.37 2.26 0.7284 0.7113 0.6396 0.6431 0.6310 0.6846 0.7456 33.72 31.47 30.46 32.48 30.93 28.89 32.99 1 8528 1 8505 1 5745 1 5154 1 6782 1 5542 1 9825 85.78 81.88 74.98 76.54 82.26 65.58 87.72 0.4761 0.8821 0.2716a 0.5982 0.8284 1.3268 1.3308 22.04 39.03 12.93 30.21 40.61 55.98 58.88 PITUITARY ABS. WT. REL. % BRW 0.011 0.012 0.011 0.012 0,011 0.012 0.016 0.51 0.53 0.52 0.61 0.54 0.51 0.71 LIVER ABS, WT. REL. % BRW 20.77 26.60 20.80 20,97 21.61 26.35 27.94 961.57 1176.99 990.48 1059.09 1059.31 1111.81 1236.28 KIDNEY LEFT ABS. REL. WT. % BRW 2.06 2.50 2.03 1.95 2.10 2.43 2.43 95.37 110.62 96.67 98.48 102.94 102.53 107.52 1077 1078 1081 2 08 2 25 2 35 0 7614 0 7545 0 7025 36.60 33.53 29.89 1 8037 1.7230 1.7244 86.72 76.58 73.38 0,8947 1.3800 1.3717 43.01 61.33 58.37 0.011 0.014 0 014 0.53 0.62 0.60 25.28 30.05 22.81 1215.38 1335.56 970.64 2.39 2.67 2.24 114.90 118.67 95.32 1082 1083 2 17 2 30 0 6989 0 6288 32.21 27.34 1.7261 1.4717 79.54 63.99 1.2924 1.3446 59.56 58.46 0 016 0 014 0.74 0.61 24.34 23.15 1121,66 1006.52 2.16 2.27 99.54 98.70 1086 1088 2 07 2 33 0 6170 0 6845 29.81 29.38 1.6474 1.6176 79.58 69.42 0.9942 1.5251 48,03 65.45 0 012 0 014 0.58 0.60 15.51 29.13 749.28 1250.21 1.79 2.22 86.47 95.28 1090 2.24 0.7019 31.33 1.6796 74.98 1.2761 56.97 0 017 0.76 21.48 958.93 2.27 101.34 1091 2.45 0.6599 26.93 1.7494 71.40 1.1454 46.75 0 014 0.57 27.07 1104.90 2.68 109 39 1094 2.28 0.6911 30.31 1.6621 72.90 1.0867 47.66 0 025 1.10 29 60 1298.24 2.39 104 82 1096 2.47 0.7465 30.22 1.7774 71.96 1.0373 42.00 0 016 0.65 32 95 1334.01 2.39 96 76 1098 2.38 0.7631 32.06 1.9639 82 52 1.1216 47.13 0 015 0.63 30 37 1276.05 2.35 98 74 1100 2.33 0.6229 26.73 1.6532 70 95 1.1903 51.08 0 024 1.03 22 79 978.11 2.59 111 16 1103 2.35 0.6993b 29.76 1.7282 73 54 0.8336 35,47 0.013 0.55 27 76 1181.28 2.54 108 08 1106 2.13 0.6575 30.87 1.6263 76 35 1.2108 56.84 0.013 0.61 22 68 1064.79 2.19 102 82 1107 2.15 0.6578 30.60 1.6277 75 71 0.9999 46.51 0.033 1.53 19.46 905.12 2.05 95 35 1110 2.33 0.6330 27 17 1.6504 70 83 0.9081 38.97 0.015 0.64 20.50 879.83 2.21 94 85 1112 2.64 0.6748 25 56 1,8656 70 67 1.4610 55.34 0.018 0,68 28.97 1097.35 2.90 109 85 1114 2.55 0.7494 29 39 1.9312 75 73 1.1564 45,35 0.023 0.90 27.29 1070.20 2.80 109 80 1116 2.36 0.6639 28 13 1.5988 67 74 1.2054 51.08 0.026 i.i0 21.37 - 905.51 2.33 98 73 1118 2.37 0.6786 28 63 1.7496 73 82 1.0908 46,02 0,023 0.97 22.51 949.79 2.74 115 61 1120 2.43 0.6911 28 44 1.9723 81.16 1.1517 .................................................................................................................................... 47.40 0.028 1.15 22.49 925.51 2.46 I01 23 [/_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Oo Rat 1066 had a small prostate; values included in group averages and statistical analyses. Damaged during processing (weight not affected) _ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 6) : BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT BRAIN KI DNEY RIGHT ADRENAL LEFT ADRENAL RIGHT S PLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL, % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW 1061 1063 1066 1067 1069 1071 1073 1077 1078 1081 1082 1083 1086 2 16 2 26 2 10 1 98 2 04 2 37 2 26 2 08 2 25 2 35 2 17 2 30 2 07 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 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 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 0.74 1.81 1.33 1.21 0.98 0.76 1.64 2.12 1.60 1.19 1.61 1.70 1.35 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 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 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 35.18 37.17 30.48 32.83 35.29 35.44 30.09 27.88 40.89 35.32 39.63 32.61 35.75 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 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 1088 1090 1091 1094 1096 1098 ii00 1103 1106 1107 1110 2 33 2 24 2.45 2 28 2 47 2 38 2 33 2 35 2 13 2 15 2 33 2.02 2.27 2.56 2.38 2.45 2.44 2 37 2 59 2 21 2 05 2 16 86.70 101.34 104.49 104.38 99.19 102.52 101.72 110.21 103.76 95.35 92.70 0.032 0.025 0.029 0.048 0.024 0.030 0.038 0.040 0.024 0.034 0.020 1.37 1.12 1.18 2.10 0.97 1.26 1.63 1.70 1.13 1.58 0.86 0 027 0 024 0 030 0 041 0 024 0 028 0 033 0.036 0.023 0.035 0.019 1.16 1.07 1.22 1.80 0.97 1.18 1.42 1.53 1.08 1.63 0.82 0 85 0 75 0 89 1 00 0 95 0 80 0 82 0 92 0 75 0 60 0 73 36.48 33.48 36.33 43.86 38.46 33.61 35.19 39.15 35.21 27.91 31.33 0.40 0.31 0.55 0 53 0 69 0 61 0 55 0 65 0 58 0 36 0 44 17.17 13.84 22.45 23.24 27.94 25.63 23.60 27.66 27.23 16.74 18.88 1112 1114 2 64 2 55 3 01 2 84 114.02 111.37 0.039 0.042 1.48 1.65 0.043 0.037 1.63 1.45 1 24 1 03 46.97 40.39 0 35 0.48 13.26 18.82 1116 2 36 2 37 100.42 0.041 1.74 0.027 1.14 0 90 38.14 0.32- 13.56 1118 2 37 2 73 115.19 0.032 1.35 0.029 1.22 1 06 44.72 0.41 17.30 1120 2.43 2 53 104.12 0.030 1.23 0.026 1.07 1 00 41.15 0.36 14.81 O_ .................................................................................................................................... ._ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00 O0 h.) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 7): BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 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 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 30.03 25.29 30.06 32.34 31.17 30.29 31.73 30.78 31.74 27.03 29.72 28.34 33.90 30.46 34.45 28.07 29.12 26.77 28.52 32.24 28.87 31.85 30.50 25.37 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 14.46 12.37 15.01 15.29 16.06 15 22 13 99 14 83 15 77 14 30 16 34 13 67 15 96 15.40 17.51 13.19 14.25 13.11 13.26 16.51 13.42 14 99 14 58 11 56 1.6159 1.8182 1.6347 1.9335 1.7682 1.7645 1.8988 67.33 75.76 74.30 84.43 79.29 79.48 79.12 1.7237 1.9009 79.43 88.00 1.6472 1.5627 71.93 72.01 1.6597 76.84 1.8607 91.21 1.6976 72.86 2.0462 86.70 1.8091 75.07 3.0171a128.39 1.7007 76.26 1.7179 75.35 1.8480 82.50 1.7050 73.81 1.9198 79.66 1.7101 76.69 1.8227 72.62 1.5221 1.6922 1.5124 1.8129 1.6707 1.6362 1.7685 63.42 70.51 68.74 79.16 74.92 73.70 73.69 1.6026 1.6834 73.85 77.94 1.5631 1.4612 68.26 67.34 1 5318 70.92 1 7494 85.75 1 6060 68.93 1 9344 81.97 1 5925 66.08 2 7687a117.82 1 4274 64.01 1 5439 67.71 1.6935 75.60 1.5581 67.45 1.7783 73.79 1.5089 67.66 1.6190 64.50 2 0470 85.29 2 3013 95.89 1 7196' 78.16 2 1930 95.76 2 3326 104.60 2 3904 107.68 2 1383 89.10 1 8500 1.3217 1 7038 1 7528 2 0896 1 8492 1 7211 2 3386 2 2078 1 9461 1 8889 2 1813 2 3263 2 0033 1 9163 2 0326 1 5592 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 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 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 1171 1173 2.31 2.41 0.5776 0.6524 25.00 27.07 0.2903 0.3273 12 57 13 58 1.5240 1.5741 65.97 65.32 1.4063 1.4256 60.88 59.15 1 8020 2 1183 78.01 87.90 1.0915 1.0216 47 25 42 39 1175 2.53 0.6272 24.79 0.2745 i0 85 1.7498 69.16 1.6409 64.86 1 7192 67.72 1.0295 40 69 1176 2.33 0.5684 24.39 0.2863 12 29 1.9718 84.63 1.8165 77.96 1 4040 60.26 0.8061 34 60 1177 2.43 0.7391 30.42 0.3494 14 38 2.2666 93.28 2.1025 86.52 2 0790 85.56 1.1398 46 90 [29 1180 2.47 0.6971 28.22 0.3350 13 56 1.9639 79.51 1.8501 74.90 2 1032 85.15 1.0329 41 82 4_ w.d .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. Rat 1153 had a large, left testis and testis minus tunica albuginea; values included in group averages and statistical IJ analyses. CD PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 8) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 1162 1164 1167 1168 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 0.6838 0.6106 0.6629 0.7111 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 28 49 25 44 30 13 31 05 30 84 31 47 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 1 6035 1 7572 1 6197 1 8049 1 7444 1 7356 1 9533 1 6461 1 8638 1 7137 1 5828 1.6204 1.8248 1.7369 2.0918 1 7336 1 7874 1 7880 1 7801 1 8539 1 6565 1 9644 1 7935 1 9170 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 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 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 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 0.42 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 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 1166.67 1133.33 1272.73 1624.45 1403 14 ii01 80 1302 08 1217 51 1137 96 1176 42 1124 88 1155 56 1184 80 1147 21 1204 66 1288.80 638.30 1409.86 1488.16 1262.95 1356.28 1281.74 1482.06 1258.96 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 97.08 100.00 95.45 112.66 126.01 109.46 105.00 113.36 115.28 109.17 102.76 101.39 107.84 96.14 116.10 107.05 104.68 121.97 107.89 113.39 112.12 110.79 114.80 97.61 1171 1173 2.31 2.41 0.5841 0.6720 25 28 27 88 1 5517 1 6114 67.17 66.86 1.0645 1.1758 46.08 48.79 0.020 0.028 0.86 1.16 25.18 27.19 1090.04 1128.22 2.09 2.28 90.48 94.60 1175 2.53 0.6517 25 76 1 7506 69.19 1.1055 43.70 0.012 0.47 26.00 .1027.67 2.21 87.35 _'_ 1176 2.33 0.6153 26 41 1 9358 83.08 0.9663 41.47 0.032 1.37 25.54 1096.14 2.56 109.87 1177 2.43 0.7824 32 20 2.2229 91.48 1.2319 50.70 0.015 0.62 34.48 1418.93 2.76 113.58 [/_ 1180 2.47 0.7608 30 80 1.9351 78.34 1.0538 42.66 0.025 1.01 28.35 1147.77 2.54 102.83 4_ .................................................................................................................................... OO WEIGHTS WERE RECORDED IN GRAMS (G) . ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Damaged during processing (weight not affected), bJ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 9) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT BRAIN KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW .................................................................................................................................... 1122 1123 1127 1129 1131 1132 1134 1135 1136 1139 1141 1142 1145 1147 1149 1151 1153 1154 1158 1159 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 2.40 2.11 2.78 2.67 2.49 2.63 2.35 2.41 2.48 2.24 2.16 2.02 2.17 2.50 2.78 2.55 2.71 2.57 2.92 96.25 i00.00 95.91 121.40 119.73 112.16 109.58 108.29 111.57 108.30 103.22 i00.00 99.02 93.13 105.93 115.35 108.51 121.52 112.72 130.36 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 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 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 0.83 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 1.02 0.80 0.75 0.83 0.95 0.59 0.95 0.75 0.72 0.56 0.94 0.65 0.69 0.86 0.77 0.91 0.93 1.01 0.86 1.08 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 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 20.42 12.08 12.73 31.44 26.46 16.67 27.50 15.21 21.30 10.48 15.67 22.22 8.82 11.59 12.71 30.29 23.40 30.04 21.49 19.64 1162 1164 1167 1168 2.31 2.41 2.23 2.51 2.71 2.62 2.56 2.43 117.32 108.71 114.80 96.81 0.027 0.035 0.029 0.029 1.17 1.45 1.30 1.16 0.027 0.030 0.031 0.029 1 17 1 24 1 39 1 16 0.78 0.80 1.17 0.94 33.77 33.20 52.47 37.45 0.35 0.44 0.73 0.40 15.15 18.26 32.74 15.94 1171 2.31 1.95 84.42 0.031 1.34 0.032 1 38 0.77 33.33 0.40 17.32 1173 2.41 2.37 98.34 0.028 1.16 0.033 1 37 0.73 30.29 0.51 21.16 1175 2.53 2.45 96.84 0.029 1.15 0.022 0 87 0.94 37.15 0.35. 13.83 1176 2.33 2.69 115.45 0.036 1.54 0.029 1.24 0.76 32.62 0.44 18.88 1177 2.43 2.79 114.81 0.034 1.40 0.030 1.23 0.89 36.62 0.36 14.81 [29 1180 2.47 2.51 101.62 0.036 1.46 0.037 1.50 1.05 42.51 0.40 16.19 _t_ .................................................................................................................................... O_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 10) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT NUMBER BRAIN WEIGHT EPIDIDYMIS LEFT ABS. REL. CAUDA EPIDIDYMIS LEFT ABS. REL. TESTIS LEFT ABS. REL. WT. % BRW WT. % BRW WT. .................................................................................................................................... % BRW L. TESTIS MINUS TUNICA ALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 1182 1184 1186 1188 1189 1192 1194 1195 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 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 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 26.34 32.02 31.13 31.14 32.05 31.28 32.00 30.02 30.54 25.89 31.94 31.31 29.33 29.59 29.93 26.48 29.70 30.04 27.80 25.92 33.72 29.09 29.00 25.93 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 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 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 75.52 83.25 72.80 77.86 76.27 80.84 79.52 77.41 81.77 70.30 76.44 78.26 78.05 76.14 78.71 76.21 74.29 77.97 77.24 77.17 98.42 73.47 71.33 70.47 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 69.86 77.26 67.34 72.64 64.58 68.76 74.41 72.93 76.02 65.56 72.14 73.32 71.94 71.51 74 59 69 27 64 83 72 84 70 92 70 09 87 65 66 58 65 90 64 21 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 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 00 103 11 95 12 96 36 71 10 1.0993 1.3573 0.7547 1.0218 0.9952 1.3117 1.1574 0.9382 1.1818 0.9225 1.0182 1.0792 1.0570 1.2076 1.1246 1.0642 1.0114 0.9204 1.1085 0.9655 1.1960 1.2959 1.0700 0.9698 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 1229 2.15 0.6796 31.61 0 3348 15.57 1.8306 85.14 1.6824 78 25 1.3942 64 85 0.8422 39.17 1232 2.22 0.6882 31.00 0 3264 14.70 1.9365 87.23 1.8148 81 75 1.8359 82 70 1.0507 47.33 1233 2.40 0.5594 23.31 0 2432 10.13 1.7079 71.16 1.5194 63 31 2.310A 96 27 1.3382 55.76 1236 2.23 0.6243 28.00 0 2962 13.28 1.7320 77.67 1.5580 69.86 1.6820 75 43 1.0255 45.99 1237 2.37 0.6220 26.24 0 2763 11.66 1.6722 70.56 1.5690 66.20 2.0813 87 82 0.9398 39.65 _J9 1240 2.32 0.8036 34.64 0.4063 17.51 2.0756 89.46 1.9055 82.13 2.5458 109 73 1.0793 46.52 "_ .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. IO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE Ii) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS TESTIS PROSTATE RAT BRAIN RIGHT RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW 1182 1184 1186 1188 1189 1192 2 23 2 30 2 16 2 20 2 40 2 22 0 6047 0 7559 0 6982 0 6993 0 7530 0 6947 27.12 32.86 32.32 31.79 31.38 31.29 1.6680 1.8710 1.6171 1.6425 1.8294 1.7973 74.80 81.35 74.86 74.66 76.22 80.96 0 3623 0 7091 0 8461 1 0337 1 2066 0 8355 16.25 30.83 39.17 46.99 50.28 37.64 0.005 0.015 0.013 0.008 0.014 0.009 0.22 0.65 0.60 0.36 0.58 0.40 25.00 30.64 20.80 27.64 32.61 30.76 1121.08 1332.17 962.96 1256.36 1358.75 1385.58 1.96 2.40 2.00 2.25 2.52 2.16 87.89 104.35 92.59 102.27 105.00 97.30 1194 2 22 0 7274 32.76 1.7765 80.02 1 2309 55.44 0.009 0.40 29.51 1329.28 2.32 104.50 1195 1198 2 16 2 36 0 6028 0 7218 27.91 30.58 1.6682 1.8638 77.23 78.97 1 0630 0 9586 49.21 40.62 0.012 0.014 0.56 0.59 26.56 35.89 1229.63 1520.76 2.25 2.65 104.17 112.29 1203 2 22 0 6076 27.37 1.6140 72.70 1 2275 55.29 0.010 0.45 26.54 1195.50 2.32 104.50 1204 2 30 0 7386 32.11 1.7777 77.29 1 1547 50.20 0.013 0.56 31.81 1383.04 2 56 111.30 1207 2 24 0 7052 31.48 1.6577 74.00 1 3065 58.32 0.012 0.54 24.11 1076.34 2.37 105.80 1209 2 22 0 6614 29.79 1.6149 72.74 1 2231 55.09 0.013 0.58 35.57 1602.25 2.23 100.45 1211 2 28 0 7154 31.38 1.7180 75.35 1 0513 46.11 0.012 0.53 27.46 1204.39 2.27 99.56 1212 2 44 0 7298 29.91 1.9154 78.50 1 3466 55.19 0.010 0.41 34.89 1429.92 2.49 102.05 1215 2 49 0 6595 26.48 1.9394 77.89 0 9439 37.91 0.014 0.56 30.79 1236.55 2.51 100.80 1216 2 30 0 6748 29.34 1.6544 71.93 1 4602 63.49 0.017 0.74 33.30 1447.83 1 98 86.09 1217 2 32 0 7102a 30.61 1.7837 76.88 1 3746 59.25 0.012 0.52 30.02 1293.96 2 17 93.53 1219 2 09 0 6257 29.94 1.6034 76.72 0 9941 47.56 0.018 0.86 27.85 1332.54 2 07 99.04 1221 2 21 0 6549 29.63 1.7229 77.96 0 9705 43.91 0.012 0.54 24.86 1124.89 1 94 87.78 1222 2 07 0 7082 34.21 1.9675 95.05 1 0687 51.63 0.013 0.63 31.71 1531.88 2 26 109.18 1224 2 39 0 7384 30.90 1.8250 76.36 1 0011 41.89 0 026 1.09 26.90 1125.52 2 42 101.26 1225 2 32 0 6937 29.90 1.6822 72.51 1 0253 44.19 0 026 1.12 31.17 1343.53 2 28 98.28 1226 2 44 0 6851 28.08 1.7896 73.34 1 1083 45.42 0 021 0.86 32.01 1311.88 2 58 105.74 1229 2 15 0 7064 32.86 1.8647 86.73 0 5994 27.88 0 013 0.60 22.60 1051.16 2 ii 98.14 1232 2 22 0 6704 30.20 1.8883 85.06 0 9128 41.12 0 015 0.68 26.98 1215.32 2 12 95.50 1233 1236 2 40 2 23 0 6843 0 6360 28.51 28.52 1.7895 1.7348 74.56 77.79 1 1748 1 1124 48.95 49.88 0 015 0 013 0.62 0.58 38.30 25.35 " 1595.83 1136.77 2 77 2 48 115.42 111.21 1237 2 37 0 6242 26.34 1.6814 70.94 0 8318 35.10 0 010 0.42 28.38 1197.47 2 00 84.39 C29 1240 2 32 0 7558 32.58 2.0720 89.31 1.2324 53.12 0 020 0.86 28.51 1228.88 2 53 109.05 _t_ .................................................................................................................................... OO WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Damaged during processing (weight not affected), t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 12) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT BRAIN KI DNEY RIGHT ADRENAL LEFT ADRENAL RIGHT NUMBER WEIGHT ABS. WT. REL. % BRW ABS . WT. REL. % BRW ABS. WT. REL. % BRW .................................................................................................................................... 1182 2 23 2 06 92.38 0.010 0.45 0.022 0.99 1184 1186 1188 1189 1192 1194 1195 2 30 2 16 2 20 2 40 2 22 2 22 2 16 2 30 1 81a 2 21 2 65 2 31 2 72 2 27 100.00 83.80 100.45 110.42 104.05 122.52 105.09 0.031 0.033 0.031 0.032 0.032 0.029 0.025 1.35 1.53 1.41 1.33 1.44 1.31 1.16 0.033 0.032 0.016 0.037 0.032 0.030 0.028 1.43 1.48 0.73 1.54 1.44 1.35 1.30 S PLEEN ABS . WT. REL. % BRW -0 67 0 72 0 69 0 78 0 85 0 92 0 81 0 76 30.04 31.30 31.94 35.45 35.42 41.44 36.49 35.18 THYMUS ABS. WT. REL. % ERW 0.35 0.39 0.27 0.56 0.35 0.73 0.30 0.37 15.70 16.96 12.50 25.45 14.58 32.88 13.51 17.13 1198 1203 1204 1207 1209 1211 1212 1215 1216 1217 1219 1221 1222 1224 1225 1226 1229 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 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 13 110.59 99.55 108.26 97.77 105.40 92.54 104.10 102.81 87.83 92.24 114.35 94.57 114.01 104.60 93.96 106.56 99.07 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 1.78 1.13 1.39 1.12 1.17 0.88 1.06 1.20 1.30 1.08 1.10 1.13 1.40 1.26 1.51 1.19 1.77 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 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 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 34.32 36.49 30.87 29.02 34.23 30.26 31.15 33.73 34.35 30.17 30.14 35.75 36.71 34.31 32.76 37.70 90.70 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 15.25 14.41 18.70 12.05 11.26 14.04 13.11 12.85 13.91 17.24 22.49 24.89 19.81 18.41 14.66 18.44 14.42 1232 1233 2 22 2 40 2 07d 2 85 93.24 118.75 0.026 0.036 1.17 1.50 0.026 0.038 1236 1237 2 23 2 37 2.44 2.02 109.42 85.23 0.028 0.026 1.26 1.10 0.024 0.021 1240 2 32 2.67 115.09 0.039 1.68 0.039 .............................................................................................................................. 1.17 1.58 1.08 0.89 1.68 0.82 1.04 0.88 0.65 0.70 36.94 43.33 39.46 27.43 30.17 0.39 0.55 0.360.27 0.24 17.57 22.92 16.14 11.39 10.34 _> [/) WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. OO Rat 1186 had moderate dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. Rat 1224 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses, t_ Rat 1229 had tan areas on the spleen analysis. that extended into the parenchyma; value included in group averages and statistical Rat 1232 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 13) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION M_ALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... EPIDIDYMIS CAUDA EPIDIDYMIS TESTIS RAT BRAIN LEFT LEFT LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... L. TESTIS MINUS TUNICAALBUGINEA ABS. REL. WT. % BRW SEMINAL WITH ABS. WT. VESICLES FLUID REL. % BRW SEMINAL WITHOUT ABS. WT. VESICLES FLUID REL. % BRW 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 1259 1261 1266 1269 1271 1273 1274 1278 1281 1282 1284 1287 1288 1289 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 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 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 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 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 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 71.98 80.43 80.26 83.68 81.17 85.51 67.12 87.55 76.05 86.26 91.60 77.64 78 71 83 92 73 69 71 82 80 71 83 26 73 79 91 18 78 26 73 81 65 26 79.20 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 63.25 74.42 75.14 77.57 76.55 80.42 63 77 82 62 70 28 81 98 84 95 72 49 72 88 78 32 66 12 64 86 74 46 78.45 66.24 84.33 72.48 67 53 59 11 73 44 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 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 77 87 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 45.62 68.29 49.39 45.76 64.03 51.22 45.86 41.18 28.86 48.80 52.73 41.26 35.18 41.43 33.66 43.62 35.26 43.17 44.23 36.20 39.94 36.20 44.61 44.63 1290 1291 2.27 2.35 0.6438 0.7084 28.36 30.14 0 2949 0 3777 12.99 16.07 1.8455 1.8660 81.30 79.40 1.6862 1.5842 74 28 67 41 1.6617 1.8949 73 20 80 63 0.8188 0.9639 36.07 41.02 1294 2.37 0.7602 32.08 0 3415 14.41 2.0868 88.05 1.8566 78 34 1.3983 59 00 0.7453 31.45 _'_ 1298 2.06 0.5738 27.85 0 2755 13.37 1.4615 70.95 1.3341 64 76 1.8111 87 92 0.8992 43.65 1300 2.18 0.7065 32.41 0 3154 14.47 1.6906 77.55 1.5934 73 09 1.9824 90 94 1.2279 56.32 [2_ .................................................................................................................................. ._ WEIGHTS WERE RECORDED IN GRAMS (G). - - ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. _O-_ rO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 14): BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS MALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT BRAIN EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW 1241 1244 1245 1247 1248 1249 1252 2.21 2.14 2.14 2.19 2.02 2.08 2.16 0.6533 0.6699 0.6880 0.6936 0.7177 0.7145 0.5818 29.56 31 30 32 15 31 67 35 53 34 35 26 94 1.6469 1.6944 1.7335 1.7629 1.7090 1.7860 1.3457 74.52 79.18 81.00 80.50 84.60 85.86 62.30 0.7133 0.4297 0.6958 1.0837 0.8798 0.8470 0.7562 32 28 20 08 32 51 49 48 43 55 40 72 35 01 PITUITARY ABS. WT. REL. % BRW 0.009 0.012 0.013 0.011 0.010 0.011 0.009 0.41 0.56 0.61 0.50 0.50 0.53 0.42 LIVER ABS. WT. REL. % BRW 33.90 37.00 35.80 30.46 23.36 22.66 29.14 1533.94 1728.97 1672.90 1390.87 1156.44 1089.42 1349 07 KIDNEY LEFT ABS. REL. WT. % BRW 2.30 2.60 2.60 1.85 1.90 1.94 1.78 104.07 121.50 121.50 84.47 94.06 93.27 82.41 1254 1255 2.00 2.29 0.6693 0.6530 33 46 28 52 1.8852 1.7597 94.26 76.84 0.9728 1.0766 48 64 47 01 0.009 0.010 0.45 0.44 24.07 32.45 1203 50 1417 03 1.91 2.13 95.50 93.01 1257 2.11 0.7350 34 83 1.8935 89.74 1.0167 48 18 0.013 0.62 29.80 1412 32 1.89 89.57 1259 1.95 0.7351 37 70 1.8626 95.52 1.1325 58 08 0.009 0.46 25.93 1329 74 1.90 97.44 1261 2.17 0.6319 29.12 1.7525 80.76 0.5891 27 15 0.011 0.51 24.08 1109 68 1.75 80.64 1266 2.09 0.6521 31 20 1.5782 75.51 1.1156 53 38 0.014 0.67 29.42 1407 66 1.90 90.91 1269 2.14 0.6597 30 83 1.7311 80.89 1.0011 46 78 0.005 0.23 32.70 1528.04 1.93 90.19 1271 2.70 0.6398 23 70 1.9298 71.47 1.0235 37 91 0.019 0.70 30.75 1138.89 2.21 81.85 1273 2.16 0.6096 28 22 1.5443 71.50 1.0554 48 86 0.021a 0.97a 27.46 1271.30 1.90 87.96 1274 2.27 0.6309 27 79 1.8951 83.48 1.0326 45 49 0.015 0.66 34.70 1528.63 2.29 100.88 1278 2.04 0.6590 32 30 1.7218 84.40 0.7614 37 32 0.024 1.18 26.59 1303.43 1.74 85.29 1281 2.08 0.6883 33 09 1.5678 75.38 0.7429 35 72 0.032 1.54 30.95 1487 98 2.10 100.96 1282 2.20 0.6620 30 09 2.0764 94.38 0.7483 34 01 0.010 0.45 29.72 1350 91 1.92 87.27 1284 2.25 0.6740 29.96 1.8308 81.37 1.0285 45 71 0.012 0.53 30.21 1342 67 2.16 96.00 1287 2.09 0.5821 27.85 1 5509 74.20 0.8656 41 42 0.010 0.48 26.56 1270 81 2.16 103.35 1288 2.22 0.5847 26.34 1 3930 62.75 0.8578 38 64 0.026 1.17 25.71 1158 11 1.96 88.29 1289 2.34 0.7166 30.62 2 0066 85.75 0.7964 34 03 0.010 0.43 33.07 1413 25 2.02 86.32 1290 1291 2.27 2.35 0.6780 0.7411 29.87 31.54 1 8514 1 8543 81.56 78.91 0.7592 0.7997 33 44 34 03 0.014 0.008 0.62 0.34 34.68 26.73 1527 75 1137 45 1.99 2.09 87.66 88.94 1294 2.37 0.7335 30.95 1 9582 82.62 0.9946 41 97 0.026 i.i0 33.81-1426 58 2.07 87.34 _'_ 1298 2.06 0.5936 28.82 1.4529 70.53 0.6132 29 77 0.011 0.53 27.51 1335 44 1.85 89.80 1300 2.18 0.7606 34.89 1.7792 81.61 0.9123 41 85 0.010 0.46 33.29 1527 06 2.06 94.50 .................................................................................................................................... ._ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. O0 Damaged during processing (weight affected); values excluded from group averages and statistical analyses. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D21 (PAGE 15) : BRAIN WEIGHTS, ORGAN WE.IGHTS AND RATIOS F1 GENERATION MALE RATS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT BRAIN KIDNEY RIGHT ADRENAL LEFT ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW 1241 1244 1245 1247 1248 1249 1252 1254 1255 1257 2.21 2.14 2.14 2.19 2.02 2.08 2.16 2.00 2.29 2.11 2.28 2.41 2.40 1.67 1.94 1.94 1.78 1.88 2.23 1.87 103.17 112.62 112.15 76.26 96.04 93.27 82.41 94.00 97.38 88.62 0.024 0.035 0.033 0.023 0.031 0.028 0.027 0.025 0.023 0.028 1 08 1 64 1 54 1 05 1 53 1 35 1 25 1 25 1 00 1 33 0.031 0.030 0.024 0.016 0.029 0.024 0.024 0.022 0.019 0.030 1.40 1.40 1.12 0.73 1.44 1.15 1.11 i. I0 0.83 1.42 0.65 0.64 0.85 0.95 0.60 0.63 0.73 0.67 0.67 0.62 29.41 29.91 39.72 43.38 29.70 30.29 33.80 33.50 29.26 29.38 0 28 0 18 0 73 0 20 0 53 0 28 0 34 0 24 0 31 0 26 12.67 8.41 34.11 9.13 26.24 13.46 15.74 12.00 13.54 12.32 1259 1261 1.95 2.17 1.79 1.93 91.79 88.94 0.023 0.021 1 18 0 97 0.016 0.025 0.82 1.15 0.69 0.59 35.38 27.19 0 22 0 21 11.28 9.68 1266 1269 2.09 2.14 2.00 2.12 95.69 99.06 0.030 0.022 1 44 1 03 0.028 0.023 1.34 1.07 0.78 0.89 37.32 41.59 0 30 0 55 14.35 25.70 1271 1273 2.70 2.16 2.50 1.86 92.59 86.11 0.038 0.033 1 41 1 53 0.037 0.029 1.37 1.34 0.69 0.75 25.56 34.72 0 51 0 47 18.89 21.76 1274 1278 1281 1282 1284 1287 2.27 2.04 2.08 2.20 2.25 2.09 2.35 1.81 2.04 2.01 1.99 2.06 103.52 88.72 98.08 91.36 88.44 98.56 0.020 0.031 0.030 0.036 0.034 0.020 0 88 1 52 1.44 1.64 1.51 0.96 0.022 0.026 0.030 0.038 0.032 0.020 0.97 1.27 1.44 1.73 1.42 0.96 0.84 0.84 0.91 0.78 0.65 0.67 37.00 41.18 43.75 35.45 28.89 32.06 0 68 0 34 0 52 0 73 0 46 0.40 29.96 16.67 25.00 33.18 20.44 19.14 1288 1289 2.22 2.34 2.12 1.97 95.50 84.19 0.028 0.019 1.26 0.81 0.022 0.015 0.99 0.64 0.84 0.71 37.84 30.34 0.31 0.39 13.96 16.67 1290 2.27 2.08 91.63 0.026 1.14 0.030 1291 2.35 2.05 87.23 0.023 0.98 0.024 1294 2.37 2.26a 95.36 0.039 1.64 0.035 1298 2.06 1.86 90.29 0.022 1.07 0.019 1300 2.18 1.99 91.28 0.026 1.19 0.024 .................................................................................................................................. 1.32 1.02 1.48 0.92 i.i0 0.81 0.72 1.14 0.52 0.78 35.68 30.64 48.10 25.2_ 35.78 0.43 0.27 0.44. 0.30 0.39 18.94 11.49 18.56 14.56 17.89 [/9 ._ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. OO Rat 1294 had slight dilation of the pelvis of the right kidney; value included in group averages and statistical analyses. bo O PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D22 (PAGE 1): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID (See footnotes at the end of this table.) COUNT - INDIVIDUAL DATA - F1 GENERATION MALE RATS ._.9_.A.gA.3._.._.?..._.........Y....._.g.Z.5.9..2..2.._..A......................................................................... RAT NUMBER MOTILE STATIC COUNT TOTAL SPERM SPERM SPERMATID SPERMATID N_.,B.ER..........M OT_ L.E...........P_RCE_NT ........._N.ONM_T_.LE!........._?,.UNT _ .........._ CgoUN.T__.........2_!!._ 1002 205 80 50 255 79 572.6 1003 220 85 40 260 60 480.6 1005 216 87 1007 198 95 31 247 53 497.8 11 209 157 1355.7 1011 224 85 40 264 115 982.2 1012 229 68 110 339 71 608.9 1013 217 75 71 288 65 586.8 1014 383 84 71 454 189 1525.9 1017 191 92 17 208 98 966.9 ........,_9..U_.L.._.........D._!.Y.,_ 26 42.3 69 118.2 44 79.8 35 68.9 49 95.6 47 81.8 50 95.9 65 107.1 39 67.4 .... 1021 226 84 1023 320 97 1026 253 90 1028 160 74 43 269 134 1113.2 44 75.5 I0 330 130 1126.2 43 78.8 29 282 107 770.0 30 47.3 56 216 104 889.3 45 80.4 1031 204 80 51 255 205 1825.8 34 59.0 1034 300 90 35 335 145 1277.6 41 79.4 1035 373 92 31 404 88 923.3 47 105.2 1040 197 87 29 226 200 2032.8 63 119.6 1041 183 86 31 214 162 1803.1 48 93.8 1043 424 91 42 466 386 3522.4 45 79.3 1045 370 86 60 430 160 1387.8 42 71.4 1047 314 89 40 354 143 1125.3 64 114.9 1048 256 74 89 345 238 2129.5 32 71.8 1050 336 78 96 432 195 1612.6 83 164.8 > 1051 244 86 39 283 129 980.5 33 52.6 _:_ 1052 295 78 85 380 92 690.5 37 . 60.2 1054 218 90 25 243 156 1181.6 59 94.7 1055 179 56 141 320 85 758.2 43 76.6 1058 202 70 88 290 88 904.6 32 61.2 OO 1059 175 81 40 215 71 699.3 36 64.9 1060 191 84 36 227 162 1498.1 34 68.6 b.) PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D22 (PAGE 2) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY (See footnotes at the end of this table.) AND SPERMATID COUNT - INDIVIDUAL DATA - F1 GENERATION MALE RATS ._9_._9__9_..!._..............._..._.L.P._.......................................................................................... RAT NUMBER MOTILE STATIC COUNT TOTAL SPERM SPERM SPERMAT ID SPERMATID -N_..9.E._........._.9_. _ 1061 189 1063 165 1066 171 1067 267 1069 193 1071 232 1073 342 1077 327 1078 203 ..........._._._ 76 77 75 78 67 78 80 76 87 ........_.N_._.T._I 61 48 57 77 94 66 83 104 30 .........-C.9..UN..T.._.........C.9..U__-_.........-D-_!!._ 250 105 854.9 213 109 955.5 228 40 418.9 344 80 801.9 287 109 1041.6 298 98 867.2 425 52 555.7 431 90 648.6 233 185 1344.9 ........._9.-U_-_d--.........._!._._ 28 49.7 57 94.1 16 28.0 31 62.0 22 38.5 48 91.9 58 90.5 58 101.6 42 73.0 .... 1081 337 94 20 357 188 1465.1 37 66.7 10823f 2193 3818 208 22491 1318 11593..87 264 3580.16 1086 348 90 40 388 75 879.4 34 64.8 1088 238 94 16 254 228 1871.6 38 71.3 1090 222 83 44 266 155 1455.7 36 68.3 1091 255 89 31 286 282 2708.3 46 98.4 1094 184 88 25 209 499 4438.7 54 107.2 1096 203 91 21 224 196 1724.4 61 112.7 1098 214 91 21 235 410 3067.8 68 111.9 1100 312 87 47 359 235 2055.0 55 103.5 1103 273 81 62 335 368 3159.7 60 111.8 1106 346 88 47 393 156 1635.6 40 81.4 1107 282 79 74 356 134 1261.8 26 52.1 1110 381 83 80 461 93 867.5 23 43.8 1112 318 1114 265 1116 624 1118 189 1120 167 75 108 426 98 823.6 61 104.4 90 28 293 104 949.3 27 42.9 89 79 703 74 733.3 21. 42.9 86 30 219 111 1085.5 30 54.7 84 33 200 123 1039.1 30 46.4 OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D22 (PAGE 3} : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY (See footnotes at the end of this table.) AND SPERMATID COUNT - INDIVIDUAL DATA - F1 GENERATION MALE RATS RAT NUMBER MOTILE STATIC COUNT TOTAL SPERM SPERM SPERMATID SPERMATID _N_..9_R"..........M OTI_ 1122 205 1123 198 1127 171 1129 186 1131 252 1132 244 1134 298 1135 292 1136 280 ...........PERCEN.L ........_N_ .N_.O_ILE_.........COUNT _ ..........._9..UN_T_ .........._!._ 93 15 220 30 250.1 78 55 253 76 740.7 80 42 213 125 1095.1 60 124 310 68 561.7 88 33 285 161 1300.5 86 41 285 123 1053.3 79 78 376 148 1274.9 87 44 336 256 2301.2 89 36 316 139 1180.5 ........._9..t_._ .........o_N_!o_._ 34 64.6 21 35.9 24 45.9 50 79.8 45 77.9 39 68.9 16 26.2 36 65.0 36 61.9 .... 1139 182 78 51 233 192 1696.4 68 125.8 1141 391 88 1142 298 85 53 444 54 352 74 603.7 29 57,4 89 871.8 43 81.2 1145 271 92 23 294 95 844.3 31 51.3 1147 183 85 32 215 194 1564.1 29 52.2 1149 204 89 25 229 144 1008.1 72 107.7 1151 271 94 17 288 407 3703.5 62 112.6 1153 236 92 21 257 214 1848.4 67 70.0 1154 232 88 31 263 209 2067.6 45 91.2 1158 395 90 46 441 104 994.8 55 103.1 1159 231 75 76 307 125 977.8 61 104.2 1162 294 81 67 361 104 970.1 40 74.3 1164 406 86 64 470 333 2666.1 44 71.6 1167 337 84 62 399 121 1076.3 33 63.3 1168 311 89 38 349 113 1126.0 33 59.0 1171 434 81 104 538 160 1594.3 21 43.2 > 1173 282 81 67 349 129 1140.1 35 71.0 1175 243 79 66 309 66 695.5 20 35.3 _'_ 1176 254 77 76 330 120 1212.5 27 43.0 1177 178 84 34 212 125 1034.9 41 56.4 i180 390 78 108 498 95 820.3 21 .............3.2...8 4__-- O0 t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D22 (PAGE 4) : CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY (See footnotes at the end of this table.) AND SPERMATID COUNT - INDIVIDUAL DATA - F1 GENERATION MALE RATS ..............m.............................................................................................................................................................. RAT NUMBER MOTILE STATIC COUNT TOTAL SPERM SPERM N_._9_R "..........M.OT_ LE ...........f_RCE.N_ ........_NONM_T_.LE !.........CO .UN___T..........._.O._UN.T_ ........._!!._o 1182 288 80 73 361 99 1063.8 1184 175 81 42 217 46 379.3 1186 188 85 34 222 189 1579.2 1188 206 87 31 237 72 634.0 1189 338 84 65 403 143 992.7 1192 239 72 92 331 110 1024.5 1194 286 89 34 320 88 747.8 1195 194 91 20 214 157 1434.9 1198 192 91 20 212 105 829.4 1203 181 83 37 218 148 1466.2 SPERMATID SPERMATID ........_9o.UN._T_.d.........DENS._!.Y._o .... 34 63.1 42 68.4 31 61.6 42 76.0 29 54.1 24 45.5 48 84.1 23 42.2 27 43.5 27 53.7 11220047 210900 6783 7923 229632 212446 11619968..28 3503 5923..33 1209 221 85 39 260 99 836.6 61 110.5 1211 233 78 67 300 123 1080.2 50 88.7 1212 194 90 22 216 213 1713.4 31 49.3 1215 189 87 28 217 238 2196.1 75 125.8 1216 252 95 14 266 233 1893.8 37 71.8 1217 294 83 60 354 205 1847.9 42 71.9 1219 338 80 87 425 108 1142.3 34 66.4 1221 229 83 48 277 290 2974.8 83 155.0 1222 263 71 108 371 103 889.7 63 100.4 1224 407 86 65 472 94 757.0 57 103.6 1225 319 75 104 423 184 1578.9 31 58.7 1226 299 77 90 389 94 907.3 25 46.2 1229 264 79 71 335 113 976.3 47 80.8 1232 341 92 30 371 165 1462.3 39 62.2 1233 292 90 33 325 40 475.8 17. 32.4 _'_ 1236 162 73 61 223 70 683.6 29 53.8 1237 340 89 44 384 116 1214.5 44 81.1 [/_ 4= .......1.2.4.0..............._.5_ ................8.1.................1.0.5.................5.5.9.................7.4.................5.2.6..9................3.0.................4.5...5................... _-_ OO PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D22 . (PAGE 5): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL (See footnotes at the end of this table.) DATA - F1 GENERATION MALE RATS ._.99..A?.9?-A!-Zv......................).A..._.P._.!................................................................................ RAT NUMBER MOTILE STATIC COUNT TOTAL SPERM SPERM SPERMATID SPERMATID .....N.U.M.B.E.R.............M.O.T.I.L.E..............P.E.R.C.E.N.T...........(.N.O.N.M.O.T.I.L.E.)...........C.O.U.N.T...a............C.O.U.N.T....b..........D.E.N.S.I.T.Y....c..........C.O.U.N.T...d...........D.E.N.S.I.T.Y...e.................. 1241 159 75 53 212 68 656.1 20 41.4 1244 330 77 97 427 60 552.4 37 67.2 1245 172 80 43 215 68 617.2 60 107.9 1247 287 84 55 342 104 900.7 39 66.4 1248 251 86 40 291 78 721.1 i0 18.7 1249 470 82 103 573 45 343.0 36 62.3 1252 289 60 196 485 52 476.3 56 117.6 1254 219 92 18 237 163 1325.6 38 66.5 1255 294 87 44 338 128 1186.8 57 102.4 1257 91 45 113 204 168 1370.9 51 85.3 1259 254 91 24 278 253 2068.0 29 50.6 1261 231 91 23 254 136 1329.5 37 68.0 1266 420 83 88 508 125 1171.7 26 49.4 1269 192 64 110 302 108 933.4 83 143.3 1271 209 95 12 221 82 814.3 80 129.6 1273 279 83 58 337 110 1158.3 32 66.1 1274 296 93 24 320 130 1131.3 50 85.6 1278 451 84 86 537 73 725.2 44 79.5 1281 310 85 54 364 279 2381.4 44 92.4 1282 256 66 130 386 67 660.3 53 82.6 1284 251 81 60 311 174 1635.8 43 76.3 1287 159 75 1288 167 83 54 213 100 989.3 53 108.6 34 201 61 649.2 23 50.7 1289 326 84 62 388 111 1066.4 34 57.2 > 1290 240 86 40 280 201 1971.6 44 75.5 1291 250 77 73 323 73 559.1 40 73.0 1294 240 71 98 338 147 1245.2 50. 77.9 1298 184 88 25 209 96 1008.0 21 45.5 1300 182 76 57 239 96 880.5 49 89.0 [_ ...................................................................................................................................................................................... ._ OO 6 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D22 (PAGE 6): CAUDA EPIDIDYMAL SPERM MOTILITY, COUNT, DENSITY AND SPERMATID COUNT - INDIVIDUAL DATA - F1 GENERATION MALE RATS FOOTNOTES: a. Sum of number motile and static count. 20 fields were evaluated. Groups of five fields were evaluated until a sperm count of at least 200 was achieved or b. Sperm count used in the calculation of sperm density. Ten fields were evaluated. c. The sperm density was calculated by dividing the sperm count by the volume in the image area (34.3 x 10 .6 mL), multiplying by 2 (dilution factor) and multiplying by 10 .6 to obtain the sperm concentration. The calculated sperm concentration value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left cauda epididymis (see Table D20 for the weight of the left cauda epididymis) to obtain from the Computer Automated Sperm Analysis because field causing a slight underestimate of the actual the sperm density. The calculated value will vary by approximately the digital image evaluated is slightly smaller (4 pixels) than the volume and an overestimate of the concentration. 0.8% actual d. Spermatld count used in the calculation of spermatid density. Ten fields were evaluated, e. The spermatid density was calculated by dividing the spermatid count by the volume in the image area (34.3 x 10 .6 mL), multiplying by 2 (dilution factor) and multiplying by 10 .6 to obtain the spermatid concentration. The calculated spermatid concentration minus tunica value (rounded to 1 decimal place) was multiplied by 50 (volume) and divided by the weight of the left testis albuginea (see Table D20 for the weight of the left testis minus tunica albuginea) to obtain the spermatid density. The calculated value will vary by approximately 0.8% from the Computer Automated Sperm Analysis because the digital image evaluated is slightly smaller (4 pixels) than the actual field causing a slight underestimate of the actual volume and an (_ overestimate of the concentration. f. Rat 1082 had less than 200 sperm per 20 fields; values excluded from group averages and statistical analyses. > O C O_ 4_ OO b-) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D23 (PAGE i): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT DETACHED NO BROKEN NO NUMBER NORMAL HEAD HEAD FLAGELLUM HOOK .................................................................................................................................... 1002 198 1 1 0 0 1003 196 1005 193 3 1 0 0 6 1 0 0 1007 195 1011 197 1012 196 1013 192 1014 195 1017 196 2 3 0 0 2 1 0 0 2 2 0 0 6 2 0 0 4 1 0 0 1 1 2 0 1021 194 1023 191 1026 197 1028 197 1031 196 1034 196 1035 195 1040 198 1041 193 1043 194 1045 196 1047 193 1048 193 1050 197 1051 198 1052 196 1054 193 3 1 2 0 5 2 2 0 1 1 1 0 2 0 1 0 2 1 1 0 3 0 1 0 3 1 1 0 1 0 1 0 5 2 0 0 4 2 0 0 2 0 2 0 4 2 1 0 4 3 0 0 2 1 0 0 2 0 0 0 1 2 1 0 5 2 0 0 1055 198 1058 195 I 0 0 0 2 3 0 0 1059 196 1060 195 1 3 0 0 2 3 0 0 .................................................................................................................................. COILED FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 BENT FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 10 20 35 25 15 20 40 25 20 30 45 15 15 20 20 25 10 35 30 20 35 35 15 10 20 35 10 25 20 25 > _'_ C_ 4_ O_ to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D23 (PAGE 2): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT NUMBER NORMAL DETACHED HEAD NO HEAD BROKEN FLAGELLUM NO HOOK .................................................................................................................................... 1061 194 1063 197 1066 195 1067 196 1069 198 2 4 0 0 2 1 0 0 3 2 0 0 3 1 0 0 2 0 0 0 1071 195 1073 193 1077 196 4 1 0 0 6 1 0 0 3 1 0 0 1078 1081 i082a 1083 1086 1088 1090 1091 1094 1096 1098 1100 1103 1106 1107 1110 1112 1114 191 193 0 196 190 196 197 194 196 196 196 195 191 197 198 190 199 199 5 3 0 1 5 2 0 0 0 0 1 0 3 0 0 1 6 4 0 0 3 1 0 0 2 1 0 0 3 3 0 0 4 0 0 0 3 1 0 0 3 1 0 0 5 0 0 0 6 3 0 0 1 2 0 0 2 0 0 0 7 3 0 0 1 0 0 0 1 0 0 0 1116 193 1118 197 4 2 1 2 1 0 1120 198 0 2 0 .................................................................................................................................... Rat 1082 had less than 200 sperm per 20 fields; values excluded 0 0 0 from COILED FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 group averages BENT FLAGELLUM 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 and statistical BENT FLAGELLUM TI P 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 analyses. PERCENT ABNORMAL 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 O0 b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS {SPONSOR'S STUDY NUMBER. PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE D23 (PAGE 3) : CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - F1 GENERATION MALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT DETACHED NO BROKEN NO NUMBER NORMAL HEAD HEAD FLAGELLUM HOOK .................................................................................................................................... 1122 193 1123 191 1127 193 1129 197 1131 196 1132 196 1134 195 1135 197 5 2 0 0 5 4 0 0 5 2 0 0 2 1 0 0 2 1 1 0 2 2 0 0 3 2 0 0 1 1 1 0 COILED FLAGELLUM 0 0 0 0 0 0 0 0 BENT FLAGELLUM 0 0 0 0 0 0 0 0 BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 3,5 4 5 3.5 1.5 2.0 2.0 2.5 1.5 11369 195 1141 194 1142 196 1145 194 1147 197 1149 195 1151 199 1153 190 1154 198 1158 193 1159 195 1162 196 1164 195 1167 196 1168 196 1171 195 1173 195 3 12 10 2 4 0 2 1 0 2 4 0 0 3 0 4 1 0 0 1 0 8 1 1 1 1 0 3 3 1 3 2 0 2 1 1 4 1 0 3 3 0 2 0 2 4 1 0 4 0 0 0 00 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 00 2.5 0 0 3.0 0 0 2.0 0 0 3 .0 0 0 1.5 0 0 2 .5 0 0 0.5 0 0 5.0 0 0 1.0 0 0 3 .5 0 0 2 .5 0 0 2 .0 0 0 2 .5 0 0 3.0 0 0 2.0 0 0 2 .5 0 0 2 .5 1175 193 6 0 1 0 0 0 0 3.5 > 1176 194 3 3 0 0 0 0 0 3.0 1177 192 4 2 1 0 1 0 0 4.0 1180 196 2 1 0 0 1 0 0 2.0 ...... _ ............................................................................................................................. _#_ 4= OO b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D23 (PAGE 4): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP IV .......................... 10 MG/KG/DAY .......................................................... ................................................ RAT DETACHED NO BROKEN NO NUMBER NORMAL HEAD HEAD FLAGELLUM HOOK .................................................................................................................................... 1182 196 1 1 2 0 1184 196 1186 195 2 1 1 0 4 0 1 0 1188 195 1189 196 2 1 2 0 2 2 0 0 1192 197 1194 198 3 0 0 0 2 0 0 0 1195 195 1198 197 3 2 0 0 1 1 0 1 COILED FLAGELLUM 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 PERCENT ABNORMAL 2.0 2.0 2.5 2.5 2.0 1.5 1.0 2.5 1.5 1203 193 1204 193 1207 196 1209 192 1211 194 1212 192 1215 194 1216 193 1217 196 1219 195 1221 199 1222 195 1224 193 1225 197 1226 197 1229 198 1232 198 4 3 0 6 1 0 4 0 0 8 0 0 3 3 0 7 1 0 4 2 0 5 1 1 3 1 0 4 1 0 1 0 0 3 0 1 4 3 0 2 1 0 2 1 0 1 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 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 3.5 0 0 3.5 0 0 2.0 0 0 4.0 0 0 3 .0 0 0 4.0 0 0 3.0 0 0 35 0 0 20 0 0 25 0 0 05 1 0 25 0 0 35 0 0 15 0 0 15 0 0 10 0 0 10 1233 198 1236 191 0 1 1 4 5 0 0 0 0 0 0 0 10 0 0 45 1237 197 2 1 0 0 0 0 0 15 C) 1240 193 3 3 1 0 0 0 0 35 .................................................................................................................................... 4_ OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE D23 (PAGE 5): CAUDA EPIDIDYMAL SPERM MORPHOLOGY - INDIVIDUAL DATA - F1 GENERATION MALE RATS .................................................................................................................................... DOSAGE GROUP V ............................... 30 MG/KG/DAY ...................................... ............................................................... RAT DETACHED NO BROKEN NO NUMBER NORMAL HEAD HEAD FLAGELLUM HOOK .................................................................................................................................... 1241 191 1244 197 1245 196 6 2 1 0 2 1 0 0 3 1 0 0 1247 193 1248 196 3 3 0 0 2 1 1 0 1249 197 1252 189 1254 195 1255 195 2 1 0 0 6 5 0 0 4 1 0 0 2 2 1 0 COILED FLAGELLUM 0 0 0 1 0 0 0 0 0 BENT FLAGELLUM 0 0 0 0 0 0 0 0 0 BENT FLAGELLUM TIP 0 0 0 0 0 0 0 0 0 1257 196 1259 197 1261 193 1266 196 1269 196 1271 198 1273 195 1274 194 1278 193 1281 192 1282 191 1284 196 1287 196 1288 194 1289 188 1290 192 1291 192 2 1 0 2 1 0 3 3 1 1 2 1 3 0 1 2 0 0 4 0 1 4 2 0 3 4 0 5 1 2 4 5 0 2 0 2 2 1 1 1 4 1 6 4 2 3 3 2 3 5 0 1294 197 1298 194 3 0 0 3 1 2 1300 191 5 3 0 ........................................................................................... 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 , ................................... PERCENT ABNORMAL 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 20 30 60 40 40 15 30 45 > _'_ 5_ 4_ OO to O ARGUS 418-020 APPENDIX E REPORT TABLES - F1 GENERATION FEMALE RATS Page 473 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E1 (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... PRECOI_KBITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION): MAXIMUM POSSIBLE FOUND DEAD INCIDENCE 3283/ 60 0 3306/ 60 2b,c 3310/ 60 ld 3281/ 60 le 3171/ 60a 6**f-k ABDOMINAL DISTENTION 47/ 6 56/ 7 29/ 4 39/ 5 72/ i0 URINE-STAINED ABDOMINAL FUR 8/ 2 48/ 5c 22/ 4d 14/ 4e 21/ 5f,g,J COLD TO TOUCH 0/ 0 i/ ib 0/ 0 I/ le 8/ 3f,g,j ANNULAR CONSTRICTION CHROMORHINORRHEA BALES OF THE TAIL 0/ 0 4/ 2 01 0 16/ 2 14/ 01 4b,c 0 0/ 0 17/ 7d 01 0 0/ 0 i/ 1 01 0 3/ 3 7/ 2f 21 2 TIP OF TAIL MISSING 0/ 0 61/ 2b 0/ 0 70/ 1 18/ 1 BACK OR HEAD: SCAB i/ i 0/ 0 0/ 0 9/ 1 6/ 1 LOCALIZED ALOPECIA: TOTAL 19/ 2 22/ 1 42/ 2 LIMBS NECK 41 1 01 0 221 1 01 0 HEAD 151 1 ol 0 .................................................................................................................................... 421 2 01 0 ol 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rats 1562 and 1563 did not have clinical observations recorded PER GROUP. on day 1 postweaning. b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweaning. f. Rat 1549 was found dead on day 8 postweaning, g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. J. Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. ** Significantly different from the Group I value (p_0.01). 18/ 2 151 1 31 1 ol 0 OBSERVATIONS. 5/ 1 51 1 01 0 ol 0 _> 4_ oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE E1 (PAGE 2) : CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION): MAXIMUM POSSIBLE INCIDENCE 3283/ 60 3306/ 60 3310/ 60 3281/ 60 3171/ 60a FOUND DEAD 0 2b, c ld le 6**f-k DECRE2LgED MOTOR ACTIVITY 0/ 0 7/ 2b,c 0/ 0 I/ le 2/ If EMACIATION TAIL BENT 4/ 1 0/ 0 16/ lc 0/ 0 2/ 2d 0/ 0 I/ 1 0/ 0 i/ Ig I/ 1 INCISORS: TOTAL MISALIGNED 4_ MISSING/BROKEN tn LACRIMATION 30/ 3 17/ 1 13/ 2 i/ 1 2/ 1 0/ 0 2/ 1 4/ 1 57/ 3 15/ 2 43/ 3 0/ 0 10/ 1 i0/ 1 0/ 0 i/ 1 0/ 0 0/ 0 0/ 0 0/ 0 RIGHT OR LEFT EYE: SWOLLEN 0/ 0 4/ 1 0/ 0 i/ 1 0/ 0 LABORED BREATHING 0/ 0 0/ 0 0/ 0 1/ le 0/ 0 SOFT OR LIQUID FECES CHROMODACRYORRHEA 0/ 0 5/ 2 I/ 1 i/ Ic 3/ 2 19/ 1 0/ 0 0/ 0 0/ 0 0/ 0 SWOLLEN EAR(S) 24/ 1 16/ 1 .................................................................................................................................... 3/ 1 0/ 0 STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rats 1562 and 1563 did not have clinical observations recorded b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweaning. f. Rat 1549 was found dead on day 8 postweaning. g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. J. Rat 1574 was found dead on day 3 postweanlng. k. Rat 1575 was found dead on day 3 postweaning. ** significantly different from the Group I value (p_0.01}. TO THE NUMBER PER GROUP. OF RATS on day 1 postweaning. WITH OBSERVATIONS. 0/ 0 > [/) 4_ OO I_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E1 (PAGE 3): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 i0 30 PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION): MAXIMUM POSSIBLE INCIDENCE 3283/ 60 3306/ 60 3310/ 60 3281/ 60 3171/ 60a FOUND DEAD 0 2b, c Id le 6**f-k DEHYDRATION 5/ 1 23/ 2c 0/ 0 0/ 0 0/ 0 HEAD: SWOLLEN 0/ 0 i/ 1 0/ 0 0/ 0 0/ 0 SNOUT: SWOLLEN 0/ 0 i/ 1 0/ 0 0/ 0 0/ 0 PTOSIS 20/ 2 0/ 0 0/ 0 0/ 0 0/ 0 4_ STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. -_ MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rats 1562 and 1563 did not have clinical observations recorded on day 1 postweaning. b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweaning. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweaning. f. Rat 1549 was found dead on day 8 postweaning. g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweaning. j. Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. ** Significantly different from the Group I value (p_0.01). > C 00 4_ OO _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION TABLE E1 (PAGE 4): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... PRESUMED GESTATION: a MAXIMUM POSSIBLE INCIDENCE MORTALITY 644/ 29 0 644/ 29 0 669/ 30 0 670/ 30 0 663/ 30 0 LOCALIZED ALOPECIA: LIMBS RIGHT AXILLA: MASS TIP OF TAIL MISSING 2/ 1 0/ 0 0/ 0 22/ 1 0/ 0 22/ 1 7/ 1 0/ 0 0/ 0 0/ 0 0/ 0 17/ 1 16/ 4 8/ 1 0/ 0 CHROMODACRYORRHEA SWOLLEN EAR(S} PTOSIS 0/ 0 65/ 4 22/ 1 0/ 0 23/ 2* 0/ 0 22/ 1 0/ 0"* 0/ 0 0/ 0 0/ 0.* 0/ 0 INCISORS: TOTAL MISALIGNED 29/ 2 29/ 2 0/ 0 0/ 0 MISSING/BROKEN 0/ 0 0/ 0 .................................................................................................................................... STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Restricted to rats with a confirmed mating date. * Significantly different from the Group I value (p_0.05). ** Significantly different from the Group I value (p_0.01). 28/ 2 0/ 0 28/ 2 3/ 1 3/ 1 0/ 0 OF RATS WITH OBSERVATIONS. 0/ 0 0/ 0"* 0/ 0 0/ 0 0/ 0 0/ 0 > C% oo _b PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E1 (PAGE 5): CLINICAL OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY } 0 1 3 10 30 .................................................................................................................................... LACTATION: MAXIMUM POSSIBLE INCIDENCE 616/ 28 616/ 28 616/ 28 616/ 28 638/ 29 MORTALITY 0 0 0 0 0 LOCALIZED ALOPECIA: LIMBS 22/ 1 22/ 1 81/ 4 33/ 2 72/ 4 RIGHT AXILLA: MASS 0/ 0 0/ 0 0/ 0 0/ 0 19/ 1 SWOLLEN EAR(S) 88/ 4 22/ 1 0/ 0 0/ 0 18/ 1 RED PERIVAGINAL SUBSTANCE 0/ 0 0/ 0 4/ 4"* 0/ 0 i/ 1 4_ SOFT OR LIQUID FECES O_ URINE-STAINED ABDOMINAL FUR 0/ 0 0/ 0 0/ 0 0/ 0 5/ 3 0/ 0 6/ 2 3/ 2 0/ 0 0/ 0 INCISORS: TOTAL MISSING/BROKEN MISALIGNED 42/ 2 19/ 1 29/ 2 0/ 0 0/ 0 0/ 0 44/ 2 44/ 2 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 CHROMODACRYORRHEA 0/ 0 0/ 0 22 / 1 0/ 0 0/ 0 TIP OF TAIL MISSING 0/ 0 22/ 1 0/ 0 22/ 1 0/ 0 PTOSIS .................................................................................................................................... 22/ 1 o/ 0 o/ o o/ o o/ o STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED TO THE NUMBER PER GROUP. OF RATS WITH OBSERVATIONS. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. ** Significantly different from the Group I value (p<0.01). - C 4= oo &_J PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E2 (PAGE 1): BODY WEIGHTS - PRECOHABITATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY} 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 60 60 60 60 58a BODY WEIGHT (G) DAY 1 MEAN+S.D. 41.4 + 6.8 39.2 + 6.3 42.9 + 8.7 43.3 + 7.3 39.2 + 7.9 DAY 8 DAY 15 MEANS.D. MEANfS.D. 71.7 + 9.9 111.3 + 13.0 66.8 + 8.5* [ 59]a 104.2 + 10.6"* 73.5 + 12.6 [ 59]a 112.7 + 13.7 72.1 + 11.5 [ 59]a 108.6 + 13.8 [ 59]a [ 59]a [ 59]a _D DAY 22 MEANfS.D. 148.9 + 14.2 142.9 + ii.i* 151.1 + 12.3 146.8 + 15.1 0_ [ 59]a [ 59]a [ 59]a [ 59]a 4_ DAY 29 MEANIS.D. 177.0 + 16.2 170.2 12.0" -_ [ 47]a [ 53]a .................................................................................................................................... 180.6 + 14.2 [ 51]a 175.0 + 14.8 [ 48]a DAY [] a. * ** = DAY POSTWEANING = NUMBER OF VALUES AVERAGED Excludes values for rats that Significantly different from Significantly different from were sacrificed the Group I value the Group I value following (p_0.05). (p_0.01). sexual maturation or found dead. 66.9 [ 102.8 + 9.9* 54]a + 13.2"* [ 54]a 139.4 + 13.4.* [ 54]a 167.9 + 16.0"* [ 45]a > C OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E2 (PAGE 2): BODY WEIGHTS - PRECOHABITATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 i0 .................................................................................................................................... RATS TESTED N 60 60 60 60 INCLUDED IN ANALYSES N 30a 30a 30a 30a BODY WEIGHT (G) DAY 36 MEANS.D. 199.9 + 15.7 193.5 + 19.7 203.8 + 15.3 198.5 + 18.1 DAY 43 MEAN+S.D. 219.8 + 18.4 212.5 + 24.6 225.6 + 13.2 219.3 + 18.4 DAY 50 MEAN+S.D. 237.1 + 19.2 228.3 29.6 243.5 + 14.7 236.0 + 18.0 PERFLUOROOCTANOATE V 30 60 30a 190.1 + 19.1 209.7 + 18.4 224.4 + 19.2" DAY 57 MEAN+S.D. 248.6 + 17.1 244.2 + 20.7 254.6 + 14.7 247.0 19.0 236.1 20.8* 4_ DAY 64 MEANS.D. 259.6 + 19.9 255.6 + 20.7 O0 [ 29] a O DAY 70b MEAN+S.D. 264.9 + 19.7 263.4 + 20.7 [ 29] a PRECOHAB - ITATION c MEAN+S.D. 276.7 + 22.9 278.1 + 23.6 [ 29]a .................................................................................................................................... 266.9 + 16.7 274.2 + 16.4 287.4 + 18.1 259.4 21.9 266.2 + 21.0 277.0 + 22.1 248.7 22.1 254.5 + 21.8 263.7 + 23.0* DAY = DAY POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. c. Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. * Significantly different from the Group I value (p<0.05). > OO O0 _:_ 00 _'_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION CONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E3 (PAGE 1).' BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 60 59a 59a 59a 54a BODY WEIGHT CHANGE (G) DAYS 1- 8 MEAN+S.D. +30.3 _ 4.6 +27.4 f 3.9** +30.4 5.6 +28.5 + 6.5 +26.6 f 4.2** DAYS 8 - 15 MEANtS.D. +39.6 _ 4.3 +37.4 f 3.8* +39.2 + 4.5 +36.5 + 5.3** +35.9 + 4.8** DAYS 15 - 22 MEANS.D. +37.6 t 5.2 +38.7 f 4.4 +38.4 f 6.0 DAYS 22 - 29 MEAN+S.D. [ 59] a +28.2 _ 5.4 +28.0 _ 5.9 [ 47]a [ 53]a .................................................................................................................................... DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation * Significantly ** Significantly different different from from the Group the Group I value I value (p_<0.05) . (p_<0.01). +28.7 6.7 [ 51]a or found dead. +38.2 + 5.5 +28.2 + 5.3 [ 48]a +36.5 + 4.9 +28.6 t 5.3 [ 45]a > C O0 6tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E3 (PAGE 2): BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 60 60 60 60 60 INCLUDED IN ANALYSES N 30a 30a 30a 30a 30a BODY WEIGHT CHANGE (G) DAYS 29 - 36 MEAN+S.D. +25.1 + 6.1 +23.3 + 9.8 +25.0 8.9 +23 9 4.2 +22.8 5.5 DAYS 36 - 43 MEAN+S.D. +19.9 + 7.9 +19.0 7.8 +21.8 8.4 +20 8 5.9 +19.6 4.7 DAYS 43 - 50 MEAN+S.D. +17.3 7.7 +15.8 7.9 +18.0 + 5.8 +16 6 + 4.5 +14.7 3.6 DAYS 50 - 57 MEANS.D. +11.5 7.6 +11.8[ 29+]a 6.5 4_ DAYS 57 - 64 MEANiS.D. +ii.0 5.9 +11.4 + 7.4 OO [ 29]a tO DAYS 64 - 70b MEAN+S.D. +5.3 i 4.7 +7.8 7.3 [ 29]a DAYS 1 - 70b MEANS.D. +223.3+ 18.0 +224.3 19.0 [ 29]a DAYS 1- PRECOHABITATION c MEANS.D. +235.2 20.9 +239.0+ 22.6 [ 29]a .................................................................................................................................... +ii.i 8.1 +12.3 5.2 +7.3 + 6.0 +231.31 18.8 +244.5 20.6 +ii 1 6.0 +12 4 + 5.7 +6 8 4.9 +222.6+ 17.5 +233.4 19.1 +11.7 + 5.3 +12.7 3.4 +5.8 5.0 +215.1+ 19.3 +224.3+ 21.0" DAY(S) = DAY(S) POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded. c. Precohabitatlon body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these > rats were 92 to 106 days of age. * Significantly different from the Group I value (p<_0.05). Oo tO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E4 (PAGE I): MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 10 .................................................................................................................................... RATS TESTED N 30 29 30 30 PERFLUOROOCTANOATE V 30 30 PREGNANT N 28 28 28 28 29 MATERNAL BODY WEIGHT (G) DAY 0 DAY 7 DAY i0 "3 DAY 14 MEANS.D. MEANS.D. MEANS.D. MEANS.D. 274.8 + 20.9 304.0 23.0 316.8 + 23.9 333.9 24.5 275.4 + 23.6 303.4 + 25.5 317.0 + 26.8 333.2 + 28.4 285.4 17.6 312.2 + 19.4 326.1 20.2 343.1 + 22.2 275.0 i 23.2 303.3 + 24.3 314.0 + 24.0 331.4 + 24.6 262.1 23.2* 287.4 22.6* 299.6 + 23.2* 316.1 25.4* 4_ DAY 18 00 MEANS.D. 380.2 + 29.6 380.8 + 31.6 394.8 + 27.7 380.6 + 28.9 366.6 + 28.9 DAY 21 MEANS.D. 417.9 + 33.0 418.0 + 32.9 427.8 + 31.3 415.1 31.1 399.2 + 34.8 [ 27]a [ 26]a [ 20]a [ 25]a .................................................................................................................................... [ 24]a DAY = DAY OF GESTATION [ ] -- NUMBER OF VALUES AVERAGED a. Excludes values for dams that delivered. * Significantly different from the Group I value (p<_0.05). > 4_ O0 t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE E5 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY - F1 GENERATION .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS TESTED N 30 29 III 3 30 PREGNANT N 28 28 28 MATERNAL BODY WEIGHT CHANGE (G) STUDY OF AMMONIUM FEMALE RATS IV 10 30 28 PERFLUOROOCTANOATE V 30 30 29 DAYS 0- 7 MEAN+S.D. +29.1 + 5.8 +28.0 7.0 DAYS 7 - 10 MEAN+S.D. +12.8 + 4.2 +13.6 + 6.7 DAYS i0 - 14 MEAN+S.D. +17.1 + 5.3 +16.2 + 6.1 DAYS 14 - 18 MEANiS.D. +46.2 11.5 +47.6 + 10.2 4_ O0 DAYS 18 - 21 MEAN+S.D. +37.6 + 9.2 +38.1 + 6.7 4_ [ 27]a [ 26]a DAYS 0 - 21 MEAN+S.D. +142.8 19.6 +143.6 17.9 [ 27]a [ 26]a .................................................................................................................................... DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for dams that delivered. +26.8 6.4 +13.9 4.4 +17.0 + 5.6 +51.7 10.3 +32.5 + 6.2 [ 20]a +141.5 18.2 [ 20]a +28.4 + 7.2 +10.6 3.8 +17.5 5.2 +49.2 11.6 +35.9 9.2 [ 25]a +141.2+ 16.8 [ 25]a +25.2 + 6.3 +12.2 + 3.8 +16.5 + 4.4 +50.6 10.6 +34.4 10.9 [ 24]a +138.4 20.5 [ 24]a > _n 4= o0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E6 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE [MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 29 III 3 30 IV V 10 30 30 30 PREGNAITY N 28 28 28 28 29 DELIVERED A LITTER N 28 28 28 28 29 MATERNAL BODY WEIGHT (G) DAY 1 MEANS.D. 313.6 24.6 314.8 25.8 325.5 23.1 313.2 + 23.4 302.0 + 24.2 DAY 5 MEANiS.D. 320.2 25.2 321.7 21.1 328.7 20.8 317.8 20.2 305.2 23.0* DAY 8 4_ DAY 11 OO t_ DAY 15 MEANiS.D. MEANiS.D. MEANS.D. 328.8 335.5 26.7 25.8 336.9 23.4 333.3 340.9 338.1 21.6 22.7 21.9 DAY 22 MEAN+S.D. 322.9 23.4 321.7 t 24.2 .................................................................................................................................... DAY = DAY OF LACTATION * Significantly different ** Significantly different from from the Group the Group I value I value (p<0.05). (p<0.01). 338.8 346.4 22.0 18.1 343.3 20.1 329.2 + 21.5 325.3 336.0 23.0 23.1 334.4 19.8 325.1 23.5 309.9 321.8 23.5** 24.7* 323.6 26.6* 315.7 20.9 > C _n oo 0 ('D 4_ O(_0% PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E7 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 30 29 III 3 30 IV V 10 30 30 30 PREGNANT N 28 28 28 28 29 DELIVERED A LITTER N 28 28 28 28 29 MATERNAL BODY WEIGHT CHANGE (G) DAYS 1 - 5 MEANfS.D. +6.6 + 9.8 +7.0 + 10.7 DAYS 5 - 8 MEAN+S.D. +8.5 + 9.2 +11.6 + 7.1 DAYS 8 - ii MEAN+S.D. +6.8 + 16.4 +7.6 + 8.8 DAYS 11 - 15 MEAN+S.D. +1.4 + 19 0 -2.8 + 13 . 4 DAYS 1 - 15 DAYS 15 - 22 MEAN+S.D. MEAN+S.D. +23.2 + 14.2 -14.0 + 15.3 +23.3 + 14.5 -16.4 + 13.1 DAYS 1 - 22 MEAN+S.D. +9.2 18.9 +6.9 + 14.8 .................................................................................................................................... DAYS = DAYS OF LACTATION +3.1 + 10.0 +10.2 + 8.1 +7.5 + 13.9 -3.0 + 13.3 +17.8 + 16.5 -14.1 + 16.0 +3.6 23.2 +4.7 + 8.9 +7.4 + 9.9 +10.7 + I0.i -1.6 + 14 .6 +21.2 17.8 -9.3 + 15.4 +11.9 22.4 +3 1 + 11.0 +4 7 + 10.8 +11 9 + 11.9 +1.9 16.5 +21 6 + 14.2 -8 0 + 17.6 +13 6 19.0 > 4_ Oo t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E8 (PAGE 1}: ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION ...... .............................................................................................................................. DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 - SUMMARY - F1 GENERATION FEMALE RATS III 3 60 IV V 10 30 60 60 INCLUDED IN ANALYSES N 60 59a 59a 59a 55a FEED CONSUMPTION (G/DAY) DAYS 1- 8 MEAN+S.D. i0.i 1.5 9.4 1.2,* i0.0 1.6 i0.0 f 1.7 9.0 1.4-* DAYS 8 - 15 DAYS 15 - 22 MEAN+S.D. MEAN+S.D. 16.4 + 2.0 19.0 + 1.9 15.0 + 18.4 + 1.5"* 1.4 16.2 + 1.9 19.1 + 2.0 15.8 + 1.8 18.8 + 2.0 14.7 + [ 54] a 18.0 + 1.5"* 2.0** DAYS 22 - 29 MEAN+S.D. 58]a,b 19.4 + 2.4 [ 57]h 19 0 + 2.2 57]b 19.9 + 2.7 19.6 + 2.5 [ 52]a,b 18.6 + 1.8 47]a 53]a,b 4_ DAYS 29 - 36 MEAN+S.D. 20.0 + 2.2 19. + 3.2 O0 30]a 30]a,b "_ DAYS 36 - 43 MEANS.D. 20.1 + 2.5 19.6 + 1.9 29]a,h 28]a,b DAYS 43 - 50 MEANS.D. 21.6 3.4 28]a,b 22.0 4.1 29]a,b DAYS 50 - 57 MEANS.D. 21.1 2.9 20.2 2.8 28]a,b 28]a,b DAYS 57 - 64 MEANiS.D. 20.6 + 2.8 19.9 + 2.6 29]a,b 28]a,b DAYS 64 - 70c MEANiS.D. 19.3 1.9 19.7 3.1 29]a,b 28]a,b DAYS 1 - 70c MEANS.D. 18.6 1.7 18.3 1.4 29]a,b 28]a,b .................................................................................................................................... 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. 3.4 28]a,b 19. 2.1 30]a 18. + 1.8 30]a [ 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,h 18.4 + 1.6 [ 29]a,b [ 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 DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Excludes values that were not recorded, as well as those associated with spillage, soiled or wet feed. c. Last weekly value recorded before cohabitation. ** Significantly different from the Group I value (p_<0.01). _t_ Oo to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E9 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 60 60 III 3 60 IV V I0 30 60 60 INCLUDED IN ANALYSES N 60 59a 59a 59a 55a FEED CONSUMPTION (G/KG/DAY) DAYS 1- 8 MEANS.D. 180.7 22.3 177.5 19.4 173.7 18.8 174.2 17.6 172.2 16.7 DAYS 8 - 15 MEANS.D. 180.6 + 16.1 176.3 16.5 DAYS 15 - 22 MEANS.D. 146.5 13.1 150.1 12.5 _I_ 58]a,b [ 57]b DAYS 22 - 29 MEANS.D. 119.5 11.6 121.9 15.5 47]a [ 53]a,b 4_ DAYS 29 - 36 MEANiS.D. 106.8 + 9.1 110.4 24.0 O0 30]a [ 30]a,b O0 DAYS 36 - 43 MEANS.D. 96.0 + 8.4 98.2 16.3 29]a,b [ 28]a,b DAYS 43 - 50 MEAN+S.D. 94.5 12.1 28]a,b 101.5 23.1 [ 29]a,b DAYS 50 - 57 MEANiS.D. 86.9 8.9 28]a,b 85.0 10.9 [ 28]a,b DAYS 57 - 64 MEANfS.D. 81.4 + 8.8 29]a,h 79.7 9.1 [ 28]a,b DAYS 64 - 70c MEANS.D. 73.4 + 5.6 29]a,b 76.2 + 13.3 [ 28]a,b DAYS 1 - 70c MEANS.D. 103.7 6.0 104.5 6.0 29]a,b [ 28]a,b .................................................................................................................................... 174.6 15 6 146.2 + 14 2 [ 57]b 120.1 + 13 8 [ 50]a,b 107.5 i 24 7 [ 30]a,b 96.2 12 2 [ 29]a,b 95.2 16 2 [ 29]a,b 82.0 80 [ 26]a,b 80.1 11.4 [ 28]a,b 73.1 6.2 [ 30]a 102.6 7.7 [ 30]a 176.9 17.3 148.1 17.4 121.5 + 15.0 46]a,b 103.1 + 7.1 29]a,b 96.6 9.4 30]a 99.6 + 23.5 26]a,b 86.6 14.3 27]a,b 80.6 11.6 26]a,b 74.5 7.4 29]a,b 103.0 7.3 29]a,b 174.2 149.3 14.1 54]a 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 10.6 27]a,b 79.2 13.2 28]a,b 76. 11.5 27]a,b 104. 9.5 27]a,b DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were sacrificed following sexual maturation or found dead. b. Excludes values that were not recorded, as well as those associated with spillage, soiled or wet feed. c. Last weekly value recorded before cohabitation. O0 4= Oo b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE El0 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY} - GESTATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 29 29 III 3 30 IV V i0 30 30 30 PREGNANT N 28 28 28 28 29 MATERNAL FEED CONSUMPTION (G/DAY) DAYS 0- 7 DAYS 7 - 10 DAYS I0 - 14 MEAN+S.D. MEAN+S.D. MEAN+S.D. 22.8 + 2.5 [ 27]a 24.2 + 3.8 [ 27]a 24.4 3.0 22.7 + 3.0 [ 25]a 24.1 + 3.6 23.7 + 3.3 22.2 + 2.7 [ 25]a 24.1 2.9 [ 27]a 24.2 + 2.9 22.3 + 2.3 [ 27]a 22.8 + 2.5 [ 27]a 23.4 + 2.1 DAYS 14 - 18 MEANS.D. 24.1 + 3.0 24.0 2.7 25.1 + 2.6 23.9 + 2.4 4_ O0 kC) DAYS 18 - 21 MEAN+S.D. 23.0 + 2.8 23.1 + [ 27]a DAYS 0 - 21 MEAN+S.D. 23.7 + 2.7 23.2 + [ 27]a .................................................................................................................................... DAYS = DAYS OF GESTATION [ ] = NUMBER OF VALUES AVERAGED 2.8 2.5 23.7 + 2.7 [ 25]a 23.7 + 2.4 [ 25]a 22.5 + 2.6 [ 27]a 23.0 + 1.9 [ 27]a a. Excludes values that were not recorded as well as those associated with spillage or wet feed. * Significantly different from the Group I value (p<_0.05). 21.0 f [ 27]a 22.0 + [ 28]a 22.8 + 2.6 2.7* 2.6 24.2 + 2.6 23.2 + 2.3 [ 26]a 22.4 + 2.2 [ 26]a > C 5_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE Ell (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) ..................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS TESTED N 29 29 PREGNANT N 28 28 MATERNAL FEED CONSUMPTION (G/KG/DAY) - GESTATION III 3 30 28 - SUMMARY - F1 GENERATION IV 10 30 28 FEMALE RATS V 30 30 29 DAYS DAYS 0- 7 7 - I0 DAYS I0 - 14 MEAN+S.D. NEANS.D. MEAN+S.D. 79.3 [ 78.3 [ + 27]a + 27]a 7.3 10.8 74.8 + 6.9 78.3 + 8.1 [ 25]a 77.6 7.6 72.7 + 6.5 74.3 7.9 [ 25]a 75.4 + 6.9 [ 27]a 72.3 + 6.6 76.9 + 7.9 [ 27]a 74.0 7.8 [ 27]a 72.7 6.1 76.6 + 9.8 [ 27]a 74.4 + 6.8 [ 28]a 74.2 + 7.7 DAYS 14 - 18 MEAN+S.D. 67.4 6.3 67.2 5.3 68.2 + 5.4 67.2 6.3 71.0 7.3 DAYS 18 - 21 MEANS.D. 57.8 6.4 58.4 6.8 58.3 f 7.0 56.7 + 7.5 61.1 + 5.9 O [ 27]a,b [ 26]a,b [ 20]a,b [ 25]a,b [ 24]a,b DAYS 0 - 21 MEANS.D. 70.0 6.0 68.8 5.0 68.0 5.8 68.8 5.8 70.3 6.5 [ 27]a,b [ 26]a,b .................................................................................................................................... DAYS = DAYS OF GESTATION [ 20]a,b [ 25]a,b [ 24]a,b [ ] = NUMBER OF VALUES AVERAGED a. Excludes b. Excludes values values that were not recorded as well as those for dams that delivered. associated with spillage or wet feed. > C 4_ OC 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE El2 (PAGE i): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - LACTATION - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 28 28 III 3 28 - F1 GENERATION IV i0 28 FEMALE RATS V 30 29 PREGNANT N 28 28 28 28 29 DELIVERED A LITTER N 28 28 28 28 29 MATERNAL FEED CONSUMPTION (G/DAY) DAYS DAYS 1- 5 5- 8 MEAN+S.D. MEANS.D. 30.3 + 6.8 | 27]a 48.1 + 8.3 30.6 5.9 48.5 + 7.0 28.6 + 4.2 [ 27]a 46.2 5.8 28.9 5.3 [ 26]a 46.7 8.7 29.2 _ 4.9 44.6 _ 6.7 DAYS 8 - II MEANS.D. 54.0 8.5 55.4 7.2 55.2 6.2 52.3 8.1 50.4 _ 7.7 [ 27]a DAYS ii - 15b MEANiS.D. 59.0 8.5 57.5 9.5 57.3 7.2 56.3 12.4 52.2 _ 9.5 _'_ [ 27] a DAYS 1 - 15b MEAN+S.D. 48.0 6.1 ! 27]a 47.4 5.3 46.5 + 4.4 46.0 f 6.7 43.6 5.5** .................................................................................................................................... DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were associated with spillage. b. Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 of lactation. feed after day 15 of lactation, maternal feed consumption values ** Significantly different from the Group I value (p<_0.01) . > O 4_ oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE El3 (PAGE 1) : MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY - F1 GENERATION FEMALE RATS ............................................................................................. DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS TESTED N 28 28 III 3 28 i ...................................... IV V i0 30 28 29 PREGNANT N 28 28 28 28 29 DELIVERED A LITTER N 28 28 28 28 29 MATERNAL FEED CONSUMPTION (G/KG/DAY) DAYS 1- 5 DAYS 5- 8 MEANS.D. MEAN_S.D. 95.7 + 18.4 [ 27]a 147.7 + 18.5 96.9 21.0 148.4 + 21.3 87.8 + 15.3 [ 27]a 138.5 + 15.9 92.6 + 18.7 [ 26]a 145.3 26.9 96.5 + 16.9 144.8 + 18.2 DAYS 8 - 11 MEAN+S.D. 162.7 + 23.8 164.6 + 21.0 161.5 21.1 158.7 + 26.1 159.5 + 21.8 4_ [ 27] a DAYS II - 15b MEANS.D. 174.7 22.6 169.1 + 25.3 166.2 f 19.3 168.2 + 37.1 161.7 + 25.9 [ 27] a DAYS 1 - 15b MEANS.D. 146.1 15.4 144.1 [ 27]a .................................................................................................................................... 16,5 138.5 15.0 141.9 21.8 139.7 _ 15.6 DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were associated with spillage. b. Because it is presumed that the pups begin to consume maternal were not tabulated on days 15 to 22 of lactation. feed after day 15 of lactation, maternal feed consumption values > O C O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE El4 (PAGE 1): SEXUAL MATURATION - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... FEMALE RATS N 60 60 60 60 60 INCLUDED IN ANALYSES N 60 58a,b 58a,b 58a,b 54a VAGINAL PATENCY c MEAN_S.D. 34.9 2.1 35.5 .................................................................................................................................... 2.3 34.1 2.6 34.8 a. Excludes values for rats that were found dead. b. Excludes values for rats in which testing was discontinued before the rat became sexually mature. c. Average day postpartum that the vagina was observed to be patent. ** Significantly different from the Group I value (p_0.01). 2.1 36.6 2.4** > C o0 t,o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E15 (PAGE I): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... ESTROUS CYCLING OBSERVATIONS III 3 - F1 GENERATION IV 10 FEMALE RATS V 30 PRECOHABITATION ESTROUS CYCLING RATS EVALUATED N 30 29a 30 30 30 ESTROUS 21 DAYS STAGES/ MEANS.D. 4.7 _ 0.9 5.0 _ 0.9 RATS WITH CONSECUTIVE 6 OR MORE DAYS OF DIESTRUS N 1 0 RATS WITH 6 OR MORE 4_ CONSECUTIVE DAYS OF ESTRUS N 0 0 4= ESTROUS STAGE AT SACRIFICE RATS EVALUATED N 30 29 DIESTRUS N 18 15 PROESTRUS N 2 I ESTRUS N 6 10 METESTRUS N 4 3 .................................................................................................................................... a. Excludes rat 1373, which was found dead prior to cohabitation. ** Significantly different from the Group I value (p_0.01). 5.0 _ 0,8 0 0 30 20 3 5 2 5.0 _ i.i 1 0 / 30 21 2 6 1 5.4 _ 0.7** 0 0 30 23 2 4 1 > C OC _b 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E15 (PAGE 2): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - SUMMARY .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS IN COHABITATION N 30 29a III 3 30 - F1 GENERATION IV i0 30 FEMALE RATS V 30 30 DAYS IN COHABITATION b MEAN+S.D. 3.0 + 2.4 3.0 + 1.1 2.4 + 1.2 2.7 + 1,6 2.5 + 1.2 RATS THAT MATED FERTILITY INDEX c RATS WITH CONFIRMED MATING DATES N(%) N/N (%) N 29(96.7) 28/ 29 (96.6) 29 29(I00.0) 28/ 29 (96.6) 29 30(100.0) 28/ 30 (93.3) 30 RATS MATING d 4_ DAYS i-7 N(%) 29(i00.0) 29{i00.0) 30(100.0) L_ RATS PREGNANT/RATS IN COHABITATION N/N 28/ 30 28/ 29 (%) (93.3) (96.6) .................................................................................................................................... 28/ 30 (93.3) a. Excludes rat 1373, which was found dead prior to cohabitation. b. Restricted to rats with a confirmed mating date and rats that did not mate. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date. 30(100.0) 28/ 30 (93.3) 30 30{i00.0) 28/ 30 (93.3) 30(100.0) 29/ 30 (96.7) 30 30(i00.0) 29/ 30 (96.7) > C _n 4= oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE E16 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS (See footnotes on the last page of this table.) STUDY OF AMMONIUM PERFLUOROOCTANOATE ...... .............................................................................................................................. DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS EXAMINED a N 60 60 III 3 60 IV V 10 30 60 60 FOUND DEAD INCLUDED IN ANALYSES N 0 N 60 2b, c 59 1 ld 60 le 60 6f-k 60 APPEARED NORMAL N 59 57b 59d 60e 59f-k LIVER: LEFT CUT LATERAL SURFACE LOBE, FIRM MASS REVEALED YELLOW AND DARK RED AREAS N 0 1 0 0 0 4_ CAUDATE LOBE ADHERED TO %O LEFT LATERAL LOBE N 0 1 0 0 0 0% KIDNEYS : BILATERAL, PELVIS, SLIGHT DILATION N 0 0 I 0 0 RIGHT, PELVIS, MODERATE DILATION N 0 0 0 0 1 URINARY WALLS BLADDER: THICKENED N 0 0 0 0 1 URETER: BILATERAL, MODERATE DILATION N 0 0 0 0 1 > ONE CALCULI LOCATED AT THE CAUDAL END N 0 0 0 -0 1 ............................................................................................ '_....................................... 4= oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE El6 (PAGE 2): NECROPSY OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... RATS EXAMINED a N 60 60 III 3 60 IV V 10 30 60 60 FOUND DEAD N 0 2b,c ld le 6f-k INCLUDED IN ANALYSES N 60 59 1 60 60 60 STOMACH: DISTENDED N 0 Ic 0 0 0 INTESTINES: DISTENDED N 0 ic 0 0 0 LUNGS : DORSAL SURFACE, RIGHT APICAL 4_ LOBE, DEPRESSED WHITE AREA N 0 _D "_ SPLEEN: Ic 0 SMALL N 1 0 0 .................................................................................................................................... 0 0 0 0 a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. b. Rat 1365 was found dead on day 4 postweaning. c. Rat 1373 was found dead on day 51 postweanlng. d. Rat 1432 was found dead on day 7 postweaning. e. Rat 1484 was found dead on day 3 postweanlng. f. Rat 1549 was found dead on day 8 postweaning. g. Rat 1559 was found dead on day 6 postweaning. h. Rat 1562 was found dead on day 2 postweaning. i. Rat 1563 was found dead on day 2 postweanlng. j. Rat 1574 was found dead on day 3 postweaning. k. Rat 1575 was found dead on day 3 postweaning. O i. Excludes rat 1362, which did not have necropsy observations recorded. C _n 4_ o0 t_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE El7 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 i0 30 .................................................................................................................................... RATS TESTED N 28 28 28 28 29 TERMINAL BODY WEIGHT MEAN+S.D. 322.9 + 23.4 321.7 24.2 329.2 + 21.5 325.1 + 23.5 315.7 + 20.9 PITUITARY MEAN+S.D. 0.017 + 0.004 0.016 + 0.003 0.015 0.003* 0.015 + 0.002* 0.015 0.003** BRAIN MEANS.D. 2.07 0.09 2.09 t 0.12 2.08 0.i0 2.10 0.12 2.07 0.i0 LIVER MEANtS.D. 16.57 1.58 15.96 1.76 16.41 1.40 16.68 1.70 16.78 1.36 KIDNEY LEFT ,_ KIDNEY RIGHT U%4 4_ ADRENAL LEFT O0 ADRENAL RIGHT MEANiS.D. MEANiS.D. MEANiS.D. MEAN+S.D. 1.36 , 0.13 1.38 + 0.12 0.043 + 0.008 0.040 0.007 1.39 0.14 1.41 0.14 0.044 0.007 0.041 + 0.007 1.41 0.09 [ 27] a 1.42 0.I0 0.044 0.006 0.041 + 0.006 1.38 0.14 1.42 + 0.16 0.046 + 0.006 0.042 + 0.006 1.34 0.18 1.40 0.20 0.045 0.008 0.041 0.006 SPLEEN MEANS.D. 0.60 f 0.07 0.61 0.12 0.60 + 0.06 0.59 0.09 0.60 0.11 THYMUS MEANiS.D. 0.20 0.06 0.19 0.05 0.21 0.07 0.20 0.08 0.22 0.09 OVARY LEFT MEANS.D. 0.050 0.012 0.054 0.012 0.051 0.012 0.049 t 0.010 0.052 0.013 OVARY RIGHT MEANS.D. 0.054 + 0.012 0.053 0.012 0.049 0.010 0.051 0.011 0.052 0.013 UTERUS NON-GRAVID MEANS.D. 0.54 0.16 0.56 0.16 .................................................................................................................................... 0.57 0.18 0.56 0.12 0.54 0.18 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes a value that appeared incorrectly recorded. > Significantly different from the Group I value (p_<0.05). * Significantly different from the Group I value (p<0.01}. C O_ 4= O0 t,J 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E18 (PAGE 1) : RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... RATS TESTED N 28 28 28 28 29 TERMINAL BODY WEIGHT MEANS.D. 322.9 f 23.4 321.7 24.2 329.2 + 21.5 325.1 + 23.5 315.7 + 20.9 PITUITARY a MEAN+S.D. 5.462 + 1.605 4.976 + 0.861 4.648 + 0.860* 4.715 + 0.898* 4.749 + 1.028" BRAIN MEANS.D. 0.644 f 0.058 0.653 + 0.054 0.632 0.045 0.648 0.063 0.659 + 0.044 LIVER KIDNEY LEFT KIDNEY RIGHT ADRENAL LEFT a %0 ADRENAL RIGHT a MEAN+S.D. MEANS.D. 5.130 f 0.305 0.421 + 0.038 MEAN+S.D. MEAN+S.D. MEANfS.D. 0.427 13.285 + 0.030 + 2.147 12.301 + 1.979 4.958 + 0.340 0.432 0.040 0.438 13.551 + 0.037 + 1.994 12.343 + 2.192 4.991 + 0.377 0.426 i 0.036 [ 27]b 0.432 13.581 + 0.034 + 2.048 12.600 1.834 5.136 f 0.409 0.426 + 0.038 0.435 14.046 f 0.046 1.831 12.881 + 1.981 5.326 0.455 0.426 + 0.055 0.444 14.209 + 0.058 2.762 13.191 + 2.177 SPLEEN MEANiSD. 0.184 + 0.021 0.189 0.041 0.184 0.019 0.183 + 0.027 0.191 0.034 THYMUS MEAN+S.D. 0.062 0.020 0.058 0.017 0.064 0.023 0.061 + 0.025 0.070 0.029 OVARY LEFT a MEANiS.D. 15.652 3.706 16.844 3.672 15.616 3.778 15.235 3.166 16.564 4.200 OVARY RIGHT a MEANfS.D. 16.754 4.015 16.742 4.266 14.955 + 3.246 15.235 + 3.016 16.496 4.132 UTERUS NON-GRAVID MEANS.D. 0.167 0.050 0.176 0.058 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was multiplied by 1000. b. Excludes a value that appeared incorrectly recorded. * Significantly different from the Group I value - (p<0.05). 0.175 0.059 0.173 + 0.044 RATIOS (%) = (ORGAN WEIGHT/TERMINAL 0.171 0.058 BODY WEIGHT) X i00. > C _n oo cb b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E19 (PAGE 1) : RATIOS (%} OF ORGAN WEIGHT TO BRAIN WEIGHT - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II III IV V DOSAGE (MG/KG/DAY) 0 1 3 I0 30 .................................................................................................................................... RATS TESTED N 28 28 28 28 29 BRAIN WEIGHT MEAN+S.D. 2.07 f 0.09 2.09 f 0.12 2.08 i 0.10 2.10 _ 0.12 2.07 + 0.10 PITUITARY MEAN+S.D. 0.84 f 0.21 0.76 + 0.14 0.74 0.14" 0.72 + 0.12" 0.72 0.16"* LIVER MEAN+S.D. 802.60 85.59 764.62 + 81.65 790.69 67.15 798.38 91.68 810.62 71.58 KIDNEY LEFT KIDNEY RIGHT MEANS.D. MEANfS.D. 65.77 f 6.04 66.76 6.09 66.51 6.49 67.36 5.83 67.59 + 5.25 [ 27] a 66.44 6.23 66.10 + 6.57 67.61 + 7.12 64.85 8.48 67.57 + 9.54 ADRENAL LEFT t21 ADRENAL RIGHT SPLEEN MEANS.D. MEANS.D. MEANS.D. 2.08 1.93 0.38 0.37 28.89 3.82 2.08 + 0.32 1.96 _ 0.34 29.10 5.58 2.14 + 2.00 + 0.30 0.29 29.08 2.59 2 18 2 00 28 35 + 0.30 0.32 4.31 2.16 0.39 2.00 0.30 29.28 + 5.67 THYMUS MEANiS.D. 9.65 2.74 9.10 + 2.84 10.23 3.44 9 69 4.04 10.69 + 4.48 OVARY LEFT MEANfS.D. 2.43 0.56 2.58 + 0.52 2.46 0.57 2 36 0.50 2.48 0.63 OVARY RIGHT MEANS.D. 2.60 0.59 2.56 0.58 2.37 0.52 2 44 0.54 2.50 0.62 UTERUS NON-GRAVID MEANS.D. 25.95 7.78 27.06 7.66 .................................................................................................................................... 27.58 8.91 26 76 6.12 26.02 + 8.40 ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Excludes a value that appeared incorrectly recorded. * Significantly different from the Group I value (p<_0.05). RATIOS (%) = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. ** Significantly different from the Group I value (p<0.01). ,-w _n 4_ oo t.J o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E20 (PAGE i): NATURAL DELIVERY OBSERVATIONS - SUMMARY - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY} 0 1 .................................................................................................................................... RATS ASSIGNED TO NATURAL DELIVERY N 28 28 III 3 28 IV V i0 30 28 29 PREGNANT N 28 28 28 28 29 DELIVERED A LITTER N(%) 28 (100.0) 28(i00.0) 28(i00.0) 28 (100.0) 29(i00.0) DURATION OF GESTATION a MEANfS.D. IMPLANTATION SITES PER DELIVERED LITTER N MEAN+S.D. 22.8 0.4 414 14.8 + 3,0 22.6 + 0.6 443 15.8 + 2.1 22.7 + 0.5 412 14.7 2.8 22.8 + 0.6 419 15.0 + 2,9 22.7 0.5 420 14.5 + 2.9 DAMS WITH STILLBORN PUPS N(%) DAMS WITH NO LIVEBORN PUPS N(%) O _-_ GESTATION INDEX b % N/N 3(10.7) 0( 0.0) 100.0 28/ 28 4(14.3) 0( 0.0) 100.0 28/ 28 3(i0.7) 0( 0.0) 100.0 28/ 28 5(18.5) 0( 0.0) 100.0 27/ 27 2( 7.1} 0( 0.0) 100.0 28/ 28 DAMS WITH DAYS 1-4 ALL PUPS POSTPARTUM DYING N(%) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) DAMS WITH ALL PUPS DYING DAYS 5-21 POSTPARTUM N(%) 0( 0.0) 0( 0.0) .................................................................................................................................... a. Calculated as the time (in days) elapsed between confirmed mating the first pup was delivered. b. Number of rats with live offspring/number of pregnant rats, 0( 0.0) (arbitrarily defined 0( 0.0) 0( 0.0) as day 0) and the time (in days) > 4_ OO PROTOCOL 418-020: ORAL (GAVAGE) NO-GENERATION (APFO) IN RATS (SPONSOR'S (ONE LITTER STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF A_ONIUM TABLE E21 (PAGE i) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUFHqARY - F2 GENERATION PUPS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... 3 i0 DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 28 28 28 PERFLUOROOCTANOATE V 30 29 PUPS DELIVERED (TOTAL) N MEANS.D. 386 13.8 2.9 388 13.8 + 2.5 394 14.1 f 3.0 385 13.8 _ 3.1 389 13.4 2.8 LIVEBORN MEAN+S.D. N(%) 13.6 + 2.9 380(98.4) 13.7 2.4 383( 98.7} 13.8 + 3.0 388(98.5) 13.5 _ 3.1 378(98.2) 13.3 2.8 387( 99.5} STILLBORN MEAN+S.D. N(%) 0.2 _ 0.5 5( 1.3) 0.2 + 0.5 5( 1.3) 0.2 + 0.6 6( 1.5) 0.2 _ 0.5 6( 1.6) 0.i + 0.2 2( 0.5) UNKNOWN VITAL STATUS N 1 La PUPS FOUND DEAD OR PRESUMED CANNIBALIZED O DAY 1 N/N (%) 0/380( 0.0) DAYS 2- 5 N/N (%) 2/380 ( 0.5) DAYS 6- 8 N/N (%) 0/378( 0.0) DAYS 9-15 N/N (%) 3/378{ 0.8) DAYS 16-22 N/N (%) 2/375( 0.5) 0 0/383( 5/383( 1/378( 2/377( 1/375( 0.0} 1.3) 0.3) 0.5} 0.3) 0 5/388( 5/383( 5/378( 0/373( 0/373( 1.3)** 1.3) 1.3) 0.0) 0.0) 1 4/378( 3/374( 1/371( 1/370( 1/369( 1.0)** 0.8) 0.3) 0.3) 0.3) 0 1/387( 3/386 ( 4/383( 0/379( 1/379 ( 0.2) 0.8) 1.0) 0.0} 0.3) VIABILITY INDEX a % N/N 99.5 378/380 98.7 378/383 97.4 378/388 98.1 371/378 99.0 383/387 LACTATION INDEX b % 98.7 98.9 N/N 373/378 374/378 .................................................................................................................................... 98.7 373/378 99.2 368/371 98.7 378/383 DAY(S) = DAY(S) POSTPARTUM a. Number of live pups on day b. Number of live pups on day 5 postpartum/number 22 postpartum/number of liveborn pups on day 1 postpartum. of live pups on day 5 postpartum. ** Significantly different from the Group I value (p_<0.01). o0 4_ OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E21 (PAGE 2): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... DOSAGE GROUP I II DOS;_GE _MG/KG/DAY ) 0 1 .................................................................................................................................... DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 28 III 3 28 IV V i0 30 28 29 SURVIVING PUPS/LITTER a DAY Ib MEAN+S.D. 13.6 + 2.9 13.7 + 2.4 13.8 _ 3.0 13.5 3.1 13.3 2.8 DAY 5 MEAIq_S.D. 13.5 2.8 13.5 + 2.3 13.5 f 2.9 13.2 3.0 13.2 2.8 DAY 8 MEAN+S.D. 13.5 + 2.8 13.5 + 2.3 13.3 _ 2.9 13.2 + 2.9 13.1 + 2.8 DAY 15 MEAN+S.D. DAY 22 MEAN+S.D. t_ O PERCENT MALE PUPS PER NUMBER OF PUPS SEXED 13.4 + 2.8 13.3 2.7 13.4 2.2 13.4 + 2.2 13.3 f 2.9 13.3 f 2.9 13.2 + 2.9 13.1 2.9 13.1 + 2.8 13.0 _ 2.7 DAY Ib MEAN+S.D. 50.2 + 11.8 51.9 11.2 51.5 f 13.1 55.6 15.7 47.3 + 13.5 DAY 5 MEAN+S.D. 49.9 12.0 52.2 11.5 51.7 13.7 55.6 15.1 47.3 f 13.5 DAY 8 MEAN+S.D. 49.9 + 12.0 52.1 + 11.5 52.1 _ 13.7 55.7 15.0 47.0 + 13.3 DAY 15 MEANS.D. 49.8 + 11.8 52.4 11.6 52.1 9: 13.7 55.8 15.0 47.0 13.3 DAY 22 MEAN+S.D. ............................................................................... 50.0 11.7 52.5 11.8 52.1 + 13.7 55.9 + 14.9 ..................................................... 47.1 13.3 DAY = DAY POSTPKRTUM a. Average number of live pups per litter, including litters with no surviving pups. > b. Includes pups born alive, found dead day 1 postpartum. O0 4_ O0 to PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E21 (PAGE 3): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... DOSAGE GROUP I II III IV DOSAGE (MG/KG/DAY) 0 1 3 10 .................................................................................................................................... DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS N 28 28 28 28 LIVE LITTER SIZE AT WEIGHING PERFLUOROOCTANOATE V 30 29 DAY 1 MEANfS.D. 13.6 2.9 13.7 2.4 13.7 2.9 13.4 3.0 13.3 + 2.8 DAY 5 MEANS.D. 13.5 2.8 13.5 2.3 13.5 2.9 13.2 3.0 13.2 2.8 DAY 8 MEAN+S.D. 13.5 + 2.8 13.5 + 2.3 13.3 2.9 13.2 + 2.9 13.1 2.8 _I_ DAY 15 MEANS.D. 13.4 2.8 13.4 + 2.2 13.3 _ 2.9 13.2 2.9 13.1 + 2.8 DAY 22 tm MEANS.D. PUP WEIGHT/LITTER (GRAMS) DAY 1 MEANS.D. 13.3 2.7 6.5 0.5 13.4 + 2.2 6.3 0.5 13.3 2.9 6.4 0.7 13.1 2.9 6.4 0.7 13.0 2.7 6.0 0.5 DAY 5 MEANiS.D. 10.2 1.2 10.0 1.2 10.1 1.6 10.2 1.5 9.6 1.2 DAY 8 MEANS.D. 14.5 2.1 14.4 1.8 14.3 2.3 14.3 + 2.3 13.5 2.0 DAY 15 MEANS.D. 25.4 4.1 25.3 3.4 25.8 4.4 24.8 3.7 23.2 3.7 DAY 22 MEANS.D. 38.7 7.1 38.9 .................................................................................................................................... DAY -- DAY POSTPARTUM 5.4 39.6 7.1 39.1 6.6 36.5 6.7 > U9 4= O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NL94BER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E22 (PAGE 1): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II MATERNAL DOSAGE (MG/KG/DAY) 0 1 LITTERS EXAMINED (N) 28 28 .................................................................................................................................... III 3 28 IV V i0 30 28 29 TRANSIENT CLINICAL OBSERVATIONS: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS COLD TO TOUCH 2/ i 5/ i i/ 1 i/ i 3/ 3 TAIL: ABRASION 0/ 0 0/ 0 0/ 0 0/ 0 i0/ 2 NO TAIL PRESENT 0/ 0 0/ 0 0/ 0 0/ 0 22/ 1 TIP OF TAIL MISSING 0/ 0 0/ 0 0/ 0 0/ 0 12/ 1 "3 TAIL: SCAB MOUTH: M_S tn o BACK: ABRASION 0/ 0 01 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 01 0 0/ 0 0/ 0 01 0 0/ 0 9/ 1 8/ 1 7/ 1 BACK: SCAB 0/ 0 0/ 0 0/ 0 0/ 0 4/ 1 PALE IN APPEARANCE 0/ 0 0/ 0 0/ 0 0/ 0 3/ 1 BASE OF TAIL: ABRASION 0/ 0 0/ 0 0/ 0 0/ 0 3/ 1 TIP OF TAIL BLACK 0/ 0 0/ 0 0/ 0 0/ 0 2/ 1 EMACIATION i/ 1 0/ 0 0/ 0 I/ 1 I/ 1 DOMED HEAD DEHYDRATION 0/ 0 _4/ ] 0/ 0 1/ 1 0/ 0 o/ o 0/ 0 2/ 2 i/ 1 o/ o TAIL BENT 0/ ............................................................................................. N/N = TOTAL FREQUENCY (DAYS x PUPS)/LITTERS WITH a. Tabulation restricted to adverse observations; 0 OBSERVATIONS. all other 0/ 0 pups appeared 0/ 0 normal. 22/ 1 0/ 0 '....................................... > __4_ Oo tO o t2_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO} IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E22 (PAGE 2): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY) LITTERS EXAMINED (N) ......................................................... I II III IV V 0 1 3 10 30 28 28 28 28 29 J .......................................................................... TRANSIENT CLINICAL OBSERVATIONS: a TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS RIGHT EYE: NOT PRESENT 0/ 0 0/ 0 0/ 0 3/ 1 0/ 0 THREAD- LIKE TAIL 0/ 0 22/ 1 0/ 0 0/ 0 0/ 0 NO ANAL OPENING PRESENT UNGROOMED COAT 0/ 0 16/ 1 I/ 1 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0 NO MILK PRESENT IN STOMACH I/ i o/ o .................................................................................................................................... N/N = TOTAL FREQUENCY (DAYS x PUPS)/LITTERS WITH OBSERVATIONS. a. Tabulation restricted to adverse observations; all other pups appeared o/ o normal. o/ o o/ o cb 0 t_ _._ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E23 (PAGE I): NECROPSY OBSERVATIONS - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II MATERNAL DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... LITTERS EXAMINED N 28 28 TOTAL PUPS STILLBORN OR FOUND DEAD a 3 6 STILLBORN N 1 3 FOUND DEAD N 2 3 NO MILK IN STOMACH b N(%) 1(50.0) 3(100.0) .................................................................................................................................... PUPS SACRIFICED AND NECROPSIED ON DAY 22 POSTPARTUM LITTERS EVALUATED PUPS EVALUATED N 28 N 168 28 168 REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE III 3 28 10 4 6 5( 83.3) 28 167 IV 10 28 10 6 4 3( 75.0) 28 164 V 30 29 6 2 4 3(75.0) 29 170 APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE KIDNEYS: PELVIS SLIGHT OR MODERATE DILATION LITTER INCIDENCE PUP INCIDENCE N(%) N(%) N(%) N(%) 27(96.4) 167(99.4) i( 3.6) i( 0.6) 27(96.4) 167(99.4) 1 3.6) i 0.6) BRAIN : THIRD AND LATERAL VENTRICLES, MARKED DILATION LITTER INCIDENCE N(%) 0( 0.0) 0 PUP INCIDENCE N(%) 0( 0.0) 0 .................................................................................................................................... a. Restricted to pups in which complete necropsles were performed. autolysis or cannibalization precluded evaluation. b. Analysis restricted to pups found dead and necropsied. 0.0) 0.0) Complete 26(92.8) 165(98.8) 2( 7.1) 2( 1.2) 27(96.4) 163(99.4) 0( 0.0) 0( 0.0) 29(100.0) 170(100.0) 0( 0.0) 0( 0.0) 0( 0.0) 0( 0.0) i( 3.6) i( 0.6) 0( 0.0) 0( 0.0) necropsies were not performed on pups in which 4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E24 (PAGE I) : PUP ORGAN WEIGHTS - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II MATERNAL DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... LITTERS EXAMINED N 28 28 TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D. 39.10 + 7.23 39.02 + 5.91 MALE PUPS MEAN + 7.43 39.73 + 6.39 FEMALE PUPS MEAN+S.D. 38.38 + 7.37 [ 27]a 38.30 + 5.98 REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE III 3 28 39.70 + 7.51 [ 27] a 39.95 + 8.48 [ 27]a 39.46 + 7.19 [ 27]a IV 10 28 40.06 + 6.88 41.15 + 6.82 38.24 + 6.47 [ 27]b V 30 29 37.02 + 6.63 [ 28] a 37.60 + 7.28 [ 28]a 36.44 + 6.35 [ 28]a BRAIN WEIGHT/LITTER ta O MJiLE PUPS O0 FEMALE PUPS SPLEEN WEIGHT/LITTER F5%_LE PUPS FEMALE PUPS MEAN+S.D. MEAN+S.D. ...... MEAN+S.D. 1.49 + 1.50 + 0,i0 0.15 1,48 + 0.11 MEAN+_S.D. MEAN+S.D. MEAN+S.D. 0.15 + 0.04 0.14 + 0.04 0.15 + 0.05 1.47 0.08 1.50 + 0.09 1.44 + 0.09 0.14 + 0.04 0.14 + 0.04 0.15 + 0.04 1.48 + 1.50 + 0.ii 0.12 1.45 + 0.11 0.14 + 0.04 0.14 + 0.05 0.14 + 0.04 1.48 + 1.50 + 0.07 0.07 1.46 + 0.10 t 27]b 0.15 + 0.15 + 0.04 0.04 0.14 + 0.04 [ 27]b 1.44 + 1.46 + 0.08 0.08 1.42 + 0.10 0.14 _+ 0.05 0.14 + 0.06 0.13 + 0.05 THYMUS WEIGHT/LITTER MEAN + 0.06 0.17 + 0.04 0.i6 + 0.05 0.17 * 0.04 0.16 + 0.05 \ 0.18 MALE PUPS MEAN+S.D. 0.19 + 0.06 0.16 + 0.05 0.16 + 0.06 0.17 + 0.05 0.16 + 0.06 [2_ .... r2_b - FEMALE PUPS MEAN+S.D. 0.18 + 0.06 0.17 + 0.04 0.17 + 0.06 0.17 + 0.04 0.16 + 0.05 OO .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). [ ] = NIR4BER OF VALUES AVERAGED a, Excludes values for pups in which the terminal body weight could incorrectly recorded. b. Excludes values for litter(s) that had no female pups examined. not be determined because pup identification appeared PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E24 (PAGE 2): PUP ORGAN WEIGHTS - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II III IV V MATERNAL DOSAGE (MG/KG/DAY) 0 1 3 10 30 .................................................................................................................................... LITTERS EXAMINED N 28 28 28 28 29 INCLUDED IN ANALYSES N 28 28 27a 28 28a RATIOS (%) OF BRAIN TO TERMINAL BODY WEIGHT WEIGHT/LITTER MEAN+S.D. 3.92 + 0.65 3.83 + 0.44 3.83 + 0,54 3.80 + 0.55 3.98 + 0.56 MALE PUPS MEAN+S.D. 3.86 + 0.69 3.83 + 0.46 3.89 + 0.70 3,73 + 0.50 3.98 + 0.57 FEMALE PUPS MEAN+S.D. 3,97 + 0.72 f 27]a RATIOS (%) OF SPLEEN TO TERMINAL BODY WEIGHT tm WEIGHT/LITTER MEAN+S.D. 0.38 + 0.07 MALE PUPS MEAN+S.D. 0.36 + 0.08 3.82 + 0.48 0.36 + 0,34 + 0.06 0.08 3.77 + 0.50 0.35 + 0.34 + 0.06 0.08 3.92 [ 27]h 0.36 + 0.36 + 0.06 0.07 3.99 + 0.59 0.37 + 0.09 0.37 + 0.10 FEMALE PUPS MEAN+S.D. 0.39 + 0.09 [ 27]a 0.39 + 0.07 0.36 + 0.06 0.36 + 0.07 [ 27]b 0.37 + 0.10 RATIOS (%) OF THYMUS TO TERMINAL BODY WEIGHT WEIGHT/LITTER MALE PUPS MEAN+S.D. MEAN+S.D. 0.47 + 0.11 0.46 + 0.ii 0,42 + 0.07 0.41 + 0.I0 0.40 + 0.08 0.40 + 0.09 0.44 + 0.08 0.42 + 0.I0 0.42 + 0.09 0.42 + 0.i0 FEMALE PUPS MEAN+S.D. 0.47 + 0.11 0.43 + 0.06 0.41 + 0.09 0.45 + 0.09 0.43 + 0.10 [ 27]a [ 27]h > ..................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS [ ] = NUMBER OF VALUES AVERAGED (G). RATIOS (%) = (ORGAN WEIGHT/T_RMINAL BODY WEIGHT) X 100. a. Excludes values for pups in which the terminal body weight could not be determined because pup identification appeared incorrectly recorded. b. Excludes values for lltter(s) that had no female pups examined. Oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E24 (PAGE 3) : PUP ORGAN WEIGHTS - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I II MATERNAL DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... LITTERS EXAMINED N 28 28 RATIOS (%) OF SPLEEN TO BRAIN WEIGHT WEIGHT/LITTER MEAN+S.D. 9.93 + 2.44 9.70 + 2.39 MALE PUPS MEAN+S.D. 9.66 + 2,62 9.04 FEMALE PUPS MEAN+S.D. 10.19 + 2.95 10.36 + 2.54 REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE III 3 28 9.44 + 2.38 9.06 + 2.72 9.82 + 2.38 IV I0 28 9.81 + 2.51 9.97 + 2.67 9.55 + 2.78 [ 27] b V 30 29 9.46 + 3,18 9.46 + 3.42 9,44 + 3,31 RATIOS (%) OF THYMUS TO BRAIN WEIGHT WEIGHT/LITTER ta _-" MALE PUPS MEAN+S.D. MEAN+S.D. 12.34 + 12.41 + 3.30 3.62 11.27 + 10,98 + 2.52 3.22 10.94 + 3.02 10.53 + 3.32 11.75 _+ 2.76 11.51 + 3.22 10.97 + 3.41 11.05 + 3.95 FEMALE PUPS MEAN+S.D. 12.28 + 3,64 11.57 + 2.40 .................................................................................................................................... ALL [] a. b. WEIGHTS WERE RECORDED IN GRAMS (G). = NUMBER OF VALUES AVERAGED Excludes values for pups in which the terminal body weight could incorrectly recorded. Excludes values for litter(s) that had no female pups examined. not 11.34 + 3.21 RATIOS (%) = (ORGAN be determined because 11.96 + 3.05 [ 27] b WEIGHT/BRAIN WEIGHT) pup identification 10.90 X 100. appeared 3.38 > O _n 4_ oo 10 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E25 (PAGE i): ANOGENITAL DISTANCE - SUMMARY - F2 GENERATION PUPS .................................................................................................................................... DOSAGE GROUP I II DOSAGE (MG/KG/DAY) 0 1 .................................................................................................................................... LITTERS WITH ONE OR MORE LIVE PUPS N 28 28 DAY 1 POSTPARTUM : ANOGENITAL DISTANCE (MM) DISTANCE/ LITTER MEAN+S.D. 1.83 + 0.20 1.86 f 0.19 MALE PUPS MEAN+S.D. 2.59 0.17 2.58 + 0.17 REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE III 3 28 IV V 10 30 28 29 1.87 + 0.22 2.60 + 0.20 1.96 _ 0.41 2.64 + 0.26 1.83 + 0.24 2.63 + 0.17 FEMALE PUPS MEANS.D. DAY 22 POSTPARTUM. tn _-_ ANOGENITAL DISTANCE (MM) 1.07 + 0.06 1.08 f 0.i0 i.i0 0.08 1.08 0.08 [ 27] a 1.12 + 0.I0 DISTANCE/ LITTER MEANS.D. 11.06 0.92 11.26 + 1.04 MALE PUPS MEAN+S.D. 13.90 i. I0 13.95 + i. I0 FEMALE PUPS MEAN+S.D. 8.24 0.78 8.28 0.60 .................................................................................................................................... [ ] = NUMBER OF VALUES AVERAGED a. Litter 1524 had no female pups. b. Excludes litter 1474, which did not have anogenital distances recorded ii.01 + 1.26 [ 27]b 13.58 1.26 [ 27] b 8.33 0.86 [ 27]b on da 7 22 postpartum. 11.31 + 1.70 13.70 1.44 8.10 0.74 [ 27]a 10.55 1.46 13.31 1.34 8.02 0.85 > O C 4= OO to PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM E26 (PAGE 1): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1301 NO ADVERSE FINDINGS 1302 NO ADVERSE FINDINGS 1303 NO ADVERSE FINDINGS 1304 NO ADVERSE FINDINGS 1305 NO ADVERSE FINDINGS 1306 NO ADVERSE FINDINGS 1307 NO ADVERSE FINDINGS 1308 DP( 62- 65) LOCALIZED ALOPECIA: LIMBS DG( 19- 20) LOCALIZED ALOPECIA: LIMBS DL( 1- 22) LOCALIZED ALOPECIA: LIMBS a 1309 NO ADVERSE FINDINGS 1310 1311 1312 1313 1314 1315 1316 1317 1318 19779 19780 DG( 16- 22) DL( i- 22) DP( 61- 68) DP 24- 25) DP 24- 28} DP 25- 28) DP 26- 28) DP 27 ) DP 27- 28) NO ADVERSE NO ADVERSE INCISORS: FINDINGS FINDINGS MISALIGNED INCISORS: MISALIGNED a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: NO ADVERSE MISSING/BROKEN FINDINGS CHROMORHINORRHEA DEHYDRATION a EMACIATION a URINE-STAINED ABDOMINAL FUR LACRIMATION PTOSIS DP 28 } CHROMODACRYORRHEA a 1321 DP 41- 55) LOCALIZED ALOPECIA: HEAD 1322 DP 27 ) HEAD: SCAB (0.5 CM IN DIAMETER) 1323 1324 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1325 NO ADVERSE FINDINGS 4_ 1326 NO ADVERSE FINDINGS O0 1327 NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION |_.) Observation confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM E26 (PAGE 2): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1328 1329 1330 1331 1332 NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS 1333 1334 1335 1336 DP( DP( DG( DL( DP ( 3814i3- 7) 12) 21) 22) 4) URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION SWOLLEN EAR(S) SWOLLEN EAR(S) a CHROMORHINORRHEA DP( 7- I0) DP ( 50- 54) ABDOMINAL DISTENTION INCISORS : MISSING/BROKEN 1337 1338 DG I- 21) DL i- 22 ) NO ADVERSE FINDINGS SWOLLEN EAR(S) SWOLLEN EAR (S) a 1339 DP 6- 12) ABDOMINAL DISTENTION 1340 DP 6- 16) ABDOMINAL DISTENTION 1341 DP 6- 15) ABDOMINAL DISTENTION DG 8 - 21 ) SWOLLEN EAR (S) DL i- 22) SWOLLEN EAR(S) a 1342 DP 57- 81) SWOLLEN EAR(S) DG 0 - 21 ) SWOLLEN EAR (S) 1343 DL 1- 22) SWOLLEN EAR(S) a NO ADVERSE FINDINGS 1344 DP( 64- 83) INCISORS: MISALIGNED DG( 0- 21) INCISORS: MI SALIGNED DL ( 1 - 6 ) INCISORS : MISALIGNED DL( 4- 22) INCISORS: MISSING/BROKEN a DL ( 22 ) INCISORS: MISALIGNED a 1345 1346 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1347 1348 DP( 6- 15) ABDOMINAL DISTENTION NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING DG Observation confirmed = DAY OF PRESUMED at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE C/_ O0 to O t21 _._ 4_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E26 (PAGE 3): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS " ................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 DP( 62- 81) DG( 0- 21) DL( i- 22) NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE PTOSIS PTOSIS PTOSIS NO ADVERSE NO ADVERSE NO ADVERSE FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS 1359 DP ( 1 - 4 ) CHROMODACRYORRHEA 1360 NO ADVERSE FINDINGS .................................................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE > O C _n 4_ oo t',.> 0 PROTOCOL 418-020: ORAL {GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS {SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE E26 {PAGE 4): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1361 1362 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1363 1364 DP( 63- 64) DP( 3- 5) INCISORS: MISSING/BROKEN CHROMORHINORRHEA 1365 1366 1367 1368 1369 DP( 1- 3) DP( 3) DP( 3) DP( 3) DP( 4) TIP OF TAIL MISSING a DECREASED MOTOR ACTIVITY CHROMORHINORRBEA a COLD TO TOUCH FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1370 1371 DP( DP ( DP { DP( DP( 9- 14) 17 ) 17 ) 17- 20) 17- 20) ABDOMINAL DISTENTION HEAD : SWOLLEN SNOUT: SWOLLEN LACRIMATION RIGHT EYE: SWOLLEN NO ADVERSE FINDINGS 1372 1373 1374 1375 1376 DP 2} DF 28- 35) DP 29- 50) DP 32- 50} DP 35 ) DP 35- 50) DP 45- 50} DP 51 ) DP 26- 31) DP 26- 35) SOFT OR LIQUID FECES CHROMORBINOR/_4EA DEHYDRATION a URINE-STAINEDABDOMINAL FUR CHROMODACRYORRHEA EMACIATION a DECREASED MOTOR ACTIVITY FOUND DEAD ANNULAR CONSTRICTION OF THE AN_ CONSTRICTION OF THE NO ADVERSE FINDINGS TAIL TAIL ....................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF Observation confirmed at necropsy. LACTATION .............................. _> [23 4_ OO I'0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE E26 (PAGE 5): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1377 1378 1379 1380 1381 1382 1383 DP ( DP [ DP( DP( 2) 2 - 3) 2- 10) 9- 19) DG( 6- 21) DL( i- 22) DEHYDRATION CHROMORHINORRHEA URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SWOLLEN EAR(S) SWOLLEN EAR(S)a NO ADVERSE FINDINGS FEMALE RATS 11338845 1386 DP( 9- 12) NNOO AADDVVEERRSSEE FFIINNDDIINNGGSS ABDOMINAL DISTENTION 1387 NO ADVERSE FINDINGS 1388 NO ADVERSE FINDINGS 1389 DP( 67- 83} SWOLLEN EAR(S) DG ( 0- 6) SWOLLEN EAR(S) 1390 DP( 8- 14} ABDOMINAL DISTENTION 1391 NO ADVERSE FINDINGS 1392 NO ADVERSE FINDINGS 1393 NO ADVERSE FINDINGS 1394 1395 NO ADVERSE NO KDVERSE FINDINGS FINDINGS 1396 NO ADVERSE FINDINGS 1397 NO ADVERSE FINDINGS 1398 1399 DP( 1- 9) URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS 1400 NO ADVERSE FINDINGS 1401 1402 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1403 NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL - DAY OF LACTATION Observation confirmed at necropsy. > ____ %J _n 4_ OO , %.J tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM E26 (PAGE 6): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .............................................................................................................................. DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1404 1405 1406 DP( 3- 6) DP( 7- 13) NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS 1407 1408 1409 1410 1411 DP( 24- 83} DG( 0- 21) DL( i- 22) TIP OF TAIL MISSING TIP OF TAIL MISSING TIP OF TAIL MISSING a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1412 DP( 6- 15) ABDOMINAL DISTENTION 1413 1413 1414 DP( 59- 83) DG( 0- 21) DL( I- 22) LOCALIZED LOCALIZED LOCALIZED NO ADVERSE ALOPECIA: ALOPECIA" ALOPECIA: FINDINGS LIMBS LIMBS a LIMBS 1415 DP( i- 7) URINE-STAINED ABDOMINAL FUR DP( 6- 16) ABDOMINAL DISTENTION 1416 NO ADVERSE FINDINGS 1417 NO ADVERSE FINDINGS 1418 NO ADVERSE FINDINGS 1419 NO ADVERSE FINDINGS 1420 NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION Observation confirmed at necropsy. PERFLUOROOCTANOATE > C 5_ O0 t'J PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE E26 (PAGE 7): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 DL( 2) DP( 2- 3) DP( 3- 5) DP( 26 ) DL( 13 ) DP 59- 66) DP 4- Ii) RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS SOFT OR LIQUID FECES URINE-STAINED ABDOMINAL FUR SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN URINE-STAINED ABDOMINAL FUR 1432 1433 1434 1435 1436 1437 1438 DP DP DP DP DPI DLI DP q 4- 6) 4- 6) 6) 7) 23 ) 1) 2- 4) DL( 5- 21) CHROMORHINORRHEA a URINE-STAINED ABDOMINAL FUR EMACIATION a FOUND DEAD CHROMORHINORRHEA RED PERIVKGINAL SUBSTANCE CHROMORH INORRHEA NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1439 1440 DP( 62- 79) DG( 15- 21} DL( 1- 22) LOCALIZED LOCALIZED LOCALIZED NO ADVERSE ALOPECIA: ALOPECIA: ALOPECIA: FINDINGS LIMBS LIMBS LIMBS a 1441 DP ( 3) EMACIATION 1442 1443 DP( 3- 10) DP( 9- 13} URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1444 1445 DP ( 1) CHROMORHINORRHEA NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF Observation confirmed at necropsy, LACTATION 2o [2_ 4_ t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM E26 (PAGE 8): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1446 1447 1448 1449 1450 1451 1452 1453 1454 1455 DL( 2) DL( 17 ) DL( 19- 20) DP ( 37 ) NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED PERIVAGINAL SUBSTANCE SOFT OR LIQUID FECES SOFT OR LIQUID FECES NO ADVERSE FINDINGS CHROMORHINORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 DPl 41- 64) DP 51- 53) DP 51- 82) DP 54 ) DP 54- 55) DP 65- 82) DG 0- 21) DG 0- 21) DL 1- 22) DL 1- 22) DL 1- 22) DL( 3- 22) DP( i- 3) NO ADVERSE NO ADVERSE FINDINGS FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS CHROMORHINORRHEA INCISORS: MISSING/BROKEN INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRBEA CNROMODACRYORRHEA INCISORS: MISSING/BROKEN CHROMODACRYORRHEA a INCISORS: MISSING/BROKEN a LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a CHROMORHINORRHEA DP( 6- 18) DP( 14- 15) ABDOMINAL DISTENTION CHROMORHINORRHEA .................................................................................................................................... DAY POSTWEANING DG s DAY OF PRESUMED GESTATION DL = DAY OF Observation confirmed at necropsy, LACTATION PERFLUOROOCTANOATE _> _n 4_ _._ to t2_ O PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E26 (PAGE 9): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 DP( 6- 12} DP( 7- 10) DL( 22 ) DL( 2) DP( 60- 63) DP( 64- 77) DG( 16- 21) DL( i- 22} ABDOMINAL DISTENTION ABDOMINAL DISTENTION NO ADVERSE FINDINGS SOFT OR LIQUID FECES NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: MISALIGNED INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS 1476 1477 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1478 NO ADVERSE FINDINGS 1479 NO ADVERSE FINDINGS 1480 DP( 57- 59) SWOLLEN EAR(S) .................................................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED a. Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE > C O_ O PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM E26 (PAGE i0) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1481 1482 1483 1484 1485 1486 DP( DP ( DP( DP( DP( DP ( DP ( DP ( 2- 8) 3) 9- 18} I- 2) 2) 2} 2} 3) DP( 5- 8) NO ADVERSE FINDINGS NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR EMACIATION ABDOMINAL DISTENTION URINE-STAINED ABDOMINAL FUR DECREASED MOTOR COLD TO TOUCH ACTIVITY LABORED BREATHING FOUND DEAD NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 DP( 9- 20) DP( 8- I0} DP( 15- 17} DP ( DP( DG( DL( DL( DL( 8- 9) 13- 83) 0- 21) 18 ) 18- 22) 1- 22) DP ( DP ( 30 ) 30 ) DP ( DP( 6) 6) ABDOMINAL DISTENTION NO ADVERSE FINDINGS NO ADVERSE FINDINGS ABDOMINAL DISTENTION LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NECK ABDOMINAL DISTENTION TIP OF TAIL MISSING TIP OF TAIL MISSING URINE-STAINED ABDOMINAL FUR SOFT OR LIQUID FECES TIP OF TAIL MISSING NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LACRIMATION LEFT EYE : SWOLLEN NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS NO ADVERSE FINDINGS .................................................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION PERFLUOROOCTANOATE [2_ _t_ O0 tO O PROTOCOL 418-020. ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE E26 (PAGE 11): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV I0 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1501 1502 1503 1504 1505 1506 1507 1508 DP( 7- 18) DP( 65- 79) DL( 5- 22) NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE ABDOMINAL LOCALIZED LOCALIZED NO ADVERSE NO ADVERSE NO ADVERSE FINDINGS FINDINGS FINDINGS FINDINGS DISTENTION ALOPECIA: ALOPECIA: FINDINGS FINDINGS FINDINGS LIMBS LIMBS a 1509 1510 NO ADVERSE FINDINGS NO ADVERSE FINDINGS 1511 1512 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1513 DP( 59- 67} BACK: SCAB (DID NOT EXCEED 0.5 CM X 0.3 CM) 1514 NO ADVERSE FINDINGS 1515 NO ADVERSE FINDINGS 1516 NO ADVERSE FINDINGS 1517 1518 DL( 8- 22) LOCALIZED ALOPECIA: NO ADVERSE FINDINGS LIMBS a 1519 NO ADVERSE FINDINGS 1520 1521 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1522 NO ADVERSE FINDINGS 1523 NO ADVERSE FINDINGS 1524 1525 NO ADVERSE NO ADVERSE FINDINGS FINDINGS 1526 NO ADVERSE FINDINGS 1527 DL( 14 ) SOFT OR LIQUID FECES 1528 DL( 15- 16) URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS ............................................................................................ DAY POSTWEANING DG = DAY OF PRESUMED Observation confirmed at necropsy. GESTATION DL = DAY OF LACTATION -'....................................... [/_ _. oo tm _.) t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E26 (PAGE 12): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1529 NO ADVERSE FINDINGS 1530 1531 1532 1533 1534 1535 1536 DP( 71- 83) DG( 0- 2) NO ADVERSE INCISORS: INCISORS: NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE FINDINGS MISALIGNED MISALIGNED FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS 1537 1538 1539 1540 NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE FINDINGS FINDINGS FINDINGS FINDINGS .................................................................................................................................... DP _ DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION > 4_ oo b O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE E26 (PAGE 13): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1541 1542 1543 1544 1545 1546 1547 1548 DP( I0- 19) DP( 10- 11) DP( DP( DP ( DL ( 61- 66) 62- 66) 56 ) 2) DP 9- 13) DL 5- 22} ABDOMINAL DISTENTION ABDOMINAL DISTENTION NO ADVERSE FINDINGS BACK: SCAB {0.5 CM X 0.2 CM) LOCALIZED ALOPECIA: LIMBS CHROMORHINORRHEA RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS ABDOMINAL DISTENTION SWOLLEN EAR(S) a 1549 DP 2- 3) DP 2- 7) DECREASED MOTOR ACTIVITY CHROMORHINORRHEA a DP 3- 7} DP 5- 7) COLD TO TOUCH URINE-STAINED ABDOMINAL FUR DP 8) FOUND DEAD 1550 DP 9- 13) DP 40 ) ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE 1551 DP 9- 14} ABDOMINAL DISTENTION DP 13 ) TAIL BENT 1552 DP 14- 31) TIP OF TAIL MISSING a NO ADVERSE FINDINGS 1553 NO ADVERSE FINDINGS 1554 NO ADVERSE FINDINGS 1555 DG( 17- 21) LOCALIZED ALOPECIA: LIMBS DL( 1- 22) LOCALIZED ALOPECIA: LIMBS a 1556 NO ADVERSE FINDINGS 1557 NO ADVERSE FINDINGS 1558 1559 DP( 8- 13) DP( 3- 5) ABDOMINAL DISTENTION URINE-STAINED ABDOMINAL FUR DP( 5) COLD TO TOUCH DP ( 5) EMACIATION a DP ( 6) FOUND DEAD 1560 NO ADVERSE FINDINGS 1561 NO ADVERSE FINDINGS 1562 DP( 2) FOUND DEAD b 1563 DP( 2) 1564 FOUND DEAD b NO ADVERSE FINDINGS ........................................................................................................... TAIL DAY POSTWEANING DG Observation confirmed Clinical observations -- DAY OF PRESUMED at necropsy. were not recorded GESTATION DL = DAY OF on day 1 postweaning. LACTATION _ ......................... _> [2_ 4_ O0 t_) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE E26 (PAGE 14): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1565 1566 1567 1568 1569 1570 1571 DP( DG( DL{ DG ( DL( 39 ) 14- 21) i- 22) 21 ) 1- 22) ANNULAR CONSTRICTIONS LOCALIZED ALOPECIA: LOCALIZED ALOPECIA: LOCALIZED ALOPECIA: LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS OF THE LIMBS LIMBS a LIMBS LIMBS a TAIL 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 DP( DP( DP( DP ( DP ( DP( DP( DP( 8- 19) 2- 3) 2- 3) 3) 3) 3- 8} 9- 13) 38 ) DG( 14- 21) DL( i- 19) DP ( 24 ) DG( 20- 21) DL ( 1 - 6 ) NO ADVERSE FINDINGS ABDOMINAL DISTENTION COLD TO TOUCH URINE-STAINED ABDOMINAL FUR FOUND DEAD FOUND DEAD URINE-STAINED ABDOMINAL FUR ABDOMINAL DISTENTION ANNULAR CONSTRICTIONS OF THE TAIL NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RIGHT AXILLA: MASS (0.5 CM X 0.5 CM X 0.5 CM) RIGHT AXILLA: MASS (DID NOT EXCEED 0.5 CM X 0 5 CM X 0.5 CM) NO ADVERSE FINDINGS NO ADVERSE FINDINGS RALES NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LOCALIZED ALOPECIA : LIMBS LIMBS .................................................................................................................................... DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF observation confirmed at necropsy. LACTATION > [29 O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NDMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E26 (PAGE 15): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT # DESCRIPTION .................................................................................................................................... 1592 DP( 6- 12) URINE-STAINED ABDOMINAL FUR DP( 7- 15) ABDOMINAL DISTENTION 1593 NO ADVERSE FINDINGS 1594 NO ADVERSE FINDINGS 1595 NO ADVERSE FINDINGS 1596 DP ( 8) RALES 1597 1598 DP( 5- 16) ABDOMINAL DISTENTION NO ADVERSE FINDINGS 1599 NO ADVERSE FINDINGS 1600 NO ADVERSE FINDINGS .................................................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION ta _O 0% > C 4_ OO 50 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 1): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1301 39. 71 107. 146. 176. 1302 1303 41. 69 105. 137. 162. 180 40. 69 109. 144. 173. 1304 1305 46. 76 115. 144. 172. 194 53. 86 131. 176. 201. 1306 1307 31. 66 107. 148. 178. 208 31. 59 99. 134. 163. 1308 1309 47. 76 116. 150. 176. 201 44. 74 115. 151. 180, 1310 1311 46. 74 123. 158. 190. 220 40. 71 108. 145, 170. 43 196. 208. 219. 215. 239. 50 206. 217. 236. 234. 249. 57 219. 233. 252. 241. 267. 64 220. 246. 260. 253. 285. 70a PRECOHABITATION b 235. 246. 264. 256. 285. 237. 266. 276. 279. 306. 1312 1313 1314 1315 49. 74 116. 158. 192. 230 248. 263. 274. 295. 304. 312. 45. 70 104. 140. 168. 194. 211. 222. 242. 254. 258. 268. 46. 83 124. 160. 196. 50. 95 144. 191. 236. 1316 1317 45. 87 134. 169. 196. 228. 248. 254. 276. 279. 288. 297. 48. 85 132. 169. 202. 1318 19779 19780 39. 72 119. 159. 192. 228, 271. 271. 284. 298. 305. 327. 32. 58 94. 136. 41. 71 108. 124. 1321 1322 1323 1324 46. 77 116. 153. 183. 196. 242. 274. 262. 274. 280. 287. 51. 84 119. 156. 188. 47. 78 117. 160. 182. 33. 59 98. 131. 152. 1325 1326 1327 1328 35. 60 97. 133. 159. 191. 203. 224. 235, 245. 253. 267, 34. 63 109. 143. 180. 33. 61 102. 151. 192. 35. 67 111. 146. 181. 199, 225. 239. 254. 268. 270. 279. 1329 1330 39. 67 103. 132, 34. 62 96. 133. ....................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 159. 162. 184. 200. 222. 230. 239. 246. 255. _ ............................ > [/_ Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning _t_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O_ Precohabltation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these 6 rats were 92 to 106 days of age. I_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 2): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 44. 72. 112 151. 183. 201. 40. 69. 110 144 173. 28. 52. 88 130 155. 28. 48. 79 120 146. 167. 40. 69. 102 146 171. 194. 37. 66. 100 136 167. 187. 47. 72. 107 152 48. 77 115 152 181. 204. 32. 59 96 141 37. 58 93 137. 168. 200. 1341 40. 72 114. 146. 174. 198. 43 223. 187. 212. 212. 229. 220. 217. 50 238, 201. 232. 226. 247. 258. 237. 57 252. 211. 250. 238. 254. 250. 253. 64 268. 225, 253. 243. 272. 272. 266. 70a PRECOHABITATION b 263. 280. 227. 268. 249. 278. 285, 263. 238. 275. 262. 303. 279. 291. 13423 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 4523.. 60. 47. 44. 36. 41 40 49 45 49 38 44 43 48 35 33 36. 37. 7931 I1i304. 14743. 91 138. 173. 80 122. 160. 76 118. 155. 68 108. 148. 68. 102. 142. 68. 106. 144. 86. 133. 172. 79. 123. 158. 85. 125. 172. 62. I00. 137. 74. 108. 140. 80. 123. 157. 83. 124. 167. 60. 99. 135. 64. 100. 137. 65. 99. 137, 70. 112. 170, 196. 186. 174. 168. 191. 163. 180. 154. 159. 200. 215. 213. 197. 190. 222. 180. 209. 177. 189. 222. 229. 232. 214. 213. 234. 205. 226. 192. 201. 237. 250. 255. 229. 234. 263. 223. 251. 211. 210. 254. 257. 268. 237. 244. 262. 240. 263. 228. 228. 274, 259. 280. 241. 259. 276. 245. 273. 232. 234. ..........=.....D.A..Y.....P.O..S.T..W.E..A.N..I.N..G.............................................................................................. WEIGHTS WERE RECORDED IN GRAMS (G}. Because was the body last weight values day on which were recorded at weekly intervals, based on the youngest rats (in this group) had a body Precohabitation body weights were recorded on the day cohabitation was rats were 92 to 106 days of age. each rat's day postweaning, weight value recorded. begun for the F1 generation 276. 261. 288. 247. 264. 275. 256. 279. 238. 239. 295. 266. 295, 253. 275. 298. 262. 295. 240. 239. day 70 postweanlng rats; at that time these _> _., O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 3): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1361 40. 66. 100. 139. 169. 1362 1363 1364 1365 1366 40. 64, 92. 124. 152. 172. 35. 66. 103. 148. 176. 201, 35. 59. 95. 143. 170. 197, 31. FOUND DEAD ON DAY 4 POSTWEANING 36. 61 98. 131. 163. 1367 1368 1369 1370 29. 48 76 112. 140. 158. 38. 64 102 138. 162. 181. 41. 70 106 137. 162. 40. 66 108 151. 186. 1371 1372 37. 65 105 146. 181. 210. 49. 80 120 156. 181. 1373 1374 44. 73 112. 151. 151. 130, 41. 70 107. 147. 177. 1375 1376 1377 40. 66 104. 143. 170. 201, 37. 62 26. 43 96. 127. 84 134. 161. 172. 194, 1378 1379 1380 47. 79 121 158. 188. 210. 49. 78 118 162. 187. 213. 40. 65 98 135. 156. 1381 1382 1383 1384 1385 1386 1387 1388 38. 62 96 136. 159. 182, 31. 58 96 133. 160. 188, 29. 49 85 124. 153. 178. 40. 68 110 140. 156. 176, 39. 76 111 150. 179. 36. 65 98 132. 160. 40. 69 111 158. 184. 221, 42. 70 107. 149. 183. 43 188. 216. 211. 177. 200. 236. 118. 221. 223. 224. 232. 202. 210. 202. 183. 240. 50 202. 228. 230. 186. 213. 251. 107. 233. 236. 242. 259. 217. 229. 219. 202. 254. 57 64 70a PRECOHABITATION b 212. 246. 241. 226. 261. 257. 236. 264. 262. 245. 282. 272. 197. 230. 202. 243. 220. 247. 223. 266. 260. 282. 281. 303. FOUND DEAD ON DAY 51 POSTWEANING 239. 267. 255. 284. 265. 296, 278. 316. 258. 267. 270. 278. 278. 280. 288. 295. 228. 239. 232. 203. 239. 249. 245. 219. 242. 248. 253. 225. 256. 265. 274. 236. 272. 286. 286. 308. 1389 1390 44. 73 113. 154. 181. 214. 237. 253. 273. 291. 291. 302. 38. 73 113. 148. 170. ....................................................................................................... = DAY POSTWEANING .............................. WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitatlon body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. tO O PROTOCOL 418-020: ORAL {GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM TABLE E27 (PAGE 4): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 43 .................................................................................................................................... 1391 36 64. 103. 142. 174. 50 57 64 70a PRECOHABITATION b 1392 1393 1394 1395 1396 38 73. 122, 158. 187 213. 235. 246. 269. 258. 289. 316. 39 65. 101. 139. 171 191. 214. 230. 234. 260. 267. 279, 40 68, 109. 153. 186 34 58. 95. 131. 166 42 74. 108. 153. 182 1397 1398 40 72. 116. 159. 189 206. 233. 253. 257. 261. 284. 301. 31 53. 88. 132. 162 1399 1400 58 85. 121. 157. 181 205. 231. 244. 251. 260. 275. 288. 57 82. 117. 150. 177 1401 1402 1403 34 63. 98. 132. 158 177. 194. 208. 222. 230. 235. 250. 38 68. 104. 138. 164 32 62. 95. 135. 153 1404 1405 1406 31 57. 94. 134. 165 188. 212. 230. 242. 258. 263. 285. 28 50. 84. 126. 166 44 72. 105. 136. 164 1407 1408 47 75. 116. 155. 183 210. 229. 242. 259. 263. 274. 277. 42 65. 101. 136. 162 1409 1410 1411 1412 41 66. 104. 142. 174 204. 212. 252. 263. 258. 269. 280. 40 72. 112. 157. 189 221. 239. 266. 275. 285. 294. 315. 44 74. 114. 154. 49 84. 128. 163. 1413 1414 40 68. 106. 148. 177. 195. 216. 237. 245. 252. 264. 273. 35 63. 98. 135. 1415 1416 1417 30 58. 89. 129. 157. 180. 208. 222. 232. 249. 250. 264. 46 74. 114. 150. 181. 203. 225. 239. 240. 248. 256. 265. 45 72. 112. 151. 1418 41 65. 99. 138. 163. 186. 206. 219. 230. 245. 246. 262. 1419 1420 38 69. 108. 149. 42 64 . 104 . 145. ....................................................................................................... = DAY POSTWEANING . ............................ WEIGHTS WERE RECORDED IN GRAMS (G). 5_ Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweanlng 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. CD PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 5): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................. DAY 1 8 15 22 29 36 .................................................................................................................................... 1421 1422 1423 31 62. 97 138. 170. 191. 34 62. 100 143. 167. 33 64. 106 143. 180. 1424 1425 37 72. 111 150. 177. 211. 32 61. 104 145. 177. 1426 1427 1428 1429 1430 34 60. 97 136. 157. 191. 44 74, 121 163. 191. 45 78. 119 158. 191. 213. 42 76. 112 150. 177. 35 65. 110. 160. 199. 233. 43 209. 223. 223. 233. 258. 50 222. 232. 238. 249. 275. 57 234. 249. 266. 260. 283. 64 245. 268. 276. 280. 297. 70a PRECOHABITATION b 251. 266, 267. 287. 289. 308. 280. 299. 307. 329. 14312 3311 5F2O.UND DEAD86.ON DAY 1378.POSTWEANI1N7G6. 209. 232. 257. 271. 282. 290. 297. 1433 1434 40 71. 112 148 . 182 . 212. 234 . 246. 263. 284. 282, 303 . 43 52. 102 147. 183. 1435 51 85. 128 169. 199. 1436 1437 1438 42 81. 124 162. 189. 217. 228. 244. 259. 271. 281. 298. 42 76. 114 145. 168. 192. 206. 227. 248. 255. 255. 264. 38 75. 113 136. 144. 1439 1440 1441 47 76. 120 160. 184. 214. 233. 254. 271. 287. 293. 304. 45 76. 122 162. 189. 32 51. 90 140. 172. 1442 1443 1444 1445 33 61. 94 143. 169. 196. 229. 237. 238, 248. 258. 278. 35 62. 94 136 166. 194. 215. 240. 261. 279. 279. 300. 37 65. 107 150 179. 39 72. 108 150 166. 1446 1447 41 70. 103 137 173. 189. 207. 222. 231. 246. 253. 260. 46 74, 109 145 191. 1448 52 80. 117 158 180. 216. 234. 256. 263. 275. 287. 302. 1449 1450 57 93. 135 156 182. 56 90. 131 159 180. 200. 218. 233. 238. 250. 263. 277. .................................................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age, to PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 6): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 56. 93. 136. 176. 208. 50. 82. 119. 151. 179. 169. 54. 96. 138. 170. 197. 57. 93. 133. 168. 189. 46. 78. 116. 151. 184. 211. 61. 96 131. 169. 192. 216. 39. 70 108. 143. 162. 38. 69 113. 154. 178. 202. 52. 93 138. 172. 207. 243. 43. 77 117. 160. 196. 1461 42. 71 108. 152. 188. 211. 14623 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 462. 763 111123.. 15489. 18716. 200. 53. 92. 139. 178. 217. 30 49. 83. 128. 164. 192. 32 53. 92. 133. 34 60. 101. 140. 36 60. 92 130. 157. 178. 38 62. 97 132. 160. 196. 33 58. 100 135. 47 78. 114 150. 46 75. Ii0 144. 170. 189. 53 83. 126 156 50 81. 121 152 175. 195. 37. 68. 103 134 46. 76. 116 156 188. 213. 67. I00. 125 173 200. 216. 57. 91. 128 166 44. 76. 120. 154 42. 71. 115. 152 185. 205. 43 224. 231. 231. 222. 258. 234. 216. 222. 206. 217. 214. 213. 237. 242. 218. 50 251. 246. 246. 232. 277. 250. 240. 242. 230. 242. 228. 220. 259. 269. 242. 57 254. 270. 250. 243. 290. 266. 253. 254. 239. 244. 243. 233. 265. 256. 244. 64 264. 288. 265. 247. 300. 273. 265. 272. 245. 258. 253. 231. 272. 268. 263. 70a PRECOHABITATION b 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 POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on was the last day on which the youngest rats (in this group) had a body Precohabitatlon body weights were recorded on the day cohabitation was rats were 92 to 106 days of age. _ ....................................... each rat's day postweaning, weight value recorded. begun for the F1 generation day 70 postweaning rats; at that time these [2_ b-,4_ Oo %--J PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 7): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1481 1482 1483 1484 i485 1486 1487 1488 1489 1490 1491 1492 48 76. 116. 155. 184. 47 75. 112. 149. 172. 200. 29 48. 82. 124. 153. 183. 28 FOUND DEAD ON DAY 3 POSTWEANING 30 53. 93 134. 170. 27 36. 63 99 136. 159. 46 78. 115 146 168. 46 78. 119 153 185. 209. 39. 70. 105 142 178. 39. 64. 104 150 186. 206. 43. 73. 102 140 169. 192. 42. 67. 104 138 168. 43 215. 202. 186. 241. 221. 219. 50 231. 221. 202. 262. 225. 231. 57 243. 231. 219. 280. 253. 240. 64 256. 247. 230. 300. 265. 246. 70a PRECOHABITATION b 270. 251. 279. 275. 232. 312. 268. 248. 248. 329. 276. 261, 1493 1494 1495 46. 82. 127, 171 196. 48. 89. i01. 161. 191. 217. 236. 248. 259. 277. 284. 290. 44. 78. ii0. 144, 164. 1496 1499 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 44. 78 116. 154. 176. 193. 217. 235. 240. 250. 265. 271. 64. 98 140. 182. 213. 233. 252. 267. 281. 294. 293. 304. 53, 55 93. 141. 182. 43. 71 107. 140. 169. 39. 66 100. 139. 167 184. 205. 216, 230. 235. 238. 254. 40. 68 102. 147. 181 42, 71, 110. 156. 186 210. 250. 256. 255. 277. 280. 304. 43. 72. 104. 143. 173 39. 67. 103. 142. 174 40 66. 99. 135. 161 184. 208. 223. 236. 247. 258. 273. 34 63. 97. 132. 162 40 69. 103. 145. 173 192. 210. 228. 233. 250. 258. 259. 54 89. 130. 171. 202 230. 247. 264. 271. 288. 296. 300. 1509 1510 53 81. 112. 147. 43 72. 117. 154. ....................................................................................................... 167 193 .............................. = DAY POSTWEANING %JJ WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning .-_ Was the last day on which the youngest rats (in this group) had a body weight value recorded. O_ Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E27 (PAGE 8): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1511 1512 38 64. 103. 139. 169 197. 46 75. 113. 157. 182 1513 1514 1515 43 75. 111. 150. 175 201. 53 90. 131. 172. 196 223. 47 73. 108. 143. 167 43 222. 217. 241. 50 238. 233. 256. 57 253. 247. 274. 64 276. 253. 283. 70a PRECOHABITATION b 275. 288. 256. 289. 268. 304. 1516 1517 1518 45 84. 121. 152. 181 202. 217. 237. 242. 257. 270. 274. 45 79. 120. 155. 183 208. 234. 250. 268. 293. 296. 311. 36 64. 105. 149. 182 1519 1520 34 58, 95. 134. 162 190. 211. 229. 242. 247. 262. 264. 52 81. 119. 159. 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 50 74. 107. 140. 159. 180. 198. 216. 225. 236. 248. 251. 49 85. 122. 157. 45 72. 102. 136. 159. 175. 194. 211. 219. 227. 241. 251. 36 63. 91. 133. 161. 186. 211. 233. 234. 247. 257. 255. 35 60. 91. 130. 52 88. 123. 164. 48 79. 119. 157. 184. 201. 225. 240. 251. 268. 269. 282. 40 70. 103. 125. 142. 162. 179. 197. 207. 214. 219. 233. 34 50. 85. 114. 50 83. 123. 163. 47 76. 117. 160. 180. 208. 220. 246. 252. 254. 264. 272. 55 86. 132. 170. 56 92. 136. 175. 199. 226. 239. 258. 274. 286. 289. 305. 44 78. 118. 154. 178. 206. 226. 247. 251. 259. 267. 277. 38 72. 114. 154. 42 67. 105. 133. 37 58. 94. 127. 158. 188. 205. 227. 234. 242. 251. 262. 36 60. 98. 135. 1539 47 73. 112. 153. 182. 210. 1540 44 71. 102. 138. .................................................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 232. 252. 267. 278. 281. 291. Because body was the last Precohabitation rats were 92 weight values were recorded at weekly intervals, based on day on which the youngest rats (in this group) had a body body weights were recorded on the day cohabitation was to 106 days of age. each rat's day postweaning, weight value recorded. begun for the F1 generation day 70 postweaning rats; at that time these _> t_ [29 4_ Oo o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E27 (PAGE 9): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 .................................................................................................................................... 1541 1542 1543 34. 53 34. 62 35. 56 84. 115. 97. 139. 86. 114. 144. 171 136 165. 1544 1545 1546 1547 37. 58 93. 143. 179 215. 33. 62 104. 140. 169 199. 36. 65 101. 142. 171 201. 34. 58 91. 135. 165 1548 1549 34. 58 88. 124. 152 174. 28. FOUND DEAD ON DAY 8 POSTWEANING 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 33. 54 80. 108. 132. 148. 42. 68 108. 150. 178. 42. 70 116. 142. 38. 59 167. 196. 85. 119. 144. 44. 70 108. 147. 172. 39. 64 94. 133. 164. 182. 43. 72 106. 139. 166. 43. 77 113. 153. 186. 212. 30. 57 91. 131. 163. 180. 22. FOUND DEAD ON DAY 6 POSTWEANING 43. 74. 110. 145. 171. 186. 39. 71. 109. 143. 179. c FOUND DEAD ON DAY 2 POSTWEANING c FOUND DEAD ON DAY 2 POSTWEANING 1564 1565 1566 1567 36. 63 97. 129. 156. 175. 40. 67 100. 135. 167. 178. 44. 73 107. 141. 176. 207. 43. 75 116. 151. 182. 1568 1569 1570 67. 106 58. 89 39. 70 152. 123. 108. 183. 151. 146. 210. 168. 178. 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. 238. 290. 264. 248. 304. 282. 273. 251. 224. 252. 250. 300. 272. 258. 234. 236. 275. 289. 239. 243. 252. 290. ....................................................................................................... = DAY POSTWEANING .............................. WEIGHTS WERE RECORDED IN GRAMS (G). Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabitation body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. _,) Value not recorded. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E27 (PAGE i0): BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 8 15 22 29 36 43 50 57 64 .................................................................................................................................... 70a PRECOHABITATION b 1571 1572 36 60. 89. 123. 153. 176. 198. 212. 216. 229. 241. 247. 44 68. 106. 150. 188. 1573 1574 1575 42 71. 110. 156. 190. 212. 234. 250. 265. 280. 286. 302. 23 FOUND DEAD ON DAY 3 POSTWEANING 23 FOUND DEAD ON DAY 3 POSTWEANING 1576 1577 25 43. 68. 108. 140 163. 190. 208. 214. 228. 241. 250. 33 54. 85. 126. 154 1578 1579 1580 35 61. 98. 135. 161 186. 207. 221. 226. 235. 246. 251. 49 77. 120. 156. 186 209. 234. 247. 269. 285. 285. 303. 46 73. 104. 145. 180 1581 48 76. 112. 149. 177 1582 1583 1584 1585 39 57. 91. 125. 41 64. 97. 140. 164. 182. 204. 220. 227. 242. 240. 245. 33 58. 94. 128. 148. 171. 200. 215. 222. 235. 245. 251. 33 57. 98. 134. 1586 1587 1588 1589 1590 1591 1592 37 62. 96. 131. 152. 168. 183. 198. 210. 217. 227. 231. 39 64. 97. 134. 157. 176. 196. 209. 220. 228. 231. 236. 45 73. 112. 149. 169. 194. 220. 230. 244. 259. 255. 275. 39 76. 117. 156. 176. 206. 216. 236. 253. 267. 274. 291. 45 73. 107. 136. 44 72. 109. 143. 169. 194. 210. 220. 233. 246. 246. 262. 44 67. 103. 140. 1593 1594 1595 1596 1597 1598 46 78. 120. 152. 195. 217. 228. 239. 244. 259. 265. 275. 47 73. 106. 139. 45 74. 115. 148. 46 71. 111. 147. 31 59. 94. 133. 36 65. 106. 141. 172. 195. 215. 239. 240. 252. 257. 266. 1599 44 69. 110. 154. > 1600 44 69. ii0. 149. 180. 206. 226. 239. 255. 273. 278. 290. ....................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). r ............................ Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 70 postweaning 4_ was the last day on which the youngest rats (in this group) had a body weight value recorded. O0 Precohabltatlon body weights were recorded on the day cohabitation was begun for the F1 generation rats; at that time these rats were 92 to 106 days of age. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E28 (PAGE 1): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # ........................ PREGNANCY DOSAGE GROUP I 0 MG/KG/DAY ............................................................................................................ STATUS DAY 0 7 10 14 18 21 .................................................................................................................................... 1302 P 1304 P 1306 P 1308 P 236. 262 266. 294 273. 306 269. 291 269. 287. 324 311. 324. 371 314. 341. 391 298. 321. 377 366. 410, 441. 1310 P 1312 P 1313 P 1316 NP 1318 P 303. 332 342. 360. 417 305. 327 338. 360. 374 264. 288 299. 316. 363 299. 304 315, 314. 315 322. 366. 379. 400. 456 451. 385. 400. 308. 498. 25 311. 1321 P 292. 325. 340. 349. 409 454. 1325 P 1328 P 1330 P 264. 296. 312. 328. 367 284. 313. 322. 344. 382 253. 274. 285. 298. 341 398. 429. 382. 1331 P 277. 307. 319. 338. 376 418. 1334 P 1335 P 239. 258. 271. 286. 324 271. 309. 327. 333. 390 351, 425. 1336 P 1338 P 264. 296 297. 324 321. 336. 396 336. 354. 412 428. 457, 1340 P 282. 312 324. 351. 380 425. 1341 P 286. 314 328. 345. 390 416. 1342 P 1344 P 281. 314 267. 298 334. 346. 395 313. 332. 373 422. 421, 1345 P 293. 311. 326. 346. 408 450. 1346 P 250. 278. 291. 309. 344 365. 1348 P 271. 306. 314. 325. 382 430. 1350 P 292. 321. 329. 351. 404 442. 1353 P 255. 293. 302. 322. 352 397. 1355 P 295. 324. 342. 349. 404 441. _> 1358 NP MATING NOT CONFIRMED 1359 P 245. 273. 284. 299. 343. 382. ............................................................................................ _ ....................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) = DAY OF PRESUMED GESTATION 4_ WEIGHTS WERE RECORDED IN GRAMS (G). O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E28 (PAGE 2): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAY 0 7 10 14 18 21 25 .................................................................................................................................... 1362 P 248. 268 275. 289 309. 336 1363 P 277. 298 315. 327 379. 422 1364 P 272. 299 311. 324 376. 413 1367 P 1368 P 1371 P 1375 P 1376 P 1378 NP 225. 262 246. 289 305. 333 277. 292 318. 354 292. 306 272. 292 294. 311 355. 376 303. 324 360. 378 304. 306 334. 385 378. 413 422. 469 378. 419 440. 474 316. 309 314. 1379 P 303. 339 353. 370. 406. 440 1381 P 1382 P 1383 P 1384 P 1387 P 1389 P 1392 P 1393 P 1397 P 1399 P 1401 P 255. 279 264. 283 275. 297 237. 261 300. 330 301. 328 322. 353 278. 308 290. 314 271. 297 255. 279 277. 297. 310. 276. 344. 345. 367. 322. 340. 307. 299. 298. 310. 323. 293. 373. 359. 380. 336. 360. 324. 309. 344. 358. 367. 347. 434. 418. 429. 385. 402. 377. 357. 381 400 395 378 477 453 417. 432. 415. 1404 P 1407 P 1409 P 1410 P 1413 P 1415 P 282. 320 334. 365. 401. 443 270. 290 306. 320. 376. 407 280. 306 320. 341. 374. 423 298. 333 346. 361. 415. 466 279. 310. 322. 334. 363. 406 262. 292. 302. 314. 359. 395 1416 P 1418 P 264. 303. 311. 329. 377. 413 256. 278. 312. 310. 358. 395 ....................................................................................................... PREGNANT NP = NOT PREGNANT = DAY OF PRESUMED GESTATION (VALUES EXCLUDED FROM AVERAGES) WEIGHTS WERE RECORDED IN GRAMS (G). _ ............................ > _'_ [2_ 4_ O0 tO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E28 (PAGE 3): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAY 0 7 10 14 18 21 25 .................................................................................................................................... 1421 P 264 282. 297. 320. 380. 417. 1424 P 275 297. 320. 328. 390. 1426 P 301 342. 359. 371. 434. 465. 1428 P 298 320. 339 356. 411. 444. 1430 P 321 348. 360 387. 458 494. 1431 P 296 322. 344 366. 429 472. 1433 P 300 324. 335 362. 432 1436 P 301 340. 352 371. 413 452. 1437 P 255 285. 299 314. 361 1439 P 296 323. 335. 366. 424 450. 1442 P 268 303. 314 327. 356. 379. 1443 P 301 1446 NP 262 1448 P 292 1450 P 278 1452 P 282 1455 P 305 1456 P 274 1458 NP 270 1459 P 315 1461 P 293 1463 P 274 1465 P 296 1468 P 271 1469 P 265 1472 P 264 1474 P 257 318. 329 287. 293 316. 327 297. 308 312. 331 338. 351 301. 315 297. 301 345. 359 315. 332 298. 314 318. 335 304. 316 287. 304 293. 300 284. 301 342. 301. 342. 320. 347. 370. 328. 316. 369. 344. 336. 357. 335. 319. 315. 316. 390. 295. 406. 369. 395. 411. 365. 321. 420. 382. 396. 416. 379. 368. 356. 362. 427. 297. 445. 406. 385. 325. 448. 417. 425. 438. 400. 390. 394. 296. 334. 1476 P 1477 P 1480 P 295 330. 346 364. 283 299. 303 316. 271 300. 306 318. ............................................................................................ PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED = DAY OF PRESUMED GESTATION 411. 370. 370. 407. FROM AVERAGES) i ....................................... [29 4_ WEIGHTS WERE RECORDED IN GRAMS (G). O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E28 (PAGE 4): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAY 0 7 10 14 18 21 25 .................................................................................................................................... 1482 P 1483 NP 1486 P 1488 P 1490 P 1491 P 1494 P 1496 P 1497 P 277. 275. 237. 326. 274. 259. 296. 271. 304. 321. 279. 266. 354. 302. 280. 330. 293 337 332 281 285 366 310 293 337. 308. 348. 358. 284. 308. 381. 340. 304. 353. 322. 365. 1500 P 1502 P 1505 P 1507 P 1508 P 1511 NP 1513 P 1514 P 252. 271 296. 329 289 272, 262. 293 296. 327 296, 319 275. 295 294 324 286. 339. 299. 299. 344. 329. 303. 336. 308. 351. 314. 314. 358. 338. 316. 348. 1516 P 1517 P 1519 P 1521 P 1523 P 1524 P 1527 P 1528 P 1531 P 1533 P 281 310 261 242 252 250 284 230. 270. 291. 304 344 289. 269. 288, 290. 303. 259. 306. 324. 309. 350. 296. 276. 296. 299 312 274 316 339 334. 368. 313 289 313 309 335 292 335 360 1534 P 1537 P 277. 304. 309 260. 289. 304 319. 322. 1539 P 300. 313. 326 351, .......................................................................................... PREGNANT NP = NOT PREGNANT = DAY OF PRESUMED GESTATION (VALUES EXCLUDED WEIGHTS WERE RECORDED IN GRAMS (G). 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 FROM AVERAGES) 290. 335. _ ......................................... _t_ O0 PROTOCOL 418-0205 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E28 (PAGE 5): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAY 0 7 i0 14 18 21 25 .................................................................................................................................... 1541 P 1544 P 1545 P 1546 P 1548 P 1550 P 1552 P 1555 P 1557 P 1558 P 1560 P 247. 300. 269. 277. 248. 224. 257. 254. 294. 268. 258. 259. 330. 299. 304. 274. 247. 276. 277 314 302 288 273. 345. 310. 311. 282. 265. 290. 286. 322. 319. 302. 287. 371. 334. 330. 296. 280. 303. 298. 349. 341. 314. 347. 405. 408. 371. 354. 333. 343. 338. 406. 393. 368. 370. 452. 455. 361. 381. 382. 435. 434. 401. 11556645 PP 1566 P 1568 P 224307.. 225662 288. 306 280. 295 227724.. 228962,, 333480 318. 337, 384 308. 326. 390 337737.. 427. 430. 1571 P 1573 P 1576 P 1578 NP 1579 P 1583 P 1584 P 1586 P 1587 P 1588 P 1589 P .236 299 244 249 299 238 247 230 230 269 282 265 317 276 258. 321. 278. 273. 260. 260. 295. 315. 280. 334. 282. 254. 332. 283. 277. 269. 273. 309 330 291, 351. 305. 261. 344. 301, 289. 284. 287. 325. 348. 342 411 360 264 408 356 324 321 340. 377. 404. 441. 394. 260. 378. 332. 359. 368. 401. 268. 1591 P 254 282. 293 308. 361. 395. 1593 P 272 292. 308 323. 347. 366. > 1598 P 268 292. 308 318. 359. 416. 1600 P 293 319. 332 348. 405. 453. C_ ........................................................................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED = DAY OF PRESUMED GESTATION FROM AVERAGES) _ ........................................ 4_ WEIGHTS WERE RECORDED IN GRAMS (G). O0 b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E29 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 267 304 324 302 342 334 292. NOT 370. 326. 308. 326. 284. 324. 338. 318. 346. 329. 308. PREGNANT 385. 338 305 329 299 331 346 329 345 339 316 396. 352. 315. 349. 303 343 363 352 361 333 289 398. 357. 318. 363. 298. 332. 341. 340. 335. 339. 318. 412. 345. 314. 356. 284. 320. 335. 357. 331. 336. 298. 369 329 323 328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 265. 322. 276. 327. 311. 350. 321. 328. 312. 314. 323. 301. 307. 329. 296. 334. 285 323 272 331 341 357 317 331 326 310 338 293 305 330. 292. 332. 258. 330, 287. 333. 349. 359. 325. 329. 325. 328. 351. 303. 321, 344. 299. 349. 297. 336, 285. 327. 364. 330. 357. 323. 321. 342. 331. 308. 348. 348. 328. 352. 1358 1359 NOT PREGNANT; 271. 279. MATING NOT CONFIRMED 298. 318. ...................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). 309. 322. 307. 346. 331. 377. 354. 341. 331 330 369 314 331 355 322 340 324. 280 300 284 324 331 345 338 316 294 333 364 325 339. 339. 293. 313. 313. ............................... _'_ [2_ 4_ O_ _b _J PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E29 (PAGE 2) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 273. 277 303. 323 309. 319 276. 290 287. 315 337. 346 303. 319 359. 370 NOT PREGNANT 355. 288. 341. 289. 296. 312. 284. 319. 326. 307. 339. 358. 328. 369. 362. 299. 323. 298 322 329 328 343 372 332. 384. 385. 312. 336. 288. 329. 315. 328. 339. 360. 321. 359. 367. 307 310 287. 308 323 297 310 352 299 360 355. 282. 308. 1383 1384 321. 328 333. 344. 368 288. 306. 313. 320. 312 350. 262. 1387 i389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 351 340 357 324 330 310 278 337 299 327 338 322 300 315. 355. 340. 346. 332. 334. 309. 305. 341. 316. 323. 339. 312. 304. 311. 367. 363. 356, 338. 355. 322. 315. 344. 328. 333 356 336 321 319 376. 353. 362, 345. 345. 336. 306. 359. 335. 337 359 360 320 321 358 357 361 355 365 318 310 349 344 340. 363. 343. 335. 336. 338. 344. 347. 330. 331. 320. 297. 332. 325. 327. 344. 320. 339. 303. 1418 290. 306. 319 326 329. 317. > ............................................................................... = DAY OF LACTATION T .................................................... WEIGHTS WERE RECORDED IN GRAMS (G). Cn O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E29 (PAGE 3): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... 1421 297. 312 320. 331. 313. 326. 1424 326. 321 321. 336. 330. 307. 1426 368. 364 374. 371. 376. 369. 1428 341. 338 353. 353. 358. 334. 1430 366. 357 357. 367. 370. 308. 1431 348. 345 364. 358. 379. 358. 1433 350. 355 364. 350. 337. 314. 1436 347. 353 357. 359. 347. 341. 1437 290. 309 320. 306. 314. 311. 1439 340. 352 371. 347. 370. 361. 1442 309. 312 330. 338. 338. 344. 1443 327. 342 341. 356. 357. 336. 1446 1448 NOT PREGNANT 328. 326. 350. 361. 344. 343. 11445502 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 330274.. 331130.. 351. 342. 328. 329. NOT PREGNANT 349. 363 333. 349 316. 315 324. 330 309. 315 298. 296 301. 303 284. 289 348. 326 331167.. 358. 334. 380. 348. 326. 343. 316. 319. 317. 296. 353. 331257.. 366. 333. 375. 362. 330. 348. 342. 341. 324. 322. 370. 332143.. 335. 343. 378. 351. 319. 337. 330. 353. 338. 320. 366. 333011.. 332. 329. 368. 336. 302. 297. 300. 317. 309. 310. 358. 1477 297. 313 317. 357. 333. 335. > 1480 309. 324 326. 353. 340. 340. = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E29 (PAGE 4): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... 1482 1483 322. 326. NOT PREGNANT 312. 315. 331. 313. 1486 1488 1490 1491 1494 1496 1497 1500 276. 351. 317. 281. 324. 313. 347. 287. 291. 350 327 292 340 310 342 300 300. 354. 331. 305. 341. 313. 378. 306. 308. 367. 353. 311. 374. 329. 385. 328. 317. 353. 356. 319. 369. 324. 375. 315. 316. 359 368 316 353 319 355 302 1502 1505 343. 344 296. 294 348. 350. 341. 322 291. 298. 321. 318 1507 1508 1511 301. 308 353. 348 NOT PREGNANT 309. 355. 333. 353 334. 332. 341. 338 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 293. 308 320. 333 309. 317 357. 333 295. 307 280. 276 294. 306 321. 318 325. 333 282. 291 323. 341. 327. 344. 320. 294. 319. 311. 328. 284. 341. 358. 347. 351. 328. 299. 327. 318. 355. 306. 317. 343. 329. 346. 322. 314. 328. 319. 326. 307. 250. 325 316 325 317 312 313 326 315 310 1531 1533 1534 319. 328 320. 327 309. 305 341. 349. 362. 350 342. 336. 345. 347 318. 313. 343. 316 1537 1539 302. 303 332. 343 310. 363. 318. 358. ..................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). 303. 373. 306. 355. _> _ .............................. _'_ O0 _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E29 (PAGE 5): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 5 8 11 15 22 .................................................................................................................................... 1541 1544 1545 264 281. 278. 294, 360 350. 348. 376. 318 322. 340. 342. 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 300 296 265 284 276 325 320. 297. 265. 280. 324. 324. 317. 276. 271. 302. 288. 324, 336. 320. 277. 280. 312. 322. 279. 310 280. 295 280. 276 315 324 294 317 333 348 330 339 325 313 277 319 291 294 314 322 336. 343 1571 1573 292. 341. 279. 334. 288. 344. 311 350. 1576 1578 1579 1583 1584 1586 1587 1588 1589 284. NOT 320. 306. 296. 270. 278 312 326 271. PREGNANT 328. 308. 291. 272. 290. 322. 317. 288. 327. 319. 295. 286. 286. 321. 334. 299. 329. 331. 295. 303. 282. 340. 339. 1591 1593 296 304. 310. 322. 314 322. 318. 328. 1598 1600 301 302. 303. 320. 325 332. 344. 373. ..................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). 291 371 332 338 303 293 310, 285. 329. 343. 348. 306. 307. 320. 338. 289. 355. 303. 356. 325. 302 289 290 350 364 306 346 333 364 296. 342. 298, 329. 306. 298. 319. 312. 319. 288. 325. 309. 275 324 339 304 336 292 346. 303. 294. 294. 300. 322. 354. 318. 342. 317. 354. _ .............................. 50 4_ O0 PROTOCOL 418-020'. ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE I) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fl GENERATION FEMALE RATS RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 29 29 - 36 36 - 43 .................................................................................................................................... 1301 63. 11 128. 129. 1302 1303 61. 11_ 70. 115 125. 119 133. 127 118. 119 1304 1305 61. 117 89. 144 140. 145 171. 197 132. 132 1306 1307 71. 125 68. 123 135. 133 129. 136 131. 131 1308 1309 89. 115 73. 113 124. 137 140 159 131. 130 1310 1311 74. 131 76. ii0 147 154 163. 167 114 120. 1312 1313 1314 1315 102. 116 143 64. 106. 123 91. 146. 147 98. 155. 181 147. 126. 183. 174. 180. 127. 167 125. 1316 1317 77. 119. 137 136. 145. 149. 56. 140. 147 143. 1318 19779 69. 107. 154 61. 97. 129 153. 157. 189. 19780 78. 126. 159 1321 1322 1323 1324 72. 123. 136 71. 106. 127 63. 110. 130 64. 104. 124 126. 124 121 112 146. 180. 1325 1326 1327 63. 96. 134 136 64. 120. 129 134 58. 102. 144 155 146. 145. 1328 48. 110. 131 132 148. 148. 43 50 109. 127. 138. 193. 161. 180. 126. 151. 157. 210. 174. 156. 50 - 57 117. 138. 134. 130. 193. 168. 129. 148. b 158. 164. 159. 57 - 64 115 131. 128 134 162 181. 127. 141. 169. 159. 165. 167. 64 - 70a 102. 107. 112. 109. 125. 141. 112. 116. 128. 123. 106. 142. 1329 1330 74. 112. 69. 104. c 126. ................................................................................ = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 116 146 122. 121. 130. 118. 120. 108. .................................................... Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 Soiled feed precluded the calculation of this value. Wet feed precluded the calculation of this value, to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 2): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1331 1332 1333 !334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 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. 108. 119. 104. 101. 92. 112. 105. 118. 107. 106. 128. 107. 131. 129. 127. 124. 109. 110 114 137 136 124 94 102 124 129 106 106 118. 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. 133. 133. 131. 139. 134. 126. 134. 134. 128. 115 135. 136. 139. 124. 142. 113. 140. 120. 166. 129. 135. 128. 144. 127. 135. 124. 145. 146. 146. 163. 139. 114. 150. 132. 129. 130. 140. 138. 146. 120. 137. 132. c 151. 145. 125. 133. 126. 151. 140. 1359 1360 74. 87 80. 106 116. 127. 134. 138. ..................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based the last interval in which a feed consumption value was recorded Spilled feed precluded the calculation of this value. Soiled feed precluded the calculation of this value. 43 - 50 b 142. 145. 132. 171. 140. 169. 139. b 182. 174. 133. 160. 121. 154. 130. 127. on each for the 50 - 57 57 - 64 64 - 70a 137. 140. 104. 120. 145. 139. 168. 126. 158. 170. 152. 167. 162. 132. 178. 140. 167. 125. b 122. 140. 136. 186. 129. 157. 149 137. b 166. 139. 175. 118. 136. 126. 139. 108. 130. b 122". 117. 108. 108. 99. 130. 122. 108. 119. 104. 129. 105. ii0. _ rat's day postweaning, youngest rats in this days group. 64-70 ............. postweaning was > [/) 4_ O0 IOV PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 3): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY ...................... - ............................................................................................................. STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 .................................................................................................................................... 1361 63. 98. 117. 114. 1362 1363 1364 1365 1366 49. 61. 57. FOUND 63. 88. 99. 91. DEAD ON 79. 109. 118. 136. 127. 133. 184. DAY 4 POSTWEANING 129 109 119. 133. 194. 114. 139. b 118. 134. b 1367 1368 1369 1370 52. 85. 116 116 109. 116. 109. 69. 115. 142 131 140. 144. 150. 76. 122. 141 136 63. 98. 129 152 b 1371 1372 65. 113. 130 138 145. 159. 175. 73. 122. 132 131 1373 1374 68. ii0. 139 196 221. 152. 137. 75. 113. 141 141 1375 1376 1377 62. 103. 130 140 134. 130. 132. 66. 95. 105 127 127. 139. 169. 44. 92. 131 151 1378 1379 1380 75. 122. 141 140 136. 137. 148. 69. 116. 146 136 141. 152. 164. 56. 104. 136 139 1381 1382 1383 1384 1385 1386 62. 101. 124 117 121. 128. 138. 66. 109. 126 141 134. 135. 189. 49. 94. 126 147 131. 133. 189. 54. 89. 118 130 111. 115. 133. 80. 122. 137 133 54. 101. 119 118 1387 1388 70. 114. 136 134 74. 108. 131 130 161. 153. 200. - 57 113. 136. b 108. 157. 150. FOUND 130. 152. 134. 156. 134. 129. 133. 119. 153. 57 - 64 64 - 70a 124. 134. 157. 181. 116. 89. 108. 174. 98. 148. 157. 127. DEAD ON DAY 51 POSTWEANING 133. 151. 113. 126. 141. 157. 125. 129. 128. 129. 131. 129. 115. 100. 108. 101. 157. 126. 1389 1390 71. 106. 75. 116. C 127 C 130 ..................................................................................................... ffiDAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). 150. 151. 179. 156. 165. 126. _ .............................. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O_ Spilled feed precluded the calculation of this value. Wet feed precluded the calculation of this value. [_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 4}: FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1391 1392 68. 101. 129, 132. 61, 102. 137. 126. 148. b 1393 1394 1395 1396 1397 1398 65 89. 130. 127. 129. 127. 64 105. 138. 135. 59 105. 129 130. 72 93. 149 127. 81 126. 152 151. 150. 161. 51 102. 130 130, 1399 1400 1401 1402 77 118. 136 126. 136. 138. 74 109. 129 123. 79 102. 125 137 123. 129. 74 116. 126 135 43 - 50 159. 122, 152. 142. 154. 50 - 57 165. 108. 139. 134, 124. 57 - 64 176. 129. 135, 126. 116. 64 - 70a 145. 106. 125. 107. 108. 1403 1404 1405 1406 1407 1408 1409 1410 68 106. 128 121 68 114. 133 134 57. 91. 123 142 69. 106 126 123 71. 125 144 116 67. 99 116 113 64. 102 113 125 68. 108 132 134 147. 154. 133. 140. 146. 157, 122. 138. 1411 1412 1413 1414 1415 1416 1417 69. 106 73, 116 67. 114 62. 103 60. 100 74. 110 72. 108 117. 126. 143. 116. 121. 130. 126. 147. 126. 135. 130. 133. 133. 129. 140. 143. 1418 1419 1420 62. 95 110. 64. 102 124. 52. 99. 120. 112. b 117. 120. ...................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based the last interval in which a feed consumption value was recorded Spilled feed precluded the calculation of this value. 157. 173. 136. 144. 136. 150. 137. 252. 151. 154. 151. 143. 144. 149, 146, 204. 166. 141. 109. 127. 138. 146. 128. b 123. 129. b 116. 116. 105. 107, 96. ........................ on each for the rat's day postweaning, youngest rats in this days 64-70 group. postweaning was [29 _ OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 5): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1421 1422 1423 61 99. 124. 121 123. 121. 67 105. 125. 121 67 109. 130. 140 i424 1425 75 114. 131. 139 120. 127. 66 116. 149. 173 1426 1427 51 82. 110. 108 124. 138. 68 120. 144. 153 1428 1429 73 113. 142. 180 141. 151. 70 Iii. 141. 161 1430 1431 1432 71 51 FOUND 131. 103. DEAD ON 164. 185 129. 147 DAY 7 POSTWEANING 175. 140. 174. 145. 1433 1434 1435 73 115. 129. 138 140. 137. 61 108. 134. 145 84 124. 149. 170 1436 1437 1438 73 129. 142. 144 140. 130. 60 115. 124. 130 128. 123. 69 117. 121. 110 1439 1440 1441 69 115. 151. 149 137. 215. 74 127. 146. 157 45 95. 126. 138 1442 1443 1444 1445 67 99. 130. 134 135. 162. 61 94. 118. 123 126. 129. 49 93. 133. 130 70 128. 173. 172 1446 1447 69 112. 120. 121 132. 130. 64 105. 125. c 1448 72 106. 134. 135. 142. 145. 43 - 50 124. 124. 150. 149. 164. 150. 145. 150. 163. 153. 158. 140. 235. 177. 50 - 57 126. 127. 149. 153. 162. 151. 149. 143. 148. 153. 136. 137. b 128. 57 - 64 127. 124. 158. 154. 172. 141. 155. 143. 132. 177. 138. 192. 124. 130. 64 - 70a 106. 104. 123. 124. 135. 123. 117. 130. 108. 134. 130. 114. 114. 117. 1449 1450 77 125. 79 124. c 161. c 124. ..................................................................................................... = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). b 139. 140. 135. 124. 125. 103. _ .............................. [29 Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was _t_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 Spilled feed precluded the calculation of this value. Wet feed precluded the calculation of this value. Iv C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 6): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1451 1452 1453 1454 85. 127 70. 129 89. 133 74. 126 146. 145 133. 135 143. 147 143. 136 276. 163. 1455 1456 1457 1458 84. 129 85. 117 82. 118 82. 121 180. 128. 128. 145. 167 117 120. 145. 202. 123. 117. b 117. 132. 1459 1460 97. 132 80. 101 145. 135. 160. 143. 162. 163. 1461 1462 76. 108 72. 100 131. 123. 148. iii. 139. 147. 1463 1464 1465 1466 1467 1468 71. 108 86 131. 125. 142. 128. 148. 136. 138. 45 84. 119. 138. 145. 157. 49 96. 127. 62 i01. 142. 59 97. 117. 116. 115. 125. 1469 1470 69 81. 101. 115. 136. 134. 64 103. 125 1471 72 125. 124 1472 1473 1474 1475 1476 71 120. 122 80. 132. 135 78. 119. 126 62. 103. 117 75. 118. 145 121. 125. 144. 119. 126. 150. 130. 127. 153. 1477 1478 87. 123. 131 73. 130. 147 135. 160. 180. 1479 1480 73. 121. 136 67. 113. 136 132. 141. 158. .................................................................................................................................. = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based the last interval in which a feed consumption value was recorded Spilled feed precluded the calculation of this value. 43 - 50 50 - 57 57 - 64 64 - 70a 182. b 205. 122. 196. 123. 127. 166. 147. 156. 191. b 110. 123. 151. 147. 147. b 189. 122. iii. 137. 129. 142. 168. 153. 96. 109. 126. 116. 129. 129. 152. 149. 148. 161. 145. 159. 109. 104. _ b 136. 162. 196. 170. 146. 150. 157. b b 151. 146. 101. 108. 123. 133. 134. 126. 126. 119. on each rat_s day postweaning, for the youngest rats in this days 64-70 group. postweaning was [/9 _Oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 7): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 50 - 57 57 - 64 64 - 70a 1481 1482 1483 1484 1485 71. 83. 45. FOUND 56. 117. 117. 92. DEAD ON Ii0. 129. 144. 144. 140. 133. 135. DAY 3 POSTWEANING 145. 170. 125. 131. 127. 127. 130. 125. 132. 126. 125. 146. 118. 104. 1486 1487 1488 1489 1490 1491 1492 1493 35. 74. 107. 122. 79. 127. 138. 137. 73. 132. 140. 145. 67. 105. 139. 145. 64. 116. 147. 169. 73. 101. 133. 120. 69. 107. 129. 131. 84. 123. 150. 140. 123. 135. 157, 133, 127. 156. 194. 146. 128. 163. 292. 189. 130. 163. 174. 150. 129. 168. 118. 146. 108. 143. b 122. 1494 1495 1496 1497 1498 1499 1500 1501 88 109. 140. 138. 138. 168. 128. 130. 139. 116. 89 124 128. 125. 82 116. 133. 129. 124. 129. 131. 123. 124. 116. 89 128. 145 146. 149. 149. 165. 149. 138. 120. 36 103. 136 150. 65 104. 127 133. 65 91. 179 c b 142. 187. 138. 128. 109. 70 115. 141 138 1502 1503 1504 1505 1506 1507 1508 67 116. 144 166 69. 104. 113 122 76. 101. 124 134 65. 110. 136 133 67. 108. 111. 124 66. 93. 123. 130 85. 127. 139. 152 165. 131. 124. 146. 177. 139. 126. 146. 206. 139. 132. 141. 149. 140. 123. 138. 173. 135. 121. 136. 163. 123. 104. 109. 1509 80. 103. 118. 115 > 1510 75. 135. 178. 155. ................................................................................ = DAY POSTWEANING .................................................... WEIGHTS WERE RECORDED IN GRAMS (G). 50 Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was /_ the last interval in which a feed consumption value was recorded for the youngest rats in this group, oo Spilled feed precluded the calculation of this value. Value was not recorded. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 8): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1511 1512 55. 105 85. 124 119. 134. 127. 136. 137. 142. 1513 1514 1515 71. 107 83. 117 69. 106 129. 128. 116. 139. 133. 115. 137. 137. 138. 140. 1516 1517 1518 91. 110 79. 120 68. 118 124. 133. 138. 126. 136. 147. 137. 127. 143. 136. 1519 1520 60. I01 70. 125 124. 127. 135. 125. 129. 1521 1522 71. 95 82. 129 119. 127. 121. 121. 124. 43 - 50 143. 173. 190. 157. 142. 125. b 50 - 57 140. 161. 166. 146. 145. 130. 138. 57 - 64 136. 177. 145. 150. 142. 116. b 64 - 70a 141. 115. 114. 128. 119. 102. 116. 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 64. i00 62. 76 59. 96 78. 116 92. 124 68. 122 52. 96 75. 113 71. 113 75. 127 81. 132 71. 118 68. 113 67. 119 58. 102 62. 110 109. 114. 114. 137. 142. 118. 109. 134. 140. 142. 144. 131. 129. 120. 123. 132. 108. 118. 144. b 140. 129. 123. 130. 115. 130. 138. 114. 145. 151. 133. 132. 124. 137. 148. 116. 143. 135. 128. 134. b b b 151. 150. 152. 143. 199. b b b 211. 144. 153. 142. 143. b 187. b h 137. 151. 148. 176. 108. 109. 121. 92. 115. 121. 101. 119. 1539 1540 69. iii 70. 102 ..................................................................... - DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS 133. 119. (G). 209. 141. 165. 167. 166. 164. 127. _ .............................................................. [29 Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 Spilled feed precluded the calculation of this value. _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APF0) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE 9): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... STATUS DAY I - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 43 - 50 50 - 57 57 - 64 64 - 70a 1541 1542 1543 49. 85 57. i01 56. 89 Iii. 133. 108. 120. 135. ii0. 114. 105. 108. 113. 116. i00. 1544 1545 1546 1547 58. 102 66. 113 65. 95 65. 96 142. 130. 119. 124. 157. 157. 119. 138. 152. 192. 123. 157. 169. 130. 158. 167. 142. 168. 181. 141. 165, 193. 137. 136. 128. 116. 1548 1549 62. 95 117. 128. 115. 130. 133. 133. 139. Iii. 15. FOUND DEAD ON DAY 8 POSTWEANING 1550 1551 57. 92 62. 103 107. 128. 115. 137. 104. 126. 121. 123. 127. 108. 1552 1553 1554 65. 107 120. 123. 119. 113. 116. 126. 125. 99. 58. 91 110. 122. 66. 104 128. 136. 1555 1556 64. 95 124. 138. 118. 131. 143. 113. 120. 106. 70. 96 ii0. 112. 1557 1558 1559 79. 63. FOUND 107 106 DEAD ON 124. 124. 137. 143. DAY 6 POSTWEANING 138. 136. 137. 146. 149. 248. 133. b 130. 141. 118. 124. 1560 1561 1562 67. 118. 141. b 137. 155. 291. 149. 140. b 72. 116. 135. 144. FOUND DEAD ON DAY 2 POSTWEANING 1563 FOUND DEAD ON DAY 2 POSTWEANING 1564 65. 100 C 125. 133. 130. 170. 136. 129. 114. 1565 1566 1567 64. 95 70. 113 70. 119 C 123. 138. 123. 131. 140. 115. b 113. 139. 113. 137. 104. 140. 107. 132. 95. 110. 1568 83. 133 138. 134. 138. 143. 145. 132. 129. 109. 1569 79. 118 122. 116. 1570 62. 93 130. 126. _. O = DAY POSTWEANING WEIGHTS WERE RECORDED IN GRAMS (G). Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ w-d the last interval in which a feed consumption value was recorded for the youngest rats in this group. Oo Spilled feed precluded the calculation of this value. Wet feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER. PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E30 (PAGE i0): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP V 30 MG/KG/DAY ...................................................................................... STATUS DAY 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 .................................................................................................................................... 1571 1572 60. 88. 110. 113. 129. 132. 54. 99. 140. 146. 1573 1574 66. 116. 143. 143. 146. b FOUND DEAD ON DAY 3 POSTWEANING 1575 FOUND DEAD ON DAY 3 POSTWEANING 1576 1577 49. 82. 114 123 130. 141. 53. 94. 116 120 1578 1579 1580 1581 56. 104. 122 143 139. 125. 66. 107. 124 130 127. 134. 63 99. 114 121 71 106. 130 128 1582 52 90. 118 1583 1584 1585 62 106. 120 115. 137. 136. 60 94. 118 126. 129. 135. G2 106. 131 1586 1587 1588 1589 1590 61 93. 113 114. 117. 121. 61 106. 129 135. 133. 134. 62 103. 114 113. 118. 128. 72 127. 174 144. 136. 133. 68 109. 141. 1591 1592 69. 108. 67. 105. 175. 120. 164. 144. 142. 1593 1594 76. 103. 63. 103. 122. 112 138. 140. 132. 1595 1596 1597 70 111. 120 59 105. 126 62 89. 134 1598 72 109. 130 135. 139. 147. 43 - 50 129. 153. 144. 148. 137. b 144. 235. b b b 204. 135. 149. _ ............................................. 50 - 57 57 - 64 64 - 70a 122. 51. 175. 155. 158. 134. 137. 107. 139. 129. 117. 128. 111. 94. b 159. 132. 140. 153. 137. b b 165. b 130. 140. 148. 125. b 156. 151. 97. 99. 103. 113. 98. b 107. 114. 156. 146. 130. 1599 63 1600 68 ............................................ = DAY POSTWEANING WEIGHTS WERE RECORDED 108. 128 104. 119 IN GRAMS (G). 133. 125. 129. 132. 145. 145. 126. Because feed consumption was recorded at weekly intervals, based on each rat's day postweaning, days 64-70 postweaning was 4_ the last interval in which a feed consumption value was recorded for the youngest rats in this group. O0 Spilled feed precluded the calculation of this value. b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NIR4BER: PER GENERATION) T-6889.6) TABLE E31 (PAGE 1): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - 10 10 - 14 14 - 18 18 - 21 .................................................................................................................................... 1302 P 125 60. 76. 77. 62 1304 P 1306 P 156 71. 91. 95. 66 149 71. 96. 91. 71 1308 P 1310 P 1312 P 1313 P 1316 NP 1318 P 156 175 167 146 141 a 68. 95. 99. 70 78. 112. 112. 73 77. 114. 105. 74 68. 92 90. 67. 64. 83 63. 52. a 126 119 82. 1321 P 1325 P 193. 93. 112 112 77. 184. 79. 116 110 84. 1328 P 1330 P 1331 P 1334 P 1335 P 1336 P 1338 P 154. 74. 95 89 66. 141. 32. 82 76 56. 148. 75. 97 92 59. 136. 68 92 94 67. 183. 85 111 117 79. 188. 87 114 107. 72. 159. 68 94 I00. 81. 1340 P 1341 P 1342 P 1344 P 1345 P 1346 P 1348 P 1350 P 147. 65 88 82. 56. 165. 77 89. 98. 64. 159. 72 94. 91. 55. 138. 88 106. 95. 69. 172. 73 99. 110. 83 160. 68 88. 87. 63 153. 68 90. 92. 62 151. 68 86. 92. 66 1353 P 154. 68. 86. 79. 64 1355 P 1359 P 189. 87. i00. 107. 77 158. 68. 86. 80. 70 ..................................................................................................... PREGNANT DAYS= DAYS NP = NOT OF PRESUMED PREGNANT GESTATION (VALUES EXCLUDED FROM AVERAGES) WEIGHTS WERE RECORDED IN GRAMS (G) Spilled feed precluded the calculation of this value. REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - F1 GENERATION FEMALE RATS _ ............................. > {/9 4_ O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E31 (PAGE 2): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - I0 10 - 14 14 - 18 18 - 21 .................................................................................................................................... 1362 P 123. 62. 77. 79. 70. 1363 P a 68. 90. 90. 61 1364 P a 67. 89. 99. 52 1367 P 139. 70. 88. 87. 67 1368 P 183. 78. 105. 112. 75 1371 P 170. 95. 117. 120. 89 1375 P 135. 59. 87. 84. 70 1376 P 182. 81. 110. 106. 69 1378 NP 149. 55. 81. 79. 50 1379 P 191. 87. 108. 105. 62 1381 P 1382 P 1383 P 136. a 144 58. 86. 90. 67 62. 84. 90. 69 67. 88. 92. 66 1384 P 148 62. 80. 88. 68 1387 P 177 83. 117. ii0. 84 1389 P 194 86. 108. 109. 80 1392 P 191 94. 118. 108. b 1393 P 163 71. 88. 93. 67 1397 P 157 83. 99. 102. 79 1399 p 130 58. 83. 93. 66 1401 P 170 73. 93. 101. 58 1404 P 175 85. 124. 106. 70 1407 P 154 65. 91. 97. 70 1409 p 143 71. 88. 87. 79 1410 P 158 69. 85. 90. 57. 1413 P 159 73. 89. 80. 67. 1415 p 142 67. 87. 88. 68. 1416 p 1418 P 179 74. 93. i00. 77. 133 59. 80. 80. 64. .................................................................................................................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES} = DAYS OF PRESUMED GESTATION WEIGHTS WERE RECORDED IN GRAMS (G). Spilled feed precluded the calculation of this value. _o"o Value was not recorded. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} TABLE E31 (PAGE 3): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - 10 10 - 14 14 - 18 18 - 21 .................................................................................................................................... 1421 P a 60. 84. 86. 68. 1424 P 134. 65. 82. 90. b 1426 P 178. 85. 104. 115, 87. 1428 P a 75. 105. 105, 72 1430 P 173. 81. 110. 126. 79 1431 P 158. 70. 101. 111. 87 1433 P 159. 68. 106. 107. 75 1436 P 184. 84. 111. 93. 64 1437 P 146 70. 88. 90. 61 1439 P 168 79. 123. 114. 77 1442 P 193 79. 108. 112. 82 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 145 136 123 128 160 183 158 152 160 146 156 a 168 129 133 135 71. 96. 99. 72 66. 85. 73. 47 56. 74. 96. 70 58. 80. 89. 66 82. i00. 102, b 90. 113. 107. 75 76. 104. 109. 80 61. 89. 83. 54 74. 93. 99. 80 68. 92. 92. 66 73. 100. 112. 64 78. 102. 106. 56 a 101. 100. 64 65. 87. 86. 65 61. 86. 88. 69 71. 86. 98. 61. 1476 P 1477 P 1480 P 163 82. 104. 95. 147 67. 87. 94. 165 65. 87. 94. ........................................................................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED = DAYS OF PRESUMED GESTATION FROM b 69. 70. AVERAGES) WEIGHTS WERE RECORDED Spilled feed precluded Value was not recorded. IN GRAMS (G). the calculation of this value. _ ........................................ [/_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E31 (PAGE 4): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION .................................................................................................................................... RAT # DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - 10 10 - 14 14 - 18 18 - 21 .................................................................................................................................... 1482 P 173. 75. I01. i01 1483 NP 128. 54. 73. 72 1486 P a 66. 95. 96 1488 P 175. 76. 102. 95 1490 P 181. b 109. 112 1491 P 165. 84. 98. 97 1494 P 176. 76. 95. 83 1496 P 144. 68. 84. 93 1497 P 168. 72. 94. 89. 1500 P 157. 63. 96. 96. 1502 P 192. 81. 107. 117. 1505 P 1507 P 153. 136. 67. 93. 96. 64. 82. 82. 1508 P 135. 73 102. 97. 1511 NP 143. 68. 88. 77. 1513 P 158 70. 91. 102. 1514 P 150 68. 86. 91. 1516 P 155 67. 97 106. 1517 P 159 55. 91 98. 1519 P 125 55. 82 93. 1521 P 132 58. 71 77. 1523 P 150 68. 91 82 1524 P 164 63. 100 95 1527 P 148 72. 98 99 1528 P 145 60. 88 85 1531 P 145. 73. 94 91 1533 P 150. 70. 104 105 1534 P 139. 57. 82 86 1537 P 175. 69. 90 i00 1539 P 165. 76. 99. 113 ........................................................................................... 64. 55. 66. 62. 82. 68. 61. 70. 61. 70. 78. 64. b 63 52. 75. 60. 78. 65. 61. 61. 56. 76. 73. 61. 81. 61. 63. 61. 84. DAYS PREGNANT NP = NOT PREGNANT (VALUES = DAYS OF PRESUMED GESTATION WEIGHTS WERE RECORDED IN GRAMS (G). Spilled feed precluded Value was not recorded. the calculation EXCLUDED FROM AVERAGES) of this value. REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - F1 GENERATION FEMALE RATS ......................................... [2_ 4_ _._ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NT24BER: PER GENERATION) T-6889.6) TABLE E31 (PAGE 5): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... PREGNANCY STATUS DAYS 0- 7 7 - 10 10 - 14 14 - 18 18 - 21 .................................................................................................................................... 1541 P 119. 63. 79. 87. 60. 1544 P 171. 87. 112 104 75. 1545 P 183. 79. 111. 119. 76. 1546 P 149. 70. 92. 91. 65. 1548 P a 57. 87. 106 b 1550 P 147. a 94. 102 66. 1552 P 143. 57 84. 79. 58. 1555 P 130. 59 78. 80. 63. 1557 P 135. 62 83. 92. 71. 1558 P 168. 76 96. 103 74. 1560 P 170. 67 102. iii. 75. 1564 P 1565 P 1566 P 1568 P 1571 P 1573 P 1576 P 1578 NP 1579 P 1583 P 1584 P 1586 P 1587 P 1588 P 1589 P 1591 P 150. 121. 131. 115. 134. 157. 156. 104. 128. c 168. 136 143. 136 166 158. 60 95. 94. 75. 57 74. 81. 66. 62 83. 86. 60. 58 92. 96. 69. 59 84. 96. b 75 95. 106 76. 65 97. 104. 78. 37 57. 57. 43. 65 72. 93. 64. 62 86. 99. 74. 56 81. 86. 62. 60 82. 81 56. 67 93. 104 78. 57 89. 92 67. 73 106 111 b 72 98. 109 71. 1593 P 1598 P 1600 P 144. 69 160. 76 97. 98 72. 94. 89 78. 162. 74 106. 106 77. ........................................................................................... PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) = DAYS OF PRESUMED GESTATION WEIGHTS WERE RECORDED IN GRAMS (G) Wet feed precluded the calculation of this value Value was not recorded. Spilled feed precluded the calculation of this value. REPRODUCTION - INDIVIDUAL STUDY OF AMMONIUM PERFLUOROOCTANOATE DATA - F1 GENERATION FEMALE RATS u ........................................ C/9 4_ _" O0 _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E32 (PAGE 1): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP I 0 MG/KG/DAY ...................................................................................... DAY 1 - 5 5- 8 8 - 11 ii - 15a .................................................................................................................................... 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 118. 125. 118. 148. 149. 153. 185. 167. b 170. 84. 101. 120. 134. NOT PREGNANT 154. 184. 129. 180. 104. 157. 515. 141. 145. 180. 176. 193. 200. 119. 138. 170. 120. 170. 180. 185. 199. 239. 255. 234. 158. 186. 270. 250. 272. 277. ............................................... 11333301 1334 1335 1336 1338 1340 1341 1342 10980.. 83. 113. 161. 195. 125. 110. 113. 111277. 107 138 168 190 132 132 150 116430.. 126. 151. 192. 150. 165. 117. 133. 213928.. b 225. 200. 254. 306. 211. 214. 1344 1345 1346 1348 1350 1353 1355 124. 131. 109. 103. 103. 115. 113. 155 159 128. 156. 151. 98. 166. 174. 184. 144. 205. 183. 159. 180. 244. 271. 227. 244. 245. 273. 246. 1358 1359 NOT PREGNANT; 96. 114. MATING NOT 177. CONFIRMED 256. ...................................................................................................... ............................... = DAY OF LACTATION WEIGHTSWERE RECORDED IN GRAMS (G). Because it is presumed that the pups begin to consume maternal feed after day 15 of lactation, maternal feed consumption values were not tabulated on days 15 to 22 of lactation. O0 Spilled feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E32 (PAGE 2): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE .................................................................................................................................... RAT # DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1- 5 5- 8 8 - 11 11 - 15a .................................................................................................................................... 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 90. 97. 122. 148. 127. 145. 137. 152. 174. 194. 142. 171. 116, 139. 122. 138. NOT PREGNANT 99. 134. 125 141. 151 166. 118. 177. 167. 171. 210. 161. 155. 164. 168. 157 215 191. 213. 197. 286. 242. 278. 200. 224. 252. 230. 303. 11338834 1387 1389 1392 1393 1397 111620 114283.. 117614 125 146. 180 161 159. 159 94 129. 162 97. 142. 170 109. 163. 147 215699.. 213. 230. 246 232 263 1399 1401 1404 1407 1409 1410 1413 1415 1416 102. 139. 129. 161. 113. 121. 93. 91. 102. 121. 146 113 163 111 177 154 141. 156. 145. 167. 159. 196. 145. 197. 190. 130. 154. 169 155 257 203 256 242 297. 222. 210. 1418 118. 160. 156. 198. .................................................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). Because it is presumed that the pups begin to consume were not tabulated on days 15 to 22 of lactation, maternal feed after day 15 of lactation, maternal RATS feed consumption values _9 4_ 00 _b t_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E32 (PAGE 3): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 - 5 5- 8 8 - 11 11 - 15a .................................................................................................................................... 1421 122. 152. 186. 212 1424 109. 143. 162. 189 1426 93. 132. 157. 230 1428 113. 154. 181. 221 1430 108. 127. 160. 238 1431 133. 154. 171. 268 1433 133. 163. 169. 230 1436 109. 117. 143. 207 1437 128. 152. 152. 230 1439 109. 148. 138. 219 1442 i443 118. 123. 121. 152. 205 1446 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 1476 NOT PREGNAN1T55. 107. 150. 99. 124. 80. 114. 110. 139. 107. 121. NOT PREGNANT 123. 177. 103. 126. 110. 135. 118. 161. 136. 114. b 130. 126. 136. 99. 128. 82. 140. 183. 177. 141. 157. 167. 133. 152. 153. 175. 179. b 176. 142. 206. 196. 262 196. 206. 171. 237. 198. 239 239 209 210 243 256 233 246 276 1477 1480 149. 147. 110. 159. 180. 307 187. 241 .................................................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). Because it is presumed were not tabulated on Spilled feed precluded that the pups begin to consume days 15 to 22 of lactation. the calculation of this value. maternal feed after day 15 of lactation, maternal feed consumption values > [/_ _t_ "Oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E32 (PAGE 4): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS RAT # DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... DAY 1 - 5 5- 8 8 - 11 11 - 15a .................................................................................................................................... 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 I00. 121. NOT PREGNANT 134. 158. i02. 158 b 152 157. 166 127. 133 99. 90 123. 152 117. 133 b 149. 118. 130. 160. 178. 178. 176. 188. 154. 166. 168. 178. 156. 113. 185. 253. 205. 198. 273. 309. 225. 238. 252. 228. 249. 1507 1508 1511 1513 1514 1516 1517 1519 1521 92. 169. 96. 122. NOT PREGNANT 114. 153. 117 155. 152 138. 87 120. 115 156. 103 140. 140. 135. 168. 190. 167. 172. 182 159 293. 143. 168. 151. 231. 248. 278. 217. 1523 1524 1527 1528 1531 126 79 123 110. 145. 145. 64. 154. 86. 155. 152 79 141 153 133 257. 112. 153. 237 274 1533 1534 116. 158. 155 261 82. 130. 137 193 1537 1539 118. 157. 178 189 154. 178. 138 289 ..................................................................... - .............................................................. = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). Because it is presumed that the pups begin to consume maternal feed after day 15 of lactation, maternal feed consumption values 4_ were not tabulated on days 15 to 22 of lactation. O0 Spilled feed precluded the calculation of this value. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E32 (PAGE 5): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... RAT # DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 - 5 5- 8 8 - 11 11 - 15a _ .............................................................................................................................. 1541 122. 130 152. 216. 1544 130. 147 171. 289. 1545 140. 179 186. 257. 1546 128. 122 112. 205. 1548 75. 113 152. 246. 1550 141. 154 151. 203. 1552 120. 137 158 181. 1555 111. 119 146 179. 1557 1558 112. 131 162 207. 131. 181 184 218. 1560 135. 151 155 241. 1564 123. 118 152 263. 1565 110. 123. 116 189. 1566 101. IIi. 115 224. 1568 121. 119. 162 216. 1571 84. 123. 168 174. 1573 120. 148. 177 223. 1576 92. 116. 145 197. 1578 NOT PREGNANT 1579 108. 142 155 194. 1583 127. 144 169 167. 1584 68. 87 91 134. 1586 1587 123. 129 164 173. 113. 126 128 173. 1588 118. 137 132 273. 1589 91. 137 143 237. 1591 140. 145 182 192. 1593 129. 120 131. 129. 1598 1600 143. 128 133. 160 153. 170. 225. 234. ..................................................................................................... = DAY OF LACTATION WEIGHTS WERE RECORDED IN GRAMS (G). Because it is presumed that the pups begin to consume were not tabulated on days 15 to 22 of lactation. maternal feed after day 15 of lactation, _ .............................. maternal feed consumption values [2_ 4_ _O"0 _0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E33 (PAGE 1): SEXUAL MATURATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................. DOSAGE GROUP - .................................................................................................................................... MG/KG/DAY I II III 0 1 3 .................................................................................................................................... VAGINAL VAGINAL VAGINAL RAT # PATENCY (DAY) RAT # PATENCY (DAY) RAT # PATENCY .................................................................................................................................... (DAY) 1301 37 1302 37 1303 36 1304 38 1305 36 1306 35 1307 36 1308 36 1309 35 1310 34 1311 36 1312 36 1313 35 1314 31 1315 29 1316 31 1317 34 1318 34 19779 36 19780 36 1321 31 1322 31 1323 31 1324 35 1361 35 1362 37 1363 37 1364 37 1365 a 1366 35 1367 35 1368 35 1369 34 1370 37 1371 35 1372 36 1373 36 1374 38 1375 38 1376 38 1377 38 1378 36 1379 34 1380 37 1381 37 1382 38 1383 39 1384 36 1421 37 1422 36 1423 33 1424 34 1425 35 1426 35 1427 33 1428 34 1429 35 1430 36 1431 38 1432 c 1433 35 1434 36 1435 33 1436 33 1437 33 1438 33 1439 35 1440 33 1441 37 1442 36 1443 40 1444 35 1325 36 1326 35 1327 34 1328 34 1329 36 1330 36 1385 33 1386 34 1387 36 1388 32 1389 31 1390 36 1445 34 1446 35 1447 35 1448 33 1449 32 1450 34 RAT # 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 DAY = DAY POSTPARTUM Rat was found dead before Sexual maturation testing Rat was found dead. the start of sexual maturation evaluation. was discontinued before rat became sexually mature. IV 10 VAGINAL PATENCY (DAY) 35 34 41 a 36 43 32 35 b 37 33 34 35 33 35 32 34 36 35 35 36 36 36 35 36 34 37 34 ' 33 34 RAT # 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 1564 1565 1566 1567 1568 1569 1570 V 30 VAGINAL PATENCY 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 (DAY) _> f29 4_ o_ i _iv PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E33 (PAGE 2): SEXUAL MATURATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP - MG/KG/DAY .................................................................................................................................... I II III 0 1 3 .................................................................................................................................... VAGINAL VAGINAL VAGINAL RAT # PATENCY (DAY) RAT # PATENCY (DAY) RAT # PATENCY .................................................................................................................................... (DAY) 1331 38 1332 36 1333 36 1334 40 1335 35 1336 34 1337 35 1338 35 1391 36 1392 35 1393 39 1394 35 1395 35 1396 32 1397 32 1398 38 1451 31 1452 31 1453 29 1454 29 1455 29 1456 35 1457 36 1458 35 RAT # 1511 1512 1513 1514 1515 1516 1517 1518 11333490 3365 1341 34 1342 36 1343 33 1344 34 1345 38 1346 34 1347 36 1348 36 1349 37 1350 31 1351 34 1352 33 1353 33 1354 34 11349090 3345 1401 38 1402 33 1403 32 1404 35 1405 43 1406 37 1407 30 1408 38 1409 b 1410 34 1411 33 1412 34 1413 36 1414 37 11445690 3331 1461 38 1462 31 1463 31 1464 31 1465 41 1466 39 1467 34 1468 b 1469 34 1470 34 1471 34 1472 38 1473 34 1474 32 1355 35 1356 32 1357 36 1358 37 1359 37 1360 36 1415 37 1416 35 1417 34 1418 35 1419 35 1420 34 1475 35 1476 34 1477 30 1478 32 1479 33 1480 35 .................................................................................................................................... ffiDAY POSTPARTUM Rat was found dead before the start of sexual maturation evaluation. Sexual maturation testing was discontinued before rat became sexually 11551290 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 mature. IV i0 VAGINAL PATENCY 34 35 36 31 34 37 34 35 3362 31 35 36 35 37 32 33 35 39 34 34 34 32 34 33 34 35 37 34 35 (DAY) RAT # 1571 1572 1573 1574 1575 1576 1577 1578 11557890 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1594 1595 1596 1597 1598 1599 1600 V 30 VAGINAL PATENCY 37 36 36 a a 41 40 39 3346 34 39 38 38 38 38 36 37 31 37 35 35 36 38 34 36 38 35 37 35 (DAY) > [29 4_ 0_ I_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E34 (PAGE 1): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... 1302 6 4 M 1304 5 2 M 1306 6 4 M 1308 5 2 M 1310 5 3 M 1312 4 1 M 1313 3 2 M 1316 5 1 M 1318 3 2 M 1321 4 3 M 1325 6 1 M 1328 6 4 M 1330 5 3 M 1331 3 4 M 1334 5 2 M 1335 5 3 M 1336 5 3 M 1338 5 2 M 1340 3a 5 M 1341 5 2 M 1342 4 2 M 1344 5 4 M 1345 4 2 M 1346 5 1 M 1348 5 1 M 1350 5 2 M 1353 4 5 M 1355 5 3 1358 5 14 1359 4 4 ................................................................................ M = MATED C = CONFIRMED NC = NOT CONFIRMED PRO = PROESTRUS E = ESTRUS MET = METESTRUS a. Six or more consecutive days of diestrus were M DID NOT M P = PREGNANT D = DIESTRUS observed. MATE NP = NOT MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C C C PREGNANT PREGNANCY STATUS P P P P P P P NP P P P P P P P P P P P P P P P P P P P P NP P . ESTROUS STAGE AT SACRIFICE MET E D D E MET D D D E D E D D D D MET D D E E D D D MET D PRO D PRO D - ..................... [2_ "00 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E34 (PAGE 2) : MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... MATING DATE PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE 1362 6 4 M 1363 5 3 M 1364 5 3 M 1367 6 4 M 1368 5 3 M 1371 5 4 M 1373 FOUND DEAD ON DAY 51 POSTWEANING 1375 6 2 M 1376 5 4 M 1378 6 3 M 1379 6 4 M C P E C P E C P MET C P E C P D C P D C P D C P D C NP E C P MET 1381 6 1382 5 1383 4 1384 5 1387 5 1389 3 1392 6 1393 5 1397 6 1399 5 1401 5 1404 5 1407 5 1409 3 1410 3 1413 6 4 M 3 M 2 M 2 M 3 M 2 M 4 M 2 M 2 M 3 M 2 M 4 M 3 M 6 M 3 M 4 M C P D C P D C P D C P E C P E C P D C P D C P E C P MET C P D C P E C P D C P D C P D C P E C P E 1415 4 1416 5 1 M 1 M 1418 5 2 M ........................................................................................... C P D C P PRO C P D '-........................................ M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP = NOT PREGNANT PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS 4_ O0 0 PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E34 (PAGE 3): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... 1421 6 1 M 1424 4 2 M 1426 6 1 M 1428 5 1430 5 1431 4 1433 6 1436 6 1437 6 1439 5 1442 5 3 M 2 M 1 M 3 M 4 M 4 M 3 M 1 M 1443 4 1446 4 1448 4 1450 5 1452 4 1455 6 2 M 4 M 2 M 3 M 2 M 4 M 1456 5 1458 5 1 M 1 M 1459 4 1461 5 1463 6 1465 5 1468 6 1469 4 1472 5 1474 5 2 M 3 M 2 M 2 M 4 M 1 M 4 M 2 M 1476 6 4 M 1477 6 4 M 1480 4 1 M ........................................................................................... M = MATED C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT NP PRO = PROESTRUS E = ESTRUS MET = METESTRUS D = DIESTRUS = NOT MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C PREGNANT - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PREGNANCY STATUS ESTROUS STAGE AT SACRIFICE F P P P P P P P P P P P NF P P P P P NP P P P P P P P P P P P .......................................... D D D MET E D PRO D D MET D PRO D D D D D E D D D E D PRO E D D E D D > _'_ [/_ 4_ O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E34 (PAGE 4): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... 1482 6 1483 5 1486 5 1488 6 1490 7 1491 5 1494 4 1496 5 1497 5 1500 5 1 M 1 M 1 M 1 M 1 M 2 M 4 M 2 M 4 M 3 M 1502 2a 1 M 1505 5 3 M 1507 6 4 M 1508 6 4 M 1511 3 7 M 1513 3 2 M 1514 5 2 M 1516 6 4 M 1517 6 i M 1519 5 1 M 1521 6 4 M 1523 6 4 M 1524 6 1 M 1527 5 4 M 1528 5 3 M 1531 4 4 M 1533 5 3 M 1534 5 1 M 1537 5 3 M 1539 4 5 M MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C M= PRO a. MATED C= = PROESTRUS Six or more CONFIRMED E = ESTRUS consecutive NC = NOT CONFIRMED MET = METESTRUS days of diestrus P = PREGNANT D = DIESTRUS were observed. NP = NOT PREGNANT PREGNANCY STATUS P NP P P P P P P P P P P P P NP P P P P P P P P P P P P P P P . ESTROUS STAGE AT SACRIFICE D E E D D E D PRO E D PRO D D D D D D D E D D MET E D D D D D D D > C [/) 4_ O_0" to 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E34 (PAGE 5): MATING AND FERTILITY, ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... ESTROUS STAGES/ DAYS IN MATING RAT # 21 DAYS COHABITATION STATUS .................................................................................................................................... 1541 6 2 M 1544 6 5 M 1545 5 3 M 1546 6 4 M 1548 5 3 M 1550 6 1 M 1552 6 3 M 1555 6 4 M 1557 5 2 M 1558 6 1 M 1560 6 1 M 1564 5 1565 5 3 M 2 M 1566 5 4 M 1568 5 3 M 1571 5 3 M 1573 5 2 M 1576 5 1 M 1578 6 3 M 1579 6 2 M 1583 5 1 M 1584 7 1 M 1586 6 4 M 1587 5 1 M 1588 5 3 M 1589 4 3 M 1591 4 2 M 1593 5 1 M 1598 5 4 M 1600 6 4 M MATING DATE C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C M = MATED C = CONFIRMED NC = NOT CONFIRMED PRO = PROESTRUS E = ESTRUS MET = METESTRUS P = PREGNANT D = DIESTRUS NP = NOT PREGNANT PREGNANCY STATUS P P P P P P P P P P P P P P P P P P NP P P P P P P P P P P P. ESTROUS STAGE AT SACRIFICE D MET D D D D E D D D D PRO D D D D E D E D D D D PRO D D D E D D C [29 /_ O0 b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E35 (PAGE i): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE (t__ ..j 4_ .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... I 0 1301 DP 32 31 1302 DL 22 P 130 1303 DP 32 31 1304 DL 22 P 128 1305 DP 32 31 1306 DL 22 P 129 1307 DP 31 30 1308 DL 22 P 126 1309 DP 31 30 1310 DL 22 P 127 1311 DP 31 30 1312 DL 22 P 126 1313 DL 22 P 126 1314 DP 30 29 1315 DP 30 29 1316 DG 25 NP 107 1317 DP 30 29 1318 DL 22 P 126 19779 DP 28 27 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 19780 DP 28 27 SPLEEN: SMALL (0.099 G). ALL OTHER TISSUES APPEARED NORMAL. 1321 1322 1323 1324 1325 DL 22 P DP 30 DP 30 DP 30 DL 22 P 126 29 29 29 124 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1326 DP 30 29 ALL TISSUES APPEARED NORMAL. 1327 DP 30 29 ALL TISSUES APPEARED NORMAL. 1328 DL 22 P 128 ALL TISSUES APPEARED NORMAL.. 1329 DP 29 28 ALL TISSUES APPEARED NORMAL. 1330 DL 22 P 125 ALL TISSUES APPEARED NORMAL. [/] -- .................................................................................................................................. DP ffiDAY POSTWEANING DG ffiDAY OF PRESUMED GESTATION DL = DAY OF LACTATION _- 00 a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E35 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY} NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... I OBSERVATIONS a 0 CONT. (_ t_ -._ t21 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 DL 22 P DP 29 DP 29 DL 22 P DL 22 P DL 22 P DP 28 DL 22 P DP 28 DL 22 P DL 22 P DL 22 P DP 28 DL 22 P DL 22 P DL 22 P DP 28 DL 22 P DP 28 DL 22 P DP 28 DP 27 DL 22 P DP 27 DL 22 P DP 27 DP 24 DP 114 NP 126 28 28 124 126 125 27 123 27 127 123 123 27 126 123 123 27 122 27 123 27 26 126 26 123 26 23 113 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES TISSUES ALL ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEAP_D APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1359 1360 DL 22 P DP 18 ...................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION a. Refer to the individual clinical observations table 116 17 ALL TISSUES ALL TISSUES APPEARED APPEARED DL -- DAY (Table E26) OF LACTATION for external observations NORMAL. NORMAL. .- ............................. confirmed at necropsy. C/_ OO _O O _fQ t21 0% PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E35 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... II 1 1361 DP 32 31 OBSERVATIONS a ALL TISSUES APPEARED NORMAL. 1362 DL 22 P 130 NECROPSY OBSERVATIONS WERE NOT RECORDED. 1363 1364 DL 22 P DL 22 P 129 ALL TISSUES APPEARED NORMAL. 129 ALL TISSUES APPEARED NORMAL. 1365 DP 4 3 FOUND DEAD ON DAY 4 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL, 1366 1367 1368 1369 1370 1371 1372 DP 32 DL 22 P DL 22 P DP 32 DP 31 DL 22 P DP 31 31 130 129 31 30 128 30 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1373 DP 51 50 FOUND DEAD ON DAY 51 POSTWEANING. STOMACH : DISTENDED. INTESTINES : DISTENDED. LUNGS: DORSAL SURFACE, RIGHT APICAL LOBE, DEPRESSED WHITE AREA (0.3 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL. 1374 1375 DP 31 DL 22 P 1376 1377 1378 1379 1380 DL 22 P DP 31 DG 25 NP DL 22 P DP 31 - 1381 1382 1383 1384 DL 22 P DL 22 P DL 22 P DL 22 P ......................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION a. Refer to the individual clinical observations table 30 127 128 30 Ii0 129 30 129 128 126 127 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEA_ED APPEARED APPEARED APPEARED APPEARED APPEARED DL = DAY (Table E26) OF LACTATION for external observations NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. confirmed ........................... at necropsy. [2_ 4_ O0 t_) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E35 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED OBSERVATIONS a .................................................................................................................................... II 1 CONT. f_ t_ -,_ _'_ 1385 1386 1387 1388 1389 1390 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 DP 31 DP 31 DL 22 P DP 30 DL 22 P DP 30 DP 30 DL 22 P DL 22 P DP 30 DP 30 DP 30 DL 22 P DP 30 DL 22 P DP 30 DL 22 P DP 29 DP 29 DL 22 P DP 29 DP 29 DL 22 P DP 29 DL 22 P DL 22 P DP 28 DP 28 30 30 127 29 126 29 29 126 125 29 29 29 126 29 127 29 124 28 28 127 28 28 125 28 129 126 27 27 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES TISSUES ALL ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPE_gRED APPEARED APPF2%RED APPE;d_ED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPE_d_ED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEA_RED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1413 1414 DL 22 P DP 28 126 27 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1415 DL 22 P 122 LIg-ER: LEFT LATERAL LOBE, FIRM MASS (2.0 CM X 1.2 CM X 0.4 CM), [J_ CUT SURFACE REVEALED YELLOW AND DARK RED AREAS; 4_ CAUDATE LOBE ADHERED TO LEFT LATERAL LOBE. OO ALL OTHER TISSUES APPEARED NORMAL. .................................................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION O 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) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E35 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ................................................................................................................. DOSAGES ADMINISTERED OBSERVATIONS a II 1 1416 DL 22 P 122 CONT. 1417 DP 28 27 1418 DL 22 P 124 1419 DP 28 27 1420 DP 28 27 .................................................................................................................................... ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED 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 NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. confirmed ................... at necropsy. tm OO > 4_ Oo PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E35 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... III 3 1421 DL 22 P 126 1422 DP 32 31 1423 DP 31 30 1424 DL 22 P 125 1425 1426 DP 31 - DL 22 P 30 125 1427 DP 31 30 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1428 DL 22 P 127 KIDNEYS: BILATERAL, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. 1429 DP 31 - 30 ALL TISSUES APPEARED NORMAL. 1430 DL 22 P 127 ALL TISSUES APPEARED NORMAL. La 1431 DL 22 P 126 ALL TISSUES APPEARED NORMAL. 1432 DP 7 - 6 FOUND DEAD ON DAY 7 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1433 1434 1435 1436 1437 1438 1439 1440 1441 DL 22 P DP 31 - DP 31 - DL 22 P DL 22 P DP 31 - DL 22 P DP 31 - DP 31 - 127 30 30 129 128 30 127 30 30 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1442 DL 22 P 126 ALL TISSUES APPEARED NORMAL. _> 1443 DL 22 P 125 ALL TISSUES APPEARED NORMAL. 1444 DP 30 - 29 ALL TIssUEs APPEARED NORMAL 1445 DP 30 - 29 ALL TISSUES APPEARED NORMAL 1446 DG 25 NP ii0 ALL TISSUES APPEARED NORMAL [2_ 1447 DP 30 - 29 ALL TISSUES APPEARED NORMAL 4_ 1448 DL 22 P 125 ALL TISSUES APPEARED NORMAL OO 1449 DP 30 - 29 ALL TISSUES APPEARED NORMAL .................................................................................................................................... _) DP - DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Refer to the individual cllnical observations table (Table E26) for external observations confirmed at necropsy. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E35 (PAGE 7): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... III 3 CONT. 1450 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 DL 22 P DP 30 DL 22 P DP 30 DP 30 DL 22 P DL 22 P DP 29 DG 25 NP DL 22 P DP 29 126 29 124 29 29 127 125 28 106 125 28 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 14612 DLP 229 P 12258 ALL TISSUES APPEARED NNOORRMMAALL.. t_ 1463 DL 22 P 124 ALL TISSUES APPEARED NORMAL. O0 1464 DP 29 28 ALL TISSUES APPEARED NORMAL. 1465 DL 22 P 124 ALL TISSUES APPEARED NORMAL. 1466 1467 DP 28 DP 28 27 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 1468 1469 DL 22 P DL 22 P 125 ALL TISSUES APPEARED NORMAL. 123 ALL TISSUES APPEARED NORMAL. 1470 DP 28 27 ALL TISSUES APPEARED NORMAL. 1471 DP 28 27 ALL TISSUES APPEARED NORMAL. 1472 DL 22 P 126 ALL TISSUES APPEARED NORMAL. 1473 DP 28 27 ALL TISSUES APPEARED NORMAL. 1474 DL 22 P 123 ALL TISSUES APPEARED NORMAL. 1475 DP 28 27 ALL TISSUES APPEARED NORMAL. 1476 DL 22 P 124 ALL TISSUES APPEARED NORMAL. 1477 DL 22 P 124 ALL TISSUES APPEARED NORMAL. 1478 1479 DP 27 DP 24 26 ALL TISSUES APPEARED NORMAL. 23 ALL TISSUES APPEARED NORMAL. 1480 DL 22 P 119 ALL TISSUES .................................................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION APPEARED NORMAL. [J_ a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. 4_ w-J OO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E35 (PAGE 8): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY} NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... IV 10 1481 DP 31 30 1482 DL 22 P 125 1483 DG 25 NP 108 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1484 DP 3 2 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL. 1485 1486 DP 31 DL 22 P 30 127 ALL TISSUES ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1487 DP 31 30 ALL TISSUES APPEARED NORMAL. w_ 1488 DL 22 P 125 ALL TISSUES APPEARED NORMAL. 1489 DP 30 29 ALL TISSUES APPEARED NORMAL. (t_a 1490 DL 22 P 125 ALL TISSUES APPEARED NORMAL. O0 1491 DL 22 P 126 ALL TISSUES APPEARED NORMAL. _-_ 1492 DP 30 29 ALL TISSUES APPEARED NORMAL. 1493 DP 30 29 ALL TISSUES APPEARED NORMAL. 1494 DL 22 P 127 ALL TISSUES APPEARED NORMAL. 1495 DP 30 29 ALL TISSUES APPEARED NORMAL. 1496 DL 22 P 126 ALL TISSUES APPEARED NORMAL. 1497 DL 22 P 127 ALL TISSUES APPEARED NORMAL. 1498 DP 30 29 ALL TISSUES APPEARED NORMAL. 1499 DP 30 29 ALL TISSUES APPEARED NORMAL. 1500 DL 22 P 126 ALL TISSUES APPEARED NORMAL. 1501 DP 30 29 ALL TISSUES APPEARED NORMAL. 1502 DL 22 P 125 ALL TISSUES APPEARED NORMAL. 1503 DP 29 28 ALL TISSUES APPEARED NORMAL. 1504 DP 29 28 ALL TISSUES APPEARED NORMAL. 1505 1506 1507 DL 22 P DP 29 DL 22 P 125 28 125 ALL TISSUES ALL TISSUES ALL TISSUES 1508 DL 22 P 127 .................................................................................................................................... ALL TISSUES DP z DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. _'_ _#_ a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy, oo to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E35 (PAGE 9): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... IV OBSERVATIONS a 10 CONT. (t__ O0 1509 1510 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 DP 29 DP 29 DG 25 NP DP 29 DL 22 P DL 22 P DP 29 DL 22 P DL 22 P DP 29 DL 22 P DP 28 DL 22 P DP 28 DL 22 P DL 22 P DP 28 DP 28 DL 22 P DL 22 P DP 28 DP 28 DL 22 P DP 28 DL 22 P DL 22 P DP 28 DP 28 28 28 112 28 124 124 28 126 122 28 124 27 125 27 126 125 27 27 125 124 27 27 125 27 125 122 27 27 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1537 1538 1539 DL 22 P DP 28 DL 22 P 124 27 127 ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1540 DP 28 27 .................................................................................................................................... ALL TISSUES APPEARED NORMAL. DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION 4_ a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM TABLE E35 (PAGE i0): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... V 30 1541 DL 22 P 128 1542 DP 32 - 31 1543 DE 32 - 31 1544 DL 22 P 129 1545 DL 22 P 127 1546 DL 22 P 128 1547 DP 31 - 30 1548 DL 22 P 126 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1549 DP 8 - 7 FOUND DEAD ON DAY 8 POSTWEANING. ALL TISSUES APPEARED NORMAL. 1550 DL 22 P 126 ALL TISSUES APPEARED NORMAL. (t__ 1551 DP 31 - 30 ALL TISSUES APPEARED NORMAL. O0 1552 DL 22 P 127 ALL TISSUES APPEARED NORMAL. t_ 1553 DP 31 - 30 ALL TISSUES APPEARED NORMAL. 1554 DP 31 - 30 ALL TISSUES APPEARED NORMAL. 1555 DL 22 P 128 ALL TISSUES APPEARED NORMAL. 1556 DP 30 - 29 ALL TISSUES APPEARED NORMAL. 1557 DL 22 P 126 ALL TISSUES APPEARED NORMAL. 1558 DL 22 P 124 ALL TISSUES APPEARED NORMAL. 1559 DP 6 - 5 FOUND DEAD ON DAY 6 POSTWEANING. ALL TISSUES APPEARED NORMAL. 1560 1561 DL 22 P DP 30 - 125 ALL TISSUES APPEARED NORMAL. 29 ALL TISSUES APPEARED NORMAL. 1562 DP 2 - 0 FOUND DEAD ON DAY 2 POSTWEANING > (DEATH OCCURRED OVERNIGHT). ALL TIssUEs APPEARED NORMAL. 1563 DP 2 - 0 FOUND DEAD ON DAY 2 POSTWEANING. ALL TISSUES APPEARED NORMAL. 1564 1565 DL 22 P DL 22 P ......................................................................................................... DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION a. Refer to the individual clinical observations table 127 ALL TISSUES APPEARED 126 ALL TISSUES APPEARED DL -- DAY (Table E26) OF LACTATION for external observations NORMAL. NORMAL. confirmed _ .......................... at necropsy. [_O 4_ OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM TABLE E35 (PAGE ii): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS PERFLUOROOCTANOATE DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGE (MG/KG/DAY} NUMBER NECROPSY STATUS .................................................................................................................................... V 30 CONT. 1566 1567 1568 1569 1570 1571 1572 1573 DL 22 P DP 30 - DL 22 P DP 30 - DP 30 DL 22 P DP 30 DL 22 P DOSAGES ADMINISTERED 128 29 127 29 29 125 29 125 OBSERVATIONS a ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1574 DP 3 3 FOUND DEAD ON DAY 3 POSTWEANING (DEATH OCCURRED 67 MINUTES AFTER DOSAGE ADMINISTRATION), ALL TISSUES APPEARED NORMAL. 1575 DP 3 2 FOUND DEAD ON DAY 3 POSTWEANING tO_O (DEATH OCCURRED OVERNIGHT) ALL TISSUES APPEARED NORMAL. 1576 1577 1578 1579 1580 1581 1582 1583 DL 22 P DP 29 DG 25 NP DL 22 P DP 29 DP 29 DP 28 DL 22 P 124 28 108 124 28 28 27 123 ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1584 1585 1586 DL 22 P DP 28 - DL 22 P 122 27 126 ALL TISSUES ALL TISSUES ALL TISSUES APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1587 DL 22 P 123 ALL TISSUES APPEARED NORMAL. > 1588 DL 22 P 125 ALL TISSUES APPEARED NORMAL. 1589 DL 22 P 123 ALL TISSUES APPEARED NORMAL, 1590 DP 28 - 27 ALL TISSUES APPEARED NORMAL. 1591 DL 22 P 124 ALL TISSUES APPEARED NORMAL. [29 1592 DP 28 - 27 ALL TISSUES APPEARED NORMAL. .................................................................................................................................... O0 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. _O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E35 (PAGE 12): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP RAT DAY OF PREGNANCY DOSAGES DOSAGE (MG/KG/DAY) NUMBER NECROPSY STATUS ADMINISTERED .................................................................................................................................... V 30 CONT. 1593 DL 22 P 123 OBSERVATIONS a KIDNEYS: RIGHT, PELVIS, MODERATE DILATION. URINARY BLADDER: WALLS THICKENED. URETER: BILATERAL, MODERATE DILATION; ONE CALCULI LOCATED AT THE CAUDAL END (i.0 CM X 0.5 CM). ALL OTHER TISSUES APPEARED NORM/d,. 1594 1595 1596 1597 1598 1599 DP 28 DP 28 DP 28 DP 27 DL 22 P DP 26 27 ALL TISSUES APPEARED NORMAL. 27 ALL TISSUES APPE_Dd_ED NORMAL. 27 ALL TISSUES APPEARED NORMAL. 26 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 25 ALL TISSUES APPEARED NORMAL. 1600 DL 22 P 123 .................................................................................................................................... ALL TISSUES APPEARED NORMAL. OO DP = DAY POSTWEANING DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION La a. Refer to the individual clinical observations table (Table E26) for external observations confirmed at necropsy. > _n 4_ oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'_ STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - F1 GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... PITUITARY BRAIN LIVER RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a 1302 1304 1306 1308 1310 1312 1313 1316 284. 320. 335. 357. 331. 336. 298. NOT PREGNANT 0.022 0.021 0.017 0.018 0.014 0.022 0.020 7.75 6.56 5.07 5.04 4.23 6.55 6.71 2 I0 2 I0 2 05 2 01 1 99 2 15 2 14 0.74 0.66 0.61 0.56 0.60 0.64 0.72 14.52 17.50 17.30 18.06 18.04 14.95 15.73 5 ii 5 47 5 16 5 06 5 45 4 45 5.28 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 1.38 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 0.027 0.044 0.050 0.041 0,040 0.036 0.036 9.51 13.75 14.92 11.48 12.08 10,71 12,08 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 369. 329. 323. 328 280 300 284 324 331 345 338 316 294 333 364 325. 0.017 0.014 0.009 0.015 0.018 0.018 0.016 0.012 0,016 0 022 0 015 0 029 0 023 0 020 0 014 0 018 4.61 4.26 2.79 4.57 6.43 6.00 5.63 3.70 4.83 6.38 4.44 9.18 7.82 6.01 3.85 5.54 2 06 2 05 2 00 2 09 2 00 2 33 1 96 1 93 2 06 2 10 2 07 2 06 1 93 2 26 2 03 2 03 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 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 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 1.53 1.36 1.35 1.41 1.22 1.11 1.26 1.28 1.42 1.56 1.60 1.17 1.22 1.61 1.28 1.35 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 1.43 1.46 1.39 1.47 1.17 1.26 1.22 1.40 1.46 1.53 1.65 1.18 1.25 1.41 1.32 1.41 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 0.039 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 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 1348 339. 0 015 4.42 2 05 0.60 18.89 5 57 1.46 0.43 1.57 0.46 0.055 16.22 1350 339. 0.016 4.72 2 03 0.60 18.24 5 38 1.37 0.40 1.42 0.42 0.063 18.58 1353 293. 0.024 8.19 2 22 0.76 15.33 5 23 1.54 0.52 1.31 0.45 0.038 12.97 1355 313. 0.007 2.24 2 04 0.65 16.39 5.24 1.40 0._5 1.38 0.44 0.037 11,82 1358 NOT PREGNANT; MATING NOT CONFIRMED [29 1359 313. 0.017 5.43 2.10 0.67 15.16 4.84 1.35 0.43 1.31 0.42 0.031 9,90 4_ .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NIP4BER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - F1 GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT NUMBER TERMINAL BODY WEIGHT ADRENAL RIGHT ABS. REL. SPLEEN ABS. REL. THYMUS ABS. REL. WT. % TBW a WT. % TBW WT. .................................................................................................................................... % TBW 1302 1304 1306 1308 1310 1312 1313 1316 284. 320. 335. 357. 331. 336. 298. NOT PREGNANT 0.028 0.038 0.037 0.041 0.047 0.035 0.030 9.86 11.88 11.04 11.48 14.20 10.42 10.07 0.63 0.53 0.59 0.72 0.66 0.57 0.62 0.22 0.16 0.18 0.20 0.20 0.17 0.21 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 OVARY LEFT ABS. REL. WT. % 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 OVARY RIGHT ABS. REL. WT. % TBW a 0 068 0 063 0 057 0 042 0 049 0 054 0 050 23.94 19.69 17.01 11.76 14.80 16.07 16.78 UTERUS NON-GRAVID ABS. REL. WT. % 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 1318 1321 1325 1328 1330 1331 369. 329. 323. 328. 280. 300. 0.036 0.041 0.035 0.047 0.040 0.037 9.76 12.46 10.84 14.33 14.28 12.33 0.64 0.71 0.57 0.61 0.56 0.56 0.17 0.22 0.18 0.18 0.20 0 19 0.24 0.16 0.23 0.15 0.16 0.20 0.06 0.05 0.07 0.04 0.06 0.07 0.055 0.045 0.037 0.044 0.040 0.050 14.90 13.68 11.46 13.41 14.28 16.67 0 054 0 051 0 032 0 053 0 046 0 050 14.63 15.50 9.91 16.16 16.43 16.67 0.49 0 38 0.78 0.87 0.33 0.66 0 13 0 12 0 24 0 26 0 12 0 22 1334 1335 1336 1338 1340 1341 1342 1344 1345 284. 324. 331. 345. 338. 316. 294. 333. 364. 0.031 0.037 0.043 0.047 0.041 0.037 0.036 0.048 0.041 10.92 11.42 12.99 13.62 12.13 11.71 12.24 14.41 11.26 0.52 0.56 0.47 0.65 0.76 0.55 0.60 0.64 0.65 0 18 0 17 0 14 0 19 0 22 0 17 0.20 0 19 0 18 0.22 0.20 0.10 0.19 0.30 0.31 0.20 0.20 0.13 0.08 0.06 0.03 0.06 0.09 0.10 0.07 0.06 0.04 0.029 0.039 0.047 0.044 0.070 0.057 0.058 0.068 0.049 10.21 12.04 14.20 12.75 20.71 18.04 19.73 20.42 13.46 0 033 0 058 0 055 0.047 0.092 0.064 0.034 0.042 0.055 11.62 17.90 16.62 13.62 27.22 20.25 11.56 12.61 15.11 0.40 0.48 0.39 0.30b 0.79 0.51 0.53 0.70 0.32b 0 14 0 15 0 12 0 09 0 23 0 16 0 18 0 21 0 09 1346 325. 0.047 14.46 0.52 0 16 0.20 0.06 0.085 26.15 0.061 18.77 0.42 0 13 1348 339. 0.052 15.34 0.57 0 17 0.18 0.05 0.063 18.58 0.062 18.29 0.60 0 18 1350 339. 0.062 18.29 0.66 0 19 0.15 0.04 0.052 15.34 0.060 17.70 0.43 0 13 1353 293. 0.035 11.94 0.52 0 18 0.26 0.09 0.061 20.82 0.075 25.60 0.52 0 18 1355 313. 0.031 9.90 0.43 0 14 0.12 0.04 0.045 14.38 0.050 15.97 0.42 0 13 1358 NOT PREGNANT; MATING NOT CONFIRMED [/_ 1359 313. 0.034 10.86 0.64 0.20 0.25 0.08 0.046 14.70 0.053 16.93 0.74 0.24 4_ .................................................................................................................................... O0 WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by 1000. _O Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - F1 GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... PITUITARY BRAIN LIVER RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... REL. % TBW KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a 1362 1363 1364 1367 1368 1371 1375 1376 1378 287. 308. 323. 297. 310. 352. 299. 360. NOT PREGNANT 0.015 0.017 0.019 0.016 0.014 0.013 0.017 0.014 5 23 5 52 5 88 5 39 4 52 3 69 5 68 3 89 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 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 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 1.28 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 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 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 355. 282. 308. 350. 262. 338. 344. 347. 330. 331. 320. 297. 332. 325. 327. 0,021 0.016 0.017 0.023 0.014 0.012 0.017 0.021 0.013 0.018 0.013 0.014 0.017 0.015 0.015 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 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 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 14.44 13.26 15.82 17.23 12.14 17.48 16.17 18.85 16.60 17.41 16.58 13.63 15.01 15.09 15.90 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 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 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 1.48 1.51 1.29 1.51 1,15 1.43 1.29 1.59 1.29 1.57 1.38 1.19 1.22 1,36 1.28 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 0.056 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 15 . 77 13.48 18.83 11.71 12.21 13.61 11.92 13.83 12.42 13.90 10.00 11.45 14.16 12.31 9.48 1410 344. 0.019 5 52 2.05 0.60 18.06 5 25 1.45 0 42 1.51 0.44 0.044 12.79 1413 320. 0.015 4 69 2.29 0.72 16.36 5 Ii 1.46 0 46 1.55 0.48 0.043 13.44 1415 339. 0.011 3 24 1.92 0.57 17.79 5 25 1.51 0 44 1.52 0.45 0.046 13.57 1416 303. 0.018 5 94 2,23 0.74 15.44 5.10 1.48 0 49 1.55 0.51 0.044 14.52 1418 317. 0.013 4 i0 2.15 0.68 15.71 4.96 1.22 0 38 1.32 0.42 0.040 12.62 50 .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00, O0 Value was multiplied by i000. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (AgFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - F1 GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... ADRENAL SPLEEN THYMUS RAT TERMINAL BODY RIGHT _ER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... REL. % TBW OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT. % TBW 1362 1363 1364 1367 1368 1371 1375 1376 287. 308. 323. 297. 310. 352. 299. 360. 0.038 0.049 0.039 0.041 0.047 0.046 0.043 0.042 13.24 15.91 12.07 13.80 15.16 13.07 14.38 11.67 0.73 0.50 0.47 0.50 0.53 0.56 0.64 0.58 0 25 0 16 0 14 0 17 0 17 0 16 0 21 0 16 0.20 0.17 0.07 0.11 0.20 0.21 0.19 0.24 0.07 0.06 0.02 0.04 0.06 0.06 0.06 0.07 0.062 0.055 0.055 0.054 0.054 0.087 0.050 0.046 21.60 17.86 17.03 18.18 17.42 24.72 16.72 12.78 0 064 0 076 0 061 0 058 0 054 0 032 0 040 0 056 22.30 24.68 18.88 19.53 17.42 9.09 13.38 15.56 0.80 0.68 0.46 0.62 0.50 0.55 0.67 0.38 0.28 0.22 0.14 0.21 0.16 0.16 0.22 0.I0 1378 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 NOT PREGNANT 355. 282. 308. 350. 262. 338. 344. 347. 330. 331. 320. 297. 332. 325. 327. 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 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 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 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 0.27 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 0.05 0.I0 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 0.054 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 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 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 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 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 0.19 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 1410 1413 344. 320. 0.035 0.054 10.17 16.88 0.58 1.03 0 17 0 32 0.20 0.17 1415 339. 0.052 15.34 0.72 0 21 0.32 1416 1418 303. 317. 0.041 0.035 13.53 11.04 0.59 0.57 0 19 0 18 0.14 0.14 .................................................................................................................................... 0 06 0 05 0 09 0 05 0 04 0.054 0.078 0.040 0.044 0.040 15.70 24.38 11.80 14.'52 12.62 0.051 0.048 0.038 0.038 0.062 14.82 15.00 11.21 12.54 19.56 0.60 1.00 0.69 0.43 0.46 0.17 0.31 0.20 0.14 0.14 _'_ [2_ ._ WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100. OO Value was multiplied by i000. Damaged during processing (weight not affected). 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 5) : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... PITUITARY BRAIN LIVER RAT TERMINAL BODY NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW 1421 1424 1426 1428 1430 1431 1433 1436 326. 307. 369. 334. 308. 358. 314. 341. 0.009 0.013 0.019 0.016 0.017 0.015 0.014 0.018 2.76 4.23 5.15 4.79 5.52 4.19 4.46 5.28 1 96 2 05 2 12 2 18 1 85 2 02 1 95 2 20 0.60 0.67 0.57 0.65 0.60 0.56 0.62 0.64 16.89 16.43 18.04 16.19 15.49 19.48 16.49 15.80 5.18 5.35 4.89 4.85 5.03 5.44 5 25 4 63 1.44 1.42 1.37 1.50b 15.30c 1.49 1.36 1.28 0.44 0.46 0.37 0.45 4.97C 0.42 0.43 0.38 1.40 1.36 1.40 1.54b 1.63 1.63 1.42 1.30 0.43 0.44 0.38 0.46 0.53 0.46 0.45 0.38 1437 1439 1442 1443 1446 311. 361. 344. 336. NOT PREGNANT 0.015 0.017 0.016 0.018 4.82 4.71 4.65 5.36 2 18 2 01 2 05 2 07 0.70 0.56 0.60 0.62 17.76 16.30 15.42 14.80 5 71 4 52 4 48 4 40 1,41 1.48 1.35 1.28 0,45 0.41 0.39 0.38 1.47 1.43 1.38 1.33 0.47 0.40 0.40 0.40 1448 1450 1452 1455 1456 1458 343. 331. 301. 332. 329. NOT PREGNANT 0.015 0.015 0.016 0.012 0.017 4.37 4.53 5.32 3.61 5.17 2.23 2.13 1.96 2.27 2.13 0.65 0.64 0.65 0.68 0.65 17.20 18.62 15.77 18.40 16.01 5.01 5.62 5.24 5.54 4.87 1.45 1.29 1,34 1.51 1.54 0.42 0.39 0.44 0.45 0.47 1.50 1.36 1.38 1.44 1.55 0.44 0.41 0.46 0.43 0.47 1459 1461 1463 1465 1468 1469 1472 368. 336. 302. 297. 300. 317. 309. 0.018 0.017 0.016 0.006 0.015 0.016 0.013 4.89 5.06 5.30 2.02 5.00 5.05 4.21 2.04 2 00 2 07 1 99 2 02 2 17 2 08 0.55 0.60 0.68 0.67 0.67 0.68 0.67 17.41 13.89 14.98 15.23 14.72 15.62 15.33 4 73 4 13 4 96 5 13 4 91 4 93 4 96 1.45 1.29 1.34 1.38 1.45 1.24 1.62 0.39 0.38 0.44 0.46 0.48 0.39 0.52 1.48 1.32 1.32 1.25 1.45 1.26 1.32 0.40 0.39 0.44 0.42 0.48 0.40 0.43 1474 310. 1476 358. 1477 335. 1480 340. ........................................ 0.014 0.013 0.021 0.018 4.52 3.63 6.27 5.29 2 I0 1 96 2.25 2.13 0.68 0.55 0.67 0.63 14.41 17.55 17.98 17.23 4 65 4 90 5 37 5 07 1.31 1.50 1.48 1.43 ............................................................................................ 0.42 0.42 0.44 0.42 1.37 1.48 1.50 1.44 0.44 0.41 0.45 0.42 WEIGHTS WERE RECORDED IN GRAMS Value was multiplied by i000. (G). ABS. WT. = ORGAN WEIGHT. Rat 1428 had slight dilation of the pelvis in both kidneys. Value was presumed incorrectly recorded; values excluded from group REL. % TBW = (ORGAN WEIGHT/TERMINAL averages and statistical analyses. BODY ADRENAL LEFT ABS. REL. WT. % TBW a 0.049 0.048 0.051 0.046 0.048 0.042 0.041 0.041 0.044 0.048 0.046 0.053 15.03 15.64 13.82 13.77 15.58 11.73 13.06 12.02 14.15 13.30 13.37 15.77 0.040 0.041 0.043 0.041 0.032 11.66 12.39 14.28 12.35 9.73 0.043 0.037 0.043 0.041 0.046 0.051 0.036 0,050 0.033 0.055 0,058 11.68 11.01 14.24 13.80 15.33 16.09 11.65 16.13 9.22 16.42 17.06 WEIGHT) X I00. _t_ _.d _D _0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 6) : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... ADRENAL SPLEEN THYMUS RAT TERMINAL BODY RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON- GRAVID ABS. REL. WT. % TBW 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 326. 307. 369. 334. 308. 358. 314. 341. 311. 361. 344. 336. NOT PREGNANT 0.043 0.046 0.046 0.047 0.042 0.043 0.050 0.039 0.039 0.044 0.042 0.052 13 19 14 98 12 47 14 07 13 64 12 01 15 92 11.44 12.54 12.19 12.21 15.48 0 58 0 64 0 61 0 62 0 58 0 71 0 55 0 64 0 58 0 52 0 73 0 60 0,18 0.21 0.16 0,18 0,19 0,20 0,18 0.19 0,19 0,14 0,21 0.18 0.23 0.20 0.21 0.14 0.20 0.29 0.28 0.26 0.07 0 23 0.II 0,22 0.07 0.06 0.06 0.04 0.06 0.08 0.09 0.08 0.02 0.06 0.03 0.06 0.034 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 0.035 0.031 0.053 0.055 0.064 0.056 0.043 0.034 0.044 0.056 0.057 0.041 10.74 i0,i0 14.36 16.47 20.78 15.64 13.69 9.97 14.15 15.51 16.57 12.20 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 1448 1450 1452 1455 1456 1458 343. 331. 301. 332. 329. NOT PREGNANT 0.037 0.039 0.037 0,028 0.042 10.79 11.78 12.29 8.43 12.76 0.70 0.58 0.62 0.67 0.70 0.20 0.18 0.20 0.20 0,21 0.20 0.21 0.23 0.35 0.29 0.06 0.06 0.08 0.i0 0.09 0.042 0.033 0.047 0.069 0.052 12.24 9.97 15.61 20.78 15.80 0.045 0.044 0.043 0.062 0.068 13.12 13.29 14.28 18.67 20.67 0.50b 0.42 0.45 0.75 0.67 0.14 0.13 0.15 0.22 0.20 1459 368 1461 336 1463 302 1465 297 1468 300 0.036 0,033 0.041 0.036 0.033 9.78 9.82 13.58 12.12 11.00 0 57 0 55 0 57 0 51 0 55 0,15 0.16 0.19 0.17 0.18 0 12 0 18 0 18 0 22 0 18 0.03 0.05 0.06 0.07 0.06 0.038 0 038 0 046 0 056 0 071 10.33 11.31 15.23 18.86 23.67 0.045 0.035 0.046 0.056 0.057 12.23 10.42 15.23 18.86 19.00 0.28 0.56 0.60 0.49 0 58 0.08 0.17 0.20 0.16 0.19 1469 317 0.039 12.30 0 56 0.18 0 17 0.05 0 054 17.03 0.056 17.66 0 51 0.16 1472 309 0.043 13.92 0 61 0.20 0 40 0.13 0 064 20.71 0.062 20.06 0 83 0,27 1474 310 0.042 13.55 0 62 0.20 0 24 0.08 0 043 13.87 0.037 11.94 0 72 0.23 _'_ 1476 358 0.038 10.61 0 51 0.14 0 19 0.05 0 050 13.97 0.059 16.48 0 56 0.16 1477 335 0.053 15.82 0 63 0.19 0 i0 0.03 0 040 11.94 0.039 11.64 0 50 0.15 50 1480 340 0.048 14.12 0 60 0.18 0 23 0.07 0 051 15.00 0.051 15.00 0 54 0.16 4_ .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. Damaged during processing (weight not affected). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 7) : TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY PITUITARY BRAIN LIVER NUMBER WEIGHT ABS. REL. ABS. REL, ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... REL. % TBW 1482 1483 313. 0.015 NOT PREGNANT 4.79 2.23 0.71 15.34 4.90 KIDNEY LEFT ABS. REL. WT. % TBW 1.26 0.40 KIDNEY RIGHT ABS. REL. WT. % TBW 1.25 0.40 ADRENAL LEFT ABS. REL. WT. % TBW a 0.045 14.38 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 316. 359 36 31{ 353 319 355 302 322 318 341 338 NOT PREGNANT 0.017 0 013 0 015 0 014 0 016 0 015 0 016 0 018 0 014 0 015 0 015 0 013 5.38 3.62 4.08 4.43 4.53 4.70 4.51 5.96 4.35 4.72 4.40 3.85 1.90 2 06 2 12 2 05 2 12 1 76 2 23 1 97 2 05 2 05 2 21 2 20 0.60 0.57 0.58 0.65 0.60 0.55 0.63 0.65 0.64 0.64 0.65 0.65 18.55 17.62 20.37 16.20 16 00 16 62 15 83 16 39 14 76 16 77 18 65 16 98 5.87 4.91 5.54 5.13 4.53 5.21 4.46 5.43 4.58 5.27 5.47 5.02 1.37 1.33 1.65 1.24 1.52 1.33 1.50 1.48 1.18 1.51 1.46 1.39 0.43 0.37 0.45 0.39 0.43 0.42 0.42 0 49 0.37 0.47 0.43 0.41 1.31 1.41 1.56 1.28 1.49 1.28 1.48 1.49 1.22 1.68 1.51 1.46 0.41 0.39 0.42 0.40 0.42 0.40 0.42 0 49 0.38 0.53 0.44 0.43 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 1513 250 1514 325 1516 316 1517 325 1519 317 1521 312 1523 313 1524 326 1527 315 0 017 0 016 0 014 0 013 0 017 0 016 0 011 0 010 0 023 6.80 4.92 4.43 4.00 5.36 5.13 3.51 3.07 7.30 2 24 2 19 2 15 2 03 2 08 2 18 2 02 1 98 2 14 0.90 0.67 0.68 0.62 0.66 0.70 0.64 0.61 0.68 13 67 15 60 15 89 17 35 17 52 15 27 15 78 13 46 18 04 5.47 4.80 5.03 5.34 5.53 4.89 5.04 4.13 5.73 1.28 1.32 1.28 1.13 1.45 1.35 1.32 1.24 1.35 0.51 0.41 0.40 0.35 0.46 0.43 0.42 0.38 0.43 1.30 1.38 1.27 1.13 1.56 1.42 1.38 1.21 1.42 0.52 0.42 0.40 0.35 0.49 0.46 0.44 0.37 0.45 0.043 0 053 0 036 0 043 0 047 0 046 0 041 0 030 0 051 17.20 16.31 11.39 13.23 14.83 14.74 13.10 9.20 16.19 1528 310 0 015 4.84 2 ii 0.68 15 96 5.15 1.46 0.47 1.53 0.49 0 044 14.19 1531 350 0 014 4.00 2.15 0.61 18 68 5.34 1.49 0.42 1.58 0.45 0 054 15.43 1533 347 0 017 4.90 2.11 0.61 19 96 5.75 1.56 0.45 1.61 0.46 0 053 15.27 1534 316 0 015 4.75 2.20 0.70 16 16 5.11 1,38 0._4 1.37 0.43 0 041 12.97 1537 306 0 015 4.90 1.93 0.63 15 08 4.93 1.21 0.40 1.25 0.41 0 046 15.03 [2_ 1539 355 0 017 4.79 2.22 0.62 18 63 5.25 1.69 0.48 1.81 0.51 0 056 15.77 _t_ ................................... _ ................................................................................................ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by I000. _o O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 8): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - INDIVIDUAL DATA - F1 GENERATION FEMALE RATS .................................................................................................................................... DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY ADRENAL RIGHT SPLEEN THYMUS NUMBER WEIGHT ABS. WT. REL. % TBW a ABS. WT. REL. % TBW ABS. WT. .................................................................................................................................... REL. % TBW 1482 1483 313. 0.035 NOT PREGNANT 11.18 0.53 0.17 0.29 0.09 1486 1488 1490 1491 1494 1496 1497 1500 1502 316. 359. 368. 316 353 319 355 302 322 0.047 0.043 0.045 0.040 0.042 0.047 0 040 0.041 0.042 14.87 11.98 12.23 12.66 11.90 14.73 11.27 13.58 13.04 0.58 0.61 0.66 0.56 0.46 0.57 0 68 0.48 0.48 0.18 0.17 0.18 0.18 0.13 0.18 0.19 0.16 0.15 0.11 0 33 0 26 0 10 0 12 0 15 0 26 0 24 0 13 0.03 0.09 0.07 0.03 0.03 0.05 0.07 0.08 0.04 OVARY LEFT ABS. WT. REL. % TBW a 0.046 14.70 0 065 0 041 0 076 0 031 0 039 0 045 0 065 0 046 0 063 20.57 11.42 20.65 9.81 11.05 14.11 18.31 15.23 19.56 OVARY RIGHT ABS. WT. REL. % TBW a 0.044 14.06 0.049 0.033 0.068 0.049 0.059 0.063 0.070 0.054 0.066 15.51 9.19 18.48 15.51 16.71 19.75 19.72 17.88 20.51[_ UTERUS NON-GRAVID ABS. WT. REL. % TBW 0.68 0.22 0.57 0.44 0.53 0.67 0.60 0.56 0.84 0.69 0.42 0.18 0.12 0.14 0.21 0.17 0.18 0.24 0.23 0.13 15057 1508 1511 31481 0.0450 338 0.042 NOT PREGNANT 124.5686 12.43 0.7504 0.64 0.2126 0.19 0 231 0 13 0.076 0.04 00 0480 0.048 151.0793 14.20 0.04556 0.044 146.14!:_. 13.02 0.412 0.74 0.132 0.22 1513 250 1514 325 1516 316 1517 325 1519 317 1521 312 1523 313 1524 326 1527 315 0 044 0 043 0 033 0 041 0 041 0 045 0 040 0 026 0 042 17.60 13.23 10.44 12.62 12.93 14.42 12.78 7.98 13.33 0.51 0.67 0.55 0.58 0.52 0.60 0.54 0.74 0.82 0.20 0.21 0.17 0.18 0.16 0.19 0.17 0.23 0.26 0 10 0 16 0 18 0 10 0 17 0 08 0 35 0 38 0 23 0.04 0.05 0.06 0.03 0.05 0.02 0.11 0.12 0.07 0 048 0 042 0 064 0 041 0 044 0 045 0 051 0 050 0 056 19.20 12.92 20.25 12.62 13.88 14.42 16.29 15.34 17.78 0.048 0.046 0.045 0.051 0.056 0.040 0.039 0.057 0.035 19.20 14.15 14.24 15.69 17.66 12.82 12.46 17.48 11.11 0.62 0.50 0.54 0.65 0.51 0.49 0.84 0.47 0.68 0.25 0.15 0.17 0.20 0.16 0.16 0.27 0.14 0.22 1528 310 0 035 11.29 0.67 0.22 0 26 0.08 0 037 11.94 0.052 16.77 0.43 0.14 > 1531 350 0 049 14.00 0.67 0.19 0 30 0.08 0 042 12.00 0.049 14.00 0.53 0.15 1533 347 0 041 11.82 0.66 0.19 0 20 0.06 0 045 12.97 0.053 15.27 0.52 0.15 1534 316 0 031 9.81 0.50 0.16 0 17 0.05 0 060 18.99 0.035 11.08 0.42 0.13 1537 306 0 051 16.67 0.51 0.17 0 15 0.05 0 044 14.38 0.043 14.05 0.49 0.16 [29 1539 355 0 052 14.65 0.57 0.16 0 29 0.08 0 061 17.18 0.075 21.13 0.40 0.11 4_ .............................. - ......................................................................................... O_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X i00. Value was multiplied by i000. to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 9): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL INDIVIDUAL DATA - F1 GENERATION FEMALE RATS BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT TERMINAL BODY PITUITARY BRAIN LIVER NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % TBW a WT. % TBW WT. .................................................................................................................................... REL. % TBW KIDNEY LEFT ABS. REL. WT. % TBW KIDNEY RIGHT ABS. REL. WT. % TBW ADRENAL LEFT ABS. REL. WT. % TBW a 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 11556604 1565 1566 1568 1571 1573 1576 1578 296. 342. 298. 329. 306. 298. 319. 312 319. 288. 0.022 0.016 0.012 0.019 0.017 0.016 0.018 0.009 0.018 0.011 332059.. 275. 324. 339. 304. 336. 292. NOT PREGNANT 00..001152 0.013 0.010 0.018 0.010 0.015 0.015 7.43 4.68 4.03 5.78 5.56 5.37 5.64 2 88 5.64 3.82 43.,6828 4.73 3.09 5.31 3.29 4.46 5.14 2.00 2 12 2 13 2 04 2 02 2 05 2 19 2 03 2 20 2 01 22 2010 2 03 2 13 2 21 1 91 2 03 1 78 0.68 0.62 0.71 0.62 0.66 0.69 0.69 0.65 0.69 0.70 00..6685 0.74 0.66 0.65 0.63 0.60 0.61 14.69 16.14 17.89 17.75 18.02 19.33 16.81 15 58 15.27 17.49 1187..1840 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 55..5786 5.24 5.25 4.57 5.25 5.10 5.35 i. II 1,57 1,40 1,32 1.49 1.29 1.43 1.21 1.30 1.50 11..3377 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 00..4424 0 40 0 40 0 36 0 38 0 36 0 41 1.20 1.65 1.47 1.45 1.50 1.33 1.56 1.25 1.24 1.55 11..5379 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 0.050 0.040 0.065 0.032 0.053 0.055 0.042 0.045 0.039 0.042 0.041 0.044 0.042 0.053 0.040 0.043 0.033 0.043 16.89 11.70 21.81 9.73 17.32 18.46 13.17 14.42 12.22 14.58 12.62 14.24 15.27 16.36 11.80 14.14 9.82 14.73 1579 1583 1584 1586 1587 346. 303. 294. 294. 300. 0.013 0.014 0.016 0.015 0.014 3.76 4.62 5.44 5.10 4.67 1 99 2 ii 2 13 2 15 2 02 0.58 0.70 0.72 0.73 0.67 17.26 16 59 13 71 15 78 15 72 4.99 5.48 4.66 5.37 5.24 1,37 1.38 1.19 1.49 1.23 0 40 0 46 0 40 0 51 0 41 1.37 1.42 1.19 1.40 1.35 0.40 0.47 0.40 0.48 0.45 0.044 0.044 0.024 0.050 0.041 12.72 14.52 8.16 17.01 13.67 1588 1589 322. 354. 0.016 0.015 4.97 4.24 2 I0 2 02 0.65 0.57 17 39 17 58 5.40 4.97 1.34 1.21 0 42 0.34 1.35 1.30 0.42 0.37 0.047 0.046 14.60 12.99 1591 318. 0.015 4.72 2 11 0.66 18 89 5.94 1.38 0.43 1.40 0.44 0.047 14.78 _'_ 1593 342. 0.023 6.72 2 04 0.60 17.20 5.03 1.98 0.58 2.18b 0.64 0.046 13.45 1598 317. 0.015 4.73 2 18 0.69 17.75 5.60 1.59 0.50 1.52 0.48 0.045 14.20 _'_ 1600 354. 0.012 3.39 2 18 0.62 18.06 5.10 1.25 0.35 1.45 0.41 0.059 16.67 4_ .................................................................................................................................... _O-0-_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100 Value was multiplied by 1000. r_ Rat 1593 had moderate dilation of the pelvis in the right kidney. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E36 (PAGE 10): TERMINAL BODY WEIGHTS AND ORGAN INDIVIDUAL DATA - F1 GENERATION WEIGHTS AND RATIOS FEMALE RATS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... ADRENAL SPLEEN THYMUS RAT TERMINAL BODY RIGHT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % TBW a WT. % TBW WT. % TBW .................................................................................................................................... OVARY LEFT ABS. REL. WT. % TBW a OVARY RIGHT ABS. REL. WT. % TBW a UTERUS NON-GRAVID ABS. REL. WT. % TBW 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 1576 1578 296. 342. 298. 329. 306. 298. 319. 312. 319. 288. 325. 309. 275. 324. 339. 304. 336. 292. NOT PREGNANT 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 14.53 14.62 18.12 13.37 16.01 17.78 12.22 12.82 10.66 13.54 13.23 15.53 16.00 10.80 10.03 14.47 8.93 13.36 0.50 0.76 0.64 0.59 0.80 0.60 0.57 0.52 0.48 0.74 0.65 0.65 0.64 0.56 0.56 0.56 0.47 0.62 0.17 0.22 0.21 0.18 0.26 0.20 0.18 0.17 0.15 0.26 0.20 0.21 0.23 0,17 0.16 0.18 0.14 0.21 0.20 0.44 0.23 0.25 0.21 0.14 0.11 0.21 0.12 0.24 0.29 0.24 0.26 0.19 0.19 0.12 0.20 0.17 0.07 0.13 0.08 0,08 0.07 0.05 0,03 0,07 0.04 0,08 0.09 0.08 0,09 0.06 0.06 0.04 0.06 0.06 0 037 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 12.50 28.65 12.75 17.63 20.26 16.78 18.18 12.82 13.79 20.14 11.69 16.50 23.27 13.89 13.57 10.53 12.80 14.73 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 16.55 26.02 22,82 19.76 16.01 16.44 17.24 9.94 13.48 20.14 20.92 22.01 19.64 13.27 15.34 11.51 12.50 18.49 0 56 0 82 0 39 0 37 0 82 0 27 0 94 0 49 0 36 0 71 0 82 0.45 0.67 0.46b 0.42 0.31 0.39 0.34 0 19 0 24 0 13 0 11 0 27 0 09 0 29 0 16 0 Ii 0 25 0 25 0 14 0 24 0 14 0 12 0 10 0 12 0 12 1579 1583 1584 1586 1587 346. 303. 294. 294. 300. 0.037 0.036 0.039 0.040 0.034 10.69 11.88 13.26 13.60 11.33 0.69 0.48 0.51 0.50 0.52 0.20 0.16 0.17 0.17 0.17 0.13 0.16 0.33 0.12 0.26 0.04 0.05 0.11 0.04 0.09 0 051 0 068 0 052 0 043 0 060 14.74 22.44 17.69 14,62 20.00 0.041 0 040 0 066 0 035 0 055 11.85 13.20 22.45 11.90 18.33 0 66 0 38 0 51 0 45 0 59 0 19 0 12 0 17 0 15 0 20 1588 322. 0.046 14.28 0.58 0.18 0.37 0,11 0 043 13.35 0 045 13.98 0 83 0 26 > 1589 354. 0.042 11.86 0.59 0.17 0.16 0.04 0 043 12.15 0 045 12.71 0 45 0 13 1591 318. 0.043 13.52 0.64 0.20 0.22 0.07 0 049 15,41 0 041 12.89 0 56 0 18 1593 342, 0.041 11.99 0.95 0.28 0.50 0,15 0 069 20._8 0 069 20.18 0 61 0 18 1598 317. 0.037 11.67 0.51 0.16 0.20 0.06 0 065 20.50 0 051 16.09 0 60 0 19 [J9 1600 354. 0.044 12.43 0.66 0.19 0.16 0.04 0 046 12.99 0 045 12.71 0 44 0 12 4_ ..................................................................... _.d ............................................................... O_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. HT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X I00. Value was multiplied by i000. b_ Damaged during processing (weight not affected). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 1): BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT NUMBER BRAIN WEIGHT PITUITARY ABS. WT. REL. % BRW LIVER ABS. WT. REL. % BRW KIDNEY LEFT ABS. REL. WT. % BRW .................................................................................................................................... 1302 2.10 0.022 1.05 14.52 691.43 1.30 61.90 1304 1306 2.10 2.05 0.021 0.017 1.00 0.83 17.50 17.30 833.33 843.90 1.38 1.45 65.71 70.73 1308 1310 1312 1313 1316 2.01 1.99 2.15 2.14 NOT PREGNANT 0.018 0.014 0.022 0.020 0.90 0.70 1.02 0.93 18.06 18.04 14.95 15.73 898.51 906.53 695.35 735.05 1.29 1.30 1.24 1.26 64.18 65.33 57.67 58.88 KIDNEY RIGHT ABS. REL. WT. % BRW 1.38 1.40 1.55 1.32 1.33 1.36 1.28 65.71 66.67 75.61 65.67 66.83 63.26 59.81 ADRENAL LEFT ABS. WT. REL. % BRW 0.027 0.044 0.050 0.041 0.040 0.036 0.036 1.28 2.10 2.44 2.04 2.01 1.67 1.68 ADRENAL RIGHT ABS. WT. REL. % BRW 0.028 0.038 0.037 0.041 0.047 0.035 0.030 1.33 1.81 1,80 2.04 2.36 1.63 1.40 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 2.06 2.05 2.00 2.09 2.00 2.33 1.96 1.93 2.06 2.10 2.07 2.06 1.93 2.26 2.03 2.03 2.05 2.03 0.017 0.014 0.009 0.015 0.018 0.018 0.016 0.012 0.016 0.022 0.015 0.029 0.023 0.020 0.014 0.018 0.015 0.016 0.82 0.68 0.45 0.72 0.90 0.77 0.82 0.62 0.78 1.05 0.72 1.41 1.19 0.88 0.69 0.89 0.73 0.79 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 18.24 843.69 910.73 857.50 832.54 630.50 619.31 770.41 819.17 834.47 886.19 819.81 783.98 730.05 769.03 873.40 852.22 921.46 898.52 1.53 1.36 1.35 1.41 1.22 1.11 1.26 1.28 1.42 1.56 1.60 1.17 1.22 1.61 1.28 1.35 1.46 1.37 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 1.43 1.46 1.39 1.47 1.17 1.26 1.22 1.40 1.46 1.53 1.65 1.18 1.25 1.41 1.32 1.41 1.57 1.42 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 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 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 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 1 75 2 00 1 75 2 25 2 00 I 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 1353 2.22 0.024 1.08 15.33 690.54 1.54 69.37 1.31 59.01 0 038 1.71 0.035 1 58 1355 2.04 0.007 0.34 16.39 803.43 1.40 68.63 1.38 67.65 0 037 1.81 0.031 1 52 1358 NOT PREGNANT; MATING NOT CONFIRMED _,_ 1359 2.10 0.017 0.81 15.16 721.90 1.35 64.28 1.31 62.38 0.031 1.48 0.034 1.62 .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 2) : BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... SPLEEN THYMUS OVARY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW ..... ............................................................................................................................... 1302 1304 2.10 2.10 0.63 0.53 30.00 25.24 0.13 0.26 6.19 12.38 0.054 0.053 2 57 2 52 1306 1308 1310 1312 1313 1316 2.05 2.01 1.99 2.15 2.14 NOT PREGNANT 0.59 0.72 0.66 0.57 0.62 28.78 35.82 33.16 26.51 28.97 0.21 0.11 0.18 0.26 0.30 10.24 5.47 9.04 12.09 14.02 0.045 0.033 0.045 0.054 0.043 2 20 1 64 2 26 2 51 2 01 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 2.06 2.05 2.00 2.09 2.00 2.33 1.96 1.93 2.06 2.10 2.07 2.06 1.93 2.26 2.03 2.03 0.64 0.71 0.57 0.61 0.56 0.56 0.52 0.56 0.47 0.65 0.76 0.55 0.60 0.64 0.65 0.52 31.07 34.63 28.50 29.19 28.00 24.03 26 53 29 02 22 82 30 95 36 71 26 70 31 09 28 32 32 02 25 62 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 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 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 2 67 2 20 1 85 2 I0 2 00 2 14 1 48 2 02 2 28 2 10 3 38 2 77 3 00 3 01 2 41 4 19 1348 1350 1353 1355 1358 1359 2.05 2.03 2.22 2.04 NOT 2.10 PREGNANT; 0.57 0.66 0.52 0.43 MATING 0.64 27 80 32 51 0 18 0 15 23.42 0 26 21.08 0 12 NOT CONFIRMED 30.48 0.25 8.78 7.39 11.71 5.88 11.90 0.063 0.052 0.061 0.045 0.046 3 07 2 56 2 75 2 20 2.19 .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. Damaged during processing (weight not affected), REL. OVARY RIGHT ABS. WT. REL. % 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 0.053 2 62 2 49 1 60 2 54 2 30 2 14 1 68 3 00 2 67 2 24 4 44 3 11 1 76 1 86 2 71 3 00 3 02 2 96 3 38 2.'45 2.52 % TBW = (ORGAN UTERUS NON-GRAVID ABS. REL. WT. % BRW 0.48 0.80 0.65 0.34 0.70 0.45 0.58 22.86 38.10 31.71 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 0.74 23.79 18.54 39.00 41.63 16.50 28.33 20.41 24.87 18.93 14.28 38 16 24 76 27 46 30 97 15 76 20 69 29 27 21 18 23 42 20 59 35.24 WEIGHT/BRAIN WEIGHT) X i00. _> _'_ [2_ _t_ O_ to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 3) : BRAIN WEIGHTS, F1 GENERATION ORGAN WEIGHTS FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... PITUITARY LIVER KIDNEY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. WT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. WT. REL. % BRW ADRENAL RIGHT ABS. WT. REL. % BRW 1362 1363 1364 1367 1368 1371 1375 1376 1378 2.09 2.13 2.10 1.98 1.95 2.34 2.00 2.05 NOT PREGNANT 0.015 0.017 0.019 0.016 0.014 0.013 0.017 0.014 0.72 0.80 0.90 0.81 0.72 0.56 0.85 0.68 14.91 15.01 17.48 13.92 15.62 19.98 14.17 16.89 713 40 704 69 832 38 703 03 801 02 853 85 708 50 823 90 1.29 1.42 1.39 1.35 1.45 1.58 1.25 1.67 61.72 66.67 66.19 68.18 74.36 67.52 62.50 81.46 1.28 1.38 1.40 1.33 1.44 1.64 1.32 1.62 61.24 64.79 66.67 67.17 73.85 70.08 66.00 79.02 0.041 0.045 0.042 0.044 0.053 0.054 0.048 0.044 1.96 2.11 2.00 2.22 2.72 2.31 2.40 2.15 0.038 0.049 0.039 0.041 0.047 0.046 0.043 0 042 1 82 2 30. 1 86 2 07 2 41 1 96 2 15 2 05 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 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 0.021 0.016 0.017 0.023 0.014 0.012 0.017 0.021 0.013 0.018 0.013 0.014 0.017 0.015 0.015 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 14.44 13.26 15.82 17.23 12.14 17.48 16.17 18.85 16.60 17.41 16.58 13.63 15.01 15.09 15.90 622 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 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 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 1.48 1.51 1.29 1.51 1.15 1.43 1.29 1.59 1.29 1.57 1.38 1.19 1.22 1.36 1.28 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 i0 65 70 62 14 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 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 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 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 1410 1413 2.05 2.29 0.019 0.015 0.93 0.66 18.06 16.36 880 98 714.41 1.45 1.46 70.73 63.76 1.51 1.55 73 66 67.68 0.044 0.043 2.15 1.88 0.035 0.054 1.71 2.36 1415 1.92 0.011 0.57 17.79 926.56 1.51 78.64 1.52 79.17 0.04.6 2.40 0.052 2.71 _'_ 1416 2.23 0.018 0.81 15.44 692.38 1.48 66.37 1.55 69.51 0.044 1.97 0.041 1.84 1418 2.15 0.013 0.60 15.71 730.70 1.22 56.74 1.32 61.40 0.040 1.86 0.035 1.63 {23 .................................................................................................................................. ._ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. OO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 4) : BRAIN WEIGHTS, F1 GENERATION ORGAN FEMALE WEIGHTS RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... SPLEEN THYMUS OVARY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW 1362 1363 1364 1367 1368 1371 1375 1376 2.09 2.13 2.10 1.98 1.95 2.34 2.00 2.05 0.73 0.50 0.47 0.50 0.53 0.56 0.64 0.58 34.93 23.47 22.38 25.25 27.18 23.93 32.00 28.29 0.20 0.17 0.07 0.11 0.20 0.21 0.19 0.24 9.57 7.98 3.33 5.56 10.26 8.97 9.50 11.71 0.062 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 OVARY RIGHT ABS. WT. REL. % 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 UTERUS NON-GRAVID ABS. REL. WT. % BRW 0.80 0.68 0.46 0.62 0.50 0.55 0.67 0.38 38.28 31.92 21.90 31.31 25.64 23.50 33.50 18.54 11337789 N2O.T32 PREGNANT 0.60 25.86 0.17 7.33 0.054 2.33 0.068 2.93 0.69 29.74 1381 1382 2.13 2.06 0.50 0.83 23.47 40.29 0.27 0.16 12.68 7.77 0.055 0.043 2.58 2.09 0.076 0.046 3.57 2.23 0.63 0.53 29.58 25.73 1383 1.97 0.59 29.95 0.24 12.18 0.059 2 99 0.066 3.35 0.57 28.93 1384 1.94 0.57 29.38 0.12 6.18 0.051 2 63 0.060 3.09 0.83 42.78 1387 2.06 0.59 28.64 0.20 9.71 0.056 2 72 0.056 2.72 0.55 26.70 1389 2.04 0.68 33.33 0.14 6.86 0.047 2 30 0.058 2 84 0.74 36.27 1392 2.23 0.61 27.35 0.12 5.38 0.047 2 11 0.056 2 51 0.38 17.04 1393 2.02 0.57 28.22 0.23 11.39 0.054 2 67 0.035 1 73 0.37 18.32 1397 2.10 0.63 30.00 0.21 10.00 0.053 2.52 0.060 2 86 0.46 21.90 1399 2.26 0.63 27.88 0.18 7,96 0.058 2.57 0.053 2 34 0.47 20.80 1401 1.95 0.67 34.36 0.21 10.77 0.042 2.15 0.045 2 31 0.57 29.23 1404 2.03 0.48 23.64 0 28 13,79 0.085 4.19 0.061 3.00 0.42a 20.69 1407 2.07 0.65 31.40 0 20 9.66 0.044 2.12 0.036 1.74 0.40 19.32 1409 2.06 0.41 19.90 0 20 9.71 0.045 2.18 0.041 1.99 0.34 16.50 1410 2.05 0.58 28.29 0 20 9.76 0.054 2.63 0.051 2.49 0.60 29.27 > 1413 2.29 1.03 44.98 0 17 7.42 0.078 3.41 0.048 2.10 1.00 43.67 1415 1.92 0.72 37.50 0 32 16.67 0.040 2.08 0.038 1.98 0.6_ 35.94 1416 2.23 0.59 26.46 0 14 6.28 0.044 1.97 0.038 1.70 0.43 19.28 1418 2.15 0.57 26.51 0.14 6.51 0.040 ................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. 1.86 0.062 2.88 0.46 21.40 REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. [2_ J_ w-_ 00 Damaged during processing (weight not affected). to O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 5): BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL F1 GENERATION FEMALE RATS DATA - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... PITUITARY LIVER KIDNEY RAT BRAIN LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. REL. HT. % BRW WT. % BRW WT. % BRW .................................................................................................................................... KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. WT. REL. % BRW ADRENAL RIGHT ABS. WT. REL. % BRW 1421 1424 1426 1428 1430 1431 1433 1436 1 96 2 05 2 12 2 18 1 85 2 02 1 95 2 20 0.009 0.013 0.019 0.016 0.017 0.015 0.014 0.018 0.46 0.63 0.90 0.73 0.92 0.74 0.72 0.82 16.89 16.43 18.04 16.19 15.49 19.48 16.49 15.80 861.73 801.46 850.94 742.66 837.30 964.36 845.64 718.18 1.44 1.42 1.37 1.50a 15.30b 1.49 1.36 1.28 73.47 69.27 64.62 68.81 827.03b 73.76 69.74 58.18 1.40 1.36 1.40 1.54a 1.63 1.63 1.42 1.30 71.43 66.34 66.04 70.64 88.11 80.69 72.82 59.09 0.049 0.048 0.051 0.046 0.048 0.042 0.041 0.041 2.50 2.34 2.40 2.11 2.59 2.08 2.10 1.86 0.043 0.046 0.046 0.047 0.042 0.043 0.050 0.039 2.19 2.24 2.17 2.16 2.27 2.13 2.56 1.77 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 2 18 2 01 2 05 2.07 NOT PREGNANT 2.23 2.13 1.96 2.27 2.13 0.015 0.017 0.016 0.018 0.015 0.015 0.016 0.012 0.017 0.69 0.84 0.78 0.87 0.67 0.70 0.82 0.53 0.80 17.76 16.30 15.42 14.80 17.20 18.62 15.77 18.40 16.01 814.68 810.94 752.20 714.98 771.30 874.18 804.59 810.57 751.64 1.41 1.48 1.35 1.28 1.45 1.29 1.34 1.51 1.54 64.68 73.63 65.85 61.84 65.02 60.56 68.37 66.52 72.30 1.47 1.43 1.38 1.33 1.50 1.36 1.38 1.44 1.55 67.43 71.14 67.32 64.25 67.26 63.85 70.41 63.44 72.77 0.044 0.048 0.046 0.053 0.040 0.041 0.043 0.041 0.032 2.02 2.39 2.24 2.56 1.79 1.92 2.19 1.81 1.50 0.039 0.044 0.042 0.052 0.037 0.039 0.037 0.028 0.042 1.79 2.19 2.05 2.51 1.66 1.83 1.89 1.23 1.97 1458 1459 1461 1463 1465 1468 NOT PREGNANT 2.04 2.00 2.07 1.99 2.02 0.018 0.017 0.016 0.006 0.015 0.88 0.85 0 77 0 30 0 74 17.41 13.89 14.98 15.23 14.72 853.43 694.50 723.67 765.33 728.71 1.45 1.29 1.34 1.38 1.45 71 08 64 50 64 73 69 35 71 78 1.48 1.32 1.32 1.25 1.45 72.55 66.00 63.77 62.81 71.78 0.043 0.037 0.043 0.041 0.046 2.11 1.85 2.08 2.06 2.28 0.036 0.033 0.041 0.036 0.033 1.76 1.65 1.98 1.81 1.63 1469 2.17 0.016 0 74 15.62 719.82 1.24 57 14 1.26 58.06 0.051 2.35 0.039 1.80 1472 2.08 0.013 0 62 15.33 737.02 1.62 77 88 1.32 63.46 0.036 1.73 0.043 2.07 1474 2.10 0.014 0 67 14.41 686.19 1.31 62 38 1.37 65.24 0.050 2.38 0.042 2.00 1476 1.96 0.013 0 66 17.55 895.41 1.50 76.53 1.48 75.51 0.033 1.68 0.038 1.94 1477 2.25 0.021 0 93 17.98 799.11 1.48 65.78 1.50 66.67 0.055 2.44 0.053 2.36 [29 1480 2.13 0.018 0 84 17.23 808.92 1.43 67.14 1.44 67.60 0.058 2.72 0.048 2.25 4_ .................................................................................................................................... O_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Rat 1428 had slight dilation of the pelvis in both kidneys - Iv Value appeared incorrectly recorded; values excluded from group averages and statistical analyses. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 6): BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS F1 GENERATION FEMALE RATS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT BRAIN SPLEEN THYMUS OVARY LEFT NUMBER WEIGHT ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. .................................................................................................................................... REL. % BRW 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1 96 2 05 2 12 2 18 1 85 2 02 1 95 2 20 2 18 2 01 2 05 2 07 NOT PREGNANT 0 58 0 64 0 61 0 62 0 58 0 71 0 55 0 64 0 58 0 52 0 73 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 0.23 0.20 0.21 0.14 0.20 0.29 0.28 0.26 0.07 0.23 0.ii 0.22 11.73 9.76 9.90 6.42 10.81 14.36 14.36 11.82 3.21 11.44 5.36 10.63 0.034 0.057 0.047 0.059 0.056 0.075 0.055 0.068 0.037 0.042 0.062 0.045 1.73 2.78 2.22 2.71 3.03 3.71 2.82 3.09 1.70 2.09 3.02 2.17 OVARY RIGHT ABS. WT. REL. % BRW 0 035 0 031 0 053 0 055 0 064 0 056 0 043 0 034 0 044 0 056 0 057 0 041 1.78 1.51 2.50 2.52 3.46 2.77 2.20 1.54 2.02 2.79 2.78 1.98 UTERUS NON-GRAVID ABS. REL. WT. % BRW 0.34 0.64 0.49 0.47 0.62 0.59 1.18 0.83 0.46 0.37 0.51 0.54 17.35 31.22 23.11 21.56 33.51 29.21 60.51 37.73 21.10 18.41 24.88 26.09 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 2.23 2.13 1.96 2.27 2.13 NOT PREGNANT 2 04 2 00 2 07 1 99 2 02 0.70 0.58 0.62 0.67 0.70 0 57 0 55 0 57 0 51 0 55 31.39 27.23 31.63 29.52 32.86 27.94 27.50 27.54 25.63 27.23 0.20 0.21 0.23 0.35 0.29 0.12 0.18 0.18 0.22 0.18 8.97 9.86 11.73 15.42 13.62 5.88 9.00 8.70 11.06 8.91 0.042 0.033 0.047 0.069 0.052 0.038 0.038 0.046 0.056 0.071 1.88 1.55 2.40 3.04 2.44 1.86 1.90 2.22 2.81 3.51 0.045 0.044 0.043 0.062 0.068 0 045 0 035 0 046 0 056 0 057 2.02 2.06 2.19 2.73 3.19 2.20 1.75 2.22 2.81 2.82 0.50a 0.42 0.45 0.75 0.67 0.28 0.56 0.60 0.49 0.58 22.42 19.72 22.96 33.04 31.46 13.72 28.00 28.98 24.62 28.71 1469 2 17 0 56 25.81 0.17 7.83 0.054 2.49 0 056 2.58 0.51 23.50 > 1472 2 08 0 61 29.33 0.40 19.23 0.064 3.08 0 062 2.98 0.83 39.90 1474 2 10 0 62 29.52 0.24 11.43 0.043 2.05 0 037 1.76 0.72 34.28 1476 1 96 0 51 26.02 0.19 9.69 0.050 2.55 0.059 3.01 0.56 28.57 1477 2 25 0 63 28.00 0.I0 4.44 0.040 1.78 0.039 1.73 0.50 22.22 [2_ 1480 2 13 0 60 28.17 0.23 10.80 0.051 2.39 0.051 2.39 0.54 25.35 .............................................................................................................................. OO WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. Damaged during processing (weight not affected), b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 7) : BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - ................................................................................ DOSAGE GROUP IV 10 MG/KG/DAY .................................................... .................................................................................................................................... RAT BRAIN PITUITARY LIVER KIDNEY LEFT NL_4BER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW KIDNEY RIGHT ABS. REL. WT. % BRW ADRENAL LEFT ABS. REL. WT. % BRW 1482 1483 2.23 0.015 NOT PREGNANT 0.67 15.34 687.89 1.26 56.50 1.25 56.05 0.045 2.02 ADRENAL RIGHT ABS. REL. WT. % BRW 0.035 1.57 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1.90 2.06 2.12 2.05 2.12 1.76 2.23 1.97 2.05 2.05 2.21 2.20 NOT PREGNANT 0.017 0.013 0.015 0.014 0.016 0.015 0.016 0.018 0.014 0.015 0.015 0.013 0.89 0.63 0.71 0.68 0.75 0 85 0 72 0 91 0 68 0 73 0 68 0 59 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 1.37 1.33 1.65 1.24 1.52 1.33 1.50 1.48 1.18 1.51 1.46 1.39 72.10 64.56 77.83 60.49 71.70 75.57 67.26 75.13 57.56 73.66 66.06 63.18 1.31 1.41 1.56 1.28 1.49 1.28 1.48 1.49 1.22 1.68 1.51 1.46 68.95 68.45 73.58 62.44 70.28 72.73 66.37 75 63 59.51 81.95 68.32 66.36 0.054 0.042 0.052 0.044 0.042 0.047 0.044 0.042 0.041 0.046 0.051 0.041 2.84 2 04 2 45 2 15 1 98 2 67 I 97 2 13 2 00 2 24 2 31 1 86 0.047 0.043 0.045 0.040 0.042 0.047 0.040 0.041 0.042 0.040 0.050 0.042 2.47 2.09 2.12 1.95 1.98 2.67 1.79 2.08 2.05 1.95 2.26 1.91 1513 1514 1516 1517 1519 1521 1523 1524 1527 2.24 2.19 2.15 2.03 2.08 2.18 2.02 1.98 2.14 0.017 0.016 0.014 0.013 0.017 0.016 0.011 0.010 0.023 0 76 0 73 0 65 0 64 0 82 0 73 0 54 0 50 1 07 13.67 15.60 15.89 17.35 17.52 15.27 15.78 13.46 18.04 610.27 712.33 739.07 854.68 842.31 700.46 781.19 679.80 842.99 1.28 1.32 1.28 1.13 1.45 1.35 1.32 1.24 1.35 57.14 60.27 59.53 55.66 69.71 61.93 65.35 62.63 63.08 1.30 1.38 1.27 1.13 1.56 1.42 1.38 1.21 1.42 58 04 63 01 59 07 55 66 75 00 65 14 68 32 61 11 66 36 0.043 0.053 0.036 0.043 0.047 0.046 0.041 0.030 0.051 1 92 2 42 1 67 2 12 2 26 2 11 2 03 1 52 2 38 0.044 0.043 0.033 0.041 0.041 0.045 0.040 0.026 0.042 1.96 1.96 1.53 2.02 1.97 2.06 1.98 1.31 1.96 1528 1531 2.11 2.15 0.015 0.014 0 71 0 65 15.96 18.68 756.40 868.84 1.46 1.49 69.19 69.30 1.53 1.58 72 51 73 49 0.044 0.054 2 08 2 51 0.035 0.049 1.66 2.28 1533 2.11 0.017 0 80 19.96 945.97 1.56 73.93 1.61 76 30 0.0S3 2 51 0.041 1.94 _'_ 1534 2.20 0.015 0 68 16.16 734.54 1.38 62.73 1.37 62.27 0.041 1 86 0.031 1.41 1537 1.93 0.015 0 78 15.08 781.35 1.21 62.69 1.25 64.77 0.046 2 38 0.051 2.64 O_ 1539 2.22 0.017 0 76 18.63 839.19 1.69 76.13 1.81 81.53 0.056 2 52 0.052 2.34 4_ ........................................................................ ............................................................ WEIGHTS WERE RECORDED IN GRAMS (G) ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X i00. CD O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 8): BRAIN WEIGHTS, ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL F1 GENERATION FEMALE RATS DATA - .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT BRAIN SPLEEN THYMUS OVARY LEFT NUMBER WEIGHT ABS. WT. REL. % BRW ABS. WT. REL. % BRW ABS. WT. REL. % BRW .................................................................................................................................... 1482 1483 2.23 0.53 NOT PREGNANT 23.77 0.29 13.00 0.046 2.06 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1.90 2.06 2.12 2.05 2.12 1.76 2.23 1.97 2.05 2.05 2.21 2.20 NOT PREGNANT 0.58 0.61 0.66 0.56 0.46 0.57 0.68 0.48 0.48 0.70 0.54 0.64 30 53 29 61 31 13 27 32 21 70 32 39 30.49 24.36 23.41 34.15 24.43 29.09 0.11 0.33 0.26 0.10 0.12 0.15 0.26 0.24 0.13 0.23 0.21 0.13 5.79 16.02 12.26 4.88 5.66 8.52 11.66 12.18 6.34 11.22 9.50 5.91 0.065 0.041 0.076 0.031 0.039 0.045 0.065 0.046 0.063 0.048 0.040 0.048 3.42 1.99 3.58 1.51 1.84 2.56 2.91 2 34 3.07 2.34 1.81 2.18 1513 1514 1516 1517 1519 1521 1523 1524 1527 2.24 2.19 2.15 2.03 2.08 2.18 2.02 1.98 2,14 0.51 0.67 0.55 0.58 0.52 0.60 0.54 0.74 0.82 22 77 30 59 25 58 28 57 25 00 27 52 26 73 37 37 38 32 0.10 0.16 0.18 0.10 0.17 0.08 0.35 0.38 0.23 4.46 7.30 8.37 4.93 8.17 3.67 17.33 19.19 10.75 0.048 0.042 0.064 0.041 0.044 0.045 0.051 0.050 0.056 2.14 1.92 2.98 2 02 2 12 2 06 2 52 2 52 2 62 1528 1531 1533 1534 1537 1539 2.11 2.15 2.11 2.20 1.93 2.22 0.67 0.67 0.66 0.50 0.51 0.57 31 75 31 16 31.28 22.73 26.42 25.68 0.26 0.30 0.20 0.17 0.15 0.29 12.32 13.95 9.48 7.73 7.77 13.06 0.037 0.042 0.045 0.060 0.044 0.061 1.75 1.95 2.13 2.73 2.28 2.75 .................................................................................................................................... WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. OVARY RIGHT ABS. WT. REL. % BRW 0.044 1.97 0.049 0.033 0.068 0.049 0.059 0.063 0.070 0.054 0.066 0.045 0.056 0.044 2.58 1 60 3 21 2 39 2 78 3 58 3 14 2 74 3 22 2 20 2 53 2 00 0.048 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 % THW = (ORGAN UTERUS NON- GRAVID ABS. WT. REL. % BRW 0.68 30.49 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 WEIGHT/BRAIN WEIGHT) X i00. _'_ [29 _t_ tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 9) : BRAIN WEIGHTS, F1 GENERATION ORGAN FEMALE WEIGHTS RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT BRAIN PITUITARY LIVER KIDNEY LEFT NUMBER WEIGHT ABS. REL. ABS. REL. ABS. WT. % BRW WT. % BRW WT. .................................................................................................................................... REL. % BRW 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 2.00 2.12 2.13 2.04 2.02 2.05 2.19 2.03 2.20 2.01 0.022 0.016 0.012 0.019 0.017 0.016 0.018 0.009 0 018 0.011 1.10 0.75 0.56 0.93 0.84 0.78 0.82 0.44 0.82 0.55 14.69 16.14 17.89 17.75 18.02 19.33 16.81 15.58 15.27 17.49 734 50 761 32 839 91 870 10 892 08 942 93 767 58 767.49 694.09 870.15 1.11 1.57 1.40 1.32 1.49 1.29 1.43 1.21 1,30 1.50 55.50 74.06 65.73 64.70 73.76 62.93 65.30 59.60 59.09 74.63 KIDNEY RIGHT ABS. REL. WT. % BRW 1.20 1.65 1.47 1.45 1.50 1.33 1.56 1.25 1.24 1.55 60.00 77.83 69.01 71.08 74.26 64.88 71.23 61.58 56.36 77.11 ADRENAL LEFT ABS. REL. WT. % BRW 0.050 0 040 0 065 0 032 0 053 0 055 0 042 0 045 0 039 0 042 2.50 1.89 3.05 1.57 2.62 2.68 1.92 2.22 1.77 2.09 ADRENAL RIGHT ABS. REL. WT, % BRW 0.043 0.050 0.054 0.044 0.049 0.053 0.039 0.040 0.034 0.039 2.15 2 36 2 54 2 16 2 42 2 58 1 78 1 97 1 54 1 94 1560 1564 1565 1566 1568 1571 1573 1576 1578 2.21 2.00 2.03 2.13 2.21 1.91 2.03 1.78 NOT PREGNANT 0.015 0.012 0.013 0.010 0.018 0.010 0.015 0.015 0.68 0.60 0.64 0.47 0.81 0.52 0.74 0.84 18.14 17.80 14.42 17.00 15.50 15.97 17.15 15.62 820.81 890.00 710.34 798.12 701.36 836.12 844.83 877.53 1.37 1.37 1.11 1.30 1.24 1.14 1.20 1.20 61.99 68.50 54.68 61.03 56.11 59.68 59.11 67.42 1.57 1.39 1 22 1 28 1 27 1 23 1 20 1 29 71.04 69.50 60.10 60.09 57.47 64.40 59.11 72.47 0 041 0 044 0 042 0 053 0 040 0 043 0 033 0 043 1.86 2.20 2.07 2.49 1.81 2.25 1.62 2.42 0.043 0.048 0.044 0.035 0.034 0.044 0.030 0.039 1 94 2 40 2 17 1 64 1 54 2 30 1 48 2 19 1579 1583 1584 1586 1587 1.99 2.11 2.13 2.15 2.02 0.013 0.014 0.016 0.015 0.014 0.65 0.66 0.75 0.70 0.69 17.26 16.59 13.71 15.78 15.72 867.34 786.26 643.66 733.95 778.22 1.37 1.38 1.19 1.49 1.23 68.84 65.40 55.87 69.30 60.89 1.37 1.42 1.19 1.40 1.35 68.84 67.30 55.87 65.12 66.83 0 044 0 044 0 024 0 050 0 041 2.21 2.08 1.13 2.32 2.03 0.037 0.036 0.039 0.040 0.034 1 86 1 71 1 83 1 86 1 68 1588 1589 2.10 2.02 0.016 0.015 0.76 0.74 17.39 17.58 828.10 870,30 1.34 1.21 63.81 59.90 1.35 1.30 64.28 64.36 0 047 0 046 2.24 2.28 0.046 0.042 2 19 2 08 1591 2.11 0.015 0.71 18.89 895.26 1.38 65.40 1.40 66.35 0 043 2.23 0.043 2 04 1593 2.04 0.023 1.13 17.20 843.14 1.98 97.06 2.18a 106.86 0 046 2.25 0.041 2 01 1598 2.18 0.015 0.69 17.75 814.22 1.59 72.94 1.52 69.72 0 045 2.06 0.037 1 70 [2_ 1600 2.18 0.012 0.55 18.06 828.44 1.25 57.34 1.45 66.51 0 059 2.71 0.044 2 02 4_ .................................................................................................................................... O_ WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X I00. Rat 1593 had moderate dilation of the pelvis in the right kidney, tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E37 (PAGE 10): BRAIN WEIGHTS, ORGAN WEIGHTS F1 GENERATION FEMALE RATS AND RATIOS (%) OF ORGAN WEIGHT TO BRAIN WEIGHT - INDIVIDUAL DATA - .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT NUMBER BRAIN WEIGHT SPLEEN ABS. WT. REL. % BRW THYMUS ABS. WT. REL. % BRW OVARY LEFT ABS. WT. REL. % BRW .................................................................................................................................... 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 1566 1568 1571 1573 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 0.50 0.76 0.64 0.59 0.80 0.60 0.57 0.52 0.48 0.74 0.65 0.65 0.64 0,56 0.56 0.56 0.47 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 0.20 0.44 0.23 0.25 0.21 0.14 0.ii 0.21 0.12 0 24 0.29 0 24 0 26 0 19 0 19 0 12 0 20 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 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 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 1576 1578 1 78 NOT PREGNANT 0.62 34.83 0.17 9.55 0 043 2.42 1579 1583 1584 1586 1587 1 99 2 11 2 13 2 15 2 02 0.69 0.48 0.51 0.50 0.52 34.67 22.75 23.94 23.26 25.74 0 13 0 16 0 33 0 12 0 26 6.53 7.58 15.49 5.58 12.87 0 051 0 068 0 052 0 043 0 060 2.56 3.22 2.44 2.00 2.97 OVARY RIGHT ABS. WT. REL. % 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 2.06 1.90 3.10 1 63 2 72 UTERUS NON-GRAVID ABS. REL. WT. % BRW 0.56 0.82 0.39 0.37 0.82 0.27 0.94 0.49 0.36 0.71 0.82 0.45 0.67 0.46a 0.42 0.31 0.39 0.34 28.00 38.68 18.31 18.14 40.59 13,17 42 92 24 14 16 36 35 32 37 i0 22 50 33 00 21 60 19 00 16 23 19 21 19 i0 0.66 0.38 0.51 0.45 0.59 33.16 18.01 23.94 20.93 29.21 1588 1589 2 i0 2 02 0.58 0.59 27.62 29.21 0 37 0 16 17.62 7.92 0 043 0 043 2.05 2.13 0.045 0.045 2 14 2 23 0.83 0.45 39.52 22.28 1591 2 II 0.64 30.33 0 22 10.43 0 049 2.32 0.041 1 94 0.5_ 26.54 1593 2 04 0.95 46.57 0 50 24.51 0 069 3.38 0.069 3 38 0.61 29.90 1598 2 18 0.51 23.39 0.20 9.17 0 065 2.98 0.051 2 34 0.60 27.52 [2_ 1600 2 18 0.66 30.28 0.16 7.34 0 046 2.11 0.045 2 06 0.44 20.18 /_ .................................................................................................................................... _._ OO WEIGHTS WERE RECORDED IN GRAMS (G). ABS. WT. = ORGAN WEIGHT. REL. % TBW = (ORGAN WEIGHT/BRAIN WEIGHT) X 100. Damaged during processing (weight not affected). O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E38 (PAGE 1): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY FEMALE RATS/F2 GENERATION LITTERS AND SEX - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F ..... _ .............................................................................................................................. 1302 22 Ii 0 11 1304 23 12 0 12 1306 22 16 0 16 1308 22 16 0 16 1310 23 14 0 14 1312 23 4 0 4 1313 23 13 1316 NOT PREGNANT 0 13 5 6 6 6 8 8 6 10 9 5 2 2 5 8 5 6 6 6 8 8 6 10 9 5 2 2 5 8 OF LIVE OF DAY 8 M F PUPS AT POSTPARTUM 15 M F 5 6 6 6 8 8 6 10 9 5 2 2 5 8 5 6 6 6 8 8 6 10 9 5 2 2 5 8 22 M F 5 6 6 6 8 8 6 10 9 5 2 2 5 7 TOTAL IMPLANTATIONS N 13 14 17 17 15 4 15 1318 23 15 0 15 9 6 8 6 8 6 8 6 8 6 16 1321 23 17 0 17 8 9 8 9 8 9 7 8 7 8 17 1325 23 11 0 11 5 6 5 6 5 6 5 6 5 6 12 1328 22 13 0 13 7 6 7 6 7 6 7 6 7 6 16 1330 23 16 0 16 7 9 7 9 7 9 7 9 7 9 16 1331 23 16 0 16 12 4 12 4 12 4 11 4 11 4 16 1334 23 9 0 9 6 3 6 3 6 3 6 3 6 3 I0 1335 23 12 0 12 6 6 6 6 6 6 6 6 6 6 13 1336 23 15 0 15 7 8 7 8 7 8 7 8 7 8 16 1338 23 17 0 17 8 9 8 9 8 9 8 9 8 8 18 1340 22 14 0 14 8 6 8 6 8 6 8 6 8 6 16 1341 23 12 0 12 4 8 4 8 4 8 4 8 4 8 14 1342 23 16 0 16 9 7 9 7 9 7 9 7 9 7 16 1344 23 15 0 15 7 8 7 8 7 8 7 8 7 8 16 1345 23 14 2 16 5 9 4 9 4 9 4 9 4 9 16 1346 23 i0 0 i0 6 4 6 4 6 4 64 6 4 i0 1348 23 14 2 16 8 6 8 6 8 6 8 6 8 6 18 1350 23 17 0 17 13 4 13 4 13 4 13 4 13 4 18 1353 22 13 0 1411] 6 7 6 7 6 7 6 7 6 7 15 1355 23 15 0 15 4 11 4 11 4 11 4 11 ' 4 11 16 1358 NOT PREGNANT; MATING NOT CONFIRMED 1359 23 13 1 14 5 8 5 8 5 8 5 8 5 8 14 4_ -l--. _.d ............................................................................................................................... O_ = MALE F = FEMALE ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E38 (PAGE 2): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY FEMALE RATS/F2 GENERATION LITTERS AND SEX - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS} BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... 1362 23 1363 22 7 0 7 17 1 18 4 3 7 i0 4 3 7 9 1364 22 1367 22 1368 23 1371 23 1375 22 15 0 15 13 0 13 15 0 15 17 0 17 14 0 14 7 8 8 5 8 7 11 6 9 5 7 8 8 5 8 7 11 6 9 5 1376 23 15 1378 NOT PREGNANT 2 17 i0 5 i0 5 13_9 23 1381 23 1382 23 1383 23 1384 22 1387 23 1389 22 1392 22 1393 23 1397 23 1399 23 1401 22 1404 23 1407 23 1409 23 12 0 12 12 0 12 13 0 13 11 0 11 13 0 13 16 1 17 16 0 16 17 0 17 11 1 12 12 0 12 10 0 10 12 0 12 15 0 15 15 0 15 12 0 12 6 6 6 6 5 8 6 5 6 7 97 8 8 9 8 5 6 7 5 4 6 57 I0 5 7 8 7 5 6 6 6 6 5 8 6 5 5 7 9 7 8 8 9 8 5 6 7 5 4 6 5 7 i0 5 7 8 7 5 1410 21 1413 23 1415 23 1416 23 1418 23 17 0 17 13 0 13 13 0 13 14 0 14 16 0 16 13 4 7 6 7 6 3 Ii 6 i0 13 3 7 6 7 6 3 ii 6 8 ................................................................................................................................... ffiMALE F = FEMALE OF LIVE OF DAY 8 M F 4 3 7 9 7 8 8 5 8 7 11 6 9 5 10 5 6 6 6 6 5 8 6 5 5 7 9 7 7 8 9 8 5 6 7 5 4 6 5 7 i0 5 7 8 7 5 13 3 7 6 7 6 3 II 6 8 PUPS AT POSTPARTUM 15 M F 4 3 7 9 7 8 8 5 8 7 11 5 95 I0 5 6 6 6 6 5 8 6 5 5 7 97 7 8 9 8 5 6 7 5 4 6 5 7 i0 5 7 8 7 5 13 3 7 6 7 6 3 ii 6 7 22 M F 4 3 7 9 7 8 8 5 8 7 11 5 9 4 i0 5 6 6 6 6 5 8 6 5 5 7 9 7 7 8 9 8 5 6 7 5 4 6 5 7 I0 5 7 8 7 5 13 3 7 6 7 6 3 11 6 7 TOTAL IMPLANTATIONS 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 (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E38 (PAGE 3): NATURAL DELIVERY, IMPIANTATION SITES, AND PUP VIABILITY FEMALE RATS/F2 GENERATION LITTERS AND SEX - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... RAT/ DURATION OF GESTATION LITTER DELIVERED LIVE STILL- TOTAL NUMBER COMPLETION LITTER NUMBER (DAYS) N BORN N BORN N BORN N 1 M F 5 M F .................................................................................................................................... OF LIVE OF DAY 8 M F 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 23 22 23 23 23 23 22 23 22 23 23 23 NOT PREGNANT 17(2) 0 17 17 0 17 13 0 13 15 0 15 17 0 17 16(1) 0 16 18 0 18 12 0 12 16 0 16 10(1) 2 12 7 0 7 14 0 14 10 5 9 8 7 6 6 9 6 11 96 i0 8 8 4 9 7 6 3 4 3 8 6 10 5 9 8 7 6 6 9 6 Ii 9 5 10 8 8 4 9 7 6 3 4 3 8 6 10 5 9 8 7 6 6 9 6 II 9 5 10 7 8 4 9 7 6 3 4 3 8 6 1448 23 14 2 16 1450 23 14 0 14 1452 22 14 0 14 1455 22 15 0 15 1456 1458 23 NOT PREGNANT 6 0 6 6 8 4 10 8 6 8 7 4 2 6 8 4 i0 8 5 6 7 4 2 6 8 4 10 8 5 5 5 4 2 1459 23 1461 23 1463 23 1465 23 1468 22 14 0 14 11 0 11 13 2 15 16 0 16 16 0 16 9 5 4 7 7 6 6 10 5 11 8 5 4 7 7 6 6 I0 5 11 8 5 4 7 7 6 6 10 5 11 1469 23 1472 23 12 0 12 i0 0 10 9 3 5 5 9 3 5 5 1474 23 1476 22 1477 22 14 0 14 17(I) 0 17 17 0 17 i0 4 7 9 8 9 i0 4 7 9 8 9 1480 23 13 0 13 3 I0 3 i0 .................................................................................................................................... = MALE F = FEMALE 9 3 5 5 i0 4 7 9 8 8 3 I0 ) _ NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. PUPS AT POSTPARTUM 15 M F 10 5 9 8 7 6 6 9 6 11 9 5 10 7 8 4 9 7 6 3 4 3 8 6 6 8 4 10 8 5 5 5 4 2 8 5 4 7 7 6 6 10 5 11 9 3 5 5 i0 4 7 9 8 8 3 I0 22 M F 10 5 9 8 7 6 6 9 6 11 9 5 10 7 8 4 9 7 6 3 4 3 8 6 6 8 4 10 8 5 5 5 4 2 8 5 4 7 7 6 6 10 5 11 9 3 5 5 i0 4 7 9 8 8 3 i0 TOTAL IMPLANTATIONS N 17 17 14 16 17 16 19 14 16 14 7 14 16 16 15 16 7 15 12 16 16 16 12 ii 15 17 17 14 > _'_ [2_ _t_ O0 t_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E38 (PAGE 4): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY FEMALE RATS/F2 GENERATION LITTERS AND SEX - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... 1482 1483 23 NOT PREGNANT 15(1) 1 16 6 8 6 8 OF LIVE OF DAY 8 M F PUPS AT POSTPARTUM 15 M F 6 8 6 8 22 M F 6 8 TOTAL IMPLANTATIONS N 16 1486 23 15 0 15 9 6 96 9 6 9 6 9 6 15 1488 23 15 0 15 8 7 8 7 8 7 8 7 8 7 15 1490 23 10 0 10 7 3 7 3 7 3 7 3 7 3 16 1491 22 14 0 15 [I] 4 i0 4 I0 4 i0 4 i0 4 i0 15 1494 23 14 (1) 0 14 8 5 8 5 8 5 8 5 8 5 17 1496 22 13 0 13 7 6 7 6 7 6 7 6 7 6 15 1497 23 11 0 11 4 7 4 7 4 7 4 7 4 7 11 1500 23 14 1 15 9 5 9 5 9 5 9 5 95 20 1502 23 13 0 13 4 9 4 8 4 8 4 8 4 8 16 1505 23 16 0 16 7 9 7 9 7 9 7 9 7 9 16 1507 22 16 0 16 9 7 97 9 7 9 7 9 7 16 1508 23 13 0 13 4 9 4 8 4 8 4 8 4 8 15 1511 NOT PREGNANT 1513 23 13 1 14 9 4 94 9 4 94 94 15 1514 23 17 0 17 9 8 9 8 9 8 9 7 9 7 17 1516 22 13 0 13 9 4 94 9 4 94 94 15 1517 22 15 0 15 8 7 8 7 8 7 8 7 8 7 15 1519 23 16 0 16 8 8 8 8 8 8 8 8 8 7 16 1521 23 12 0 12 7 5 7 5 7 5 7 5 7 5 12 1523 22 12 (i) 0 12 7 4 74 7 4 74 74 14 1524 25 2 0 2 2 2 2 - 2 2 4 1527 23 17 0 17 11 6 i0 6 i0 6 i0 6 10 6 17 1528 23 i0 0 i0 6 4 64 6 4 64 6 4 ii _> 1531 23 13 2 15 8 5 8 5 8 5 8 5 8 5 15 1533 22 19(1) 0 19 6 12 6 12 6 ii 6 ii 6 11 20 1534 23 12 0 12 6 6 6 6 6 6 6 6 '6 6 14 1537 23 14 1 15 i0 4 10 4 10 4 10 4 10 4 15 1539 23 14 0 14 9 5 9 5 9 5 9 5 9 5 16 .................................................................................................................................... O_ = MALE F = FEMALE ) = NUMBER OF PUPS DYING PRIOR TO WEIGHING ON DAY 1 POSTPARTUM. ] = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E38 (PAGE 5): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY FEMALE RATS/F2 GENERATION LITTERS AND SEX - INDIVIDUAL DATA - F1 GENERATION .................................................................................................................................... DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DURATION OF LITTER DELIVERED NUMBER RAT/ GESTATION LIVE STILL- TOTAL COMPLETION LITTER (DAYS) BORN BORN BORN 1 5 NUMBER N N N N M F M F .................................................................................................................................... 1541 23 1544 23 1545 23 1546 22 1548 22 1550 22 1552 23 1555 23 14 0 14 13 1 14 19 0 19 15 0 15 13 1 14 12 0 12 14 0 14 15 0 15 4 I0 6 7 9 i0 8 7 4 9 5 7 7 7 7 8 4 i0 6 6 9 9 8 7 4 9 5 7 7 7 7 8 OF LIVE OF DAY 8 M F PUPS AT POSTPARTUM 15 M F 4 I0 6 6 9 9 8 7 4 9 5 7 7 7 7 7 4 10 6 6 9 9 8 7 4 9 5 7 7 7 7 7 11555578 2233 1560 23 1136 00 1136 15 0 15 105 86 7 8 105 86 7 8 1564 23 13 0 13 1565 23 12 0 12 1566 23 15 0 15 1568 23 13 0 13 1571 22 13 0 13 1573 23 15 0 15 1576 22 13 0 13 1578 NOT PREGNANT 1579 22 15 0 15 1583 22 12 0 12 1584 23 4 0 4 1586 23 13 0 13 1587 22 11 0 11 6 7 6 6 2 13 7 6 6 7 7 8 8 5 8 7 5 7 3 1 7 6 5 6 6 7 6 6 2 13 7 6 6 7 7 8 8 5 8 7 4 7 3 1 7 6 5 6 1588 23 1589 22 1591 23 1593 23 1598 23 13 0 13 14 0 14 14 0 14 6 0 6 17 0 17 4 9 6 8 I0 4 2 4 7 I0 4 9 6 8 i0 4 2 4 7 I0 1600 23 15(i] 0 15 i0 4 I0 4 .................................................................................................................................... = MALE F = FEMALE ) = NUMBER OF PUPS DYING PRIOR T0 WEIGHING ON DAY 1 POSTPARTUM. 105 86 6 8 6 7 6 6 2 13 7 6 6 7 7 8 6 5 8 7 4 7 3 1 7 6 5 6 4 9 6 8 i0 4 2 4 7 i0 i0 4 105 86 6 8 6 7 6 6 2 13 7 6 6 7 7 8 6 5 8 7 4 7 3 1 7 6 5 6 4 9 6 8 I0 4 2 4 7 i0 i0 4 22 M F 4 10 6 6 9 8 8 7 4 9 5 7 7 7 7 7 105 86 6 8 6 7 6 6 2 13 7 6 6 7 7 8 6 5 8 7 4 7 3 1 7 6 5 6 4 9 6 8 i0 4 2 4 7 10 I0 4 TOTAL IMPLANTATIONS N 15 15 19 17 14 14 16 15 1147 15 15 16 15 17 15 16 13 15 12 5 13 13 14 16 14 6 17 17 _'_ _') 4_ O_ hO.) PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LIttlER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E39 (PAGE 1): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT/ LITTER DAY 1 DAY 5 DAY 8 NUMBER M F T M F T M F T .................................................................................................................................... 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 6.9 6.3 6.6 6.5 6.1 6.3 6.2 5.9 6.1 6.2 6.1 6,1 6.8 6.1 6.5 8.4 8.0 8.2 6.7 6.2 6.4 NOT PREGNANT 7.3 7.0 7.2 6.4 6.2 6.3 11.7 11.6 9.7 8.3 10.7 13.8 i0.8 10.4 10.5 9.9 8.6 10.2 14.2 10.5 11.0 11.1 9.8 8.4 10.5 14.0 10.6 12.3 8.8 12.2 8.6 12.2 8.7 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 17.6 12.3 17.6 12.5 DAY 15 M F 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 28.2 16.4 28.3 17.6 DAY 22 M F 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 48.3 31.2 48.1 27.4 11332258 66..82 66..60 66..71 109..78 109..65 109..76 1154.49 1154,.33 1154..36 1330 6.6 6.3 6.5 8.8 8.3 8.5 11 5 10,9 11.2 1331 6.1 6.0 6.1 8.8 8.2 8.6 11 8 11,0 11.6 1334 7.2 6.5 7.0 11.1 10.4 10.9 15 3 14.7 15.1 1335 6.6 6.0 6.3 9.8 9.4 9.6 14 8 14.2 14.5 1336 7.1 6.9 7.0 10.4 10.4 10.4 15 6 15,8 15.7 1338 6.4 6.3 6.3 10.4 10.0 10.2 15 0 14 6 14.8 1340 6.4 59 6.2 10.9 10.2 10.6 14 6 13 8 14.3 1341 7.2 67 69 11.3 10.7 10.9 16 2 15 7 15.8 1342 63 58 61 10.3 9.5 I0.0 14 6 13 2 14.0 1344 70 66 68 10.7 9.9 10.3 14 5 14 0 14 2 1345 73 65 68 10.6 9.9 10.1 15 7 14 9 15 1 1346 62 58 60 ii.I 10.6 10.9 16.8 16.2 16 5 1348 63 60 62 9.1 8.7 9.0 13.4 12,9 13 2 1350 61 57 60 8.6 8.0 8.4 12.1 11.2 11 9 1353 1355 6.3 6.1 6.2 Ii.0 10.5 i0._ 13.0 12,4 12 7 6.8 6.5 6.6 9.9 9.8 9.8 14.4 13.8 14 0 1358 1359 NOT PREGNANT; MATING NOT CONFIRMED 6.3 6.0 6.1 9.3 9.2 9.3 12.3 12,0 12.1 .................................................................................................................................... 2289 61 21 3 22 0 28 4 25 4 24 8 20,2 27.0 28.7 23.6 25.0 29.4 31._ 26.4 21.3 24.4 26.5 2287 29 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 2288.45 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 3468..59 27.9 30.8 38.7 41.6 40.9 29.0 42.5 47.6 38.2 43.8 40.0 42.2 37.1 25.8 41.4 41.3 3465,.24 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 41.9 39,7 MALE WEIGHTS F = FEMALE WERE RECORDED T = TOTAL IN GRAMS (SUM (G). OF PUP WEIGHTS/NUMBER MEAN LITTER WEIGHTS OF LIVE PUPS) INCLUDE ONLY DAY WEIGHTS = DAY POSTPARTUM OF LIVE PUPS, T 45 6 44 4 34 1 28 2 43 0 53 2 39.4 48.2 29.2 3467.,33 25.4 30.0 38.5 40.7 41.1 28.4 41.7 46.1 36.2 43.1 39,6 41.6 36.3 25.4 40,9 40.2 "40.5 _n _t_ O0 d:, 1"3 Q PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E39 (PAGE 2}: PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT/ LITTER NUMBER DAY 1 M F T DAY 5 M F T DAY 8 M F T .................................................................................................................................... 1362 6.6 6.2 6.4 12.0 11.5 11.7 17.6 17.1 17.4 i363 1364 6.0 5.7 5.8 5.4 5.1 5.3 86 8.5 8.6 12.8 12.4 12.6 91 8.7 8.9 13.5 12.8 13.1 1367 1368 1371 1375 1376 1378 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 11 1 10 9 89 10 2 91 10.8 10.2 9.0 9.1 9.2 11.0 10.6 8.9 9.8 9.2 16.0 15.8 12.0 14.6 12.9 15.5 15.1 12.1 12.8 13.0 15.8 15.5 12.0 14.0 12.9 DAY 15 M F 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 DAY 22 M F 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 31.7 36.7 40.6 34.5 33.3 36.4 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 6.6 6.4 6.5 11.0 10.0 10.5 16.0 14.8 15.4 28.9 27.2 28 0 38.8 36.0 37.4 7.6 6.8 7.2 12.3 11.1 11.7 16.9 15.2 16.0 29.3 27.0 28 2 50.9 47.3 49.1 6.3 5.7 5.9 10.2 9.1 9.5 15.7 14.1 14.7 31.0 28.5 29 5 38.3 35.1 36.3 6.4 6.1 6.2 10.7 10.4 10.6 15.9 15.8 15.8 29.9 29.8 29 9 46.8 47.1 46.9 7.1 6.5 6.8 11.9 11.2 11.5 17.5 16.7 17.0 28.3 27.6 27 9 41.8 41.5 41.7 6.9 6.4 6.7 10.4 9.9 10.2 14.6 14.3 14.5 24 4 24 7 24 5 36.0 36.4 36.2 6.0 5.3 5.6 83 8.0 8.2 12.3 11.6 11.9 23 0 21 3 22 1 36.8 34.7 35.7 5.9 5.6 5.7 86 7.7 8.2 12.3 11.2 11.8 22 8 21 7 22 3 30.2 28.6 29.4 6.6 6.1 6.4 11 2 10.4 10.8 17.1 16.1 16.5 32 4 31 1 31 7 44.4 43.0 43.6 7.5 7.4 7.5 12 1 12.3 12.2 17.9 17.4 17.7 26 7 26 0 26.4 49.5 47.1 48.5 7.0 6.7 6.8 12 4 11.8 12.0 17.3 16.3 16.7 27 9 26 2 26 9 47.4 45.0 46.0 6.8 6.6 6.6 11 4 11.2 11.3 15.9 15.9 15.9 24 7 24 3 24 5 44.3 41.5 42.6 6.1 5.8 6.0 i0 1 i0.0 i0.I 12.9 12.5 12.8 23 4 21 9 22 9 37.2 33.4 35.9 6.5 6.1 6.3 87 8.7 8.7 13.0 13.1 13.0 21 4 21 6 21 6 34.5 35.7 35.1 6.0 5.8 5.9 10 1 10.0 10.1 14.1 14.0 14.0 27 7 27 0 27 4 47.5 45.2 46.6 6.0 5.5 5.9 96 9.2 9.5 14.0 13.0 13.8 24 2 22 0 23 8 39.5 36.2 38.9 6.5 5.9 6.2 94 8.5 9.0 12.8 12.2 12.5 26 1 25 7 25 9 45.2 43.6 44.5 1415 1416 1418 6.6 6.0 6.4 6.3 6.5 6.4 6.4 6.0 6.2 94 8.8 9.1 93 9.2 9.2 90 8.0 8.4 13.2 12.9 13.9 12.5 13.2 11.4 12.9 13.1 12.5 22 6 21 9 23 2 21 4 21 9 20 6 22 1 21 9 21 8 37.8 35.3 36.2 36.6 35.4 32.7 37.2 35.4 34.3 ........................................................................................... MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS WERE RECORDED IN GRAMS (G). MEAN WEIGHTS/NUMBER LITTER WEIGHTS OF LIVE INCLUDE PUPS) ONLY DAY WEIGHTS = DAY _,........................................ POSTPARTUM OF LIVE PUPS. C/_ 4_ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPOMSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E39 (PAGE 3): PUP BODY WEIGHT LITTER AVERAGES PROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL..DO.SAG.E .GR.OU.P .II.I ............3.MG./KG./DA.Y ........................................ LITTER DAY 1 DAY 5 DAY 8 NUMBER M F T M F T M P T .................................................................................................................................... 1421 1424 1426 1428 1430 1431 6.7 63 66 9.8 9.6 98 13.9 13.2 13.6 5.5 52 53 8.3 7.8 81 12.2 11.4 11.8 6.7 62 65 10.2 9.5 99 14.0 13.4 13.7 6.9 62 65 10.4 9.7 10 0 15.1 14.1 14.5 6.7 61 63 9.4 8.7 90 12.3 11.4 11.7 6.3 65 64 10.3 10.3 10 3 14.7 14.6 14.7 1433 1436 6.1 59 60 9.4 9.0 92 13.6 13.8 13.7 6.4 58 62 10.4 9.8 10 2 15.3 14.3 14.9 1437 1439 1442 1443 1446 6.0 5.9 60 6.8 6.5 67 8.3 7.9 81 6.3 6.2 62 NOT PREGNANT 9.4 11.3 14.3 i0.0 9.2 10.8 14_i i0.0 93 ii 2 14 2 i0 0 13.4 17.4 20.6 14.5 13.0 16.5 20.0 14.4 13.2 17.1 20.3 14.5 DAY 15 M F T 24.5 20.0 27.5 24.6 21.8 26.9 23.4 27.7 23.7 32.6 37.4 26.6 22.6 19.2 25.6 22.5 19.7 26.2 24.2 25.9 21.5 29.9 36.8 26.2 23.8 19.6 26.6 23.3 20.4 26.6 23.7 27.1 22.8 31.7 37.2 26.4 DAY 22 M F T 31.6 27.5 35.7 39.6 32.9 43.3 37.1 37.8 39.1 54.2 52.0 40.3 30 0 27 2 33 8 37 2 30 2 43 0 38 8 35 8 36.8 50.7 53.1 40.0 31 0 27 4 34 8 38 2 31 1 43 2 37 8 37 2 38 1 53 0 52 4 40 2 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 6.8 6.3 6.5 6.1 6.0 6.0 5.6 5.0 5.3 6.0 5.6 5.8 7.1 6.8 7.0 NOT PREGNANT 6.3 5.9 6.2 6.8 6.7 6.7 6.5 6.0 6.3 6.9 6.7 6.8 5.9 5.5 5.6 6.4 6.5 6.4 8.3 7.9 8.1 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 10.7 10.6 9.8 10.7 9.1 9.8 13.0 10 8 10 4 i0 1 i0 8 94 98 13 6 14.6 12.6 12.7 15.2 19.4 16.5 14.8 14.5 14.8 13.0 13.5 19.0 13.0 12.5 11.8 14.2 18.0 16.3 16.1 13.4 14.8 11.9 13.8 17.1 13.7 12.5 12.4 14.7 18.9 16.4 15.6 14.0 14.8 12.2 13.6 18.0 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 25.6 30.2 24.0 24 3 20 8 27 1 26 8 25.8 29.5 24.5 24.8 20.6 27.4 27.8 42.3 31.4 34.1 49.0 50.1 44.8 49.1 37.3 43.7 32.4 36.1 49.9 37.8 29.7 32.9 45.1 49.4 44.4 49.9 37.7 40.8 31.6 35.1 46.5 39.8 30.2 33.6 47.0 49.9 44.6 49.6 37.5 41.9 31.9 35.8 48.2 1474 6.5 6.4 6.5 10.2 9.7 i0 0 13.8 13.9 13.8 1476 6.0 5.7 5.8 8.1 7.5 78 11.3 10.4 10.8 1477 5.5 5.5 5.5 8.5 8.3 84 I0.0 10.2 10.1 1480 7.7 7.4 7.4 12.1 11.6 11.7 17.1 16.4 16.5 .................................................................................................................................... 24 9 23.4 18.8 28.2 24 8 23 2 20 9 28 4 24.8 23.3 19.8 28.3 40.9 36.5 29.9 4'6.1 39.8 35.4 34.7 44.6 40.6 35.9 32.3 45.0 MALE F = FEMALE T -- TOTAL (SUM 0P PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E39 (PAGE 4) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT/ LITTER DAY 1 DAY 5 DAY 8 NUMBER M F T M F T M F T .................................................................................................................................... 1482 1483 7.1 6.8 6.9 NOT PREGNANT 10.8 10.1 10.4 14.3 12.8 13.4 DAY 15 M F T 23.6 21.4 22.4 DAY 22 M F T 37.9 34.5 35.9 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 7.1 6.8 7.0 65 6.0 6.3 79 7.1 7.7 60 5.7 5.8 67 6.0 6.4 63 6.3 6.3 70 G.9 6.9 61 6.2 6.2 6.4 5.8 6.0 6.3 6.1 6.2 5.5 5.4 5.4 6.5 5.7 6.0 NOT PREGNANT 10.4 10.8 14.1 10.0 10.2 9.2 11.4 9.0 11.4 9.3 7.7 Ii.i 9.9 9.8 13.1 9.2 9.4 9.7 11.0 8.8 10.4 8.6 7.6 10.O 10.2 10.3 13.8 9.4 9.8 9.4 11.2 9.0 10.8 8.9 7.7 10.4 14.6 15.6 19.8 14.3 14 0 11 3 17 2 12 4 16 6 12 1 I0 8 16 0 14.1 14 2 18 3 13 2 13 0 11 2 17 0 12 7 15 5 11 9 10.4 15.0 14.4 15.0 19.4 13.5 13.6 11.2 17.1 12.5 15.9 12.0 10.6 15.3 25.7 26.9 31.0 27.3 24.7 22.1 30.2 24.6 31.1 19.4 22.6 29.4 25.2 24.3 28.7 25.7 23.6 22.0 30.3 24.2 28.4 19.4 21.1 27.7 25.5 25.7 30.4 26.1 24.3 22.0 30.3 24.5 29.3 19.4 22.0 28.2 33.1 39.4 52.2 34.1 43.3 37.7 52.4 40.1 47.9 29.3 33.6 40.8 34.4 36.1 49.3 31.8 40.1 37.7 48.3 40.7 45.9 29.3 31.4 39.9 33.6 37.9 51.4 32.4 42.1 37.7 49.8 40.3 46.5 29.3 32.7 40.2 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 68 6.7 6.8 63 61 6.2 68 68 6.8 58 56 5.7 63 57 6.0 71 69 7.0 61 58 6.0 86 --- 8.6 63 59 6.2 71 65 6.8 67 58 6.3 10.1 9.2 11.4 9.8 9.8 10.7 10.6 15.0 9.3 11.0 10.8 10.2 8.8 11.1 9.3 8.4 10.4 10.1 --8.6 10.2 9.7 10.1 9.0 11.3 9.6 9.1 10.6 10.4 15.0 9.0 10.7 10.4 14 7 13 3 16 3 14 2 13 3 14 5 15 8 21 5 13 2 13 0 15 7 13.7 12 1 15 7 13 2 11 9 14 1 14 7 --12.0 12.1 13.9 14.4 12.8 16.1 13.7 12.6 14.3 15.4 21 5 12 7 12 6 15 0 23.7 20.7 28.6 26.8 23.1 24.7 30.1 33.6 18.7 26.4 24.4 22.4 19.4 27.2 25.8 19.8 23.3 27.0 --16.8 24.3 22.9 23.3 20.1 28.2 26.4 21.4 24.1 29.0 33.6 18.0 25.6 23.8 38.3 32.4 46.2 35.0 36.4 43.2 46.8 54.4 28.5 44.1 40.0 36.6 31.0 43.8 31.9 33.2 41.3 44.3 --25.4 40.5 37.4 37.8 31.8 45.4 33.6 34.9 42.4 45 9 54 4 27 3 42 6 39 0 1533 56 53 5.4 8.9 8.4 8.6 12 6 12.9 12 8 21.1 21.9 21.6 35.2 36.0 35 7 1534 73 69 7.1 I0.i 9.6 9.8 13 8 13.2 13 5 22.5 22.2 22.4 39.4 37.8 38 6 1537 6.4 58 6.2 i0.0 8.6 9.6 14 1 12.2 13.6 22.6 20.6 22.0 34.9 33.2 94.4 1539 6.4 6.4 6.4 11.2 11.2 11.2 16 3 16.3 16.3 25.4 24.8 25.2 40.6 40.7 40.6 .................................................................................................................................... _#_ MALE F = FEMALE T - TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER {APFO) IN RATS {SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E39 (PAGE 5): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... RAT/ LITTER DAY 1 DAY 5 DAY 8 NUMBER M F T M F T M F T .................................................................................................................................... 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 6.0 5.6 5.7 10.4 9.6 9.8 14.4 13.4 13.6 6.4 6.4 6.4 11.1 10.9 Ii.0 15.7 15.0 15.3 6.3 6.1 6.2 9.5 8.7 9.1 13.8 12.4 13.1 5.6 5,4 5.5 9.4 9.1 9.2 13.0 12.3 12.7 5,3 5.2 5.2 8.7 8.6 8.6 12.6 12.4 12.4 6.6 6.0 6.2 10.5 9.6 10.0 14,9 13.8 14.2 6.3 6.0 6.2 9.0 8.6 8.8 12,6 12.6 12.6 6.3 5.4 5.8 9.0 8.3 8.7 12.8 11.9 12.4 6.8 6.5 6.6 11.3 11.1 11.1 15.5 15,3 15,4 6.5 6.5 6.5 9.9 10.2 i0.0 13,9 13.9 13.9 DAY 15 M F T 25.1 30.3 21.8 18.7 24.3 24.0 21.1 21.7 27,3 23.3 23.8 29.7 19.9 17.8 23.9 22.3 21.1 20.2 27.3 22.9 24.2 30.0 20.9 18.3 24.0 23.0 21.1 20.9 27.3 23.1 DAY 22 M P T 33 2 45 0 33 4 32 0 37 0 41 0 34 0 31.4 33.5 34.5 33 3 45 0 32 5 31 3 36 5 37 3 33 5 28 4 33.8 34.8 33.3 45.0 33.0 31.7 36.7 38.9 33.7 29.9 33.7 34.6 1560 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 5.8 5.5 5.7 6.2 5.8 6.0 6.2 5.8 6.0 6.2 5.9 5.9 6.8 6.5 6.7 5.6 5.2 5.3 6.5 6.0 6.3 5.8 5.8 5.8 NOT PREGNANT 6.4 6.0 6.2 5.4 5.2 5.3 6.8 6.5 6.8 5.7 5.4 5.6 5.8 5.6 5.6 6.4 6.0 6.2 5.7 5.4 5.5 7.4 10.2 ii.0 9.4 10.4 8.0 10.3 7.3 7.0 9.2 9.9 8,4 10.3 7.4 9.5 7.4 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 10.1 9.6 10.9 9.0 9.3 9.5 7.8 10.3 9.8 12.0 9.2 9.5 9.4 8.1 10,6 13.0 15.4 12.4 14.3 11.3 14.2 10.5 10.0 12.3 13.9 11.4 14.4 10.4 13.9 10.8 10.2 12.6 14.6 11.5 14.4 10.8 14.1 10.7 14.0 15 5 18 6 13 1 13 9 13 1 11 4 13.5 14.6 17.4 12.7 13.9 13.5 10.8 13.8 14.9 18.3 12.9 13.9 13.4 11.1 20.3 22.9 24 6 21.7 25.7 21.3 24.2 20.3 18.1 21.6 23.0 19.2 25.7 19.8 23.4 20.5 21.7 25.2 35.5 21.3 23.7 23.8 21.0 20.9 24.4 32.0 20.4 22.6 24.4 20.7 19.0 22.2 23.8 19.5 25.7 20.5 23.8 20.4 21 3 24 7 34 6 20 9 23 1 24 2 20 8 33.4 38.7 38 9 37.8 43.5 31.2 37.6 32.2 29.9 35.3 38 1 33.5 45.4 29.2 36.8 32.9 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 32.8 40.8 50.7 36.6 37.6 39.6 25.9 33.5 40.5 56.4 37.2 38.4 39.5 25.8 1591 6.1 5.9 6.0 9.9 9.6 9.8 13 7 14.0 13.8 1593 7.0 7.1 7.1 12.4 12.9 12.7 19 0 19.6 19.4 1598 5.9 5.8 5.8 9.3 8.8 9.0 11.6 ii.0 11.3 1600 6.3 5.7 6.1 10.4 9.6 10.2 14.6 13.5 14.3 .................................................................................................................................... 22.1 30.1 19.8 23.4 22.0 31.3 18.5 21.8 22 1 30.9 19.0 23.0 35.5 51.6 27.8 3_.i 35.4 53.8 26.2 36.0 35.5 53.1 .26.9 37.5 MALE F ,, FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM 4_ WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. OO bJ PROTOCOL418-020: T_LE E40 (PAGE ORAL(GAVAGE) mO-GE_TION(O_ (APFO) IN RATS (SPONSOR'S STUDY LI_ERPERGE_TION)_PRODU_IONST_YOFAMMONI_PERFLUOR_CT_OATE NUMBER: T-6889.6) 1): PUP BODY _IG_S FROM BIRm TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F2 GENE_TION PUPS .................................................................................................................................... PUP _ 1 2 3 4 5 6 7 8 9 i0 Ii 12 13 14 15 16 17 18 19 20 .................................................................................................................................... _r/ LI_ER # _TE_ _SAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... POSTP_T_ 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 70 69 6.9 7.2 6.5 5.8 6.9 6.3 6.7 6.0 6.2 63 65 7.2 6.8 6.4 5.7 6.4 5.8 5.8 6.5 5.6 6.4 64 62 6.4 6.4 6.6 5.6 6.3 6.0 5.8 6.1 5.6 5.4 5.8 5.9 6.2 6.3 59 65 6.3 6.3 6.2 6.2 6.5 6.1 6.1 5.8 6.1 6.3 5.9 5.7 6.6 5.8 65 69 7.1 7.3 6.7 6.7 6.7 6.3 6.8 6.5 6.2 6.4 5.9 5.5 81 86 8.4 7.5 6.8 64 6.8 6.8 6.8 6.7 6.6 6.3 5.9 6.1 5.9 6.1 6.4 N_P_GNANT 7.5 7.8 7.7 7.4 _.9 7.2 6.7 7.6 6.8 5.8 7.2 7.3 6.9 7.4 7.2 6.2 6.7 6.6 6.7 6.2 6.0 6.4 6.4 6.3 6.2 6.1 6.5 6.1 6.0 6.5 5.7 6.0 6.3 6.4 7.1 6.7 7.5 6.0 6.6 6.9 6.0 7.3 6.5 6.1 6.2 6.6 6.2 6.1 5.6 6.5 6.1 5.8 6.1 5.8 6.0 6.1 6.7 6.8 6.5 6.8 6.3 6.9 6.3 6.3 6.2 6.2 6.0 6.5 6.4 6.7 6.5 6.3 6.8 5.4 6.1 6.0 5.7 6.1 6.7 5.9 6.7 6.0 6.1 6.2 5.6 6.4 6.2 5.8 7.2 7.3 7.3 7.1 7.3 7.1 6.9 6.5 6.2 6.9 6.1 6.9 6.6 6.6 6.2 5.9 5.9 6.2 6.0 6.1 6.0 6.8 7.4 7.4 6.5 7.1 7.0 7.6 7.1 7.2 6.7 6.5 6.5 7.2 7.2 6.8 6.6 6.4 6.3 5.8 6.4 6.7 6.2 6.6 6.5 6.3 6.6 5.9 6.8 6.5 6.3 5.7 6.3 6.7 6.0 6.3 5.8 6.6 7.0 6.5 6.5 6.5 5.3 6.0 5.8 5.5 6.3 7.1 7.1 7.5 7.3 6.7 6.8 6.6 6.0 7.0 6.6 7.0 6.9 6.6 6.4 6.2 6.1 6.1 6.2 6.7 6.1 6.3 5.7 5.7 5.7 5.6 5.9 6.2 5.8 7.1 7.4 6.9 6.8 6.7 7.1 7.3 6.3 6.6 6.7 6.4 7.2 7.1 6.8 5.6 7.6 6.5 7.3 7.6 7.5 MS 6.7 6.8 6.3 7.2 7.0 6.2 6.1 5.8 6.7 FS 6.4 6.3 6.2 6.2 6.2 6.0 5.6 6.1 5.7 5.8 5.9 6.8 5.7 5.9 6.5 6.8 MS 6.2 6.7 5.8 6.8 6.7 4.9 5.5 6.4 FS 6.1 6.0 6.7 6.1 5.3 5.4 5.9 7.0 6.9 6.5 4.8 6.0 6.8 6.8 5.5 4.9 5.6 6.0 6.5 7.4 6.7 5.5 5.5 6.1 6.1 6.2 6.4 6.0 5.7 6.1 FU 1355 1358 1359 6.6 6.7 7.0 6.9 6.7 6.5 6.4 6.3 6.5 6.3 NOT P_GNANT; _TING NOT CONFI_ED 6.4 6.7 5.7 6.2 6.5 6.3 6.1 5.9 6.1 6.0 ........................................................................................... _L _IGHTS _ _CO_ED IN GRAMS (G). ME_ LITER _IG_S INCL_E FIRST SECO_ LE_ER LE_ER -- M-MALE, F-FEMALE, U-SEX -- S-STILLBO_, U-_CERTAIN, UNDETE_IN_LE D-DIED, M-MISSING (P_S_ED NUMBER FOLLOW_NG "SECO_ LE_ER" I_ICATES mE DAY POSTP_T_ mE EVE_ 6.3 6.8 6.2 5.7 ONLY WEIGHTS CANNIBALIZED) OCCURRED. 6.4 6.1 OF 6.4 6.7 FS ......................................... LIVE PUPS. O PROTOCOL418-020: T_LE E40 (PAGE ORAL(GAVAGE) (APFO) IN _TS _O-GE_TION(O_ (SPONSOR'S STUDY LI_ERPERGE_TION)_PRODUCTIONST_YOFAMMONI_ NUMBER: T-6889.6) 2) : PUP BODY _IG_S FROM BIRTH TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F2 GENE_TION PERFLUOR_OATE PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 .................................................................................................................................... RAT/ LITER # _TE_ _SAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... ii 12 13 14 15 POSTP_T_ DAY 1 16 17 18 19 20 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 1382 1383 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 1416 6.8 6.4 6.7 6.3 6.5 5.9 6.1 5.7 6.3 6.3 6.3 5.6 6.0 6.1 5.5 5.6 6.2 4.7 5.0 6.6 5.6 6.0 6.1 5.6 FS 5.5 5.6 5.1 5.6 5.0 5.3 5.9 5.1 5,5 5,2 5.3 4.5 5.1 5.0 5.4 6.6 7.4 7.0 7.4 6.6 6.7 7.0 6.8 6.4 6.7 6.6 6.2 7.0 6.6 5.7 6.7 7.1 6.7 6.6 6.5 6.0 5.8 5.2 6.0 6,3 5.4 5.7 7.2 6.3 7.2 6.5 6.4 6.7 6.4 6.5 6.7 6.6 6.6 6.6 6.3 6.1 6.3 6.7 6.4 6.4 6.4 6.9 7.2 6.7 6.4 6.6 6.4 6.6 6.5 6,4 6.1 5.5 5.5 6.3 6.4 6.6 6.2 6.7 6.2 6.0 5.8 6.2 5.8 5.8 MS MS 6.6 5.9 6.3 6.1 5.4 N_ P_GNANT 6.4 6.2 6.6 7.0 6.8 65 5.9 6.8 6.3 6.7 6.5 6.4 7.6 "7.9 7.0 8.2 7.1 76 7.4 6.8 65 68 6.5 6.7 6.1 6.0 6.0 6.9 6.3 57 5.8 5.8 59 56 5.5 5.6 5.9 5.4 6.3 7,0 6,6 6.2 68 6.1 6.0 57 67 6.0 7.3 6.9 7.1 6.7 6.6 70 6.8 6.7 69 61 6.3 7.2 6.8 6.4 6.1 6.0 FS 6.3 6.0 6.2 6.3 6.0 52 6.1 5.6 52 52 5.7 5.4 5.0 5.3 5,4 5.4 55 5.6 6.5 6.2 6.1 61 5.8 5.7 58 55 5.6 5.9 5.1 5.8 5,7 5.4 5.4 70 7.3 6.5 6,4 6.0 MS 6,4 6.5 6.6 66 5.4 5.3 78 7.5 7.3 8.1 6.8 7.6 7.7 7.1 7.4 74 8.1 6.9 71 72 71 6.7 6.5 6.8 7,3 7.3 6.1 6.4 69 69 62 7.0 7.0 7.1 6,0 6.1 6.7 6.9 6.5 6.6 57 62 64 6.4 6.8 5.0 5,7 6.4 6.0 6.2 6.4 5.6 5.4 6.0 5.7 65 62 61 65 6.3 6.8 7.2 6.6 5.6 6.3 6.0 6.4 6.1 5.8 6,3 62 61 59 60 6.2 6.0 5.8 5.8 5.4 5.8 5.7 6.3 57 60 59 57 6.0 6.0 6,7 5.7 6.2 6.2 6.2 5.2 6.3 5.8 6.2 5.4 4,5 6.5 6.4 66 64 6.9 6.7 6,3 6.0 5.9 6.1 5.5 6.5 5.4 6.5 6.4 67 66 6.7 6.9 6,6 5.8 6.0 5.8 5.9 6.8 6.0 6.2 6.7 6.1 64 6.0 6.6 6.6 6.4 6.5 6.5 6.8 6.5 6.8 6.3 1418 6.6 6.6 6.4 60 6.6 ............................................................................... 6.0 5,9 6.0 6.1 6.2 _L _IG_S _ _CO_ED IN GRAMS (G). MEW LI_ER _IGHTS INCL_E FIRST LETTER - M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECO_ NUMBER LE_ER -- S-STILLBO_, U-_CERTAIN, FOL_WING "SECO_ LE_ER" I_ICATES D-DIED, M-MISSING _E DAY POSTP_TUM (P_S_ED THE E_ 5.8 ONLY 6.0 6.3 6.2 5.7 6.0 - .................................................... _IGHTS OF LIVE PUPS. CANNIB_IZED} OCCURRED. tJ PROTOCOL418-020: ORAL(GAVAGE) _O-GE_TION(O_ (APFO) IN _TS (SPONSOR'S STaY LITERPERGE_TION) NUMBER: T-6889.6) REPRODU_IONST_YOFAMMONI_ PERFLUOR_OATE T_LE E40 (PAGE 3): PUP BODY _IG_S FROM BIRTH TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F2 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITER # _TE_AL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... POSTP_T_ DAY 1 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1448 1450 1452 1455 1456 7.3 6.3 6.6 6.8 6.6 68 7.1 65 6.8 6.6 6.2 6.9 5.9 6.2 6.4 FD 1 FD 1 5.9 5.8 5.4 5.4 5.4 51 5.4 53 5.6 5.4 5.4 5.2 4.9 4.9 5.0 5.1 5.3 6.8 6.5 6.7 6.9 7.1 67 6.3 62 5.9 6.1 6.4 6.6 6.2 7.0 6.3 7.2 6.8 7.0 69 5.8 56 61 6.8 6,0 6.7 6.4 6.6 6.2 6.2 7.2 6.7 6.7 6.6 70 5.7 61 60 6.2 7.0 5.8 6.1 5.9 6.5 6.4 5.6 6.4 6.6 5.6 6.8 6.3 64 6.6 65 5 9 MD 1 6.6 6.6 6.1 6.4 6.2 6.9 6.2 6.1 61 5.6 5.9 54 6.4 6.2 67 6.7 6.0 6.0 5.5 6.2 5.8 5.8 6.0 5.6 5.8 6.5 66 6.4 6.8 69 6.2 6.0 58 5.8 5.9 5.6 6.4 5.9 55 6.2 6.4 60 6.2 6.7 51 6.1 6.2 6.0 6.1 5.7 5.5 5.8 6.7 6.9 71 6.7 6.6 6.5 6.2 6.4 6.9 FD 1 FS FS 8.78.2 80 8.3 8.3 8.0 7.4 6.4 G.4 63 6.6 6.4 6.5 6.8 5.1 6.1 6.4 6.5 6.1 6.0 6.0 NOT P_GNANT 66 74 68 66 73 6.1 MS MS 6.4 6.1 6.0 6.0 5.9 65 67 65 5.8 6.6 5.7 6.3 6.2 6.4 5.6 5.6 6.3 5.9 6.6 5.9 6.0 5.8 5.8 5.4 5.7 5.5 5.8 5.5 5.3 5.4 5.5 4.5 5.4 5.2 4.7 4.9 6.2 5.7 5.9 5.8 5.9 6.1 6.0 6.4 5.4 5.2 5.9 5.5 5.2 5.8 5.9 7.2 6.9 7.1 7.1 6.9 6.6 1458 NOT P_GNANT ;_ 1459 6.8 6.0 6.0 6.1 6.2 6.4 6.2 6.8 6.3 5.9 6.4 6.0 5.5 5.9 1461 7.0 6.5 7.2 6.6 7.2 6.0 6.7 6.7 7.1 6.6 6.6 1463 6.4 6.5 6.0 6.5 6.9 6.5 6.9 MS 5.9 5.9 5.9 6.5 5.9 5.9 FS 1465 6.6 7.3 6.9 6.6 6.7 7.1 6.8 6.4 7.1 7.0 6.5 6.3 6.9 6.1 7.0 6.7 1468 5.9 5.9 6.1 5.7 6.0 4.7 5.7 5.3 5.4 5.5 5.7 5.8 5.6 5.8 5.5 5.8 1469 6.3 6.5 6.8 6.0 5.9 5.9 6.3 7.0 6.6 6.3 6.3 6.8 1472 8.7 8.8 8.5 7.7 7.8 8.5 7.6 7.6 7.7 8.2 1474 6.7 6.3 6.0 6.5 7.0 6.7 6.0 6.5 6.5 6.8 6.4 6.3 6.5 6.6 1476 1477 1480 6.0 5.7 5.6 6.2 6.0 6.4 6.1 _ 1 6.0 5.4 5.9 5.8 5.0 5.0 6.1 4.9 5.1 6.2 5.9 4.8 8.0 7.6 7.5 8.0 7.7 7.4 7.2 7.3 7.5 7.1 ........................................................................................... _L _IG_S _ _CO_ED IN GRAMS (G). ME_ LITER WEIGHTS INCL_E FIRST SECO_ LETER LETER -- M-MALE, F-FEMALE, U-SEX -- S-STILtOn, U-_CERTAIN, UNDETE_IN_LE D-DIED, M-MISSING (P_S_ED NUMBER FOLLOWING "SECO_ LE_ER" I_I_TES _E DAY POSTP_T_ _E E_ 5.3 6.1 6.1 5.9 7.4 7.6 ONLY _IGHTS CANNIB_IZED) OCCURRED. 6.1 4.9 6.5 OF 5.3 5.9 5.7 5.3 5.7 5.2 5.3 5.5 ,......................................... LI_ PUPS. O PROTOCOL418-020: ORAL(GAVAGE) (APFO) IN _TS mO-GE_TION(O_ (SPONSOR'S STUDY LI_ERPERGE_TION)_PRODU_IONSTUDYOFAMMONI_ NUMBER: T-6889.6) PERFLUOR_CT_OATE T_LE E40 (PAGE 4): P_ BODY _IGHTS FR_ BIRTH TO DAY 22 POSTP_T_ I_IVIDUAL DATA - F2 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITER # _TE_ _SAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... POSTP_TUM DAY 1 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 7.2 7.2 7.1 7.3 7.0 G.9 6.3 5.9 6.9 7.3 7.1 7.1 6.9 6.7 FD 1 FS NOTP_GNANT 7.1 7.3 7.7 6.8 7.4 7.4 6.5 7.2 6.5 6.7 7.3 6.7 6.2 7.1 6.7 6.1 7.2 6.3 6.0 6.0 6.7 6.5 7.2 6.1 6.5 6.2 6.2 5.7 6.1 5.6 8.5 7.5 8.1 8.9 7.1 66 8.5 7.5 6.2 7.7 5.9 6.1 5.9 6.0 5.7 59 4.8 6.2 5.9 5.6 5.8 6.0 5.9 4.9 6.2 6.6 6.9 6.6 7.0 67 66 6.9 MD 1 6.4 5.6 6.7 4.9 6.2 6.6 5.7 6.7 6.4 6.2 68 59 60 63 6.5 6.3 6.1 6.5 6.9 7,2 6,9 7,0 6.8 68 66 73 68 6,5 7.4 6.3 6.0 6.5 6.8 5.9 52 59 63 63 6.3 6.1 6.2 6.4 6.0 FS 6.3 6.6 6.7 6.2 5.5 56 60 58 65 5.7 5.7 6.2 5.5 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 6.6 6.1 6.2 6.1 6.7 6.6 60 63 61 6.1 5.7 6.0 5.9 6.6 5.7 6.3 5.9 5.6 5.3 5.4 5.6 5.4 5.4 57 49 5.8 5.5 4.8 5.3 5.5 5.4 5.5 6.2 7.0 6.4 6.4 5.6 5.4 5.9 56 56 5.3 5.4 6.8 5.9 N_ P_GNANT 7.0 6.5 6.7 7.3 6.0 7.2 7.1 6.8 6.9 6.7 6.4 6.6 7.0 MS 6.7 6.5 6.5 6.8 6.0 6.6 6.0 5.6 6.2 5.7 5.9 60 6.3 6.3 5.7 6.4 6.2 6.8 7.1 7.0 6.9 6.7 7.1 6.3 6.4 7.4 7.2 6.8 67 6.7 6,3 6.0 5.5 5.4 5.5 6.0 5.9 6.1 5.8 5.6 5.6 59 5.6 5.5 5.4 5.9 6.3 6.7 6.4 5.8 6.4 6.4 6.2 6.5 5.5 5.0 61 7,0 7.7 6.3 7.4 7.5 7.0 6.7 6.6 7.2 6.7 7.1 68 6.3 5.3 5.6 5.3 6.4 6.3 6.6 6.2 6.3 6.6 4.6 MD 1 4.6 5.9 6.2 66 8.4 8.9 6.5 6.9 6.5 6.7 6.3 6.3 6.8 6.3 4.4 6.6 6.5 5.7 5.6 6.4 6.0 5.5 6.0 7.1 7.6 6.6 7.0 7.3 7.0 6,3 6.6 6.5 6.5 6.6 7.2 6.5 6.2 7.0 6.3 6.7 6.9 MS 4.9 6.2 5.8 5.9 6.3 FS 5.0 5.5 5.7 6.2 5.7 5.5 5.4 5.3 5.9 5.4 5.8 5.7 2.9 5.3 5.3 5.9 5.0 5.7 FD 1 1534 6.9 7.2 7.8 7.6 6.8 7.4 7.3 7.2 7.0 6,6 6,5 6.8 > 1537 6.2 6.6 6.9 5.6 6.4 6.7 6.3 6.6 6.6 6.5 5.8 6.1 4.9 6.3 FS 1539 6.9 6.6 6.1 6.7 6.4 6.4 6.4 6.7 5.8 6.5 6.3 6.4 6.5 6.5 ........................................................................................... _ ......... " ............................. _L _IG_S _ _CO_ED IN GRAMS (G). ME_ LI_ER _IG_S INCL_E ONLY WEIGHTS OF LI_ PUPS. FIRST SECO_ LE_ER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE LETTER -- S-STILtOn, U-_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIB_IZED) NUMBER FOL_WING "SECO_ LE_ER" I_ICATES mE DAY POSTP_TUM mE EVE_ OCCURRED. O PROTOCOL 418-020: ORAL (GAVAGE) (APFO) IN _TS _O_GE_TION (SPONSOR'S (O_ LITER STaY NUMBER: PER GE_TION) T-6889.6) REPRODUCTION STaY OF AMMONI_ PERFLUOROOCT_OATE T_LE E40 (PAGE 5): PUP BODY WEIGHS FROM BIRTH TO DAY 22 POSTP_T_ - I_IVIDUAL DATA - F2 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITER # _TE_ _SAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... POSTP_T_ DAY 1 1541 5.8 5.8 6.2 6.4 5.7 5.7 5.2 6.1 5.6 54 5.4 5.8 5.7 5.3 1544 5.1 7.3 66 6.7 6,1 6.3 6.3 6.4 6,2 64 6.2 6.5 6.6 FS 1545 6.2 6.6 53 6.3 6.6 6.6 6.5 6.5 5,8 70 5.0 6.0 4.6 6.3 6.1 6.2 6.2 6.6 6.6 1546 5.9 5.6 57 4.9 59 5.5 6.0 5.1 5,0 52 5.9 5.4 5.3 5.3 5.7 1548 5.5 5.4 51 5.2 5 1 5.2 5.7 5.6 5,0 50 5.0 5.4 5.0 FS 1550 1552 6.3 6.6 66 6.9 68 5.8 6.4 6.4 6.0 57 5.6 5.9 5.6 6.8 55 6.4 5 9 7,4 6.7 6.4 5.9 6.0 5.4 6.2 60 5.9 1555 6.9 6.1 6.0 6.2 54 7.0 6.5 5.8 5.3 5.6 5.4 5.4 58 4.9 5.3 1557 7.0 6,6 7.0 6.4 6 8 6.3 6.4 6.4 6.7 6.8 6.3 6.4 66 1558 6.8 6.4 6.2 6.9 68 6.2 6.8 6.6 6,3 6.1 6.5 6.8 64 6.4 6.5 6.6 1560 5.8 5.7 5.5 6.0 5.9 6.1 6.0 5.7 5.8 5.3 5.3 5.7 52 5.7 5.3 1564 1565 6.2 6.1 6.8 6.6 5.4 6.0 6.2 6.1 5.1 5.7 5.5 5.8 59 6.3 5.7 6.3 6.3 6.2 6.4 5.5 5.6 6,0 5.6 5.8 6.0 1566 6.2 6.2 5.6 5.7 5.5 6.2 6.5 6.2 6,1 5.9 5.6 5.6 5.3 6.2 6.1 1568 7.3 4.7 7.5 7.2 7.9 7.1 5.8 6.9 6.7 6.5 6.9 6,2 5.9 1571 5.6 5.8 5.0 5.1 5.9 5.9 5.3 5.3 4,8 5.1 5.3 5.1 5.3 1573 6.2 7.1 6.1 6.2 6.8 6.7 6.5 6,6 6.0 5.6 6.3 5.8 5.7 6.3 6.1 1576 6.6 5.8 5.8 5.6 5.5 5.6 5.6 5.9 6.1 5.3 5.7 5.9 5.8 1578 N_ P_GNANT 1579 6.5 6.6 6.3 5.8 6.4 6.9 6.2 6.7 6.7 6.3 6.1 5.8 5.4 6,0 6.1 1583 5.7 5.2 5.7 5.1 5.4 4.8 5.2 5.0 5,4 5.1 5.4 5.2 1584 6.9 6.9 6.7 6.5 1586 5.4 5.9 4.9 5.8 5.8 6.2 6.0 5.4 5,0 5.7 5.6 5.2 5.7 1587 6.2 5.6 5.3 6,2 5.5 5.7 5.4 5.5 5.6 5.5 5.7 1588 6.3 5.9 6.7 6.7 6.3 6.3 6.0 6.5 5.7 5.8 6.6 5.8 5.5 1589 5.7 5.7 5.5 5.9 5.6 5.8 5.4 5.0 5,2 5.0 5.3 6.0 5.1 6.0 1591 6.3 6.4 6.0 6.1 6.2 4.9 6.1 6.5 6,3 6,0 6.1 6.0 6.7 4.7 1593 1598 7.0 7.0 7.6 6.5 7.8 6.6 5.9 5.6 6.3 6.0 6,1 6.0 5.6 6.0 6,0 5.9 5.4 6.2 5.6 5.4 5.5 5.8 6.2 1600 6.2 7.1 5.9 6.3 6.6 6.3 6.5 6.0 6.1 6.0 MD 1 6.0 5.5 5.6 5.8 . ........................................................................................... _ ........................................ ALL _IG_S _ _CO_ED IN GRAMS (G). ME_ LI_ER WEIGHTS INCL_E FIRST LE_ER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECO_ LE'I_ER -- S-STILLBO_, U-_CERTAIN, D-DIED, M-MISSING {P_S_ED NUMBER FOL_WING "SECO_ LE_ER" I_ICATES THE DAY POSTP_TUM _E E_ ONLY WEIGHTS CANNIBALIZED) OCCURRED. OF LI_ PUPS. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 6): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 5 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1340 1341 1342 1344 1345 1346 1348 1350 1353 11.6 12.9 11.5 11 0 11.7 11.2 11.4 11.2 10.9 10.6 7.4 12.2 11.6 10.3 12 6 11.8 11.3 10.7 8.3 11.5 10.6 10.2 11.7 9.5 10.3 9.0 9 5 10.4 9.6 9,7 9.8 11.0 9.9 10.2 8.8 8.8 10.2 9.9 10.2 8.4 7.8 8.1 90 8.2 8.1 8.3 9.3 8.3 8.1 8.7 7.9 9.2 7.8 9.4 8.6 10.6 10.9 10.8 10 3 10.1 10.4 11.0 10.9 11.2 9.5 9.5 10.8 10.4 10.6 14.2 13.5 13.6 14 9 11.2 10.3 11.2 11.0 10.5 10.1 11.1 10.5 10.6 9.9 10.4 10.7 11.0 NOT PREGNANT 12.0 ii.0 11.9 12.5 13.3 13.5 11.4 12.8 MM 2 12.1 13.0 13.0 10.6 12.0 12,2 8.3 9.0 8.5 9.5 9.2 7.4 9.6 8.9 8,0 8.2 9.0 8.4 8.8 8.5 8.4 9.1 8.6 9.9 10.3 11,0 11.6 10.7 11.5 10.2 9.7 11.3 10.9 10.2 9.9 9.4 10.3 9.9 8.9 9.8 10.3 10.2 9.4 9.0 9,4 9.5 9.4 8.6 9.1 9.0 9.0 8.4 9.1 8.1 8.1 9.0 8.7 7.3 8.1 8.6 8.2 7.9 9,0 10.3 9.5 9.2 8.4 8.6 7.4 8.8 8.4 9.1 8.6 9.4 7.8 8.2 8.2 7.7 8.8 10.3 11.4 11.2 11.2 11.3 11.4 i0.0 10.5 10.7 10.0 9.7 i0.0 9.8 9.3 10.1 9.5 9.5 9.4 9.6 9.4 8,9 10.5 10.7 10.4 10.8 I0.0 10.2 10.6 10.6 10,2 10.0 10.7 11.3 10.7 10.9 8.8 10.1 11.2 10.2 9.2 10.3 11.2 10.3 10.9 11.4 10.2 9.1 9.9 9.1 9.3 10.5 11.1 9.5 10.8 11.1 10.4 11,2 11.4 10.7 10.5 10.8 10.8 9.3 10.6 10.2 10.6 9.5 12.3 10.8 ii.0 11.2 9.8 11.3 10.8 10.0 11.2 10.8 9.9 12.1 10.6 10.9 9.5 10.9 9.6 10.9 11.0 10.1 9.2 9.6 9.6 9.6 9.2 8.6 9.7 10.5 10.7 11.5 10,3 10.8 10.9 10.9 10.0 9.3 I0.0 9.5 11.1 10.5 10.3 10.1 8.4 10.3 11.0 11.1 I0,2 MD 4 MS 8.8 9.5 9.4 11.0 10.3 10.2 9.5 10.3 10.2 FS 11.1 12.1 10,7 11.0 10.7 11.0 10.3 9.9 10.4 11.7 8.8 8.7 9.3 8.6 9.7 9.1 MS 9.8 9.1 9.7 I0.0 i0.0 6.9 8.3 7.5 FS 8.7 9.1 8,8 8.5 7.6 9.4 8.3 9.5 9.3 8.5 7.6 8.1 8.4 7.2 7.8 8.9 8.0 10.4 12.3 11.4 9,8 10.6 11,2 11.6 9.4 10.5 10.8 10.6 10.8 10.0 FU 1355 1358 10.6 I0.0 9.7 9.4 9.9 9.8 NOT PREGNANT; MATING NOT CONFIRMED 1359 9.1 9.5 I0.0 9.5 8.6 9.6 ........................................................................................... 10.6 9.2 10.4 9.4 9.8 9.0 9.0 9.2 9.4 8.9 9,7 9.5 9.6 9.2 10.2 9.4 FS .......................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 7): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS 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 II 1 MG/KG/DAY .................................................................................................................................... 1362 11.4 12.1 12.1 12.2 10.9 ii 5 12.0 POSTPARTUM DAY 5 1363 1364 1367 1368 1371 1375 1376 1378 8.3 8.1 10.6 10.8 7.0 I0.0 9.5 NOT 9.0 8.0 9.3 9.2 10.9 11.2 11.0 10.5 8.5 10.6 7.6 10.0 9.1 9.3 PREGNANT 8.8 9.7 11.2 11.5 8.0 10.1 9.7 8.8 9.8 11.6 10.8 8.7 10.1 8.4 90 88 11 2 99 98 i0 9 83 8.0 8.9 11.7 12.2 9.3 9.9 9.7 9.3 9.2 10.5 10.5 10.1 10.1 9.5 8.3 9.2 10.3 9.6 10.0 10.5 9.1 9.2 7.6 11.2 9.9 8.9 9.2 8.7 9.7 9.4 10.8 8.9 9.6 8.5 MS 7.2 9.2 10.7 9.9 9.3 10.2 MS 9.3 8.5 10.9 11.7 9.0 9.8 9.3 7.8 8.8 10.6 8.3 7.6 8.5 7.3 7.7 11.1 10.2 10.1 8.8 FD 4 FS 9.1 8.1 8.5 9.7 1379 1381 1382 1383 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 11.6 11.8 11.4 11.1 12.8 11.2 8.3 7.6 11.2 11.3 12.5 11.7 10.5 9.2 10.5 10.4 9.0 8.9 11.8 12.6 9.8 9.0 11.5 9.8 7.2 9.7 12.0 12.2 12.6 12.0 10.3 7.4 10.1 9.9 9.9 9.8 10.9 11.7 10.2 11.1 11.7 9.5 8.0 8.0 10.8 12.0 11.9 10.8 10.4 9.5 9.8 9.5 9.7 9.1 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 I0.I 9.1 9.0 9.7 10.7 12.6 I0.0 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 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 9.8 Ii.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 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 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 9.8 i0.i 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 9.9 12.1 8.5 10.8 10.9 9.5 8.0 7.6 9.8 12.7 11.2 10.7 8.8 10.4 9.9 8.0 8.9 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 8.4 11.2 8.7 7.6 8.1 10.2 9.6 9.5 8.9 8.5 9.5 8.2 8.1 10.4 8.9 8.6 10.6 8.2 7.4 8.7 8.7 9.7 10.3 7.7 7.7 9.4 FS 7.5 FM 5 1416 1418 9.7 8.5 9.7 8.9 9.4 8.9 8.8 8.9 9.2 10.5 8.0 9.9 i0.0 9.0 7.2 8.6 9.6 9.1 9.8 9.7 7.0 7.9 8.1 6.4 6.8 8.9 9.5 9.2 FD 3 FM 3 ............................................................................... i .................................................... 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 %0 SECOND LETTER-- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) _t_ NI,94BER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. OO _O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 8} : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 .................................................................................................................................... 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 5 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 ii.0 7.8 10.2 10.9 9.0 10.7 10.1 10.3 9.4 11.3 14.9 9.8 8.0 10.5 10.7 9.3 11.5 9.7 10.6 9.8 11.1 14.2 9.3 8.9 10.7 10.8 9.4 10.5 10.1 10.9 9.6 11.5 13.2 9.5 7.6 10.2 9.6 9.1 10.0 8.8 9.9 10.8 11.2 15.0 9.7 8.5 9.8 10.6 9.5 10.6 10.5 9.8 7.9 11.2 14.1 10.1 7.8 9.4 10.0 10 0 99 96 10 3 95 11 7 14 6 10.0 8.0 10.5 9.6 8.1 10.9 9.1 10.4 8.9 11.1 13.7 10.3 8.9 9.8 10.4 8.3 i0,i 8.7 11.0 10.5 10.8 10.0 9.1 8.5 9.3 8.9 8.3 9.1 9.8 8.7 10.5 8.7 7.9 10.3 8.9 8.9 MD 1 8.3 9.8 9.1 FD 1 9.1 8.0 8.6 9.7 8.7 10.9 9.5 9.7 9.5 FS 9.8 8.0 9.2 9.5 9.2 10.8 9.1 10.0 8.3 FS 9.5 8.4 10.6 10.4 8.1 9.8 9.7 9.5 9.9 7.7 i0.0 9.5 9.9 8.2 9.1 9.8 7.9 9.8 8.5 10.2 8.3 9.5 FD 1 7.1 FD 1 7.7 9.1 FM 2 9.2 9.4 8.8 7.5 10.6 1443 1446 10.3 10.4 10.3 NOT PREGNANT 9.5 10.3 8 1 10.4 10.5 9.9 i0.5 9.2 10.3 i0.0 i0.0 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 11.1 8.9 8.4 10.1 12.8 NOT 11.5 8.9 11.2 11.2 10.2 9.9 14.0 9.9 11.3 7.5 ii.i 9.2 8.5 8.9 10.4 6.5 12.9 13.3 PREGNANT 11.1 9.7 10.3 9.8 10.3 10.9 11.6 10.6 10.4 10.2 9.4 9.3 14.5 13.9 ii.0 I0.0 9.4 Ii.i 10.7 MS MS 9.1 9.6 9.5 8.9 9.4 8.8 8.4 8.1 9.2 8.1 8.4 8.8 8.8 8.6 7.1 8.9 7.1 8.1 7.4 10.6 9.4 9.9 MD 5 MM 3 6.6 9.3 6.5 13.6 13.0 12.4 10.4 I0 7 10 4 10 0 96 97 13 9 9.4 11.0 10.9 8.9 10.4 9.7 10.1 14.5 10.1 11.7 10.0 10.1 11.8 9.9 11.0 12.6 10.2 10.5 10.5 10.7 10.9 8.9 9.1 12.6 9.8 11.0 ii.I MS 9.4 9.2 9.8 13.3 11.2 MD 2 11.0 9.8 10.5 9.2 10.5 13.3 9.8 11.4 9.3 10.4 11.1 8.9 9.3 13.0 10.1 10.8 11.7 10.0 9.4 9.7 10.7 10.0 8.8 8.4 10.4 9.5 9.5 7.9 8.6 7.6 9.1 FM 2 9.5 9.1 9.6 9.6 9.9 10.1 11.2 9.4 10.4 6.5 9.5 9.8 10.6 8.7 9.4 11.6 8.7 FS 11.9 10.4 9.1 9.6 10.2 8.5 ii.0 10.1 1476 1477 1480 7.6 7.5 7.8 8.9 8.9 7.7 8.2 MD 1 8.2 6.9 7.9 8.1 7.2 7.7 7.0 6.9 7.9 8.2 8.5 8.8 7.0 9.4 10.0 7.4 8.7 7.7 9.0 8.6 8.7 8.8 7.9 7.9 6.9 9.1 12.0 12.1 12.2 11.5 12.3 12.6 10.9 10.4 11.2 12.5 Ii.i 12.0 ii.i ........................................................................................... '_........................................ 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 4_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING [PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 9): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV I0 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 5 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 10.7 NOT 10.3 11,5 PREGNANT 10.7 10.8 10,9 10.1 9.4 10.4 10.0 9.5 9.9 11.0 10,3 FD 1 FS 9.3 9.8 11.0 10.0 11.1 10.8 11.1 9.4 11.1 8.9 10.2 9.9 9.3 11.0 10,3 10.7 11,9 11.0 10.6 10,7 10.1 11.8 9.2 10.5 9,8 10.2 9.6 9.6 10.5 8.6 14.8 15.3 15,0 13.5 15.4 12.8 11.7 11.5 13.9 14.0 10.4 9.2 10,8 9.7 9.4 6.9 7.7 10.3 10.2 9.4 9.9 8.8 i0,0 9.1 UU 10.3 10.4 10,9 9,8 9.6 9.3 10.2 10.7 MD 1 9.9 9.5 9.8 9,6 8.0 9.6 9.1 10.3 8.1 9.6 9.6 8.5 9.9 9.4 10,7 10.1 9,1 8,9 10.8 11.9 11.2 11.6 10.8 11.6 11.6 12.0 10.4 10,7 10.3 9.1 9.9 10.3 8.7 9.2 7.5 7.8 9.3 9.5 8.3 8.9 9.2 8.7 9.0 FS 11.4 11.8 II.0 11.3 10.2 11.2 10.8 11,1 10.4 10,2 9,5 10.1 FD 2 11550057 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 97..41 97..04 98..48 107..14 88..75 87..53 97..95 87,.08 97,.59 87..93 87,,49 87,.43 88..60 87..68 86,,87 88..32 11.6 8.9 12.2 11.6 7.8 10.2 10.8 10,6 11,7 i0,0 9,7 9,1 FD 2 NOT PREGNANT 10.3 9.9 9.9 10.2 10.2 10.4 9,0 10.7 10.4 9.2 10.6 10,3 10,7 MS 9,5 9.6 9.3 8.8 7.4 10,5 8,9 10,2 8,4 7.6 9.4 8.0 9,1 8.7 8.8 9.4 9.2 11.6 11.7 12.9 11.4 10.9 11,4 10.2 12,1 10,4 11,1 12.0 10.2 11,2 10.2 9.7 9.0 10.2 10.1 10,2 8.7 10.5 8.9 9.2 10.0 9,9 9.8 9.0 8.3 9.5 9.8 10.5 9.8 9.9 9.4 9.6 9.8 8.7 7,6 9.9 8.1 9.4 8.3 7.4 8.1 10.7 10.6 10.2 10.8 10.4 11.0 11.1 11.1 9.6 10,3 10.7 10.1 10.9 11.4 11.3 10.6 7.6 11.1 11,1 MD 1 10.7 7.5 11.6 10.6 14.8 15.2 9.6 9.6 8.4 9.2 9.5 8 8 10.1 10.2 8.9 8.9 MM 5 9.1 8.7 8.1 9.0 8.3 8.4 11.5 10.4 10.5 11.9 10.8 10 8 9,9 10.6 9.6 10.9 10.9 11.1 10.8 10.7 11.2 11 2 10.0 10.3 MS 10.6 11.0 9.7 10.1 7.3 FS 8.3 8.5 9.2 9.6 7.9 97 9.3 8.1 9.0 9.0 8.6 4.0 9.5 9.1 9.5 8.7 8.7 7.8 FD 1 1534 1537 10.5 10.2 10.1 9.7 10.5 94 8.9 8.3 7.7 11.6 10.3 10.6 i0.0 10.2 9.7 10.3 i0.0 9 6 10.4 10.2 10.4 8.8 8.8 9.1 7.5 9.0 FS 1539 11.3 10.9 11.9 10.3 10.5 10.9 11.4 11.2 12.3 10.4 11.8 10.9 ii.0 11.9 ........................................................................................... '_ ........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. I_IRST LEq_fER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIL_4 PERFLUOROOCTANOATE TABLE E40 (PAGE i0) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 II 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... POSTPARTIB_ DAY 5 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 10.4 10.1 10.6 10,4 9.5 9,9 8,6 9.0 9.7 99 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 90 7.7 93 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 94 8.3 89 9.5 9.0 9.5 9.1 8.9 90 7.7 8.4 8.9 7.8 8.5 8.6 85 8.9 89 9.2 FS 11.8 9.8 10 4 10.3 10.2 9.6 10.2 10.2 9.8 95 8.3 96 9.8 9.3 83 9.3 8.4 8.5 9.3 8.6 8.9 7.8 9.3 83 8.4 8.6 8.6 10.3 88 7.9 9 5 9.2 9.0 7.8 7.5 8.1 8.0 95 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 98 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 1564 1565 1566 1568 1571 1573 1576 10.2 II.I 9.2 11.3 8.1 11.9 6.8 9.8 11.6 9.5 7.4 7.3 10.0 7.1 9.2 11.2 7.4 11.8 7.9 10.6 6.8 i0.0 11.1 9.1 10.6 8.2 8.9 7.6 11 1 10 6 85 11.7 8.3 10.4 7.7 10.7 10.7 7.0 9.0 7.9 9.9 7.6 9.3 10.2 8.2 10.8 6.7 10.6 7.5 9.5 9.9 8.6 10.5 7.8 9.4 7.1 9.6 9.6 9.0 10.6 7.5 9.5 7.6 i0.i 8.8 8.5 10.4 7.4 9.9 7.7 8.9 10.5 7.8 9.5 7.6 9.0 7.2 9.1 10.3 9.2 10.7 7.3 9.6 7.0 8.3 8.4 i0.0 7.3 8.8 7.4 8.5 8.4 9.9 10.2 1578 1579 NOT 10.2 PREGNANT 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 1583 1584 1586 1587 1588 1589 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 i0.0 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 1591 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 1593 1598 1600 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 I0.0 11.6 11.2 I0.i 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. [_0 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER - S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 11) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ..... - .............................................................................................................................. PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 8 1302 1304 16.1 16.9 17.5 16 9 15.8 18.6 15.4 18.4 16.4 15.4 16.0 16.9 14.8 16.0 11.2 17.2 15.6 13.0 16.2 16.4 16.3 14.8 16.1 1306 1308 1310 1312 1313 1316 1318 1321 16.0 12.1 14.5 20.4 15.9 NOT 18.8 11.4 14 5 15.3 12 2 12.2 17 2 17.0 22 0 22.5 16 2 15.8 PREGNANT 17.5 18.9 12.9 12.7 13.2 11.0 15.6 21.0 15.6 16.2 13.6 13.1 13.2 16.0 13.2 11.3 15.5 14.1 14.6 17.5 12 8 19.1 11.2 12.5 12.7 15.9 14.8 18.0 14.5 14.6 10.5 15.7 14.6 15.5 12.7 13.4 12.2 16.1 14.0 11.6 15.8 14.7 14.5 MM 2 12.0 17.8 10.5 11.9 11.5 15.4 13.8 11.9 14.0 14.8 15.4 17 3 13 0 18.7 12.9 13.6 10.7 13.9 14.6 15.7 13.0 14.1 10.9 15.2 17.4 10.8 12.9 10.9 18.8 13.0 13.2 12.6 11.9 13.9 1325 16.0 16.6 15.0 14.5 14 7 15.0 15.7 14.6 15.8 16.4 14 5 11332380 1141..14 1152..01 1131..42 1160..00 1125 73 1141..65 1331 11.8 12.1 13.7 12.7 11 1 12.8 1334 14.3 16.1 14.6 15.9 15 1 15.7 1335 14.4 14.2 14.9 15.5 14 9 15.1 1336 15.7 14.7 16.1 15.9 15.4 15.1 1338 13.0 14.8 16.9 13.9 15.5 14.2 1340 14.2 14.4 14,6 14.9 14.9 14.5 1341 1342 15.5 15.1 15.3 13.2 16.4 15,4 17.5 13.0 16.3 14.4 16.0 15.4 1344 14.7 13.3 15.5 13.4 14.8 14.1 1345 15.7 16.1 15.5 15.5 MD 4 MS 1346 16.5 16.2 18.2 16.6 16.1 16.9 1348 12.0 13.5 13.3 13.9 12.8 14.3 1350 12.8 11.3 12.9 10.4 12.0 13.3 1353 13.2 14.8 11.7 13.4 12.6 12.6 1355 15.2 13.5 14.1 14.7 13.4 14.8 1358 1359 NOT 12.6 PREGNANT; MATING NOT CONFIRMED 12.9 12.4 12.3 11.5 12.6 ........................................................................................... 1152..41 11.4 14.8 14.1 16.0 16.8 15.2 16.5 14.4 15.7 12.8 15.8 MS 13.2 11.3 14.3 11.6 1132..20 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 1130..78 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 1131..74 96 1150 09 90 1150..18 14 0 1150..07 I0 4 10.3 11.2 11.7 10.8 9.8 11.4 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 14.6 16.5 12.8 14.1 14.8 10.8 16.1 15.0 13.7 10.1 12.4 11,7 13.3 15.5 17.0 14.0 16.7 13.8 14.3 16.0 14.2 11.5 12.8 15.8 16.0 13.5 13.2 13.9 14.1 15.1 11.9 12.4 12.7 13.5 16.1 13.8 13.7 14.1 11.2 14.4 12.8 10.3 FU 12.4 16.5 16.1 12.3 12.5 14.8 10.2 10.1 13.4 13.8 13.9 FS FS 10.2 14.9 14.0 11.6 11,7 11.7 12.4 FS -'........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. (2_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) O0 NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. tO C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 12): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 .... mr/ ............................................................................................................................ LITTER # MATERNAL DOSAGE GROUP II i MG/KG/DAY POSTPARTUM DAY 8 .................................................................................................................................... 1362 18.2 17.6 17.9 16.5 16.1 17 5 17.8 1363 1364 1367 12.3 12.9 12.9 12.9 12.6 13 6 12.3 14.5 12.9 11.8 11.3 13.1 13.7 8.3 13.9 11.8 FD 4 FS 13.3 13.6 13.7 14.5 13.6 14 4 11.4 11.4 13.7 11.7 12.9 13.3 12.2 12.6 14.4 16.6 16.1 15.6 16.5 16.8 15 3 16.3 15.2 15.1 14.9 16.0 15.3 16.0 1368 1371 1375 14.2 13.9 14.1 15.5 13.0 14.4 17.0 10.1 15.1 15.9 13.1 13.0 16.2 11.1 15.1 15 7 10 9 15 2 15.5 11.3 14.6 16.1 9.8 15.0 14.3 12.2 14.6 15.6 13.0 13.8 14.9 13.8 13.7 15.7 10.1 14.5 14.3 11.5 12.1 14.1 13.8 10.1 17.0 12.8 13.7 10.8 1376 1378 13.6 13.9 12.3 13.1 12.1 13 8 13.0 12.9 11.5 12.7 MS NOT PREGNANT MS 13.3 12.9 14.0 12.3 12.3 1379 1381 17.2 16.3 16.1 17.0 16.3 17.1 14.6 15.5 15.6 17.4 16.1 17.9 15 1 15 6 15.4 13.1 14.8 15.4 14.8 15.1 14.1 16.7 14.8 15.6 1382 1383 15.4 16.7 15.5 16.0 15.5 13.8 17.1 15.7 14.8 16.4 14.9 16 " 7 14 3 14 9 14.3 15 . 6 13.0 16.3 14.9 17.0 13.0 15.1 13.4 15.2 1384 1387 1389 18.3 17.5 17.3 18.3 16.1 MM 4 16 8 16.8 16.3 16.7 17.3 16.8 16.3 13.9 15.0 15.2 15.7 14.9 13.5 15 9 14.2 13.1 15.3 15.4 13.2 14.6 13.5 14.7 13.7 FS 11.5 8.4 13.1 12.9 12.9 13.9 13.4 MD 7 12.1 11.3 12.6 11.4 12.6 9.9 13.2 I0.0 1392 1393 1397 1399 1401 12.4 17.7 16.8 17.7 14.6 11.4 17.3 18.8 17.4 16.1 11.7 17.9 17.9 16.6 16.3 13.0 16.2 18.3 17.4 16.5 11.0 16.4 18.4 15.4 16.1 13.8 MS 17 0 15 1 15 9 12.7 15.4 18.0 15 9 16 0 11.9 16.9 15.8 17.4 16 1 12.8 17.0 18.0 16.5 15 1 11.9 17.1 19.0 17.4 14.7 10.8 14.6 17.1 17.2 11.3 15.5 17.1 16.3 10.9 12.9 11.0 10.4 10.3 1404 1407 1409 13.8 12.6 14.3 13.0 15.0 14.6 15.0 14.2 14.1 12.2 12.1 14.6 11.7 12.7 13.8 12 6 11 0 13 7 12 1 13 2 13 5 13 8 13 2 13 6 11 8 12 3 13 5 13.3 14.2 13.9 12.0 14.3 15.0 13.3 11.9 14.1 12.4 10.5 11.3 14.6 13.7 13.6 1410 1413 1415 14.0 12.6 12.5 13.9 13.5 14.0 13.7 12.6 13.3 14.3 13.1 13.5 12.2 12.5 12.9 14 3 12 8 13 9 15 5 12 2 12 5 13 1 12 2 12 9 12 8 12 0 12 7 13.1 11.6 12.5 15.1 12.5 12.0 14.8 12.7 12.5 14.6 12.2 12.2 11.8 13.1 14.1 FM 5 1416 1418 13.5 13.4 12.1 13.6 13.0 15.0 13.3 15.2 12.8 15.2 13 1 10 9 14 6 14.4 13.4 14.4 14.4 13.3 13.3 11.6 12.1 8.4 12.3 7.5 13.4 12.1 12.1 9.6 FD 3 FM 3 ..................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. - .............................. [2_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) 4_ W.d NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 13): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 8 19 20 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 13.5 10.5 14.5 14.7 11.8 12.1 15.8 15.8 13.0 17.7 20.7 15.2 NOT 13.9 14.2 13.7 11.2 14.2 12.9 15.2 13.9 13.2 12.7 15.6 14.2 13.3 16.8 15.7 16.0 14.7 11.7 17.1 16.6 21.0 19.2 15.1 14.2 PREGNANT 13.8 10.5 12.8 15.5 12.3 15.0 11.2 15.5 14.0 17.7 21.3 15.3 14.6 12.3 14.7 15.6 12.8 15.6 11.4 14.9 10.7 17.6 20.1 14.4 12.7 12.1 14.7 15.8 11.1 15.3 13.5 13.9 14.2 17.9 19.9 11.9 14.0 12.8 14.1 14.5 10.2 14.2 14.6 15.6 15.6 16.4 20.0 14.6 13.9 13.0 13.8 13.5 11.4 14.6 15.8 14.8 13.3 16.9 15.3 12.7 14.1 13.5 15.2 12.8 16.0 12.0 14.6 13.8 16.2 14.8 15.6 12.0 15.2 12.8 11.0 MD 1 11.7 14.1 12.2 FD 1 14.2 11.4 12.4 14.4 11.7 14.9 17.2 14.1 13.6 FS 13.6 14.4 10.7 10.8 11.7 13.8 10.3 14.6 14.7 14.3 12.7 FS 14.7 13.8 11.0 13.7 14.7 12.1 13.9 13.4 12.4 14.7 13.7 9.6 13.4 11.4 14.3 11.1 15.1 10.7 14.0 12.1 14.3 14.6 13.4 13.2 14.5 FD 1 12.9 FD 1 11.9 11.2 FM 2 13.1 11.4 13.1 13.6 FD 8 1448 1450 1452 1455 1456 1458 1459 1461 1463 1465 1468 1469 1472 1474 15.8 13.7 13.4 16.6 19.8 NOT 15.4 15.3 13.7 14.2 13.7 12.7 19.0 14.6 14.2 13.1 15.4 13.0 12.4 13.3 13.7 16.1 19.8 19.6 PREGNANT 17.5 15.8 15 9 15 2 15.5 15 7 16.5 15 2 13.7 12 3 12.8 15 0 18.6 18.7 15.3 13.1 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 12.9 12.5 12.6 14.8 18.6 14.3 12.1 13.5 MM 6 17.5 MS 12.4 14.3 MD 5 MS 11.0 11.7 MM 3 11.4 13.2 13.1 13.9 12.8 13.0 ii.i 13.9 14.1 13.3 11.7 14.4 16.2 17.4 13.9 14.6 12.8 14.0 19.4 13.8 15.9 16.6 14.8 15.2 12.3 12.6 17.5 12.9 17.1 14.1 12.3 14.7 11.9 12.8 17.7 14.7 16.4 16.0 MS 16.0 12.9 13.6 17.1 13.0 MD 2 16.7 12.8 15.1 12.7 13.7 16.6 14.1 16.7 15.4 13.3 12.1 8.3 13.2 16.6 12.4 17.6 16.6 13.5 13.0 13.2 14.4 14.2 15.0 10.3 10.9 14.2 16.4 13.5 15.8 12.6 13.9 12.7 11.6 14.5 12.1 14.5 15.4 13.4 14.9 11.8 14.3 13.1 12.3 FM 2 FM 6 13.0 FD 6 12.8 15.6 13.6 14.2 11.3 FS 16.3 12.8 15.5 11.0 14.4 1476 10.2 10.7 12.4 12.0 10.7 11.9 11.4 MD 1 10.1 11.4 10.4 9.3 10.2 10.1 8.9 11.1 11.9 > 1477 10.8 11.1 I0.I 9.6 9.0 9.2 10.6 9.7 9.9 9.4 ii.i 10.5 10.3 10.2 9.8 10.8 FD 6 1480 17.2 16.9 17.2 15.9 15.4 15.9 18.2 16.9 16.2 17.4 15.2 16.8 15.9 _'_ ........................................................................................... L ........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. O0 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER-- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. _O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 14) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 I0 11 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 8 .................................................................................................................................... 1482 1483 14.5 14.4 14.9 13.9 15.2 12.7 11.5 12.5 13.8 14.6 11.0 13.5 13.5 11.8 FD 1 FS NOT PREGNANT 1486 1488 1490 16.1 15.5 20.5 15.8 13.5 20.8 14.9 15.9 16.4 14.7 16.1 21.5 13.1 15.3 19.5 14.7 15.6 18.4 12.9 16.4 21.6 14.5 16.8 16.7 14.8 14.7 18.5 14.6 14.2 19.7 15.3 14.2 13.0 14.6 14.9 13.7 12.4 13.8 14.2 14.3 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 13.5 14.2 12.5 17.8 13.7 16.9 13.0 10.8 18.1 NOT 16.3 13.3 12.5 14.9 11.6 16.6 10.7 17.3 12.6 11.3 15.9 16.7 13.4 11.6 10.7 10.6 11.9 16.6 PREGNANT 15.0 14.2 10.5 16.9 14.1 17.1 13.3 10.8 17.3 14.4 14.9 12.7 16.6 12.8 16.0 11.3 i0 " 8 15.7 11.4 13.2 10.5 17.5 12.2 16.6 11.7 9.5 16.5 14.8 13.5 10.6 17.6 12.6 15.0 10.6 10.7 16.2 13.2 14.2 11.3 16.5 10.2 15.2 11.4 11.5 13.3 9.1 MD 1 10.2 16.4 12.0 14.9 11.6 12.1 12.1 15.7 13.9 12.7 17.6 13.5 14.6 10.6 10.4 18.0 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 14.0 14.6 UU 13.8 12.8 10.9 13.0 FD 2 12.3 9.3 FD 2 12.6 II.I I0 . 5 FS 13.4 i0 . 2 12.4 10 . 4 1513 1514 1516 1517 1519 1521 1523 1524 15.2 12.2 16.9 14.3 13.1 14.6 17.1 21.4 14.5 14.2 15.2 15.0 12.9 13.8 16.5 21.6 14.1 13.9 14.9 14.2 13.5 14.8 16.9 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 14.4 11.3 17.4 13.7 12.8 14.7 17.1 16.1 13.3 16.4 13.0 13.0 14.9 16.2 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 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 12.4 12.1 16.0 12.1 11.1 MS 11.8 12.3 14.6 8.9 13.4 13.2 13.2 10.7 11.7 1527 1528 1531 1533 1534 1537 13.7 13.0 15.7 10.9 12.4 13.9 13.2 13.0 16.3 13.2 14.3 15.2 12.3 12.7 15.9 11.2 14.0 11.3 12.5 13.8 14.9 14.1 13.8 15.1 13.1 12.5 16.3 13.0 14.2 14.2 12.6 13.0 16.8 13.5 14.2 14.3 13.8 12.1 14.3 13.8 14.4 14.2 11.8 12.2 15.4 14.1 12.1 14.2 14.3 12.5 MS 13.7 13.7 14.1 14.2 11.6 14.0 13.8 12.6 14.5 MM 5 11.7 10.1 13.9 14.6 10.2 15.4 12.0 11.5 12.4 11.6 15.1 13.7 13.6 12.6 14.8 14.3 12.7 12.0 11.3 FS 9.6 11.0 FS 13.1 11.7 FM 6 FD 1 1539 16.3 14.9 15.8 18.7 15.4 17.5 16.8 16.4 15.2 15.5 16.9 16.1 17.5 15.5 . ................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. SECOND NUMBER LETTER -- S-STILLBORN, U-UNCERTAIN, FOLLOWING "SECOND LETTER" INDICATES D-DIED, THE DAY M-MISSING POSTPARTUM (PRESL_4ED CANNIBALIZED) THE EVENT OCCURRED. _._ _'_ [/) 4_ O0 b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 15): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 11 ...................... - ............................................................................................................. RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 12 13 POSTPARTUM 14 15 DAY 8 16 17 18 19 20 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 14.0 15.7 14.6 14.8 13.4 16.8 12 3 13 0 15 8 13 4 i0 8 14.7 16.6 13.9 12.4 13.1 14.8 12.4 12.6 16.2 13.9 11.7 14.2 16.5 15.4 13.4 12.1 14.1 14.2 14.6 15.7 14.3 11.6 14.6 16.0 12.0 11.9 11.7 14.1 11.4 12.9 14.9 13.9 93 13.2 12.0 12.6 12.1 12.8 14.7 12.5 11.5 15.0 13.5 i0 6 12 3 17 3 11 2 13 4 12 2 13 8 12.3 12.1 15.1 13.1 9.6 13 4 15 8 13 7 13 8 12 0 14 3 13 0 13 0 14 7 13.2 MD 7 12 8 15 9 15 7 12 1 12 9 14 2 13 3 12 3 15 8 15.3 ii.i 13.3 14.0 15 3 12 4 12 6 14 1 12 0 11 1 15 8 13.8 8.3 14.2 14.9 13.2 12.3 12 8 Ii 9 13 0 12 7 16 0 14 8 81 13.9 14.9 11.8 12.6 12.5 14.0 12.3 11 5 15 0 13 8 i0 4 13.7 14.3 13.7 13.2 12.7 14.0 13.2 11 6 15 6 12 6 97 12.7 FM 2 12.5 12.9 10.8 11.6 11.2 14.3 13.3 10.4 14.0 FS 11.9 11.5 FS 12.8 12.8 14.9 i0 8 8.6 11.5 FD 6 15.0 i0 8 13.6 13.9 12.9 13.3 FD 3 1564 1565 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 13 7 15.5 12.3 16.1 i0.4 13.9 10.8 NOT 14.3 16.4 18.3 11.8 15.4 13.4 12.4 13.9 11.8 15.1 12.5 14.2 ii.8 14.5 9.6 PREGNANT 13.2 15.1 18.4 14.1 13.0 13.9 ii.I 15.2 12.8 14.6 12.1 15.8 I0.9 13.5 10.3 14.6 15.6 19.0 13.1 14.5 12.1 10.8 13.7 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 13.1 15.4 10.1 14.4 11.0 14.8 10.9 12.7 15.6 10.7 12.3 ii.5 13.5 11.0 12.5 12.2 12.6 11.3 i0.9 14.7 MM 8 12.7 14.8 10.9 15.4 9.6 14.0 MD 7 10.4 13.6 12.0 14.6 9.9 13.0 10.6 14.0 MM 3 14.7 13.2 13.1 14.9 14.3 14.7 13.9 14.9 12.9 11.3 13.1 11.3 14.1 13.0 13.4 13 1 12 3 14 5 13.9 13.9 13.0 10.9 10.3 13.0 13.9 13.2 10.3 13.1 12.9 14.1 13.4 10.3 14.0 11.8 14.3 10.4 13.5 9.6 14.5 11.6 13 5 14 2 13 0 15 4 11.1 13.6 11.2 12 2 14 4 ii.0 13.4 i0.4 13.3 10.1 12.8 10.3 14.2 11.0 14.5 10.6 14.0 15.0 14.5 15.1 12.6 14.7 14.3 12.9 14 .i 14.7 10.4 14.4 12.0 13.8 14.1 12.0 14.6 12.9 14.4 11.6 14.2 12.6 12.2 10.4 12.5 11.3 14.3 14.0 10.8 14.7 12.1 14.2 11.2 1593 1598 19.0 12.3 18.9 12.7 21.4 12.1 19.7 10.7 19.8 10.2 17 5 12 3 10.9 1600 12.7 15.4 13.8 14.9 15.3 15 4 15.1 ..................................................................................................... 10.9 15.4 10.8 15.1 10.7 12.8 10.3 MD 1 11.0 13.4 11.4 12.0 11.5 14.4 12.1 14.2 9.6 12.2 " .............................. 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 _t_ SECOND LEFI"_R -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 16): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 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 28 1 25 6 26 3 22 9 28 3 38 8 24 2 NOT 29.1 15.4 30.0 29.4 28.3 28.7 28.9 25.1 22.3 20.7 23.4 27.3 28.4 35.0 39.1 24.8 23.3 PREGNANT 28.4 26.6 19.0 17.8 27.7 27.2 27.4 31.2 20.7 21.7 25.9 39.3 24.9 26.0 20.4 29.8 28.7 28.0 24.0 21.1 27.2 25.0 30.5 20.9 28.1 26.7 29.0 22.7 22.8 27.5 22.7 29.4 18.6 27.9 27.5 28.7 22.2 21.6 28.1 15.7 26.7 20.3 27.4 28.1 25.9 22.1 19.8 27.9 20.8 30.3 MMII 29.7 27.7 24.7 19.7 23.1 29.4 20.9 25.7 24.4 19.1 25.7 23.3 23.9 MM 2 16.4 27.4 28.5 16,0 29.6 28.1 26.7 23.6 22.3 24.4 23.8 28.5 15.0 27.2 26.1 22.8 22.9 24.5 21.8 29.4 18.1 22.5 23.7 26.3 24.3 27.6 15.9 19.5 25.9 24.0 26.5 16.9 24.0 25.7 28.6 20.7 23.3 19.8 12.4 FD10 11332380 1331 2272..75 20.6 3211..65 24.7 3202..21 22.0 2281..53 19.5 2272..82 23 3 3200..00 21.5 2179..78 24.9 2260..21 20.6 2270..60 23.4 2168,.93 21.8 2290..76 20.0 2189..52 MMI2 2189..69 20.5 18.7 19.0 17.0 20.0 17.0 20.4 1334 1335 1336 1338 28.4 25.1 21.8 18.4 28.1 27.0 24.4 22.9 29.1 23.1 25.2 18.4 28.3 25.9 23.7 21.4 27.4 25.3 25.7 18.8 29.1 26.2 27.1 18.2 28.8 25.1 25.5 18.8 27.9 24.4 23.6 24.7 27.8 24.2 27.1 18.8 26.5 28.1 20.5 24.6 25.8 20.2 25.3 26.1 15.3 24.5 15.6 25.4 18.7 23.4 15.8 18.4 16.2 1340 1341 1342 1344 1345 1346 1348 1350 27.2 27.9 25.2 29.1 29.5 30.5 27.7 20.2 27.2 29.1 25.7 27.0 30.6 32.7 27.3 24.5 27.3 28.9 22.4 25.6 28.5 32.7 26.9 18.4 26.5 28.8 25.7 24.1 28.9 30.5 27.2 22.7 29.4 28.9 21.5 25.5 MD 4 33.9 25.9 22.4 27.9 28.2 19.7 21.2 MS 30.5 26.5 22.9 25.2 25.2 22.7 22.9 30.4 30.2 MS 19.4 25.3 30.0 25.3 23.1 28.4 30.0 25.8 21.5 23.7 26.5 24.2 23.9 28.7 30.4 24.0 20.4 27.2 26.6 20.7 25.1 28.5 32.7 26.1 24.6 24.6 28.3 16.4 28.0 27.1 25.5 23.8 24.4 27.1 20.2 24.5 29.8 25.3 16.4 26.6 20.2 21.6 25.5 20.5 20.3 24.0 19.4 24.5 27.6 26.9 19.3 20.0 24.0 28.6 28.0 17.1 21.6 FS FS 18.6 23.3 1353 23.1 24.2 25.6 23.6 24.0 25.6 25.1 23.5 23.8 22.8 24.5 22.8 23.2 FU 1355 1358 1359 26.5 NOT 25.0 25.4 25.9 28.2 26.7 26.2 PREGNANT; MATING NOT CONFIRMED 25.8 25.9 24.8 24.4 24.3 26.3 24.0 26.4 23,3 27.0 24.9 24.8 23.7 28.4 23.9 23.0 25.0 22.4 22.5 26.5 FS 22.8 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. 5_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) O0 NUMBER FOLLOWING 'ISECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER' PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 17): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ..... - .............................................................................................................................. PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 .................................................................................................................................... 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 33.6 33.9 31.1 33.4 21 8 21.6 21 6 20.2 22.1 22.1 23.5 20.9 22.3 22 8 19.7 21.5 18.8 24.8 14.3 21.0 FD 4 FS 23 5 24.1 22 8 23.2 22.1 21.4 23.8 22.1 22.5 22 4 19.6 23.2 20.8 23.2 18.0 30 9 28.3 30 8 29.5 29.2 26.5 27.8 27.5 27.7 28 5 28.2 24.3 28.4 23 6 25.8 23 9 24.2 23.5 26.6 25.1 26,3 23.2 21 8 23.8 22.8 23.9 26.6 25.6 20 1 22.2 21 5 17.1 24.0 21.1 23.8 21,9 23.1 21 9 18.1 26.1 22.8 18.3 22.8 22.3 FD 9 26 0 26.6 25 7 26.6 26.5 26.7 27.2 23,6 25.9 24 4 13.9 25.3 23.5 23,7 21 7 21.3 22 6 23.5 20.4 22.9 22.1 21.8 22.9 24 7 MS MS 20.6 22.1 24.4 22.1 22.0 NOT PREGNANT 26.1 28.7 29.1 31.0 28.6 30.0 27.2 26.4 26.3 28.1 27.7 27.3 29.2 28.5 30.2 28.5 28.3 31.0 27.4 27.4 30.6 27.0 26.4 23.5 30.4 30.3 31.6 29.8 33.0 31.1 30.7 27.8 29.3 30.5 28.5 30.0 26.7 28.2 31.6 28.2 27.7 29.6 27.7 30.8 30.3 32.3 26.9 28.9 27.5 28 8 27.9 29.8 27 . 5 MM 4 27.3 28.3 27.0 26.4 28.4 27.9 27 . 7 25.2 19.3 23.7 24.7 25.1 26.5 23.4 24.7 26.9 24.7 25.6 24.1 26.6 24.8 23.0 24.1 FS 17.7 24.6 24.5 19.7 24.0 25.6 24.9 MD 7 21.6 19.1 20.8 22.5 23.6 21.8 21.5 19.8 26.8 25.5 19.2 23.6 19.8 22.4 22.8 23.4 21.9 25.9 22.6 22.1 23.6 23.3 18.1 19.0 18.9 32.2 33.6 32.2 32.2 31.7 MS 29.8 29.3 32.9 30.3 32.7 31.5 26.8 27.3 25.7 28.1 26.7 26.4 25.9 25.0 25.2 28.0 26.1 25.5 28.8 25.9 28.4 28.6 26.7 26.6 27.0 27.7 25.6 23.6 23.9 24.2 24.3 25.1 26.1 24.8 23.6 23.3 24.3 24.6 24.5 25.1 23.6 23.3 20.1 24.0 24.8 23.5 21.4 23.9 24.5 25.0 24.2 25.2 21.6 18.1 20.2 23.9 23.1 21.0 18.0 21.3 22.4 20.5 23.2 19.9 18.5 22.8 19.5 21.6 23.2 24.5 28.1 28.7 27.0 26.2 29.4 26.7 27.6 27.2 27.6 26.5 27.4 26.1 24.0 23.3 24.3 24.6 24.4 24.4 27.2 24.1 25.1 23.0 23.1 24.7 23.1 23.1 21.2 21.7 FM 5 26.7 26.1 26.0 27.4 23.6 28.1 24.9 25.8 24.1 26.7 25.9 25.7 26.0 21.4 21.7 23.5 22.7 23.6 22.9 22.5 22.1 20.3 21.4 21.9 21.2 21.6 21.0 24.3 23.7 24.4 21.1 19.9 23.4 24.4 22.4 23.5 21.2 23.0 22.0 24.3 21.3 18.1 21.4 16.2 21.7 23.6 20.0 15.5 21.3 24.2 22.9 22.3 23.3 FMI4 FD 3 FM 3 ...................................................................................................... . .............................. ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 0_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) /_ NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 18): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 .................................................................................................................................... 19 20 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 15 1421 1424 1426 1428 24.3 23.3 28.5 23.6 23.9 17.1 27.1 26.5 26.1 18.8 27.7 24.2 26.1 22.4 27.7 25.0 25.4 20.2 27.2 25.4 24.9 20.4 28.6 23.0 23.5 20.3 25 8 22 5 23.3 20.5 24.6 24.4 24.4 16.9 27.4 23.9 22.8 19.4 26.3 23.6 25.5 20.2 26.4 22.4 24.6 19.3 23.8 21.6 21.9 19.4 25.1 18.9 19.7 20.9 24.4 21.1 19.8 20.6 FD 1 16.0 FD 1 19.0 1430 1431 1433 1436 1437 24.0 28.0 23 1 26 8 27 7 22.8 29.0 25.7 26.0 23.6 21.0 28.4 25.1 28.6 24.0 20.7 26.8 19.0 26.2 19.3 18.9 29.2 26.0 27.8 24.1 23.1 22.5 18.7 29.6 24.7 20 4 24 4 26 3 28 8 25 0 20.9 25.1 24.2 27.5 19.9 20.4 28.5 24.5 25.3 25.0 19.8 MD 1 21.4 27.4 20.1 19.7 24.9 18.3 26.4 22.1 15.7 27.3 25.1 24.6 21.0 18.0 25.5 21.3 21.1 18.9 26.5 28.2 19.9 20.0 26.6 24.5 22.8 22.1 FM 2 24.8 21.3 26.9 23.8 FD 8 1439 1442 34 2 32.8 33.4 30.8 33.4 31.1 31.3 29.6 28.9 FD 1 FS FS 39 5 35.5 36.9 37.8 37.2 37.2 36.0 1443 1446 1448 1450 28 1 NOT 27.9 25.2 27.1 23.1 PREGNAITr 27 2 24 5 26.2 25.1 28.9 23 0 19.9 25.9 26 3 22.5 27.8 26.5 19.4 26.6 MS 23.5 25.1 MS 25.6 26.2 26.7 26.6 25.4 26.8 25.6 24 8 25.5 25 1 22.9 23 6 25.5 21 1 20.7 24 6 24.8 20 8 24.6 26 8 22 3 1452 1455 1456 1458 1459 1461 1463 1465 20.3 35.1 37.3 NOT 27.6 28.0 25.5 29.6 22.4 22.3 30.4 32.8 34.2 39.2 PREGNANT 26.6 26.8 30.1 25.8 25.2 22.6 24.6 25.0 23.8 32.5 36.3 24.2 29.8 26.6 22.6 21.6 30.3 37.5 22.7 MM 6 35.8 21.8 MD 5 23.4 MM 3 21.0 30.0 21.5 29.1 27.2 27.8 25.1 27.1 25.3 30.7 26.3 24.6 23.6 28.8 23.7 27.1 25.8 30.1 MS 27.3 MD 2 31.0 24.7 26.0 26.0 30.6 23.6 23.8 22.4 29.8 25.4 32.1 23.3 23.4 20.4 27.8 25.4 24.8 27.4 20.5 30.8 24.5 22.9 22.4 FM 2 FM 6 FD 6 26.7 24.7 23.9 FS 18.8 23.0 1468 1469 22.9 26.4 16.0 27.4 22.1 29.2 18.9 28.1 20.5 27.9 21.5 27.2 14.9 27.2 21.9 27.6 22.6 26.9 22.2 27.5 20.2 25.8 25.2 28.0 17.0 23.1 18.6 22.2 1472 1474 29.6 24.5 28.0 26.0 29.7 24.0 29.0 24.0 27.8 25.4 27.3 24.3 27.4 23.9 27.0 25.5 27.0 23.7 25.5 27.5 24.4 23.7 25.1 25.8 1476 24.4 24.5 25.1 22.5 19.4 27.5 20.7 MD 1 27.1 22.8 21.7 22.4 24.5 25.6 21.3 21.9 22.0 > 1477 21.5 21.8 14.6 17.4 23.0 19.8 17.2 14.7 21.0 20.8 20.5 22.8 20,5 23.3 17.9 20.4 FD 6 1480 27.2 28.2 29.1 31.7 27.8 28.0 28.0 26.0 30.1 30.6 29.4 24.8 27.6 ........................................................................................... ,......................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [2_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED} O0 NI_4BER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 19): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY POSTPARTUM DAY 15 .................................................................................................................................... 1482 1483 22.4 22.3 25.5 23.5 24.8 23.4 23.7 21.9 20.4 18.3 20.8 21.8 22.5 21.7 FD 1 FS NOT PREGNANT 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1516 1517 1519 1521 1523 1524 24.7 26.9 32.8 30.4 26.3 17.3 32.6 24.8 30.9 19.5 21.5 30.1 NOT 24.9 22.1 26.3 26.6 23.3 25.3 31.1 31.3 23.3 25.6 28.2 24.4 25.1 22.1 29.7 23.4 31.0 25.0 27.3 31.1 27.9 25.6 20.7 29.2 28.1 32.9 21.7 24.3 25.2 PREGNANT 18.6 22.6 30.8 24.1 21.1 28.5 28.0 22.1 23.7 32.6 35.9 24.1 21.0 29.7 26.6 24.4 24.9 30.3 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 24.3 29.9 30.5 25.0 24.0 22.3 31.7 26.5 27.9 21.4 23.7 28.2 28.0 25.9 28.7 25.5 23.4 21.8 30.8 25.1 29.5 19.0 23.9 25.5 21.1 19.6 28.8 25.3 21.3 27.8 30.4 21.9 23.4 31.5 28.6 23.5 24.9 31.4 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 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 22.1 24.2 29.2 28.3 23.6 22.4 32.8 24.0 29.5 20.3 20.7 27.1 21.1 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 21.7 16.2 24.9 24.2 19.7 22.6 27.7 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 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 24.9 23.7 23.3 24.5 29.4 24.1 20.3 19.3 20.7 25.0 FD 2 20.1 21.9 FD 2 23.9 22.0 19.4 22.4 20.6 26.1 26.8 19.0 MS 19.4 26.8 22.0 27.7 25.2 UU FS 17.7 21.0 19.2 25.6 20.8 19.5 21.0 21.5 22.1 FD12 1527 1528 1531 1533 1534 1537 18.7 28.1 23.7 20.2 22.5 23.9 20.2 29.8 28.4 24.9 21.5 23.3 20.3 24.3 20.5 21.5 23.4 22.5 18.4 27.0 23.1 21.8 22.1 22.8 17.5 22.3 25.1 21.4 22.6 22.6 19.9 27.2 26.8 16.9 22.8 23.6 17.8 24.6 27.6 23.0 24.1 24.1 18.7 20.9 20.2 18.4 21.7 17.5 18.5 26.5 MS 23.6 21.4 21.9 17.4 25.2 28.2 24.8 20.6 23.5 MM 5 19.5 24.4 22.4 23.2 21.8 22.3 17.6 22.4 22.3 17.1 13.4 24.0 17.1 16.4 26.2 23.0 21.4 16.6 FS 22.6 FS 16.6 20.3 14.7 21.2 FM 6 FD 1 1539 25.9 26.2 26.8 24.4 25.6 25.2 24.8 24.4 25.1 26.4 25.0 25.3 23.8 ........................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) 23.5 , ........................................ LIVE PUPS. NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. _,_ [/_ 4_ _O"O O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 20): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ..... _ .............................................................................................................................. 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 15 1541 1544 1545 1546 1548 1550 1552 1555 1557 1558 1560 26.0 31.2 22.8 19.8 25.6 23.9 20.9 22.0 27.5 22.7 19.6 25.1 31.8 17.5 18.5 25.1 25.9 20.1 21.4 27.2 23.1 21.1 24.5 30.1 23.0 16.7 24.2 23.7 24.2 21.2 27.3 24.2 18.5 24.8 25.4 24.0 18.0 22.4 23.9 21.6 22.9 27.6 22.9 21.2 24.6 31.1 23.7 18.9 19.6 22.7 18.9 21.2 27.1 22.3 21.9 23.4 32.4 22.9 18.8 25.9 22.8 21.9 22.7 27.9 22.5 19.5 23.7 31.9 19.6 19.5 23.4 23.1 20.4 20.5 28.2 24.4 MD 7 24.2 29.1 17.8 19.6 24.5 22.3 21.0 20.1 25.9 26.1 13.9 22.7 31.5 25.2 18.2 23.8 19.8 20.4 20.2 27.9 22.1 19.3 22.7 30.1 21.3 17.0 23.0 22.0 20.3 19.4 26.6 22.5 16.4 24.4 29.0 22.2 16.9 24.8 23.1 22.0 20.0 27.5 19.1 20.2 22.0 26.5 22.2 19.2 24.9 23.0 20.0 21.7 27.6 24.3 17.2 25.3 FM 2 20.9 17.2 24.9 25.4 FS 9.0 18.0 FS 21.4 19.5 26.6 23.4 20.7 22.4 20.3 20.1 20.2 23.8 18.3 18.4 FD 6 25.9 16.9 24.4 23.0 18.6 FD 3 11556645 2223..93 2234..49 2235..06 2232..77 2235..42 2215..82 2214..70 2222..37 2223..26 2212..28 1566 22.8 20.6 17.8 20.4 17.2 21.2 19.8 17.5 15.8 19.1 1568 27.5 27.6 24.6 27.4 26.1 22.5 24.2 27.6 24.5 26.5 1571 21.9 20.3 19.6 22.3 21.7 21.9 18.2 21.6 19.5 18.7 1573 22.8 24.7 23.7 22.5 26.2 24.4 25.5 24.5 22.1 23.7 1576 1578 21.0 NOT 20.7 20.4 PREGNANT 18.5 20.1 21.2 MM 8 MD 7 21.1 20.1 1579 21.5 22.6 20.6 22.8 21.5 19.2 22.0 23.6 22.7 21.5 1583 25.8 26.1 23.8 25.1 MM 3 24.6 25.0 24.3 21.4 25.3 1584 37.1 35.5 33.9 32.0 1586 22.7 22 8 20.7 19.1 21.1 21.1 21.7 21.4 20.8 18.2 1587 22.6 23 5 25 0 26.3 21.2 22.9 23.1 19.9 23.1 23.2 1588 23.0 24 3 24 8 23.3 23.2 24.7 24.7 25.0 24.1 23.1 1589 22.4 20 6 22 0 21.5 20.8 18.9 23.1 20.8 20.1 20.0 1591 23.4 24 2 18 1 21.9 21.7 21.4 23.2 23.0 22.4 21.9 1593 1598 29.7 21.2 30 5 20 8 28 9 17 8 33.3 20.4 32.7 20.6 30.2 19.4 18.3 17.9 19.4 18.8 1600 23.7 24 1 24 8 23.4 22.6 23.5 24.9 23.6 22.6 21.1 .................................................................................................................................... 2221..03 19.0 26.3 22.0 24.5 20.6 2203..17 21.0 25.2 18.5 23.2 20.8 20.5 24.6 19.8 25.5 20.3 23.6 25.7 19.9 22.7 20.7 24.3 21.4 20.6 20.5 MD 1 19.7 23.2 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 ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LE'_-_R" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 20.7 19.8 21.7 24.4 20.8 18.5 18.7 22.5 17.5 22.5 19.3 22.4. LIVE PUPS. 16.0 18.5 > [2_ 4_ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION {ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUN PERFLUOROOCTANOATE TABLE E40 (PAGE 21): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 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 45.1 45.5 42.0 28.7 45.5 54.7 39.4 NOT 51.8 33.4 35.8 50.0 28.9 28.7 39.1 44.9 40.8 35.6 41.2 50.4 41.0 49.9 39.9 43.5 34.7 25.6 43.4 46.2 48.1 43.9 52.5 35.9 30.7 27.7 26.7 47.7 43.6 51.3 53.2 40.3 41.5 PREGNANT 46.9 44.4 34.9 30.1 37.2 38.6 46.5 26.6 43.2 29.5 35.8 26.9 38.3 39.1 41.0 36.9 41.1 41.9 29.9 26.2 37.5 44.9 46.4 45.8 41.7 38.4 44.3 45.3 39 7 41.7 40 8 43.3 39 6 37.4 22 6 29.5 44 9 39,1 47.4 46.4 40.3 28.5 41.7 53.4 41.3 50.4 44.2 31.9 28.7 44.7 41.0 47.2 41.0 33.0 25.6 42.6 36.9 48.2 33.3 36.0 49.4 32.3 33.8 36.2 42.4 45.0 34.2 39.7 47.7 39.9 41.2 38 8 43 5 32 9 29 0 38 9 52.6 31.5 34.7 53.2 23.7 27.6 38.9 42.4 34.1 19.9 45.0 45.0 37.3 37.9 MD 4 41.7 39.2 24.3 41.0 49.0 31.3 35.2 52.8 28.8 31.1 40.4 41.8 40.3 29.1 44.4 46.3 40.1 41.9 MS 40.7 37.2 27.4 41.4 47.4 40.1 28.8 27.3 43.3 36.5 45.4 24.1 38.1 47.5 25.7 32.6 38.7 38.1 42.9 29.5 45.1 45.4 41.6 46.1 37.2 43.5 MS 27.3 43.0 44.1 39.8 31.4 28.4 46.0 44.0 47.2 34.3 24.4 46.0 46.9 44.3 34.0 31.1 44.9 39.1 38.0 38.4 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 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 46.2 31.8 36.1 46.7 26.9 28.5 40.0 43.4 30.0 43.3 44.7 33.7 40.8 42.5 39.5 35.8 27.3 37.3 34.8 43.2 30.9 32.3 41.4 45.1 37.1 28.6 41.2 39.0 41.2 49.1 27.0 34.3 47. 7 24.0 34.8 48.4 28.3 44.7 22.5 MMI2 37.4 42.7 29.0 40.3 45.8 36.2 38.6 37.2 41.1 41.7 32.8 37.0 46.0 35.9 42.8 40.9 38.0 23.4 39.2 38.1 25.3 41.2 33.1 31.5 35.1 FDI7 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 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 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 34.3 28.4 20.1 19.5 27.2 23.9 36.3 FS FS 23.0 FD10 FD16 29.1 1355 38.7 42 2 43,9 40 4 41.7 37.0 41.7 41.2 36.5 43.6 40.3 39.9 38.2 39.2 38.4 > 1358 NOT PREGNANT; MATING NOT CONFIRMED 1359 43.1 43.2 38.4 43.4 41.5 38.5 40.0 37.7 38.1 42.3 38.9 41.6 40.2 FS ........................................................................................... ! ........................................ ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4_ SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) O0 NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. _O C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 22}: PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 ii 12 13 14 15 16 17 18 19 20 ....................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 22 - ............................ 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1381 42.5 42.4 43.3 42.6 43.6 43 8 39 6 31.4 36.0 31.0 34.4 27.1 34 1 33 6 34.0 35.7 37.7 28.1 33.6 35.2 34.9 27.5 22.1 FD 4 FS 32.3 32.3 32.7 40.8 28.1 31 5 32 5 32.0 33.2 31.2 32.7 27.6 25.1 32.2 30.8 38.9 39.5 39.5 40.0 36.4 37 1 33 5 33.9 36.3 36.5 32.8 37.5 35.7 45.5 38.3 40.1 44.2 45.2 37 2 42 7 44.3 41.0 36.4 40.7 39.3 38.8 39.1 36.0 41.9 31.3 35.9 36.0 39.8 29 5 31 9 35.2 28.4 34.7 26.2 33.9 29.9 38.3 39.3 39.5 FD 9 35.4 34.5 36.3 34.9 33.5 35 0 34.3 32.0 35.0 31.1 30.4 29.3 31.2 FDI7 36.8 37.6 42.0 32.3 37.7 36 3 37.7 34.5 37.9 34.1 MS MS 38.1 40.2 28.6 36.7 36,2 NOT PREGNANT 34 6 39.4 39.7 40 1 39 1 39.7 34.5 37.6 34.4 36.0 37 8 36.0 48 6 49.1 49.7 54 7 53 9 49.5 52.3 46.7 47.4 42.7 50 1 44.4 11338823 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 3468 38 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 4379..91 44 8 32.4 32.0 33.1 43.9 48.4 50.3 42.8 34.2 38.0 48.3 42.4 42.3 36.2 3483..12 41 4 35.4 41.4 30.9 45.8 48.8 49.3 42.3 38.2 34.4 50.2 40.3 42.6 41.1 3476 83 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 4408 11 36 7 35 9 40 2 28 3 43 6 49.8 46.4 45.0 32.1 31.1 46.0 38.2 48.3 38.7 3486..54 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 3469..65 41.7 40.9 27.8 28.6 41.5 52.4 45.6 41.9 38.6 33.3 48.2 40.8 48.8 38.3 3436..45 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 3455..30 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 3439..39 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 3434 47 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 35.7 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 34.7 41 7 38.4 25.8 30.9 37.9 36.7 40.2 44.4 37.7 36.6 36.9 31.9 32.7 38.1 37.9 43.1 39.3 25.7 31.6 31.2 33,5 33.3 31.1 25.1 37,2 FS 24.9 FM 5 1416 39.2 34.9 31.7 36.9 36.8 33.3 32.9 34.7 35.4 34.1 35.2 38.1 38.0 33.9 > 1418 37.6 38.8 36.6 30.8 37.9 35.6 37.0 38.1 35.5 37.7 27.8 26.2 26.8 FM14 FD 3 FM 3 ..................................................................................................... _ .............................. ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF L_VE 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. O0 b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889,6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 23): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ..... - .............................................................................................................................. PUP # 1 2 3 4 5 6 7 8 9 I0 II 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 22 1421 34.3 33.3 30.2 32.5 33.3 31.5 27.9 30.0 28.8 33.9 33.6 27.9 34.0 25.5 28.8 FD 1 FD 1 1424 28.8 26.1 27.9 32.2 25.5 28.3 30.1 27.0 21.8 24.4 28.1 28.6 27.3 27.1 28.6 28.2 25.6 1426 36.0 33.1 36.6 36.4 35.3 36.6 35.8 34.9 31.2 32.9 34.1 34.2 35.7 1428 37.2 40.9 40.9 40.1 37.4 41.0 34.3 37.7 41.5 34.1 40.9 36.8 39.4 35.5 34.6 1430 37.6 34.4 32.6 29.0 26.3 37.4 31.4 33.8 31.3 30.7 24.2 24.7 32.2 33.8 30.2 31.3 28.4 1431 45.1 40.3 37.5 40.6 43.6 45.9 48.1 42.6 46.2 MD 1 43.8 40.3 40.9 44.2 45.9 FM 2 1433 42.4 39.6 41.2 37.2 30.0 34.8 40.6 38.3 36.2 31.0 35.0 38.8 39.2 41.9 32.1 41.4 43.6 FD 8 1436 37.7 39.5 37.4 37.9 35.9 40.5 35.0 38.6 37.0 35.3 35.6 35.5 1437 40.5 41.5 34.0 39.4 42.4 39.2 41.9 38.6 34.8 39.1 37.6 36.8 34.7 37.5 34.1 38.0 1439 54.6 54.5 52.4 51.3 58.9 53.3 50.7 53.2 48.3 FD 1 FS FS 1442 53.5 52.8 52.8 48.7 50.8 53.9 54.6 1443 1446 41.0 NOT 43.7 41.8 PREGNANT 39.7 40.2 34.7 43.5 37.6 41.4 39.2 40.9 37.0 38.5 43.0 1448 43.9 43.6 39.3 41.2 45.4 40 3 MS MS 37.7 40.2 35.5 36.3 43.1 32.2 36.5 41.3 1450 1452 31.6 34.7 27.7 35.4 32.3 35.9 34.2 34.9 30.8 34.9 31.4 31.2 27.8 33.7 28.8 32.3 26.2 33.0 30.5 31.6 32.1 32.0 31.5 36.3 29.5 31.5 28.5 FM 2 1455 48.7 50.8 46.8 53.1 45.4 MM 6 MD 5 MM 3 41.9 46.9 45.5 47.6 43.5 FM 6 FD 6 1456 52.1 50.0 50.2 48.1 51.0 47.8 1458 NOT PREGNANT 1459 42.0 44.5 47.0 44.8 43.3 43.4 46.8 46.6 MD 2 48.7 44 3 44.1 42.3 42.7 1461 50 3 44.7 51.1 50.2 47.9 51.0 52.4 45.5 50.1 50 7 51 9 1463 37 2 38.8 36.2 41.1 39.5 35.3 33.1 MS 37.2 37 8 39 0 41.2 36.2 35.0 FS 1465 38 5 47.9 41.4 49.8 43.3 41.2 44.1 43.9 45.9 41 9 32 5 38.8 38.9 37.3 41.1 43.6 1468 33 8 35.8 26.2 30.2 36.0 31.0 35.5 36.2 34.3 35 3 32 6 34.3 26.3 29.8 21.4 31.3 1469 37 6 36.3 39 5 35.0 33.9 35.1 36.2 35.5 35.7 35 9 35 6 33.8 1472 50 3 49.5 51 1 49.5 49.2 48.6 47.6 41.3 44.7 50 3 1474 38 4 43.3 42 1 41.6 37.8 41.0 42.3 39.4 42.4 40.8 41.9 39.9 38.8 38.8 1476 41.3 39.8 38 5 28.8 40.4 35.1 31.6 MD 1 40.2 39.6 33.3 34.5 33.5 36.9 37.7 32.2 31.0 > 1477 37.4 36.6 26 8 19.5 27.1 35.9 34.5 21.3 32.6 39.7 38.1 33.4 39.6 33.5 26.2 34.3 FD 6 1480 45.0 46.5 46 9 43.9 43.0 41.8 47.1 41.8 44.7 45.8 46.7 47.1 44.1 C ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. [29 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED) OO NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 24): PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA _ F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 19 20 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... POSTPARTUM DAY 22 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 38.1 33.8 38.4 43.5 39.1 34.3 33.5 37.3 33.7 34.0 35.8 33.6 34.4 33.4 FD 1 FS NOT PREGNANT 37.1 31.1 35.8 32.1 36.5 31.6 32.6 32.7 28.2 31.5 37.2 36.9 34.3 34.0 32.6 37.4 41.7 40.1 39.7 38.4 38.8 39.9 39.1 35.7 37.1 36.8 38.0 34.6 37.0 33.8 48.3 52,3 49.3 52.7 55.9 51.9 55,1 52.7 50.0 45.3 36.3 36.3 31.3 32.4 30.2 35.0 36,2 30.1 29.7 29.4 29.9 36.2 36.1 24.8 UU 45.4 40.1 46.5 45.6 39.5 42.2 44.4 42.6 MD 1 39.6 44.0 45.0 29.0 43,1 38.8 42.1 31.4 35.3 44.4 36.1 35.9 37.4 34.5 38.5 41.6 39.1 35.2 43.0 55.2 54.0 57.5 50.7 49.5 49.0 54.6 43.1 47.0 44.4 32.7 40.5 40.4 45.7 38.2 43.1 40.8 40.8 38.7 42.8 40.8 39.2 38.9 42.0 FS 50.2 47.1 49.3 44.9 47.6 45.5 49.0 44.2 45.6 46.0 44.8 44.3 FD 2 11550057 2385,.34 3347..27 3300..89 1396..72 2394..15 3323..68 3303..41 3310..92 3310..88 2350,.44 3342..23 2299..87 2363..52 1508 1511 39.5 NOT 42.9 40.5 PREGNANT 40.4 43.0 38.7 39.6 38.2 41.5 40.2 39.3 38.4 FD 2 1513 1514 34.5 34.9 39.2 35.4 40.0 34.3 37.4 37.8 39.6 27.5 36 0 32 6 37.9 30.6 38.6 32.0 41 7 27 0 34 8 29 8 38 1 33 5 36.1 34.0 37.3 34,2 1516 1517 1519 1521 1523 1524 43.3 36.8 36.3 43.4 48.2 58.4 47.3 36 9 40 8 42 2 50 4 50 5 44.4 36.3 37.2 42.7 50.1 44.5 34.8 33.5 47.5 47.7 48.3 36.6 35.4 42.0 31.4 46 0 33 0 36 3 40 2 48 5 43.4 32.4 33.6 44.4 51.1 46.8 33.6 38.4 38.7 MD 1 51 6 31 7 38 9 43 1 47 0 43 7 33 0 30 3 44 2 47 0 46 8 31 8 35 0 40 8 34 6 41.1 31.1 29.8 39.9 48.6 43.7 32.5 30,6 1527 1528 32.6 47.6 28 0 42 2 25.3 47.3 33.3 49.0 26.1 37.2 32,3 41.1 29.5 41.2 27.8 43.7 26.7 41.5 23.4 35.6 MM 5 24.8 30.5 1531 1533 41.6 36.6 46 2 42.1 36.3 38.2 41.9 26.6 38.1 36.9 34.5 31.0 46.6 37.3 34.5 38.0 MS 40.7 43.9 28.9 40.5 37.2 42.6 31.2 21.9 37.4 1534 1537 1539 39.0 37.4 41.5 37.7 37.3 39.9 41.4 39.2 39.6 40.0 33.0 39.5 42.0 38.4 41.5 36.1 36.4 41.8 37.1 24.4 42.4 36.8 35.5 39.6 35.4 31.1 39.3 43.0 36.2 43.6 39.9 36.8 40.6 34.3 35.5 41.0 36.1 37.2 ........................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF 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. 3312..26 3310..12 2311..97 MS 29.2 30.7 36.8 33.2 32.4 30.8 23.1 FDI8 FD12 23.2 21.6 27,2 25.2 38.3 39.8 FS 36.1 32.9 36.1 24.5 FS 41.1 _'........................................ LIVE PUPS. FM 6 FD 1 [/_ _t_ OO bO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E40 (PAGE 25) : PUP BODY WEIGHTS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... 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 .................................................................................................................................... 1541 1544 34.1 47.2 33.2 44.8 33.8 35.6 31.8 49.5 33.4 45.9 32.0 47.1 34.5 44.6 33.0 44.8 31.6 46.6 31.8 40.8 1545 1546 1548 1550 1552 1555 1557 1558 1560 1564 1565 34.7 34.9 33.7 40.2 33.9 27.9 34.4 37.1 33.3 38.8 39.7 39.2 30.6 38.4 40.1 34.0 32.8 34.5 39.3 33.0 35.1 37.3 35.5 31.8 37.6 45.5 40.6 32.6 33.0 35.8 36.3 37.4 39.1 28.7 31.6 38.4 38.1 33.6 29.7 33.6 35.0 29.8 41.4 40.5 45.0 35.8 34.7 41.1 33.4 32.8 32.1 33.7 36.3 39.6 36.1 32.5 31.0 39.0 38.3 30.9 34.0 32.9 35 9 31 9 39 9 40 5 35.1 32.1 38.3 37.1 31.3 30.0 34.3 33.8 MD 7 37.0 35.9 27.2 27.8 36.3 39.6 34.6 28.6 34.5 31.6 32.9 31.3 39.1 22.4 31.9 34.9 33.0 32.2 30.2 33.6 31.1 32.0 36.6 35.3 34.5 34.7 38.9 39.3 33.6 29.3 33.7 31.3 28.5 34.4 38.2 33.3 47.2 32.9 28.5 31.1 38.0 31.9 29.1 31.0 37.6 33.1 35.5 40.8 POSTPARTUM DAY 22 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 34.8 FM 2 37.4 32.9 37.3 33.3 FS 29.7 29.6 FS 33.5 25.8 35.6 34.1 24.8 36.5 32.1 26.0 39.4 26.1 31.3 31.0 28.9 FD 6 28.3 25.6 32.3 30.1 FDI6 FD 3 1566 1568 1571 1573 1576 1578 1579 1583 1584 1586 1587 1588 1589 1591 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 40.5 45.3 31.6 35.4 32.8 PREGNANT 36.1 42.4 58.7 39 5 41 9 39 6 24 8 36 8 36.4 44.9 32.5 38.1 33.4 36.1 38.1 55.1 37.2 46.2 39 5 26 3 37 4 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 26.7 40.6 30.5 38.1 32.7 36 6 46 8 29 8 37 4 30 5 32.5 45.2 32.2 37.1 MM 8 30.9 44.7 29.7 35.9 MD 7 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 40.3 37.2 37.7 25.9 37.5 34.0 40.5 40.2 28.3 36.8 37.7 37.6 41.6 25.9 27.8 37.6 37.7 39.3 25.6 35.0 36.1 47.9 27.6 39.4 31.7 36.3 40.0 31.6 37.0 39.7 28.6 32.7 34.6 47.1 27.3 37.9 33.1 31.6 41.5 38.3 35.5 39.1 24.5 38.7 34.5 45.6 28.5 34.2 34.3 34.5 33.9 37.4 38.5 24.6 32.4 35.9 42.8 30.3 37.2 32.0 32.5 36.8 39.3 24.9 35.8 36.3 35.6 26.9 25.0 34.9 30.2 38.0 33.6 1593 1598 1600 51 2 31.2 38.7 51 9 27.4 40.8 50 6 23 4 40 6 52.4 29.3 39.9 56.3 29.4 42.1 56.1 25.0 37.5 29.3 35.7 23.7 34.9 26.7 33.2 29.0 37.6 23.8 MD 1 29.0 38.2 27.5 38.6 27.9 36.9 22.1 30.3- 27.7 24.8 .................................................................................................................................... ALL WEIGHTS WERE RECORDED IN GRAMS (G). MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS. FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 4= SECOND LETTER -- S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED} O0 NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E41 (PAGE 1): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ..... - .............................................................................................................................. PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... 1302 1304 1306 1308 1310 1312 1313 1316 1318 1321 1325 MA MA MA MA MA MA MA NOT MA MA MA MA MA MA MA MA MA MA MA M A MA MA FA MA MA PREGNANT M A MA MA MA MA MA MA MA FA MA M A M A MA MA MA MA MA MA MA MA MA FA MA MA FA M A MA MA M A M A MA M A MA FA FA F A F A F A FA F A F A F A MA M A F A F A FA F A F A F A MA M A M A F A FA F A F A F A M A M A MM 2 F A M A MMII P A F A FA F A F A F A FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FD17 FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA F A FDI0 11332380 MM AA MM AA MM AA MM AA MM AA MM AA MM AA FF AA 1331 1334 M A M A M A M A M A M A MA M A M A MA M A M A M A M A FA F A 1335 M A M A M A M A M A M A F A F A 1336 M A M A M A M A M A M A M A F A 1338 M A M A M A M A M A M A M A M A 1340 M A M A M A M A M A M A M A M A 1341 M A M A M A M A F A F A F A F A 1342 M A M A M A M A M A M A M A M A 1344 M A M A M A M A M A M A M A F A 1345 M A M A M A M A MD 4 M S F A F A 1346 M A M A M A M A M A M A F A F A 1348 M A M A M A M A M A M A M S M A 1350 M A M A M A M A M A M A M A M A 1353 M A M A M A M A M A M A F A F A 1355 M A M A M A M A F A F A F A F A 1358 1359 NOT PREGNANT; MATING NOT CONFIRMED M A M A M A M A M A F A FA FA ........................................................................................... FF AA MA FA FA FA FA FA FA MA FA FA FA MA MA FA FA FA FF AA MA FA FA FA FA FA FA FA FA FA FA MA FA FA FA FF AA FF AA M A MMI2 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 FA FF AA FA FA FA FA FA FA FA FA MA 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 F A FD16 FA FS FS F A 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 NIR4BER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. CANNIBALIZED) X-OTHER [2_ 4_ O0 6b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E41 (PAGE 2) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 1362 1363 MA MA MA MA MA MA MA MA FA MA FA MA FA MA FA FA FA FA FA 1364 1367 MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA FA FA FA FA FA FA FA FA 1368 1371 1375 1376 1378 1379 1381 MA MA MA MA MA MA MA MA MA MA MA M A NOT PREGNANT MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA MA MA MA MA FA FA FA MA MA MA FA FA FA MA FA MA FA FA FA MA FA MS FA FA FA FA FA MS FA FA FA FA FA FA FA FA FA FA FA F A FD17 FA FA FA FA FA FA FA F A FD 4 F S F A FD 9 FA FA 1382 1383 M A M A M A M A M A F A FA F A F A F A F A F A F A M A M A M A M A M A M A FA F A F A F A F A 1384 1387 1389 1392 1393 1397 1399 1401 1404 1407 1409 1410 1413 1415 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA M A MM 4 MA MA M A MA MA MA MA MS MA M A FA FA MA FA MA MA MA MA MA MA MA MA MA MA MA MA FA MA FA MA M A MD 7 MA MA FA F A MA FA FA F A FA F A MA M A MA F A MA F A MA M A MA MA FA FA FA MA FA MA FA FA FA FA MA FA FA MA FA FA FA FA FA FA FA FA FA FA MA FA FA MA 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 MA 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 FS FA F A FM 5 1416 1418 MA MA MA MA MA MA FA MA FA MA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA F A F A FMI4 FD 3 FM 3 ...................................................................................................... ............................... _'_ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER--A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER NI3MBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. 4_ OO PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E41 (PAGE 3) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 .................................................................................................................................... 19 20 21 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 1421 1424 1426 1428 1430 1431 1433 1436 1437 1439 1442 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA 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 FA FA MA MA MA MA FA FA MA MA FA FA FA MA MA MA MA FA MA MA FA FA FA MA MA FA MA FA MA FA FA FA FA MD 1 MA FA FA FD 1 FA FA FA FA FA FA FA FA FA FS 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 1 FD 1 FA FA FA FA FA FA FA FA FM 2 FA FA F A FD 8 FA FA 11444436 1448 1450 1452 1455 MNOTA PRMEGANANTM A M A M A M A M A M A F A F A F A F A F A F A MA MA MA MA MA MA MS MS FA FA FA FA FA FA FA FA MA M A M A M A FA F A FA FA FA FA FA FA FA FA M A M A M A M A M A M A M A M A F A F A F A F A F A FM 2 M A M A M A M A M A MM 6 MD 5 MM 3 F A F A F A F A F A FM 6 FD 6 1456 1458 1459 1461 1463 1465 1468 MA MA MA NOT PREGNANT MA MA MA MA M A MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA FA MA MA MA FA MA FA MA MA FA MA FA MA Fk FA M A MD 2 FA FA M S 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 FA FA 1469 1472 1474 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA FA MA MA FA MA MA FA MA FA FA MA FA FA FA FA FA FA 1476 M A M A M 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 F A F A > 1477 M A M A M A M A M A M A M A M A F A F A F A F A F A F A F A F A FD 6 1480 MA M A M A FA FA F A FA FA FA FA FA FA FA C_ ........................................................................................... '-........................................ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE O_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-OTHER 4_ NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. O0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E41 (PAGE 4): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS ..... - .............................................................................................................................. PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 19 20 21 .................................................................................................................................... 22 23 RAT/ LITTER # MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... 1482 1483 1486 1488 1490 1491 1494 1496 1497 1500 1502 MA MA MA NOT PREGNANT MA MA MA MA MA MA MA M A MA MA MA MA MA MA M 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 MA FA MA MA FA MA FA MA MA MA MA FA MA MA FA MA FA FA MA MA MA FA MA MA FA MA FA FA FA MA MA MA FA FA FA FA FA M A MD 1 FA FA 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 F A FD 2 F A FD 1 FA FA FA FA FA FA UU FA FS FS 11550057 MM AA MM AA MM AA MM AA MM AA MM AA MM AA FM AA FM AA FF AA FF AA FF AA FF AA FF AA FF AA FF AA 150181 1513 1514 1516 1517 1519 1521 1523 1524 1527 1528 1531 1533 MNOTA PRMEGANANTM A MA MA MA MA MA MA M A M A MA MA MA MA M A M 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 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 MA MA MA MA MA MA MA FA F A MA M A MA M A MA M A MA M A MA M A MA F A M A MD 1 MA FA MA FA MA FA MA FA FA MA MA MA FA FA FA FA MA FA MS FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA M A MM 5 FA FA FA FA FA F A FD 2 FA FA FA FA FA FA F A FA FA F A FA FA FA FA FA FA FA FA MS FA FA FA FA FA FA F A F A FD12 FA F A FD18 F A FA F A FS FA FA F A FM 6 FD 1 1534 1537 MA MA MA MA MA MA MA MA MA MA MA MA FA MA FA MA 1539 M A M A M A M A M A M A MA M A ........................................................................................... FA MA MA FA MA FA FA FA FA FA FA FA FA FA FA FA FS ........................................ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LK"I'rER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) X-OTHER 4_ NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. OO b_ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E41 (PAGE 5): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 Ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT/ LITTER # MATERNAL DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... 1541 1544 1545 1546 MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA MA FA MA MA MA FA MA MA MA FA FA MA MA FA FA MA MA FA FA MA FA FA FA FA FA FA FA FA FA FA FA F A FM 2 FA FA FA FA FA FS FA FA FA FA FA F A FDI6 FD 3 1548 1550 1552 1555 1557 1558 1560 MA MA MA MA 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 F A FA F A FA M A MA M A MA F A FA M A MA M A MD 7 FA FA FA FA FA MA FA FA FA FA FA FA MA 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 FS FA F A FD 6 FA FA FA FA FA 1564 1565 M A M A M A M A M A M A FA F A F A F A F A F A F A M A M A M A M A M A M A FA F A F A F A F A F A 1566 1568 1571 1573 1576 1578 1579 1583 MA MA MA MA MA NOT MA MA MA FA MA MA MA MA MA MA MA MA PREGNANT MA MA MA MA FA MA MA MA MA FA MA MA MA MA MA MA M A MM 3 FA MA MA MA MA FA MA FA MA MM 8 FA FA FA FA MD 7 M A MA M A F A FA F A FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA 1584 1586 1587 1588 1589 1591 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 FA MA MA MA FA FA MA MA MA FA FA FA MA FA FA FA FA MA FA FA FA FA MA FA FA FA FA MA FA FA FA FA FA FA FA FA FA FA FA FA FA FA FA 1593 M A M A FA FA FA F A > 1598 M A M A M A M A M A M A MA F A FA FA FA FA FA FA FA FA FA 1600 M A M A M A M A M A M A M A M A M A M A MD 1 F A F A F A F A ........................................................................................... i ........................................ FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE 0'_ SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) X-OTHER _pt._. NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. OO b_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NIR4BER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E42 (PAGE i): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... I 0 1308 22 OBSERVATIONS a 16/16 PUPS: DEHYDRATION; UNGROOMED COAT.b 1313 16 1/13 PUPS: DEHYDRATION. 1321 10 1/17 PUPS: EMACIATION; NO MILK PRESENT IN STOMACH. 1348 3 2/14 PUPS: COLD TO TOUCH. 1350 21 17/17 PUPS: DEHYDRATION. II 1 1404 1-22 1/15 PUPS: THREAD-LIKE TAIL; NO ANAL OPENING PRESENT. 2-22 1/15 PUPS: THREAD-LIKE TAIL. 1418 2 4/16 PUPS: COLD TOUCH. TO (3% 12 1/14 PUPS: COLD TO TOUCH; DEHYDRATION. 12 1/14 PUPS: DEHYDRATION. III 3 1424 4 1/17 PUPS: COLD TO TOUCH. IV 10 1517 1 1/15 PUPS: COLD TO TOUCH. 1519 16 17 1/16 1/16 PUPS: PUPS: EMACIATION. DEHYDRATION. 1523 1 2-22 20-22 22 1/12 1/11 i/ii i/II PUPS: PUPS: PUPS: PUPS: TAIL BENT (0.7 CM FROM BASE).b TAIL BENT (DID NOT EXCEED RIGHT EYE: NOT PRESENT.b 3.2 CM FROM DOMED HEAD.b BASE}.b 1527 22 ......................................................................................................... a. Tabulation b. Observation restricted confirmed to adverse observations; at necropsy. all other 1/16 PUPS: pups appeared normal. DEHYDRATION. ............................ > [/_ O0 O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E42 (PAGE 2): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 22 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S} POSTPARTUM .................................................................................................................................... V 30 1545 15 OBSERVATIONS a 1/18 PUPS: EMACIATION. PUPS 1548 1 1/14 PUPS: COLD TO TOUCH. 1550 1-22 1/12 PUPS: NO TAIL PRESENT. 1557 8-15 1/13 PUPS: MOUTH: MASS (DID NOT EXCEED 0.5 CM X 0.2 CM X 0.2 CM). 1565 2 3 4-7 1/12 PUPS: 1/12 1/12 PUPS: PUPS: BACK: ABRASION COLD TO TOUCH. (0.5 CM X 0.2 CM); BACK: COLD BACK: ABRASION TO TOUCH. (0.5 CM X SCAB (0.5 CM X 0.2 0.2 CM}. CM); -._ 1568 I-7 1/13 PUPS: TAIL: ABRASION (0.3 CM FROM BASEl. 1573 5 1/15 PUPS: COLD TO TOUCH. 1583 5-7 8-10 11-12 13-21 22 1/11 1/11 1/11 1/11 PUPS: PUPS: PUPS: PUPS: I/ii PUPS: BASE OF TAIL: ABRASION (0.5 CM X 0.3 CM) . TAIL: ABRASION (2.5 CM X 0.5 CM). TIP OF TAIL BLACK; TIP OF TAIL MISSING. TIP OF TAIL MISSING; TAIL: SCAB (0.2 CM X 0.2 CM). TIP OF TAIL MISSING. 1600 1 2-3 1/15 1/14 PUPS: PUPS: PALE PALE IN APPEARANCE. IN APPEARANCE. ..a.........T..a.b..u.l..a.t..i.o..n.........r.e..s.t..r.i..c.t..e.d.........t.o....a..d.v..e.r..s.e........o.b..s.e..r.v..a.t..i.o..n.s..;.........a..l.l.....o..t.h..e.r......p.u..p.s.... appeared normal. C cn o0 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION TABLE E43 (PAGE I) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... I 0 1302 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1304 22 1 PUP: KIDNEY: PELVIS, DILATED, ALL OTHER TISSUES APPEARED ALL OTHER PUPS EXAMINED APPEARED SLIGHT. NORMAL. NORMAL. 1306 22 1308 22 1310 22 1312 22 ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. g: OO 1313 17 22 1318 22 1 PUP: FOUND DEAD. NO MILK PRESENT AUTOLYSIS PRECLUDED FURTHER ALL PUPS EXAMINED APPEARED NORMAL. IN STOMACH. EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. 1321 10 22 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1325 22 1328 22 1330 22 1331 22 1334 22 1335 22 1336 22 1338 16 22 ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. > 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. _'_ ALL PUPS EXAMINED APPEARED NORMAL. _n 1340 22 ALL PUPS EXAMINED APPEARED NORMAL. 1341 22 ALL PUPS EXAMINED APPEARED NORMAL. OO .................................................................................................................................... O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... I 0 CONT. 1342 22 1344 22 OBSERVATIONS ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED NORMAL. NORMAL. 1345 1 4 22 2 PUPS: STILLBORN. AUTOLYSIS PRECLUDED EVALUATION. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED ALL PUPS EXAMINED APPEARED NORMAL. FURTHER NORMAL. 1346 22 ALL PUPS EXAMINED APPEARED NORMAL. 1348 1 2 PUPS: STILLBORN. EVALUATION. AUTOLYSIS PRECLUDED FURTHER 22 ALL PUPS EXAMINED APPEARED NORMAL. (% 1350 22 ALL PUPS EXAMINED APPEARED NORMAL. %O 1353 22 ALL PUPS EXAMINED APPEARED NORMAL. 1355 22 ALL PUPS EXAMINED APPEARED NORMAL. 1359 1 22 .................................................................................................................................... 1 PUP: STILLBORN. ALL TISSUES APPEARED ALL PUPS EXAMINED APPEARED NORMAL. NORMAL. C% O_ C_ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... II 1 1362 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1363 1 4 22 I PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1364 22 1367 22 1368 22 ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. (TQ 1371 9 i PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. f_ AUTOLYSIS PRECLUDED FURTHER EVALUATION. 0% t_ 22 ALL PUPS EXAMINED APPEARED NORMAL. o 1375 17 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 22 ALL PUPS EXAMINED APPEARED NORMAL. 1376 1 22 2 PUPS: ALL PUPS STILLBORN. ALL TISSUES APPEARED EXAMINED APPEARED NORMAL. NORMAL. 1379 22 1381 22 1382 22 ALL PUPS ALL PUPS ALL PUPS EXAMINED EXAMINED EXAMINED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1383 22 1 PUP: KIDNEY: RIGHT, PELVIS, MODERATE DILATION. 5 PUPS: ALL OTHER APPEARED TISSUES NORMAL. APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. 1384 22 ALL PUPS EXAMINED APPEARED NORMAL. 1387 1 22 ......................................................................................................... 1 PUP: STILLBORN. AUTOLYSIS PRECLUDED FURTHER EVALUAT ION. ALL PUPS EXAMINED APPEARED NORMAL. - .......................... > C 4_ O0 _'-) O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY] NUMBER DAY (S} POSTPARTUM OBSERVATIONS .................................................................................................................................... II 1 CONT. 1389 7 22 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1392 22 ALL PUPS EXAMINED APPEARED NORMAL. 1393 1 22 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1397 22 1399 22 1401 22 ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1404 22 ALL PUPS EXAMINED APPEARED NORMAL. 0% 1407 22 ALL PUPS EXAMINED APPEARED NORMAL. t_ 1409 22 ALL PUPS EXAMINED APPEARED NORMAL. _-" 1410 22 ALL PUPS EXAMINED APPEARED NORMAL. 1413 22 ALL PUPS EXAMINED APPEARED NORMAL. 1415 22 ALL PUPS EXAMINED APPEARED NORMAL. 1416 22 ALL PUPS EXAMINED APPEARED NORMAL. 1418 3 1 PUP: FOUND DEAD. NO MILK PRESENT AUTOLYSIS PRECLUDED FURTHER 22 ALL PUPS EXAMINED APPEARED NORMAL. .................................................................................................................................... IN STOMACH. EVALUATION. > O C OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... III 3 1421 1 22 OBSERVATIONS 2 PUPS: ALL PUPS FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. EXAMINED APPEARED NORMAL. 1424 22 1426 22 1428 22 1430 22 ALL PUPS ALL PUPS ALL PUPS ALL PUPS EXAMINED EXAMINED EXAMINED EXAMINED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. 1431 1 22 1 PUP: FOUND DEAD. ALL TISSUES APPEARED ALL PUPS EXAMINED APPEARED NORMAL. NORMAL. 1433 8 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. (_ AUTOLYSIS PRECLUDED FURTHER EVALUATION. 0% t2_ 22 ALL PUPS EXAMINED APPEARED NORMAL. to 1436 22 ALL PUPS EXAMINED APPEARED NORMAL. 1437 22 ALL PUPS EXAMINED APPEARED NORMAL. 1439 1 22 2 PUPS: 1 PUP: STILLBORN. FOUND DEAD. ALL TISSUES APPEARED NORMAL. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1442 22 1443 22 ALL PUPS ALL PUPS EXAMINED EXAMINED APPEARED APPEARED NORMAL. NORMAL. 1448 1 22 2 PUPS: ALL PUPS STILLBORN. AUTOLYSIS PRECLUDED EVALUATI EXAMINED ON. APPEARED NORMAL. FURTHER 1450 22 ALL PUPS EXAMINED APPEARE'D NORMAL. 1452 22 ALL PUPS EXAMINED APPEARED NORMAL. {/_ 1455 5 6 22 .................................................................................................................................... 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. O0 ALL OTHER TISSUES APPEARED NORMAL. _:_ 1 PUP: FOUND DEAD. CANNIBALIZATION PRECLUDED FURTHER O EVALUATI ON. ALL PUPS EXAMINED APPEARED NORMAL. PROTOCOL 418-020: ORAL (GAVAGE) TW0-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... III 3 CONT. 1456 22 1459 2 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 1 PUP: KIDNEYS: ALL OTHER BILATERAL, PELVIS, MODERATE TISSUES APPEARED NORMAL. DILATION. ALL OTHER PUPS EXAMINED APPEARED NORMAL. 1461 22 ALL PUPS EXAMINED APPEARED NORMAL. 1463 1 22 2 PUPS: ALL PUPS STILLBORN. ALL TISSUES APPEARED EXAMINED APPEARED NORMAL. NORMAL. 1465 22 ALL PUPS EXAMINED APPEARED NORMAL. 0t%a 1468 22 ALL PUPS EXAMINED APPEARED NORMAL. L_ 1469 22 ALL PUPS EXAMINED APPEARED NORMAL. 1472 22 ALL PUPS EXAMINED APPEARED NORMAL. 1474 22 ALL PUPS EXAMINED APPEARED NORMAL. 1476 1 22 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: KIDNEY: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS EXAMINED APPEARED NORMAL. 1477 6 22 1 PUP: FOUND DEAD. NO MILK PRESENT AUTOLYSIS PRECLUDED FURTHER ALL PUPS EXAMINED APPEARED NORMAL. IN STOMACH. EVALUATION. 1480 22 ALL PUPS EXAMINED APPEARED NORMAL. ...................................................................................................... ............................... C 5O 4= 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 7): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... IV 10 1482 1 22 OBSERVATIONS 1 PUP: 1 PUP: ALL PUPS FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. STILLBORN. ALL TISSUES APPEARED NORMAL. EXAMINED APPEARED NORMAL. 1486 22 1488 22 1490 22 1491 22 ALL PUPS ALL PUPS ALL PUPS ALL PUPS EXAMINED EXAMINED EXAMINED EXAMINED APPEAREDNORMAL. APPEARED NORMAL. APPEARED NORMAL. APPEARED NORMAL. 1494 1 1 PUP: FOUND DEAD. ALL TISSUES NO MILK APPEARED PRESENT NORMAL. IN STOMACH. 22 ALL PUPS EXAMINED APPEARED NORMAL. C_ t_ 1496 22 ALL PUPS EXAMINED APPEARED NORMAL. 4_ 1497 22 ALL PUPS EXAMINED APPEARED NORMAL. 1500 1 22 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1502 22 1505 22 1507 22 ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. 1508 2 22 1 PUP: FOUND DEAD. NO MILK PRESENT AUTOLYSIS PRECLUDED FURTHER ALL PUPS EXAMINED APPEARED NORMAL. IN STOMACH. EVALUATION. 1513 1 22 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1514 12 22 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. 1516 22 1517 22 ............................................................................................................................. ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED NORMAL. NORMAL. [2_ _t_ OO b_ O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE 8): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... IV 10 CONT. 1519 18 22 OBSERVATIONS 1 PUP: FOUND DEAD, NO MILK PRESENT AUTOLYSIS PRECLUDED FURTHER ALL PUPS EXAMINED APPEARED NORMAL. IN STOMACH. EVALUATION. 1521 22 ALL PUPS EXAMINED APPEARED NORMAL. 1523 1 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. 22 1 PUP: BRAIN: THIRD AND LATERAL VENTRICLES, MARKED DILATION. ALL OTHER TISSUES APPEARED NORMAL. _I_ ALL OTHER PUPS EXAMINED APPEARED NORMAL. 1524 22 ALL PUPS EXAMINED APPEARED NORMAL. 0t%_ 1527 22 ALL PUPS EXAMINED APPEARED NORMAL. t_ 1528 22 ALL PUPS EXAMINED APPEARED NORMAL. 1531 1 22 2 PUPS: ALL PUPS STILLBORN. ALL TISSUES APPEARED EXAMINED APPEARED NORMAL. NORMAL. 1533 1 22 i PUP: FOUND DEAD. ALL TISSUES APPEARED ALL PUPS EXAMINED APPEARED NORMAL. NORMAL. 1534 22 ALL PUPS EXAMINED APPEARED NORMAL. 1537 1 22 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1539 22 ALL PUPS EXAMINED APPEARED NORMAL. .................................................................................................................................... O C 4_ Oo 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE E43 (PAGE 9): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTUM .................................................................................................................................... V 30 1541 22 OBSERVATIONS ALL PUPS EXAMINED APPEARED NORMAL. 1544 1 22 1 PUP: STILLBORN. ALL PUPS EXAMINED ALL TISSUES APPEARED APPEARED NORMAL. NORMAL. 1545 3 16 22 1 PUP: 1 PUP: ALL PUPS FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. EXAMINED APPEARED NORMAL. 1546 22 ALL PUPS EXAMINED APPEARED NORMAL. (% 1548 i i PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 0% t21 22 ALL PUPS EXAMINED APPEARED NORMAL. C_ 1550 22 ALL PUPS EXAMINED APPEARED NORMAL. 1552 22 ALL PUPS EXAMINED APPEARED NORMAL. 1555 6 22 1 PUP: FOUND DEAD. NO MILK PRESENT AUTOLYSIS PRECLUDED FURTHER ALL PUPS EXAMINED APPEARED NORMAL. IN STOMACH. EVALUATION. 1557 22 1558 22 ALL PUPS ALL PUPS EXAMINED EXAMINED APPEARED APPEARED NORMAL. NORMAL. 1560 7 22 1 PUP: FOUND DEAD. AUTOLYSIS PRECLUDED FURTHER EVALUATION. ALL PUPS EXAMINED APPEARED NORMAL. > 1564 22 ALL PUPS EXAMINED APPEARED NORMAL. C_ 1565 22 ALL PUPS EXAMINED APPEARED NORMAL. 1566 22 ALL PUPS EXAMINED APPEARED NORMAL. 1568 22 ALL PUPS EXAMINED APPEARED NORMAL. 4_ 1571 22 ALL PUPS EXAMINED APPEARED NORMAL. O_ 1573 22 ALL PUPS EXAMINED APPEARED NORMAL. 1576 7 22 O 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. .................................................................................................................................... PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) (APFO) IN RATS (SPONSOR'S STUDY NUMBER: T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E43 (PAGE I0): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP LITTER MATERNAL DOSAGE (MG/KG/DAY) NUMBER DAY (S) POSTPARTt_ .................................................................................................................................... V 30 CONT. 1579 22 1583 22 1584 22 1586 22 1587 22 1588 22 1589 22 1591 22 1593 22 1598 22 OBSERVATIONS ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED ALL PUPS EXAMINED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. 1600 1 22 _% .................................................................................................................................... 1 PUP: FOUND DEAD. NO MILK PRESENT IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS EXAMINED APPEARED NORMAL. > oo O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE E44 (PAGE 1): PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... RAT/ LITTER NL_4BER BRAIN M F T SPLEEN M F T THYMUS M F T .................................................................................................................................... 1302 1.72 1.61 1.66 0.20 0.21 0.20 0.31 0.30 0.30 1304 1.59 1.55 1.57 0.16 0.15 0.16 0.20 0.17 0.18 1306 1308 1310 1312 1313 1316 1.42 1.29 1.58 1.75 1.48 NOT 1.32 1.35 1.48 1.67 1.39 PREGNANT 1.37 1.32 1.53 1.71 1.44 0.16 0.09 0.22 0.20 0.15 0.11 0.15 0.30 0.17 0.17 0.14 0.12 0.26 0.18 0.16 0.13 0.09 0.20 0.31 0.21 0.08 0.09 0.19 0.26 0.26 0.10 0.09 0.20 0.28 0.24 1318 1321 1325 1328 1330 1331 1334 1335 1336 1338 1.69 1.45 1.56 1.56 1.44 1.58 1.53 1.52 1.56 1.23 1.56 1.48 1.45 1.54 1.41 1.46 1.50 1.46 1.54 1.30 1.62 1.46 1.50 1.55 1.42 1.52 1 52 1 49 1 55 1 26 0.24 0.13 0.18 0.17 0.ii 0.14 0.10 0.14 0.19 0.13 0.19 0.14 0.11 0.16 0,08 0.09 0.12 0.14 0.23 0.14 0.22 0.14 0.14 0.16 0.I0 0.12 0.11 0.14 0.21 0.14 0.26 0.24 0.12 0.20 0.15 0.15 0.16 0.22 0.24 0.14 0.24 0.18 0.14 0.23 0.i0 0.08 0.18 0.23 0.22 0.16 0.25 0.21 0.13 0 22 0 12 0 12 0 17 0 22 0 23 0 15 1340 1341 1342 1344 1345 1346 1348 1350 1.05 1.58 1.44 1.56 1.53 1.57 1.50 1.34 1.80 1.55 1.36 1.47 1.47 1.52 1.41 1.26 1 42 1 56 1 40 1 52 1 50 1 54 1 46 1 30 0.15 0.15 0.10 0.15 0.08 0.09 0.13 0.07 0.16 0.20 0.09 0.15 0.15 0.14 0.15 0.08 0.16 0.18 0.i0 0.15 0.12 0.12 0.14 0.08 0.20 0.25 0.12 0.14 0.14 0.22 0.18 0.06 0.17 0.24 0.12 0.16 0.21 0.22 0.19 0.09 0 18 0 24 0 12 0 15 0 18 0 22 0 18 0 08 TERMINAL M BODY F WEIGHT T 48.1 45.5 42.0 28,5 45.5 54.7 39.4 44.0 39.8 34.3 28.4 44.9 53.2 36.5 46.0 42.6 38.2 28.4 45,2 54.0 38.0 52.6 33,4 35,8 43.2 26,6 33.8 39.1 44.9 45.0 29,9 41,2 46,4 38.4 44.3 39.9 43,5 34.7 22.6 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 49.4 33.4 35.6 42.5 25.0 30.3 38.9 44.6 44.2 28.6 40.7 46.4 36.0 43.6 40.4 41.6 35.2 23.2 1353 1355 1358 1.44 1.52 1 48 0.11 1.63 1.51 1 57 0.14 NOT PREGNANT; MATING NOT 0.15 0.13 0.14 0.14 CONFIRMED 0.16 0.24 0.21 0.23 0 18 0 24 41.0 38.7 43.0 41.7 42.0 40.2 1359 1.53 1.46 1.50 0.20 0.17 0.18 0.22 0.18 0.20 .................................................................................................................................... MALE F = FEMALE T = TOTAL 41.5 40.2 40:8 WEIGHTS WERE RECORDED IN GRAMS (G) " _O'__ Pup's identification appeared incorrectly recorded; therefore, terminal body weight could not be determined. tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO} IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E44 (PAGE 2) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... MATERNAL DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... RAT/ LITTER BRAIN SPLEEN THYMUS NUMBER M F T M F T M F T .................................................................................................................................... 1362 1363 1364 1367 1368 1371 1375 1376 1378 1379 1.54 1.45 1.43 1.29 1.42 1.60 1.35 1.57 1.42 1.42 1.30 1.35 1.39 1.34 1.48 1.53 NOT PREGNANT 1.57 1.41 1.50 1.36 1.38 1.58 1.42 1.32 1.36 1.50 1.49 0.13 0.09 0.11 0.I0 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 0,15 0.16 0.17 0.Ii 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 0.21 0.20 TERMINAL M BODY F WEIGHT 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 34.5 37 1 11338812 1383 1384 1387 1389 1392 11..5369 1.64 1.54 1.56 1.45 1.41 11..6321 1.59 1.44 1.39 1.38 1.42 11..5395 1.62 1.49 1.48 1.42 1.42 00..1140 0 15 0.23 0.14 0.12 0.06 00.,1182 0.19 0.19 0.20 0.11 0.12 00..1I6I 0.17 0.21 0.17 0.12 0.09 00..2154 0.19 0.24 0.14 0.16 0.13 00..2126 0.19 0.20 0.16 0.19 0.ii 00..2145 0.19 0.22 0.15 0.18 0.12 4396..73 47.9 41.4 38.9 32.0 28.6 4363..73 49 5 43.2 38.4 35.0 27.6 4384 28 48 7 42 3 38 6 33 5 28.1 1393 1397 1.54 1.55 1.49 1.55 1 52 1 55 0.14 0.19 0.17 0.23 0.16 0.21 0.15 0.23 0.16 0.18 0.16 0.20 43.3 48.4 41.5 44.9 42.4 46.6 1399 1401 1404 1407 1409 1410 1413 1.67 1.48 1.43 1.37 1.50 1.56 1.64 1.61 1.40 1.48 1.34 1.46 1.40 1.48 1 64 1 44 1 46 1 36 1.48 1.48 1.56 0.17 0.20 0.13 0.15 0.19 0.14 0.20 0.18 0.21 0,17 0.12 0.15 0.08 0.20 0.18 0.20 0.15 0.14 0.17 0.11 0.20 0.23 0.22 0.12 0.14 0.19 0.28 0.22 0.24 0.22 0.15 0.14 0.23 0.13 0.19 0.24 0.22 0.14 0.14 0.21 0.20 0.20 50.3 45.8 37.2 34.4 48.3 45.1 48.3 46.4 45.0 37.9 31.8 44.6 33.5 44.4 48.4 45.4 37.6 33.1 46.4 39.3 46.4 1415 1.52 1.39 1.46 0.18 0.15 0.16 0.12 0.17 0.14 38.3 35.4 36.8 > 1416 1.42 1.46 1.44 0.08 0.12 0.i0 0.Ii 0.12 0.12 31.7 36.8 34.2 1418 1.49 1.38 1.44 0.i0 0.17 0.14 0.15 0.16 0.16 37.6 38.1 37.8 ........................................................................................... '......................................... -- MALE F s FEMALE T = TOTAL [/) ALL WEIGHTS WERE RECORDED IN GRAMS (G). 4_ OO 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (OWE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION TABLE E44 (PAGE 3) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE MATERNAL DOSAGE ...................... RAT/ GROUP III 3 MG/KG/DAY _ ............................................................................................................. LITTER NUMBER BRAIN M F T SPLEEN M F T THYMUS M F T .................................................................................................................................... 1421 1424 1.44 1.28 1.37 1.32 1.40 1.30 0.09 0.11 0.10 0.I0 0.10 0.i0 0.11 0.09 0.08 0.06 0.10 0.08 1426 1428 1430 1431 1433 1436 1437 1439 1442 1443 1446 1.50 1.57 1.38 1.44 1.49 1.56 1.59 1.53 1.82 1.58 NOT 1.39 1.44 1.32 1.47 1.49 1.45 1.47 1.50 1.83 1.43 PREGNANT 1.44 1.50 1.35 1.46 1.49 1.50 1.53 1.52 1.82 1.50 0.10 0.11 0.10 0.09 0.11 0.10 0.13 0.20 0.24 0.18 0.08 0.13 0.12 0.12 0.13 0.11 0.13 0.20 0.23 0.17 0.09 0.12 0.11 0.10 0.12 0.10 0,13 0.20 0.24 0.18 0.15 0.14 0.09 0.15 0.22 0.16 0.12 0.25 0.30 0.17 0.14 0.17 0.16 0.23 0.19 0.15 0.15 0.23 0.32 0.17 0.14 0.16 0.12 0.19 0.20 0.16 0.14 0.24 0.31 0.17 TERMINAL M BODY F WEIGHT T 34.3 27.9 36.4 37.2 34.4 37.5 40 6 39 5 41 5 54 6 52 8 39 7 27.9 27.1 34.9 40.9 31.4 40.3 41.9 37.0 39.1 50.7 50.8 41.4 31.1 27.5 35.6 39.0 32.9 38.9 41.2 38.2 40.3 52.6 51.8 40.6 1448 1450 1452 1455 1456 1458 1.52 1.36 1.43 1.25 1.51 1.32 1.51 1.49 1.67 1.56 NOT PREGNANT 1.44 1.34 1.42 1.50 1.62 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 0.18 0.I0 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 43.9 31.6 34.7 50.8 50.0 40.2 27.8 31.6 46.9 51.0 42.0 29.7 33.2 48.8 50.5 1459 1461 1463 1465 1468 1469 1472 1.56 1.57 1.57 1.45 1.30 1.38 1.55 1.50 1.53 1.49 1.60 1.38 1.41 1.56 1.53 1.55 1.53 1.52 1.34 1.40 1.56 0.17 0.17 0.12 0.21 0.10 0.08 0.16 0.17 0.19 0.13 0.16 0.10 0.15 0.15 0.17 0.18 0.12 0.18 0.10 0.12 0.16 0.17 0.24 0.16 0.15 0.12 0.12 0.22 0.16 0.24 0.16 0.21 0.13 0.13 0.22 0.16 0.24 0.16 0.18 0.12 0.12 0.22 42.0 51.1 38.8 38.5 26,2 36.3 51.1 44.3 50.7 37.8 43.9 35.3 35.9 44.7 43.2 50.9 38.3 41.2 30.8 36.1 47.9 1474 1.51 1.48 1.50 0.17 0.14 0.16 0.11 0.17 0.14 a a a _> 1476 1.55 1.45 1.50 0.15 0.13 0,14 0,14 0.II 0.12 41.3 34.5 37.9 1477 1.22 1.33 1.28 0.06 0.10 0.08 0.03 0.11 0.07 19.5 33.4 26,4 1480 1.58 1.54 1.56 0.19 0.22 0.20 0.20 0.19 0.20 46.5 43.9 45_2 .................................................................................................................................... _#_ MALE F = FEMALE T = TOTAL WEIGHTS WERE RECORDED IN GRAMS (G). OO Pup's identification appeared incorrectly recorded; therefore, terminal body weight could not be determined. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION TABLE E44 (PAGE 4) : PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... RAT/ LITTER BRAIN SPLEEN THYMUS NUMBER M F T M F T M F T .................................................................................................................................... 1482 1483 1486 1488 1.50 1.41 NOT PREGNANT 1.42 1.42 1.51 1.43 1.46 1.42 1.47 0.i0 0.13 0.11 0 14 0.11 0.11 0.12 0.11 0.12 0.20 0.06 0.22 0.19 0.11 0.16 0.20 0.08 0.19 1490 1491 1.52 1.42 1.48 1.78 1.50 1.60 0 25 0 10 0.27 0.10 0.26 0.10 0.29 0.13 0.26 0.09 0.28 0.11 1494 1496 1497 1500 1502 1505 1507 1508 1511 1513 1514 1.56 1.54 1.49 1.45 1.63 1.44 1.39 1.54 NOT 1.63 1.39 1.42 1,45 1.48 1.41 1.53 1.38 1.29 1.57 PREGNANT 1.49 1.39 1.49 1.50 1.48 1.43 1.58 1.41 1.34 1.56 1.56 1 39 0 15 0 i0 0 17 0.14 0.16 0.15 0.08 0.22 0.14 0.16 0.21 0.17 0.14 0.I0 0.10 0.18 0.14 0.13 0.19 0.16 0.15 0.12 0.09 0.20 0.17 0.16 0.17 0.10 0.17 0.13 0 19 0 15 0 15 0 18 0 25 0 ii 0 21 0.20 0.17 0.20 0.21 0.24 0.19 0.21 0.19 0.23 0.14 0.14 0.15 0.11 0.18 0.18 0.18 0.21 0.22 0.16 0.20 0.22 0.14 0 12 1516 1517 1.48 1.57 1.44 1.44 1 46 1 50 0.21 0.11 0.17 0.09 0 19 0 10 0.18 0.14 0.20 0.15 0 19 0 14 1519 1521 1523 1524 1527 1528 1531 1.52 1.60 1.53 1.65 1.39 1.49 1.57 1.46 1.54 1.44 .... 1.28 1.53 1.51 1 49 1 57 1 48 1 65 1.34 1.51 1.54 0.12 0.16 0.13 0.20 0.11 0.21 0.20 0.11 0.14 0.15 .... 0.08 0.18 0.16 0 12 0 15 0 14 0 20 0 10 0 20 0 18 0.10 0.18 0.23 0.21 0.12 0.25 0.20 0.14 0.19 0.22 .... 0.08 0.18 0.19 0 12 0 18 0 22 0 21 0.10 0.22 0.20 1533 1.45 1.44 1.44 0.16 0.16 0 16 0.15 0.18 0.16 1534 1.50 1.49 1.50 0.12 0.Ii 0 12 0.14 0.16 0.15 1537 1.45 1.35 1.40 0.14 0.i0 0 12 0.16 0.14 0.15 1539 1.46 1.55 1.50 0.14 0.13 0.14 0.18 0.16 0.17 .................................................................................................................................... TERMINAL M BODY F WEIGHT T 38.1 34.0 36.0 32.6 40 1 52 3 36 3 45 4 35 3 43 0 40.5 50.2 30.8 30.9 42.9 36 9 34 6 52 7 29 7 44 0 34 5 49 0 42 8 45 5 34 2 29.7 38.7 34.8 37.4 52 5 33 0 44 7 34 9 46 0 41 6 47 8 32 5 30 3 40.8 39.2 35.4 48.3 36.8 36.3 42.2 50.4 58.4 32.6 47.6 46.2 42.1 41.4 37.4 39.6 34.8 29.8 43.7 31.8 38.9 38.7 47,0 .... 24.8 41.2 40.5 40.7 37.1 36.1 41.1 37.0 32.6 46.0 34.3 37.6 40.4 48.7 58.4 28.7 44.4 43.4 41.4 39.2 36.8 40.4 = MALE F = FEMALE T = TOTAL 4_ ALL WEIGHTS WERE RECORDED IN GRAMS (G). O0 0 PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION TABLE E44 (PAGE 5): PUP ORGAN WEIGHTS - INDIVIDUAL DATA - F2 GENERATION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... MATERNAL DOSAGE GROUP V 30 MG/KG/DAY T/ ............................................................................................................................ LITTER NUMBER BRAIN M F T SPLEEN M F T THYMUS M F T .................................................................................................................................... 1541 1.39 1.44 1.42 0.13 0.ii 0 12 0.16 0.15 0.16 1544 1.56 1.63 1.60 0.17 0.15 0 16 0.22 0.17 0.20 1545 1.58 1.48 1.53 0.13 0.12 0 12 0.19 0.12 0.16 1546 1.38 1.40 1 39 0.12 0.09 0 10 0.i0 0.14 0.12 1548 1.48 1.40 1 44 0.21 0.17 0 19 0.21 0.19 0.20 1550 1.54 1.49 1 52 0.16 0,ii 0 14 0.18 0.17 0.18 1552 1.44 1.39 i 42 0.12 0.13 0 12 0.17 0.14 0.16 1555 1.39 1.35 1 37 0.09 0.09 0 09 0.09 0.II 0.i0 1557 1.49 1.46 1 48 0.09 0.i0 0 i0 0.10 0.i0 0.i0 1558 1.48 1.55 1.52 0.16 0.18 0 17 0.14 0.20 0.17 1560 1564 1.40 1.42 1.36 1.46 1.38 1.44 0.13 0.12 0.09 0.15 0 II 0 14 0.16 0.15 0.13 0.17 0.14 0.16 1565 1566 1.44 1.46 1.27 1.42 1.36 1.44 0.12 0.12 0.10 0.16 0 ii 0 14 0.17 0.17 0.16 0.09 0.16 0.13 1568 1571 1.45 1.46 1.52 1.44 1.48 1.45 0.17 0.07 0.15 0.07 0 16 0.07 0.24 0.11 0.18 0.10 0.21 0.10 1573 1.40 1.37 1.38 0.08 0.09 0.08 0.13 0.10 0.12 1576 1578 1.31 1.08 1.20 NOT PREGNANT 0.11 0.14 0.12 0.12 0.13 0.12 1579 1583 1584 1586 1587 1588 1589 1.48 1.61 1.66 1.43 1.61 1.38 1.39 1.41 1.51 1.48 1.43 1.53 1.37 1.36 1.44 1.56 1.57 1.43 1.57 1.38 1.38 0.09 0.19 0.28 0.10 0.21 0.11 0.15 0.14 0.15 0.26 0.12 0.16 0.15 0.13 0 12 0 17 0 27 0 11 0 18 0 13 0 14 0.13 0.25 0.33 0.11 0.19 0.14 0.09 0.16 0.22 0.23 0.18 0.20 0.11 0.16 0.14 0.24 0.28 0.14 0.20 0.12 0.12 TERMINAL M BODY F WEIGHT T 33.2 44.8 a 30.6 38.4 40.2 33.9 32.8 34.4 35.8 33.0 35.1 39.1 35.0 46.8 31.6 38.1 30.8 34.8 47.2 a 31.9 31.1 37.1 33.6 29.1 34.5 39.4 32.0 37.0 35.9 30.9 44.6 28.7 34.2 31.7 34.0 46.0 a 31.2 34.8 38.6 33.8 31.0 34.4 37.6 32.5 36.0 37.5 33.0 45.7 30.2 36.2 31.2 36.2 39.0 60.9 34.9 46.2 39.2 26.7 36.3 40.4 50.7 37.6 40.5 39.3 25.0 36.2 39.7 55.8 36.2 43.4 39.2 25.8 1591 1593 1.52 1.45 1.50 1.41 1.51 1.43 0.17 0.28 0.i0 0.28 0 14 0 28 0.14 0.33 0.16 0.32 0.15 0.32 36.8 51.2 38.7 50.6 37.8 50.9 1598 1593 1.38 1.41 1.37 1.43 1.38 1.42 0.05 0.12 0.07 0.14 0 06 0 13 0.08 0.13 0.08 0.14 0.08 0.14 27.4 40.6 29.0 38.6 28.2 39'.6 .................................................................................................................................... _#_ MALE F = FEMALE T -- TOTAL 4_ WEIGHTS WERE RECORDED IN GRAMS (G). OO Pup's identification appeared incorrectly recorded; therefore, terminal body weight could not be determined. O PROTOCOL 418-020: ORAL (GAVAGE) _O-GE_TION (APFO) IN RATS (SPONSOR'S (O_ LITTER STaY NUMBER: PER GE_RATION) T-6889.6) TABLE E45 (PAGE I): AN_ENITAL DISTANCE - I_IVIDUAL DATA - F2 GENE_TION REPRODUCTION PUPS STUDY OF AMMONI_ PERFLUOROO_ANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 ii 12 13 14 15 16 17 18 19 20 21 .................................................................................................................................... 22 23 RAT # MEAN _SAGE GROUP I 0 MG/KG/DAY DAY 1 POSTPART_ .................................................................................................................................... 1302 / MA MA _ MA MA FA FA FA FA FA FA 1.8 3.1 2.8 2.6 26 2.3 0.9 1.1 1.1 1.0 1.3 1.0 1304 / MA MA MA MA _ MA FA FA FA FA FA FA 1.8 2.6 2.4 2.6 2 5 2.4 2.4 1.2 1.1 i.i 1.0 1.0 1.3 1306 / MA MA _ MA _ MA MA MA FA FA FA FA FA FA FA FA 1.8 2.5 2.4 2.4 24 2.6 2.3 2.5 2.5 1.0 1.0 1.1 1.1 1.0 1.1 1.1 1.0 1308 / MA MA MA MA _ MA FA FA FA FA FA FA FA FA FA FA 1310 1.6 2.5 2.5 2.5 25 / MA MA MA MA 2.5 2.7 1.0 1.0 1.1 1.0 0.9 1.1 1.1 1.0 1.0 1.0 MA MA MA MA MA FA FA FA FA FA 1312 1.9 2.5 2.6 2.7 2 3 2.5 2.5 2.2 2.3 2.5 i.i 1.0 1.0 1.0 1.0 / MA MA FA FA 2.2 3.0 3.2 i.I 1 3 1313 / MA MA MA MA 1.5 2.2 2.1 2.5 26 _ FA FA FA FA FA FA FA FA 2.3 1.0 1.0 1.1 1.0 1.1 1.1 1.0 1.1 1316 NOT P_GNANT 1318 1321 1325 1328 1330 1331 / MA MA MA MA MA _ MA MA MA FA FA FA FA FA FA 2.1 3.0 3.0 3.0 2 7 2.8 2.8 2 5 3.0 2.7 1.1 1.1 1.1 i.i 1.0 1.0 / MA MA MA MA MA _ MA _ FA FA FA FA FA FA FA FA FA 1.8 2.4 2.5 2.4 25 2.4 3.0 25 2.5 1.0 1.0 1.1 1.0 1.1 1.2 1.1 1.0 1.1 / MA MA MA MA MA FA FA FA FA FA FA 1.7 2.8 2.4 2.6 2 4 2.5 1.0 1 1 1.1 1.1 1.0 1.0 / MA MA MA MA MA _ MA FA FA FA FA FA FA 1.9 2.5 3.2 2.5 2 6 2.6 2.5 2 5 1.1 1.0 I,i 1.4 1.0 1.2 / MA MA MA MA MA _ _ FA FA FA FA FA FA FA FA FA 1.7 2.5 2.5 2.3 2 7 2.6 2.6 2 7 i.i 1.0 1.0 1.2 1.1 1.1 1.1 1.2 1.0 / MA MA MA MA MA _ MA MA _ MA MA MA FA FA FA FA 2.0 2.3 2.7 2.3 2 5 2.2 2.5 2 1 2.5 2.6 2.4 2.1 2.3 1.1 1.0 1.0 1.0 1334 / MA MA MA MA MA _ FA FA FA > 2.0 2.7 2.5 2.6 2 5 2.6 2.3 0 7 1.0 1.0 1335 / MA MA MA MA MA _ FA FA FA FA FA FA 2.0 3.2 2.6 2.9 3 0 2.6 2.7 1.2 1.0 1.0 1.2 1.3 1.0 1336 / MA MA MA _ MA _ _ FA FA FA FA FA FA FA FA 1.8 2.5 2.4 2.8 27 2.5 2.7 2.6 1.1 1.2 1,1 1.1 1.0 1.1 1.1 1.1 1338 / MA MA MA MA MA _ MA MA FA FA FA FA FA FA FA FA FA 1.6 2.5 2.5 2.6 23 2.4 2.6 2.4 1.2 1.1 1,0 .................................................................................................................................... 1.0 1.0 1.2 1.1 1.0 1.2 I.i FIRST LETI"ER -- M-MALE, F-FEMALE, U-SEXUNDETE_INABLE O SECOND LETTER DISTANCES -- A-ALIa, S-STILLBORN, U-_CERTAIN, WE_ _CORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (P_S_ED CANNIB_IZED), X-MISSING; SACRIFICED _EN FOUND PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENE_TION (APFO) IN RATS (SPONSOR'S (ONE LITTER STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E45 (PAGE 2): AN_ENITALDISTANCE- INDIVIDUAL DATA - F2 GE_RATION REPRODUCTION PUPS STUDY OF AMMONIUMPERFLUOROOCTANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 .................................................................................................................................... 18 19 20 21 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 1 POSTPARTUM 1340 1341 1342 1344 1345 1346 1348 1350 1353 1355 1358 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 2.0 2.6 2.7 2.8 2.5 2.6 2.7 2.7 2.9 1.1 1.0 1.2 i.i 1.2 i.i / MA MA MA MA FA FA FA FA FA FA FA FA 1.5 2.6 2.4 2.2 2.5 1.3 1.0 1.0 1.0 1,2 i.i 1.0 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.7 2.5 2.5 2.3 2.5 2.5 2.7 2.5 2.2 1.2 1.0 i.i 1.0 1.0 1.0 1.2 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.8 2.7 2.7 2.6 2.5 2.4 2.6 2.5 I.i I.i 1,0 1.0 I.i i.I 1.0 1.0 / MA MA MA MA MA MS FA FA FA FA FA FA FA FA FA FS 1.7 2.8 3.0 2.7 3.0 2.8 1.0 1,0 I.i 1.0 1.0 1.2 i.i 1.0 1.2 / MA MA MA MA MA MA FA FA FA FA 2.0 2.9 2.9 2.5 2.6 2,6 2.4 0.9 0.9 1.0 1.0 / MA MA MA MA MA MA MS 2.0 2,7 3,3 2.7 2.8 2.5 2.7 MA MA FA FA FA FA FA FA FS 2.5 2.4 1.3 1.2 1.2 i.i i.i 1.1 / MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2.3 2.6 3.0 2.6 2.5 2.6 2,5 2.5 3.0 2.5 2.4 3.4 2.5 2.5 i.i 1.2 1.2 i.I / MA MA MA MA MA MA FA FA FA FA FA FA FA FU 1.8 2.2 2,7 2.8 2.8 2.4 2.4 1.2 1.0 i.I I.i 1.0 1.0 I.i / MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.7 2.4 2.7 I.i 1.0 i.i 1.1 1.2 1.0 1.1 1.0 1.1 1.1 1.1 NOT P_GNANT; MATING NOT CONFIRMED 1359 / MA MA MA MA MA FA FA FA FA FA FA FA FA FS 1.6 2.6 2.4 2.4 2.7 2.8 0.9 0.9 1.1 1.0 1.1 1.0 1.0 1.2 .................................................................................................................................... FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER--A-ALIVE, S-STIL_ORN, U-_CERTAIN, D-DIED, M-MISSING (P_SUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM). > PROTOCOL 418-020: ORAL (GAVAGE) TWO-GE_TION (APFO) IN RATS (SPONSOR'S (On LITER STaY NUMBER: PER GE_TION) T-6889.6) REPRODUCTION STaY OF AMMONI_ PERFLUOROO_ANOATE TABLE E45 (PAGE 3): AN_ENITAL DISTANCE- I_IVIDU_ DATA- F2 GE_RATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1 POSTPART_ 1362 1363 1364 1367 1368 /_ MA MA MA FA FA FA 2.1 3.1 2.9 2.7 2 7 1.1 1.0 1 1 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FS 1.6 2.5 2.2 2.2 2 5 2.6 2.5 2 5 1.1 1.0 1.0 0.9 0.9 1.0 1.0 1.2 1.0 1.0 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2.6 2.5 2.5 26 2.5 2.3 23 1.0 1.1 1.0 1.0 0.9 0.8 1.0 0.9 / MA MA MA MA _ MA MA _ FA FA FA FA FA 2.1 2.6 3.0 2.9 2 9 2.7 2.4 2 6 2.5 1.2 I.i i.i 0.9 1.3 / MA MA MA MA _ _ MA MA FA FA FA FA FA FA FA 1.8 2.7 2.5 2.8 2 6 2.5 2.8 2 5 2.5 0.9 1.0 0.9 1.0 1,0 1.1 1.0 1371 / MA MA MA MA 2.0 2.5 2.7 2.3 26 MA HA MA 2.3 2.7 26 MA MA MA MA FA FA FA FA FA FA 2.9 2.6 2.7 2.6 1.0 1.0 1.1 1.1 1.1 1.0 1375 2.3 / M2A.9 M2A.9 M2A.9 M3A.1 _2.6 _3.0 M2A 9 M3A.1 M3A.1 F1A.0 F1A.1 F1A.1 F1A.0 F1A.0 1376 / MA MA MA MA MA _ MA _ MA MA MS MS FA FA FA FA FA . 2.0 2.3 2.4 2.5 2.6 2.4 2.6 2.5 2.6 2.5 2.3 1.0 1.1 1.2 1.1 1.0 1378 N_ P_GNANT 1379 / MA MA MA MA MA _ FA FA FA FA FA FA 1.8 2.5 2.5 2.6 2.7 2.4 2.6 1.1 i.I 1.0 1.0 0.9 1.3 1381 / MA MA _ MA MA _ FA FA FA FA FA FA 2.0 2.7 2.9 3.0 3.1 2.9 2.8 1.2 1.1 1.2 1.3 1.2 1.2 1382 /_ MA _ MA MA FA FA FA FA FA FA FA FA 1.7 2.3 2.5 2.8 2.8 2.7 1.1 1.2 1.0 1.0 1.0 1.2 1.1 1.2 1383 / MA MA MA MA MA _ FA FA FA FA FA 1.9 2.5 2.4 2.3 2.5 2.5 3.2 1.0 1.0 1.0 1.0 I.I 1384 / MA MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.5 3.1 2.6 2.4 2.7 2.8 1.1 1.1 1.2 1.0 1.2 1.1 1.0 1387 /_ MA MA MA MA _ MA MA _ FA FA FA FA FA FA FA FS > 1.9 2.5 2.6 2.7 2.5 2.6 2.7 2.8 2.7 2.5 i.i 1.0 1.1 1,0 1.1 1.0 1.0 1389 / MA MA MA MA MA _ MA MA FA FA FA FA FA FA FA FA 1.7 2.3 2.5 2.6 2.4 2.6 2.4 2.3 2.2 0.9 i.i 1.0 1.0 1.0 0.9 1.0' I.I 1392 / MA MA MA MA MA _ MA MA MA FA FA FA FA FA FA FA FA 1.8 2.5 2.4 2.6 2.6 2.5 2.2 2.4 2.5 2.5.0.9 1.0 1.0 1.1 0.9 1.0 1.0 1.0 1393 / MA MA MA MA MA MS FA FA FA FA FA FA 1.7 2.6 2.5 2.4 2.5 2,7 1.0 1.0 1.0 1.2 .................................................................................................................................... 1.1 1.2 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE O SECOND LETTER - A-ALIa, S-STILtOn, U-_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIB_IZED), X-MISSING; SACRIFICED _EN FO_D DISTANCES _ _CO_ED IN MILLIMETE_ (_). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GE_TION (APFO) IN RATS (SPONSOR'S (On LITER STUDY NUMBER: PER GE_RATION) T-6889.6) _PRODU_ION STaY OF AMMONI_ PERFLUOROOCTANOATE TABLE E45 (PAGE 4): AN_ENITAL DISTANCE - I_IVIDUAL DATA - F2 GE_RATION PUPS .................................................................................................................................... P_ # 1 2 3 4 5 6 7 8 9 i0 Ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT # MEAN _SAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 1 POSTPART_ 1397 / MA MA MA MA _ _ MA FA FA FA 2.0 2.7 2.5 2.6 2.8 2.6 2.7 2.8 1.1 1.0 1.1 1399 / MA MA _ MA FA FA FA FA FA FA 1.9 2.7 3.1 2.9 2.7 1.1 1.2 1.3 1.2 1.2 1.2 1401 / MA MA MA MA MA FA FA FA FA FA 1.8 2.8 2.8 3.1 2.8 2.8 1.1 1.0 1.0 I.I 1.0 1404 / MA MA MA MA MA _ MA MA MA MA 2.1 2.2 2.5 2.3 2.5 2.5 2.2 2.2 2.4 2.5 2.6 1407 / MA MA MA MA MA MA MA FA FA FA 1.7 2.6 2.4 2.3 2.5 2.5 2.3 2.6 1.1 1.0 1.0 1409 / MA MA MA MA _ _ MA FA FA FA 1.8 2.4 2.2 2.4 2.6 2.5 2.5 2.5 1.0 1.2 1.0 1410 / MA MA MA MA _ _ MA MA MA MA 2.0 2.5 2.3 2.5 2.3 2.4 2.3 2.5 2.3 2.2 2.3 1413 / MA MA MA MA MA _ MA FA FA FA 1.8 2.2 2.4 2.2 2.4 2.5 2.6 2.3 1.0 1.0 i.i 1415 / MA MA MA MA _ _ MA FA FA FA 1.9 2.3 2.4 2.5 2.5 2.5 2.8 2.6 1.2 1.1 1.2 1416 / MA MA MA FA FA FA FA FA FA FA 1.4 2.4 2.3 2.4 1.2 1.0 1.1 1.2 1.0 1.1 1.1 1418 / MA MA MA MA _ _ FA FA FA FA 1.6 2.8 2.6 2.3 2.2 2.5 2.6 1.0 1.0 1.2 1.0 .................................................................................................................................... FA 1.4 FA i.i 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 i.i FA 1.0 MA 2.5 FA 1.3 FA 1.0 FA 1.1 FA i.i 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 FIRST LETTER SECOND LETTER ALL DISTANCES -- M-MALE, F-FEMALE, U-SEXUNDETE_INABLE -- A-ALIa, S-STILtOn, U-_CERTAIN, _ _CO_ED IN MILLIMETERS (MM). D-DIED, M-MISSING (P_S_ED CANNIBALIZED), X-MISSING; 19 20 SACRIFICED 21 22 23 _EN FOUND > 4= oo PROTOCOL 418-020: ORAL (GAVAGE) _O-GE_TION (APFO} IN RATS (SPONSOR'S (O_ LITER STUDY NUMBER: PER GE_TION) T-6889.6) _PRODUCTION STaY OF _MONI_ PERFLUOROO_OATE T_LE E45 (PAGE 5): _ENIT_ DIST_CE - I_IVIDU_ DATA - F2 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 .................................................................................................................................... 22 23 RAT # MEAN _SAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... DAY 1 POSTP_T_ 1421 1424 1426 1428 1430 1431 /_ _ _ _ _ _ _ _ _ _ FA FA FA FA FA FDI FD1 2.0 2.7 2.5 2.3 2.3 2.4 2.6 2.3 2.5 2.3 2.6 1.0 1.2 1.0 1.2 1.0 /_ _ _ _ _ _ _ _ _ FA FA FA FA FA FA FA FA 1.8 2.5 2.5 2.2 2.7 2.4 2.5 2.5 2.8 2.4 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.9 / MA _ _ _ MA _ _ FA FA FA FA FA FA 1.8 2.3 2.2 2.5 2.6 2.7 2.4 2.5 0.9 0.9 1.2 1.0 1,1 1.2 /_ MA _ MA _ _ 1.7 2.7 2.5 2.6 2.5 2.82.5 FA FA FA FA FA FA FA FA FA 1.1 1.0 1.3 1.2 1.2 1.1 1.2 1.0 1.3 / MA _ _ MA MA _ FA FA FA FA FA FA FA FA FA FA FA 1.6 2.6 2.6 2.5 2.7 2.62.7 1.2 1.0 1.0 1.2 1.0 1.1 1.1 1.0 1.0 1.2 1.2 /_ MA _ _ _ _ 2.0 2.4 2.5 2.4 2.9 2.72.8 _ MA _ MDI FA FA FA FA FA FA 2.5 2.7 2.5 1.2 I.I 1.1 1.0 1.1 I.I 1433 1436 1437 1439 1442 1443 1446 / MA _ _ _ _ _ _ _ _ MA FA FA FA FA FA FA FA FA 1.8 2.7 2.7 2.7 2.2 2.2 2.3 2.6 2.5 2.8 2.2 1.0 1.0 1.0 1.0 0.9 1.1 1.1 1.0 /_ _ _ _ _ _ _ _ FA FA FA FA 2.1 2.9 2.6 2.6 2.7 2.7 2.5 2.4 2.5 I.I 1.0 1.0 i.i /_ _ _ _ _ _ 2.0 2.7 2.7 2.3 2.6 2.52.6 _ _ _ FA FA FA FA FA FA FA 2.7 2.9 2.5 1.1 1.1 1.1 1.0 1.1 1.2 1.2 /_ _ _ _ _ _ FA FA FA FD1 FS FS 2.2 2._ 2.8 2.8 2.5 3.0 2.5 1.2 1.0 1.1 /_ _ _ _ FA FA FA 2.3 3.5 2.8 3.2 3.2 1.2 1.2 0.9 /_ _ _ _ _ _ 2.1 2.8 2.7 3.2 2.5 2.52.7 NOT P_GNANT _ _ FA FA FA FA FA FA 2.7 2.6 i.i 1.2 I.i 1.6 1.2 1.3 1448 /_ _ _ _ _ _ 1.7 2.2 2.8 2.6 2.5 2.52.3 MS MS FA FA FA FA FA FA FA FA 1.2 i.i 1.0 1.3 1.0 1.0 1.0 1.0 1450 /_ _ _ _ FA FA FA FA FA FA FA FA FA FA > 1.5 2.5 2.3 2.6 2.8 1.2 i.i 1.0 1.1 1.0 0.9 1.0 i.i 0.9 1.0 1452 /_ _ _ _ _ _ 1.8 2.4 2.4 2.5 2.3 2.22.2 _ _ FA FA FA FA FA FA 2.5 2.4 1.0 1.0 1.0 1.0 0.9 1.0 1455 /_ _ _ _ _ _ _ _ FA FA FA FA FA FA FA 1.9 2.7 2 5 2.5 2 7 2.5 2 4 2.6 2.8 I.i 1 2 0.9 1 0 1.2 1 0 i.I 1456 /_ _ _ _ FA FA 2.1 2.5 2.7 2.5 2.8 1.2 1.0 .................................................................................................................................... O FIRST LE_ER-- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE SECOND LETTER -- A-_I_, S-STILtOn, U-_CERTAIN, D-DIED, M-MISSING (P_S_ED CANNIB_IZED), X-MISSING; SACRIFICED _EN FO_D DISTANCES _ _CO_ED IN MILLIM_E_ (_). PROTOCOL 418-020: ORAL (GAVAGE) _O-GE_TION (APFO) IN RATS (SPONSOR'S (On LITTER STaY NUMBER: PER GE_RATION) T-6889.6) T_LE E45 (PAGE 6): AN_ENITALDISTANCE- I_IVIDUALDATA- F2 GENERATION REPRODU_ION PUPS STaY OF AMMONI_ PERFLUOROO_ANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT # MEAN _SAGE GROUP III 3 MG/KG/DAY .................................................................................................................................... 1458 NOT P_GNANT DAY 1 POSTPART_ 19 20 21 22 23 1459 1461 1463 1465 1468 / MA MA MA MA MA MA MA MA MA FA FA 2.0 2.7 2.2 2.7 2.5 2.5 2.4 2.4 2.2 2.5 1.3 1.4 / MA MA MA MA FA FA FA FA FA FA FA 1.6 2.7 2.5 2.4 2.5 1.2 1.1 1.4 1.2 1.1 1.0 1.1 / MA MA MA MA MA MA MA MS FA FA FA 1.7 2.5 2.1 2.3 2.5 2.2 2.1 2.2 1.0 1.0 0.9 / MA MA MA MA MA MA FA FA FA FA FA 1.8 3.0 3.0 3.1 3.0 3.1 2.5 1.1 1.2 1.1 1.1 1.1 / MA MA MA MA MA FA FA FA FA FA FA 1.6 2.8 2.5 2.8 2.5 2.7 1.1 1.1 1.0 1.0 1.2 1.0 1469 2.2 / M2A.6 M2A.5 M2A.5 M2A.5 M2A.4 M2A.6 M2A.5 M2A.7 M2A.3 F1A.0 1472 / MA MA MA MA MA FA FA FA FA FA 2.0 3.0 2.9 3.0 2.7 2.7 1.3 1.1 1.1 1.2 1.2 1474 / MA MA MA MA MA MA MA _ MA MA 2.1 2.5 2.4 2.4 2.7 2.7 2.5 2.4 2.5 2.5 2.5 1476 / MA MA MA MA MA _ MA MDI FA FA 1.6 2.2 2.3 2.5 2.2 2.52.6 2.3 1.1 1.0 1477 / MA MA MA MA MA MA 1.8 2.4 2.6 2.5 2.4 2.92.4 MA MA FA FA 2.5 2.6 1.2 1.0 1480 / MA MA MA FA FA FA FA FA FA FA 1.6 2.9 2.9 3.2 1.4 1.3 1.2 1.2 1.2 1.2 1.2 .................................................................................................................................... F1A.1 FA 1.1 FA 0.9 FA i.i FA 1.2 FA 1.3 FA 1.0 FA 1.1 FA i.i 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 i.I 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 FIRST LETTER SECOND LETTER ALL DISTANCES -- M-MALE, F-FEMALE, U-SEXUNDETE_IN_LE -- A-ALIa, S-STILtOn, U-_CERTAIN, _ _CO_ED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESSED CANNIBALIZED), X-MISSING; SACRIFICED _EN FOUND O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GE_TION (APFO) IN RATS (SPONSOR'S (0_ LITTER STUDY NUMBER: PER GE_RATION) T-6889.6) T_LE E45 (PAGE 7): AN_ENITAL DISTANCE - INDIVIDUAL DATA - F2 GE_RATION _PRODU_ION PUPS STUDY OF AMMONI_ PERFLUOROO_ANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN _SAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DAY 1 POSTP_TUM 1482 1483 / MA MA MA MA MA _ FA FA FA FA FA FA FA FA FD1 FS 1.7 2.6 2.7 2.8 2.4 2.5 2.7 1.0 1.1 1.0 1.2 1.0 1.0 1.0 1.0 NOT P_GNANT 1486 1488 1490 1491 / MA MA MA MA MA _ MA MA MA FA FA FA FA FA FA 2.1 2.8 2.9 3.0 3 0 2.9 2.9 2.7 2.8 2.5 i.i i.I 1.3 1.0 1.2 1.0 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.8 28 / MA MA 2.5 23 MA MA 2.7 2.5 2.4 2.8 1.0 1.2 1.1 1.2 1.0 1.1 1.0 MA _ MA FA FA FA 2.6 3.2 30 3.6 35 3.0 2.7 3.1 1.2 1.3 1.2 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA UU 1.4 2.4 2 4 2.5 2 5 1.2 1.0 1 0 1.1 1.0 1.0 1.1 1.1 1.0 1.0 1494 1496 1497 1500 1502 1505 1507 1508 /MA MA 1.9 2.4 24 MA MA 2.6 26 MA _ MA 2.5 2.4 27 MA _I 2.6 FA FA FA FA FA 1.1 1.0 1.1 0.9 0.9 / MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.8 27 / MA MA 3.0 26 MA MA 2.9 2.6 25 FA FA FA 0.9 1.0 1.1 1.0 1.0 1.2 FA FA FA FA 1.6 2.5 2 6 2.7 2 7 1.0 1.1 1 1 1.2 1.2 1.1 1.0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FS 1.9 2.7 23 2.6 24 2.5 2.2 22 2.2 2.4 1.1 1.0 1.0 0.9 1.1 / MA MA MA MA FA FA FA FA FA FA FA FA FA 1.4 2.3 2 2 2.5 2 6 1.0 1.0 1 0 1.0 I.i 1.0 1.1 1.0 1.0 / MA MA MA MA _ _ MA FA FA FA FA FA FA FA FA FA 1.7 2.4 2 5 2.5 2 3 2.6 2.5 2 5 1.1 1.2 1.1 1.1 1.1 1.0 1.0 1.1 1.2 / MA MA MA MA MA _ MA MA MA FA FA FA FA FA FA FA 1.8 2.5 27 / MA MA 2.4 24 MA MA 2.1 2.4 23 FA FA FA 2.5 2.4 0.9 1.0 1.0 0.9 1.0 0.9 1.1 FA FA FA FA FA FA 1.5 2.6 2 8 2.4 2 5 I.i 1.0 1 1 0.9 1.0 1.2 0.9 1.1 1.1 1511 N_ P_GNANT 1513 1514 / MA MA MA MA MA _ MA MA MA FA FA FA FA MS 2.1 3.0 2.5 2.5 2.5 2.6 2.4 2,5 2.5 2.9 i.i i.i 1.0 1.1 / MA MA MA MA MA _ MA MA MA FA FA FA FA FA FA FA FA 2.1 2.9 2.7 2.8 3.1 3.1 2.8 2.9 2.9 2.7 1.2 1.2 1.2 1.0 1.2 1.4 1.0 1.0 1516 / MA MA MA MA MA MA MA MA MA FA FA FA FA 2.2 2.3 2.7 2.7 2.6 2.5 2.5 2.5 2.6 2.6 1.4 .................................................................................................................................... i.i 1.4 1.4 FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETE_IN_LE O SECOND LETTER DISTANCES -- A-ALIa, _ _CORDED S-STILLBO_, U-_CERTAIN, IN MILLIMETE_ (MM). D-DIED, M-MISSING (P_S_ED CANNIBALIZED), X-MISSING; SACRIFICED _EN FOUND PROTOCOL 418-020: ORAL (GAVAGE| TWO-GENERATION (ONE LITTER (APFO} IN RATS (S_NSOR'S STaY NUMBER: PER GENERATION) T-6889.6) TABLE E45 (PAGE 8): AN_ENITAL DISTANCE - INDIVIDUAL DATA - F2 GENE_TION REPRODUCTION PUPS STaY OF AMMONI_ PERFLUOROOCTANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT _ MEAN DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DAY i POSTPART_ 1517 1519 1521 1523 1524 1527 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 2.0 4.1 2.6 2.6 2.4 2.4 2.9 2.6 2.8 1.3 0.8 1.1 0.9 1.0 1.0 1.2 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.9 2.8 2.7 2.7 2.3 2.9 2.5 2.8 2.9 1.2 1.0 1.2 i.i 1.0 1.0 1.0 1.1 / MA MA MA MA MA MA MA FA FA FA FA FA 2.0 2.6 2.5 2.3 2.5 2.5 2.7 2.7 1.3 1.2 1.2 1.1 1.1 / MA MA MA MA MA MA MA MDI FA FA FA FA 1.9 2.6 2.4 2.5 2.5 2.4 2.2 2.2 1.0 1.1 1.3 1.0 / MA MA 3.6 3.6 3.7 / MA MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 1.9 2.5 2.5 2.2 2.8 2.7 2.4 2.7 2.1 2.0 2.4 2.7 1.0 0.9 1.0 1.0 1.1 I.i 1528 1.9 / M2A.6 M2A.4 M2A.7 M2A.4 M2A.6 M2A.4 F1A.0 F1A.0 F1A.0 F1A.1 1531 / MA MA MA MA MA MA MA MA MS 1.9 2.4 2.4 2.5 2.6 2.7 2.2 2.4 2.6 FA FA FA FA FA FS 1.0 i.i 1.1 1.0 1.2 O 1533 / MA MA MA _ MA MA FA FA FA FA FA FA FA FA FA FA FA FA FDI 1.6 2.8 2.5 2.8 2.6 2.92.5 1.1 1.1 1.0 1.1 1.1 1.0 0.9 1.0 1.0 1.0 1.0 1.0 1534 / MA MA MA MA MA MA FA FA FA FA FA FA 2.0 2.7 2.9 2.9 2.8 2.6 2.8 1.0 1.3 1.0 1.0 1.2 1.2 1537 / MA MA MA MA MA MA MA MA _ MA FA FA FA FA FS 2.1 2.7 2.5 2.6 2.7 2.5 2.5 2.8 2.5 2.5 2.5 1.0 1.0 1.0 1.0 1539 / MA MA MA MA MA MA MA MA MA FA 2.1 2.7 2.5 2.7 2.6 2.5 2.6 2.5 2.6 2.9 i.I .................................................................................................................................... FA I.i FA i.I FA 1.0 FA I.I FIRST LETTER -- M-MALE, F-FEMALE, U-SEXUNDETE_INABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-_CERTAIN, D-DIED, M-MISSING (PRESSED CANNIBALIZED), X-MISSING; SACRIFICED HEN FO[_D ALL DISTANCES WERE RECO_ED IN MILLIMETERS (MM). > O < tO O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOR_CTANOATE TABLE E45 (PAGE 9): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENE_TION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 II 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY .................................................................................................................................... DAY 1 POSTPARTUM 1541 1544 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.9 2.4 2.5 1.1 1.1 1.1 1.0 1.2 1.2 1.1 1.1 1.0 1,0 / MA MA MA MA I_ MA FA FA FA FA FA FA FA FS 1.7 2.7 2,7 2.3 2.5 2.4 2.5 1.2 1.0 1.1 1.2 1.0 1.1 1.0 1545 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.8 2.5 3.1 2.3 2.7 2.9 2.7 2.4 2.5 2.5 1.1 1.0 1.1 1.0 1.1 1.2 1.1 1.2 1.1 1.2 1546 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 1.9 2.5 2.5 3.1 2.5 2.7 2.5 2.7 2.5 1.2 1.0 1.1 i.I 1.1 1.1 1.0 1548 / MA MA MA MA FA FA FA FA FA FA FA FA FA FS 1.4 2.4 2.4 2.4 2.5 1.0 1.0 1.0 1.1 1.0 1.0 1.0 1.0 1.1 1550 / MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.9 3.1 2.7 2.3 2.4 1.1 1.6 1.1 1.2 1.1 1.2 13 1552 1555 / MA MA MA MA MA MA MA FA FA FA FA FA 1.8 2.2 2.6 2.7 2.8 2,3 2,7 2.7 1.0 1.0 1.1 0.9 i0 FA FA 1.0 1.0 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2.4 2.6 2.3 2.1 2.4 2.6 2.7 1.0 0.9 1.1 1.0 1 1 1.1 1.1 1.0 1557 / MA MA MA MA MA FA FA FA FA FA FA FA FA 1.6 2.7 2.8 2.7 2.5 2.2 1.1 1.1 1.0 1.0 1.1 1.1 1 0 1.1 1558 / MA MA MA MA _ MA MA MA MA MA FA FA 2.1 3.2 2.5 2.6 2.8 2.6 2.7 2.4 2.8 2.5 2.7 1.4 12 FA FA FA FA 1.3 1.2 1.1 1.0 1560 1564 / MA MA MA MA _ MA MA FA FA FA FA FA FA FA FA 1.8 2.5 2.6 2.5 2.7 2.2 2.5 2.6 1.2 1.0 1.1 1.2 1 I 1.2 1.1 1.0 / MA MA MA MA MA MA FA FA FA FA FA FA FA 1.8 2.5 2.5 2.6 2.3 2.5 2.9 1.2 1,0 1.0 1.0 1,2 1.1 1.2 1565 / MA MA MA MA MA MA FA FA FA FA FA FA 1.7 2.2 2.2 2.4 2.4 2.5 2.3 1.0 1.1 0.9 1.1 1,2 1.0 1566 / MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA 1.4 2.6 2.9 1.1 1.1 1.1 1.3 1.2 1.2 1.1 1.3 1.0 1.1 1.0 1.2 1.1 1568 / MA MA MA MA MA MA MA FA FA FA FA FA FA > 2.2 3.3 2.5 3.2 3.1 3,2 3.1 2.6 1.3 1.5 1.4 1,4 1.2 1.2 .................................................................................................................................... FIRST LETTER SECOND LETTER DISTANCES -- M-MALE, F-FEMALE, U-SEXUNDETE_INABLE -- A-ALiVE, S-STILLBO_, U-_CERTAIN, _ RECORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESUMED CANNIBALIZ'ED), X-MISSING; SACRIFICED WHEN FOUND IJ 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E45 (PAGE I0): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION REPRODUCTION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... PUP # I 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................. .................................................................. RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY DAY 1 POSTPARTUM ..... y .............................................................................................................................. 1571 / MA MA MA MA MA MA PA FA FA FA FA FA FA 1573 1576 1.8 2.6 2.5 2.3 2.5 2.8 2.6 1.4 1.3 1.2 1.2 1.4 1.1 1.2 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.9 2.7 2.8 2.6 2.4 3.2 2.8 2.8 1.2 1.3 1,0 1.2 1.1 i.i 1.2 1.1 / MA MA MA MA MA MA MA MA FA FA FA FA FA 1578 2.0 2.5 2.2 2.9 2.6 2.3 2.5 2.7 2.5 1.0 1.0 1.3 1.0 1.0 NOT PREGNANT 1579 1583 / MA MA MA MA 2.0 3.0 2.7 2.6 28 / MA MA MA MA 1.7 2.8 2.7 2.4 23 MA MA MA MA FA FA FA FA FA FA FA 2.9 2.8 2.8 2.9 1.1 1.0 1.1 1.1 1.1 1.0 1.0 MA FA FA FA FA FA FA FA 2.7 1.2 1.0 1.2 1.1 1.1 1.2 1.0 1584 2.5 / M2A.8 M3A.0 M2A.9 F1A 2 0% 1586 / MA MA MA MA MA MA MA FA FA FA FA FA FA "_ 1.9 2.5 2.6 2.4 2 6 2.7 2.6 2 5 1.2 1 0 1.2 I.i i.I i.I 1587 / MA MA MA MA MA FA FA FA FA FA FA 1588 1589 1591 1593 1.7 2.8 2.4 2.5 2 6 2.6 I.D 1.0 1.0 1.0 0.9 1.0 / MA MA MA MA FA FA FA FA FA FA FA FA FA 1.5 2.5 2.8 2.8 2 4 1.1 1.0 1.0 1.1 1.1 1.1 1.2 1.1 0.9 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1.7 2.5 2.5 2.5 2 6 2.6 2.4 1.2 1.0 1.1 1.0 1.0 1.2 1.2 1.4 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA 2.0 2.6 2.8 3.2 2 3 2.4 2.0 2.4 2.2 2.5 2.2 i.I 1.0 1.0 1.1 / MA MA FA FA FA FA 2.0 3.3 3.0 1.5 14 1.6 1.5 1598 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA 1.8 3.0 2.8 2.7 2 7 2.5 2.7 2.5 i.I 1.2 1.0 1.0 1.1 1.3 1.4 1.2 1.1 1.2 1600 / MA MA MA MA 2.2 2.5 2.6 2.6 24 MA MA MA 2.3 2.7 2.6 ............................................................................... FIRST LETTER SECOND LETTER ALL DISTANCES -- M-MALE, F-FEMALE, U-SEXUNDETERMINABLE -- A-ALIVE, S-STILLBORN, U-_CERTAIN, WERE RECORDED IN MILLIMETERS (MM). MA MA MA 2.8 2.6 2.9 MDI FA 1.1 FA FA FA 1.1 1.1 1.2 ..................................................... D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND O PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 11} : ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 Ii 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY .................................................................................................................................... DAY 22 POSTPARTUM 1302 / MA MA MA MA MA FA FA FA FA FA FA 11.2 13.6 13.5 14.5 15.1 15.2 8.5 7.9 8.7 8.1 9.1 8.8 1304 11.9 / MA 15.9 MA 15.2 MA 14.9 MA 14.5 MA 15.2 MA 13.2 FA FA FA FA 8.1 8.3 9.2 10.0 FA FA 9.0 9.5 1306 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 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 FA FA FA FA FA FA FA FA FA FA 9.0 12.8 12.0 11.9 11.8 12.7 11.6 7.8 6.6 6.4 7,0 7.9 6.2 7.8 6.8 7.6 7.3 1310 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA 11.7 14.6 13.3 13.0 13.4 13.4 14.3 12.9 13.3 13.8 8.6 8.0 8.2 8.6 8.7 i312 / MA MA FA FA 12.5 14.8 15.0 10.3 9.8 '_ 1313 / _ _ _ _ _ FA FA FA FA FA FA FA FD17 11.3 13.3 14.0 15.0 15.6 1G.o 9.1 9.3 9.9 7.1 8.1 9.1 9.2 (0% 1316 NOT PREGNANT t_ 1318 / MA MA MA MA MA MA MA MA MM2 FA FA FA FA FA FA 12.3 16.3 14.6 13.5 14 7 14.9 15.0 15.5 16.3 8.6 9.2 8.2 8.5 8.7 7.9 1321 / MA MA MA MA MA MA MA MMll FA FA FA FA FA FA FA FA FD10 9.8 13.6 13.9 12.8 13 7 12.0 12.6 11.8 7.0 7.1 6.8 7.2 6.9 7.2 7.6 6.6 1325 / MA MA MA MA MA FA FA FA FA FA FA 9.6 11.7 14.1 12.0 11 3 11.2 7.2 7.5 8.4 7.9 7.2 7.6 1328 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.7 14.6 15.1 12.9 14 1 14.4 15.3 14.2 7.8 9.8 8.1 8.6 8.6 8.4 1330 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 9.0 12.0 12.6 12.2 11 8 11.5 11.6 11.7 6.9 7.0 6.9 7.4 6.3 6.8 6.2 6.9 6.8 1331 / MA MA MA MA MA MA MA MA MA MA MA MMI2 FA FA FA FA 11.4 12.5 13.0 12.0 13 2 12.7 12.7 11.9 11.9 12.4 13.3 13.2 7.1 8.3 7.9 8.2 1334 / MA MA MA MA MA MA FA FA FA > 12.3 15.2 13.9 13.8 14.9 15.2 13.5 7.8 8.5 7.8 1335 / MA MA MA MA MA MA FA FA FA FA FA FA 11.5 15.6 14.2 14.6 13.0 14.2 14.0 9.0 8.3 8.8 8.6 8.3 9.1 1336 11.6 / MA 15.0 MA 14.0 MA 14.3 MA 14.9 MA 13.8 MA 14.5 MA 15.5 FA FA FA FA FA FA FA FA 9.2 8.7 9.2 9.4 8.7 8.2 9.4 9.1 1338 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FDI6 0 10.3 13.7 12.4 10.7 14.0 14.1 12.4 12.4 12.9 6.4 8.7 7.9 8.4 8.4 7.2 8.4 7.0 .................................................................................................................................... |_) FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE O SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISsING; SACRIFICED W}fEN FOUND ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM}. PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 12): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 .................................................................................................................................... 22 23 RAT # MEAN DOSAGE GROUP I 0 MG/KG/DAY ..................................................................................................................................... DAY 22 POSTPARTUM 1340 1341 1342 1344 1345 1346 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 12.2 13.2 13.1 15.5 14.9 15.4 13.3 15.6 15.2 8.6 9.9 8.9 8.7 9.0 9.0 / HA HA HA HA FA FA FA FA FA FA FA FA 11.4 16.0 15.9 15,6 16.0 9.0 9.9 9.4 10.2 8.6 9.4 8,1 9.0 / HA HA HA HA HA HA HA HA MA FA FA FA FA FA FA FA 11.6 14.4 15.2 15.1 15.0 14.0 15.8 14.5 13.8 12.6 8.5 8,1 9.0 7.5 6.8 7.8 8.4 / HA MA MA MA HA MA MA FA FA FA FA FA FA FA FA 10.9 15.2 14.7 14,5 14.6 13.2 13.2 13.5 8.0 7.2 8.4 7.5 9.3 8.0 8.4 8.0 10.8 / HA 15.6 MA 15.4 MA 14.6 HA 15.1 MD4 MS FA FA FA FA FA FA FA FA FA FS 8.5 9.4 8.6 9.3 8.2 9.2 9.1 8.8 8.3 / MA HA MA HA MA MA FA FA FA FA 11.6 13.6 13.0 14.4 14.0 14.5 14.1 8.5 7.5 9.2 7.4 1348 11.2 /13H.A3 14M.A1 14M.A6 13H.A2 14H.A3 13H.A4 MS 14H.A2 14H.A7 F7A.7 F7A.9 F7A.2 F8A.8 F7A.2 F6A.9 FS (_ 1350 / HA HA HA HA MA HA MA MA HA MA HA MA MA FA FA FA FA "_ 10.5 12.8 11.6 12.2 12.7 11.5 12.5 11.1 9.8 10.9 12.8 11.4 11.3 12.2 6.3 6.2 6.3 7.7 4_ 1353 / HA HA HA HA MA MA FA FA FA FA FA FA FA FU 10.6 14.9 13.9 13.0 12.5 13.5 13.3 7.9 8.0 8.6 7.9 7.7 8.7 8.6 1355 10.4 / HA 14.6 HA 15.2 HA 14.6 HA 15.1 FA FA FA FA FA FA FA FA FA FA FA 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 HA MA MA FA FA FA FA FA FA FA FA FS 10.8 14.4 14.5 13.3 14.9 13.6 8.5 8.5 9.0 8.6 9.2 7.8 8.8 8.8 .................................................................................................................................... FIRST LETTER SECOND LETTER ALL DISTANCES -- M-HALE, F-FEMALE, U-SEX UNDETERMINABLE -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, WERE RECORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND > CD C _n G_ o PROTOCOL 418-020: ORAL (GAVAGE} TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 13): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 11 12 13 14 15 16 17 18 19 20 21 22 23 ............................................................................................................................... RAT # MEAN DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... DAY 22 POSTPARTUM 1362 1363 1364 1367 1368 1371 / MA HA HA HA FA FA FA 11.9 14.4 14.9 14 7 13.6 8.8 8.5 8.5 / HA HA HA HA HA HA HA FA FA FA FA FA FA FA FA FA FD4 FS 10.4 13.1 13.5 12 9 15.6 12.7 13.5 12.6 8.7 8.9 8.3 8 1 7.8 8.3 7.6 8.7 6.9 / HA HA MA HA MA HA MA FA FA FA FA FA FA FA FA 10.4 14.1 14.0 13 1 13.3 12.5 13.5 13.0 7.6 8.7 8.1 8 1 7.2 7.7 7.9 7.5 / MA HA MA HA HA HA HA HA FA FA FA FA FA 11.6 13.3 13.5 13 7 14.4 14.3 14.4 13.4 13.3 8.8 8.5 7 6 8.2 7.6 / MA HA HA HA HA HA HA MA FA FA FA FA FA FA FA 11.5 15.4 13.G 13 5 14.9 15.3 13.4 14.0 14.1 8,6 8.1 8 3 8.7 9.2 7.7 8.3 / MA HA HA MA MA HA MA HA HA MA HA FA FA FA FA FA FD9 11.2 13.3 12.5 13 6 13.0 13.3 12.1 12.2 12.7 11.3 13.6 11 9 7.7 8.1 7.4 8.9 7.8 1375 1376 1378 / MA MA MA HA HA HA HA HA MA FA FA FA FA FD17 12.2 15.4 14.1 13.0 14.6 14.3 14.6 14.3 13.2 13.8 8.9 7 9 6.4 8.6 / MA HA HA HA HA HA HA MA HA MA MS MS FA FA FA FA FA 11.5 13.0 12.9 13.9 12.7 13.5 13.0 12.4 12.9 13.6 12.6 7.8 8.3 8.7 8.9 8.5 NOT PREGNANT 1379 10.5 / MA 12.6 HA 14.1 HA 12.6 HA 13.4 HA 13.2 HA 13.7 FA FA FA FA FA FA 7.8 7.9 6.8 8.3 8.0 7.4 1381 12.3 / MA 16.1 HA 15.4 HA 15.0 HA 15.2 HA 16.0 HA 16.1 FA FA FA FA FA FA 8.1 9.2 9.7 9.4 8.6 9.0 1382 / HA HA HA HA HA FA FA FA FA FA FA FA FA 10.7 14.5 13.5 14.3 13.8 14.9 9.2 8.4 8.4 8.8 8.0 8.3 8.6 8.8 1383 11.9 / HA 14.7 HA 15.2 MA 15.5 HA 14.1 HA 13.8 HA 14.9 FA FA FA FA FA 8.5 7.6 8.5 9.4 9.0 1384 / MA HA MA HA MA MM4 FA FA FA FA FA FA FA 10.6 14.2 14.2 15.0 14.6 13.0 8.3 7.7 8.0 7.2 7.4 9.0 8.0 1387 / HA HA MA HA HA HA HA MA HA FA FA FA FA FA FA FA FS > 11.3 13.7 13.6 13.4 12.9 13.0 14.3 13.1 14.7 14.3 8.5 8.5 8.3 8.1 8.1 8.7 8.2 1389 / HA HA HA MA HA HA HA MD7 FA FA FA FA FA FA FA FA i0.0 12.2 13.0 13.9 13.0 15.1 13.4 11.5 7.7 7.0 7.3 7.8 6.8 7.1 8.0 6.8 1392 / HA HA HA HA HA HA HA MA HA FA FA FA FA FA FA FA FA _'_ 9.6 10.8 11.6 11.8 11.8 11.8 11.6 11,3 12.5 12.4 7.5 7.4 7.2 7.2 7.8 7.0 7.0 6.5 4_ 1393 / MA HA HA HA MA MS FA FA FA FA FA FA O_ 11.3 14.7 15.0 14.8 15.5 15.4 8.0 8.1 7.6 9.0 8.1 8.3 _D .................................................................................................................................... |,_ FIRST LETTER SECOND LETTER DISTANCES -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, WERE RECORDED IN MILLIMETERS (MM} . D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISsING; SACRIFICED WHEN FOUND _._ (_ -,_ (_% PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 14): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 i0 Ii 12 13 14 15 16 17 18 .................................................................................................................................... RAT # MEAN DOSAGE GROUP II 1 MG/KG/DAY .................................................................................................................................... 1397 1399 1401 1404 1407 1409 13.2 12.1 10.9 11.6 10.4 / MA 16_0 / MA 16.5 / MA 14.0 / MA 13.5 / MA 12.0 / MA MA 15.0 MA 16.6 MA 15.0 MA 12.1 MA 13.3 MA MA 15.6 MA 17.1 MA 13.4 MA 12.8 MA 12.9 MA MA 15.5 MA 14.4 MA 15.7 MA 13.4 MA 13.1 MA MA 16.3 FA 9.7 MA 14.6 MA 12.1 MA 12.1 MA MA 16.9 FA 9.8 FA 8.4 HA 13.6 MA 13.5 MA MA 15.6 FA 9.3 FA 8.4 MA 13.6 MA 12.2 MA FA 9.9 FA 9.4 FA B.0 MA 15.0 FA 8.7 FA FA 9.6 FA 9.0 FA 7.2 MA 13.0 FA 7.7 FA FA 9.7 FA 9.6 FA 8.8 MA 13.5 FA 8.8 FA FA 9.1 FA 8.5 MA 8.7 FA 8.4 FA FA 9.3 FA 9.2 FA 8.2 FA 8.7 FA FA 9.2 FA 8.1 FA 7.2 FA 8.3 DAY 22 POSTPARTUM FA 8.4 FA 8.8 13.3 16.8 15.9 16.6 15.0 15.5 16.3 15.8 8.9 9.8 9.4 9.6 10.0 1410 / MA MA MA MA MA MA MA MA MA MA MA MA MA FA FA FA FM5 12.9 14.8 14.1 13.3 14.8 13.8 14.2 14.0 16.2 13.0 13.9 13.0 13.8 14.4 7.9 8.0 7.9 1413 / MA MA MA MA MA MA MA 11.7 14.8 13.8 14.3 12.2 15.3 13.8 14.5 FA FA FA FA FA FA 8.8 8.0 8.1 9.4 9.3 9.3 1415 10.2 / MA 12.5 MA 12.7 MA 12.6 MA 11.9 MA 12.7 MA 12.2 MA 11.5 FA FA FA FA FA FA 8.0 6.8 8.0 8.5 7.3 7.7 1416 / MA MA MA FA FA FA FA FA FA FA FA FA FA FA 9.1 14.4 12.8 13.0 8.1 8.1 8.0 7.3 8.1 7.6 8.5 7.9 8.0 8.0 7.8 1418 / MA MA MA MA MA MA FA FA FA FA FA FA FA FMI4 FD3 FM3 10.4 13.6 15.5 13.6 11.5 15.4 13.0 8.8 8.2 7.8 7.3 7.1 6.1 7.6 .................................................................................................................................... FIRST LETTER SECOND LETTER ALL DISTANCES -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, WERE RECORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; 19 20 SACRIFICED 21 22 23 WHEN FOUND > /, OO cb IJ PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E45 (PAGE 15): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION REPRODUCTION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP III 3 MG/KG/DAY DAY 22 POSTPARTUM 1421 MA MA MA MA MA MA MA MA MA FA FA FA FA FA FDI FDI 10.5 11.9 12.8 11.4 12.5 11.9 12.3 11.6 11.8 11.7 12.5 8.1 6.7 8.3 7.0 7.5 1424 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 1426 9.0 10.6 / MA 10.6 MA 11.2 MA 12.5 MA 10.8 MA 10.9 MA 12.0 MA 10.1 FA 10.2 FA 6.6 6.5 6.7 6.6 6.8 FA FA FA FA 7.4 7.1 6.7 10.4 11.3 12.6 12.5 14.4 12.6 13.4 12.3 7.6 6.9 8.4 7.1 8.7 7.7 1428 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 10.6 13.814.613.314.715.012.6 7.8 8.8 8.2 7.8 8.6 7.7 8.8 8.6 8.6 1430 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 9.5 13.313.213.812.811.913.6 6.7 8.6 8.4 7.4 6.9 6.7 8.9 7.7 6.5 7.7 7.3 1431 / MA MA MA MA MA MA MA MA MA MD1 FA FA FA FA FA FM2 12.8 i433 11.4 16.2 / 14M.A6 14.8 14M.A4 15.2 13M.A3 15.0 13M.A8 14.9 13M.A1 15.4 13M.A8 16.5 13M.A5 14.9 12M.A7 13.9 1M4A.1 13M.A1 7.9 7.8 9.4 9.1 8,7 F8A.0 F8A.6 F9A.0 F8A.7 F8A.2 F7A.5 F8A.3 FD8 1436 / MA MA MA MA MA MA MA MA FA FA FA FA 11.7 12.5 13.4 13.9 12.7 13.6 13.3 12.4 13.5 8.8 8.8 8.4 8.7 1437 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.6 13.313.512.113.214.312.913.713.012.7 6.6 8.0 8.8 6.8 6.4 6.2 8.6 1439 / MA MA MA MA MA MA FA FA FA FDI FS FS 13.9 15.4 15.8 16.7 15.8 16.3 14.9 10.6 9.9 9.5 1442 / MA MA MA MA FA FA FA 13.0 17.0 15.4 15.6 14.2 10.7 9.0 9.0 1443 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA 11.4 13.8 14.6 14.2 13.9 14.3 13.1 15.1 12.0 7.5 8.6 7.4 8.9 8.7 8.0 1446 NOT PREGNANT 1448 / MA MA MA MA MA MA MS MS FA FA FA FA FA FA FA FA 10.2 13.813.514.513.113.712.8 7.1 8.8 8.1 7.6 8.3 6.8 8.1 7.0 1450 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA > 9.3 12.812.112.413.6 7.9 8.4 8.1 7.7 7.3 7.7 8.8 8.2 7.4 7.4 1452 / MA MA MA MA MA MA MA MA FA FA FA FA FA FM2 10.6 10.9 11.6 12.4 12.9 11.8 12.5 12.6 11.6 9.4 8.0 8.5 7.9 7.2 1455 / MA MA MA MA MA MM6 MD5 MM3 FA FA FA FA FA FM6 FD6 (29 10.9 13.5 13.8 13.8 14.6 12.7 8.0 8.6 7.9 7.8 8.3 1456 / MA MA MA MA FA FA C_ 12.2 12.6 12.3 14.2 15.9 9.1 9.4 .................................................................................................................................... _ FIRST LETTER -- M-MALE, F-FEMALE, U-SEXUNDETERMINABLE O SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND DISTANCES WERERECORDED IN MILLIMETERS (MM). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 16): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS 4 .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP Ill 3 MG/KG/DAY .................................................................................................................................... 1458 NOT PREGNANT DAY 22 POSTPARTUM 1459 12.1 / MA 13.6 MA 14.7 MA 14.7 MA MA 15 0 14.1 MA 14.3 MA 15.9 MA 14.0 MD2 FA 10.0 FA FA FA FA 9.0 7.7 7.0 7.0 1461 12.1 / MA 15.1 MA 15.5 MA 15.8 MA FA 14 6 10.0 FA 10.4 FA 10.2 FA 10.1 FA 10.1 FA 10.2 FA 10.9 1463 / MA MA MA MA MA MA MA MS 10.8 13.4 14.1 12.4 13 2 13.6 13.5 14.0 FA FA FA FA FA FA FS 8.4 8.0 7.3 7.1 8.2 7.3 1465 11.1 / MA 14.1 MA 16.1 MA 14.5 MA MA 15 4 14.0 MA 15.5 FA FA FA FA FA FA FA FA FA FA 9.3 9.5 9.0 8.0 8.8 8.7 8.7 8.5 8.5 9.3 1468 / MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA 9.2 12.7 13.3 11.4 12 7 13.4 6.3 8.5 8.3 7.7 8.6 7.7 7.9 7.2 7.5 6.1 7.5 _D 1469 / MA MA MA MA MA MA MA MA MA FA FA FA (_ 11.8 13.8 13.2 14.2 12 6 12.0 12.4 11.6 12.6 13.0 8.6 8.3 9.0 <_% 1472 / MA MA MA MA MA FA FA FA FA FA OO 12.4 14.6 16.1 15.0 14 5 15.1 9.8 10.2 9.7 8.3 11.2 1474a 1476 / MA MA MA MA MA MA MA MD1 FA FA 9.9 11.9 13.6 12.9 11.3 13.3 12.4 12.0 8.6 8.0 1477 / MA MA MA MA MA MA MA MA FA FA 9.6 14.3 12.9 10.3 9.2 11.3 11.8 12.6 10.2 7.2 7.3 1480 i0.I / MA 14.1 MA 14.4 MA 16.0 FA FA FA FA FA FA FA 8.8 9.1 8.8 8.7 7.9 7.6 8.4 .................................................................................................................................... FA 7.7 FA 7.4 FA 9.0 FA 8.0 FA 7.7 FA 9.1 FA 7.7 FA 8.3 FA 9.0 FA 8.7 FA 8.0 FA 8.2 FA 6.5 FIRST LETTER SECOND LETTER ALL DISTANCES -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, WERE RECORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESUMED CANNIBALIZED), a. Anogenital distances for litter 1474 were not recorded. FA FA 7.0 7.1 FA FD6 8.3 X-MISSING; SACRIFICED WHEN FOUND U9 4_ d:, 0 PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6} REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 17): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP IV 10 MG/KG/DAY .................................................................................................................................... DAY 22 POSTPARTUM 1482 1483 10.4 / MA 13.4 NOT MA MA 12.6 12.9 PREGNANT MA 13.4 MA 14.4 MA 12.6 FA FA FA FA FA FA FA FA FD1 FS 8.0 8.9 9.1 7.8 8.5 7.8 8.6 7.3 1486 1488 1490 1491 1494 1496 1497 1500 1502 1505 1507 1508 1511 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 11.5 13.3 12.2 14.8 13.2 14.9 12.8 14.1 13.6 12.4 8.9 8.2 7.9 8.9 9.1 8.4 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 12.7 15.2 / MA 15.5 MA 15.0 MA 16.8 MA 16.6 MA 15.1 MA 16.9 MA 12.6 FA 9.6 9.4 10.0 FA FA 8.7 9.4 10.0 10.4 14.4 16.1 15.4 15.5 17.7 17.6 16.6 17.3 9.5 9.3 8.6 / MA MA MA MA FA FA FA FA FA FA FA FA FA FA UU 9.4 13.9 13.8 12.1 12.2 7.5 8.3 8.4 7.7 8.1 8.5 7.8 8.8 7.7 6.9 / MA MA MA MA MA MA MA MA MDI FA FA FA FA FA 11.9 14.6 13.0 14.9 13 7 15.8 14.1 14.1 12.7 8.5 8.3 8.8 7.0 8.8 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.0 13.8 13.6 12.9 13 6 15.1 13.9 12.8 8.5 7.8 7.1 8,3 8.4 7.2 / MA MA MA MA FA FA FA FA FA FA FA 11.3 12.9 14.7 14.6 16 3 9.2 9.9 i0.0 9.5 9.3 8.7 9,0 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FS 11.9 12.5 13.3 14.3 13 8 13.7 15.0 13.1 14.4 14.8 9.0 8.1 8.3 8.1 7.8 / MA MA MA MA FA FA FA FA FA FA FA FA FD2 11.0 14.7 15.7 16.2 16 0 8.9 7.5 9.4 9.3 9.2 7.5 8.1 8.9 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA 9.1 11.0 12.6 11.5 9 0 11.0 12.0 11.3 7.7 7.8 6.2 8.3 7.6 7.2 7.7 7.7 6.6 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.2 12.9 12.3 11.7 12 4 13.4 11.9 12.5 12.0 11.6 7.5 7.9 8.0 7.3 8.3 7.0 7.2 / MA MA MA MA FA FA FA FA FA FA FA FA FD2 9.9 12.7 14.3 13.0 14 4 8.2 8.5 7.4 8.2 7.9 9.0 7.9 7.7 NOT PREGNANT 1513 / MA MA MA MA MA MA MA MA MA FA FA FA FA MS C) 11.9 12.5 13,7 14.3 13.3 13.7 13.6 13.0 13.5 14.0 7.0 8.8 8.7 8.5 1514 / MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA FDI2 _') 11.3 14.8 15.0 13.8 14.0 13.1 14.4 13.6 13.3 12.0 7.3 8.6 8.5 9.1 7.4 8.1 7.5 1516 / MA MA MA MA MA MA MA MA MA FA FA FA FA OO 12.3 13.4 14.5 13.0 14.3 13.9 15.2 14.4 13.4 14.6 7.8 8.7 9.0 8.3 .................................................................................................................................... |_) FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE O SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND DISTANCES WERE RECORDED IN MILLIMETERS (MM). PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS {SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E4S {PAGE 18): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP IV i0 MG/KG/DAY .................................................................................................................................... DAY 22 POSTPARTUM 1517 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 9.6 12.4 11.7 11.8 11.6 12.9 11.5 10.9 10.6 7.2 6.9 8.0 7.0 7.2 6.9 6.9 1519 10.6 / MA 13.7 MA 14.5 MA 13.5 MA 14.1 MA 11.8 MA 14.2 MA 13.6 MA 13.4 FA FA FA FA FA FA FA FD18 8.0 6.3 8.0 7.1 7.0 8.2 6.4 lS 21 11.0 / MA 12.7 MA 13.0 MA 14.0 MA 13.6 MA 12.0 MA 13.0 MA 12.5 FA FA FA FA FA 8.8 8.6 8.3 7.7 8.4 1523 / MA MA MA MA MA MA MA MD1 FA FA FA FA 12.4 14.8 14.9 15.2 14.3 12.1 15.0 15.5 9.4 8.4 8.0 8.8 1524 17.5 / MA 18.4 MA 16.6 1527 / MA MA MA MA MA MA MA MA MA MA MM5 FA FA FA FA FA FA 9.2 ii.i 11.3 10.8 12.4 11.3 11.6 11.6 12.7 i0.0 9.2 6.5 6.8 5.5 5.1 6.4 5.7 1528 11.6 / 14M.A4 14M.A1 15M.A0 14M.A0 13M.A5 13M.A1 F8A.2 F7A.8 F8A.2 F8A.0 0O%O 1531 / MA MA MA MA MA MA MA MA MS FA FA FA FA FA FS O 11.8 13.3 14.4 15.0 14.8 13.4 12.9 13.7 13.9 9.3 8.3 9.0 5.9 9.2 1533 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA FA FA FA FM6 FD1 9.9 13.7 14.6 13.8 11.0 12.9 12.0 8.6 8.0 8.0 6.9 9.1 8.1 8.9 7.3 7.5 8.6 9.0 1534 / MA MA MA MA MA MA FA FA FA FA FA FA 10.2 12.6 12.7 14.4 12.7 12.7 12.4 8.0 7.1 7.3 7.5 7.9 7.5 1537 10.6 / MA 11.8 MA 12.0 MA 12.1 MA 11.6 MA 12.9 MA 13.4 MA 10.5 MA 12.0 MA 11.6 MA 12.4 FA FA FA FA FS 7.5 7.3 7.7 6.1 1539 12.0 / MA 14.8 MA 14.0 MA 14.9 MA 14.1 MA 13.6 MA 14.3 MA 15.2 MA 13.3 MA 13.1 FA FA FA FA FA 8.1 8.1 7.9 8.3 8.9 .................................................................................................................................... FIRST LETTER SECOND LETTER ALL DISTANCES -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, WERE RECORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESUMED CANNIBALIZED), X-MISSING; SACRIFICED WHEN FOUND > CD C cn oo IJ o PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE TABLE E45 (PAGE 19}: ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION PUPS .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 .................................................................................................................................... RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY DAY 22 POSTPARTUM .................................................................................................................................... 1541 1544 1545 1546 1548 1550 / MA HA MA MA FA FA FA FA FA FA FA FA FA FA 9.7 12.4 13.9 13.8 _3.6 9.0 8.0 7.8 8.3 8.3 8.1 8.1 7.8 8.2 8.8 11.4 / MA 14.6 MA 12.4 MA 13.9 MA 16.0 MA 12.5 MA 15.0 FA FA FA FA FA FA FM2 FS 9.1 8.9 8.3 8.7 9.1 8.7 / MA MA MA HA MA HA MA MA MA FA FA FA FA FA FA FA FA FDI6 FD3 9.8 12.0 11.8 12.7 11.4 14.3 12.8 12.3 10.6 10.0 7.6 7.8 7.0 7.6 6.8 8.2 6.3 7.3 / HA MA MA MA MA MA MA HA FA FA FA FA FA FA FA 9.6 12.4 11.7 12.3 11.8 12.6 12.2 12.3 10.8 7.3 7.1 7.2 6.8 6.6 6.3 6.9 / MA HA MA HA FA FA FA FA FA FA FA FA FA FS 9.6 12.3 14.5 13.3 13 9 7.8 8.1 8 1 8.6 7.7 7.9 7.5 7.2 8.3 / HA MA MA MA MA FA FA FA FA FA FA FA 10.5 13.413.114.414014.0 9.3 86 8.6 71 8.7 7.4 7.9 1552 / MA MA MA MA MA HA MA FA FA FA FA FA FA FA 10.2 13.0 13.2 13.4 13 4 12.6 11.6 12 0 7.9 7 7 8.1 7.7 6.8 7.9 6.8 (_ 1555 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FD6 Oo 9.5 11.5 12.3 11.8 11 7 11.6 12.2 12 5 7.3 7 1 6.7 7.6 7.2 7.0 6.2 1557 / MA MA HA MA MA FA FA FA FA FA FA FA FA 10.3 14.0 13.8 13.1 13 5 12.7 8.6 8 3 8.2 8 0 8.3 8.0 8.7 9.2 1558 / MA MA MA MA MA MA MA MA MA MA FA FA FA FA FA FA 11.4 13.1 13.8 14.4 13 4 12.9 14.2 13 4 13.9 12 5 14.2 9.0 8.1 7.2 8.7 7.1 7.0 1560 / MA MA MA MA MA MA MD7 FA FA FA FA FA FA FA FA 9.2 12.6 11.7 12.0 11.8 12.5 11.8 7.0 8 0 6.4 7.0 8.8 6.3 6.3 6.0 1564 10.3 / MA 13.1 MA 13.0 MA 13.3 MA 12.4 MA 13.0 MA 13.3 FA FA FA FA FA FA FA 8.1 7.2 8.1 7.9 8.3 8.2 7.5 1565 / HA HA MA MA MA MA FA FA FA FA FA FA 11.8 14.914.014.214.513.814.9 9.6 9.4 8.5 9.1 9.1 9.4 1566 / MA MA FA FA FA FA FA FA FA FA FA FA FA FA FA 8.3 13.112.2 8.1 7..9 7.4 7.5 7.8 7.2 7.4 8.2 8.3 7.1 7.8 8.3 6.9 1568 / MA MA MA MA MA MA MA FA FA FA FA FA FA > 11.9 14.315.014.713.014.215.614.2 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 (2_ ALL DISTANCES WERE RECORDED IN MILLIMETERS (MM). IO PROTOCOL 418-020: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER (APFO) IN RATS (SPONSOR'S STUDY NUMBER: PER GENERATION) T-6889.6) TABLE E45 (PAGE 20): ANOGENITAL DISTANCE - INDIVIDUAL DATA - F2 GENERATION REPRODUCTION PUPS STUDY OF AMMONIUM PERFLUOROOCTANOATE .................................................................................................................................... PUP # 1 2 3 4 5 6 7 8 9 I0 11 12 13 14 15 16 17 18 19 20 21 22 23 r .............................................................................................................................. RAT # MEAN DOSAGE GROUP V 30 MG/KG/DAY r .............................................................................................................................. 1571 / MA MA MA MA MA MA FA FA FA FA FA 9.7 12.2 11.9 13.4 11.6 13.0 12.5 7.2 8.0 7.0 7.9 6.8 FA 6.7 FA 7.7 DAY 22 POSTPARTUM 1573 11.0 / MA 15.1 MA 13.3 MA 13.6 MA 14.4 MA 14.3 MA 14.8 MA 13.3 FA FA FA FA FA FA FA FA 8.5 7.3 8.1 8.7 8.1 8.2 9.2 8.7 1576 1578 10.2 / MA 12.0 NOT MA MA 12.4 13.0 PREGNANT MA 11.7 MA 12.4 MA 12.0 MM8 MD7 FA FA FA FA FA 7.0 7.4 8.5 8.2 7.5 1579 1583 / MA MA MA MA MA MA MA MA FA FA FA FA FA FA FA 10.5 14.0 12.7 14.5 13.0 12.8 13.7 11.5 13.6 8.2 7.1 7.4 7.5 8.1 5.9 7.3 / MA MA MA MA MM3 FA FA FA FA FA FA FA 10.7 14.0 14.1 14.6 14.7 8.4 9.0 8.8 8.8 9.0 8.5 8.0 1584 16,3 / 18M.A4 17M.A9 18M.A9 10F.A1 1586 / MA MA MA MA MA MA MA FA FA FA FA FA FA 11.4 13.7 15.0 12.4 13.3 12.9 14.9 12.3 8.2 8.4 8.8 9.1 9.4 9.3 1587 / MA MA MA MA MA FA FA FA FA FA FA 10,7 14.0 13.9 14.1 12.8 12.2 9.5 8.9 9.0 8.3 7.6 7.8 1588 I0.I / MA 12.9 MA 13.5 MA 13.9 MA 12.5 FA FA FA FA FA FA FA FA FA 9.3 8.6 7.9 9.2 8.4 8.0 8.9 9.0 8.7 1589 / MA MA MA MA MA MA FA FA FA FA FA FA FA FA 9.0 11.0 11.2 11.8 11.2 12.4 12.0 8.1 7.0 6.7 7.6 6.9 7.0 6.4 6.3 1591 11.6 / MA 12.5 MA 13.2 MA 13.2 MA 13.2 MA 14.6 MA 13.0 MA 12.1 MA 12.7 MA 13.4 MA 12.3 FA FA FA FA 8.0 6.9 7.7 9.0 1593 / MA MA FA FA FA FA 11.3 15.2 15.0 9.8 8.6 9.3 9.8 1598 / MA MA MA MA MA MA MA FA FA FA FA FA FA FA FA 8.7 11.8 11.5 10.7 12.0 11.6 11.6 11.8 5.9 7.4 7.6 6.6 6.6 6.8 7.2 5.9 i600 11.2 / MA 13.6 MA 13.4 MA 14.0 MA 13.8 MA 12.8 MA 12.7 MA 12.2 MA 12.2 MA 11.3 MA 12.1 MDI FA FA FA FA 8.2 7.1 6.6 6.9 ..................................................................................................... FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER DISTANCES -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, WERE RECORDED IN MILLIMETERS (MM). D-DIED, M-MISSING (PRESUMED CANNIBALIZED), FA FA 7.0 5.9 - .............................. X-MISSING; SACRIFICED WHEN FOUND > _'_ [29 /-_ OO _b ARGUS 418-020 APPENDIX F PROTOCOL AND AMENDMENTS Page 683 ARGUS 418-020 .arguRsesearchLaboraloncsI.nc. Telephone:(215_443-87I0 Telefaxf:215)443-8587 PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 STUDY TITLE: Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO) in Rats PURPOSE: TESTING FACILITY: The purpose of this study is to provide information concerning the effects of Ammonium Perfluorooctanoate (APFO) on the male and female reproductivesystems in CrI: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. The study is also designed to provide informationabout effects on neonatal morbidity, mortality and preliminarydata on potential prenatal developmental toxicity,as well as to serve as a guide for use in the design of subsequent tests. For further information on functional deficiencies and development, additional study segments can be incorporated into the protocolbased on the guidelines for developmental toxicityand developmental neurotoxicity. Argus Research Laboratories, Inc. 905 Sheehy Dnve, BuildingA Horsham, Pennsylvania 19044-1297 Telephone: (215) 443-8710 Telefax: (215) 443-8587 STUDY DIRECTOR: Raymond G. York, Ph.D., DABT Associate Director of Research raymond.york @primedica.com SPONSOR: 3M Corporate Toxicology 3M Center, Building220-2E-02 St. Paul, Minnesota 55144-1000 Page 684 ARGUS 418-020 STUDY MONITOR: John Butenhoff, Ph.D., DABT, CIH 3M Corporate Toxicology 3M Medical Department Telephone: (651) 733-1962 Telefax: (651) 733-1773 REGULATORY CITATIONS: Protoco4l18-020 Page2 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. U.S. Environmental Protection Agency. Federal Insecticide, Fungicideand Rodenticide Act/Toxic Substances Control Act (FIFRNTSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160/Part 792. Organization for Economic Cooperation and Development (1998). The Revised OEGD Principles of Good Laboratory Practices [C(97)186/Final]. REGULATORY COMPLIANCE: This study will be conducted in compliance with the Good Laboratory Practice (GLP) regulationscited above. All changes or revisionsof this protocolshall be documented, signed by the Study Director and the Sponsor, dated and maintained withthe protocol. The Testing Facility's Quality Assurance Unit (QAU) will audit the protocol,the raw data and the report, and will inspect critical phases of those portions of the study conducted at the Testing Facility in accordance with the Standard Operating Procedures of Argus Research Laboratones, Inc. Should any portion of the study be conducted by a subcontractoror by the Sponsor, the QAU for that facility will conduct criticalphase inspectionsand audit respective results and reports for that study portion according to the SOPs of that facility. Such critical phase inspection reports and report audits will be submitted by that facilityto the Study Director. The dates of the inspections and report submissionswill be incorporated into a QAU Statement generated by that facility and provided to the Testing Facilityfor inclusionin the final report. The final report will include a compliance statement signed by the Study Directorthat the report accurately reflects the raw data obtained during the performance of the study Page 685 ARGUS 418020 Protocol418-020 Page 3 and that all applicable GLP regulations were followed in the conduct of the study. Should significantdeviations from GLP regulationsoccur, each will be described in detail, together with how the deviation mightaffect the quality or integrityof 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. The Sponsor will provide to the Testing Facility documentation or certification of the identity, composition,method of synthesis, strengthand purity of the test substance. Vehicle: Reverse Osmosis Membrane Processed Deionized Water (R.O. deionized water). Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the vehicle that would interfere with the resultsof this study. Therefore, no analyses other than those mentioned in this protocolwill be conducted. Safety Precautions: Gloves, dust-mist/HEPA-filtered mask, appropriate eye protection and uniform/lab coat to be worn during formulation preparation and dosage. In addition, Tyvek sleeves and a half-face respirator will be worn and preparation will be conducted in a chemical fume hood when using the bulk test substance. The Material Safety Data Sheet (MSDS) is attached to the protocol(ATTACHMENT 2). Storaqe: Bulk Test Substance: Vehicle: Prepared Formulations: Room temperature. Room temperature. Refrigerated, protected from light. All test substance shipments should be addressed to the attention of Julian Gulbinski, Manager of Formulations, at the previouslycited Testing Facilityaddress and telephone number. Shipments should include information concerningstorage conditionsand shipping Page 686 ARGUS 418-020 Protoco4l18-020 Page4 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). Adiustment for Purity: The test substance will be considered 100% pure for the purpose of dosage calculations. Testing Facility Reserve Samples: The Testing Facilitywill reserve a 1 g sample of each lot of bulk test substance and a 5 mL sample of vehicle used during the course of the study. Samples will be stored under the previouslycited conditions. ANALYSES: Results of requiredanalyses will be providedto the Testing Facility for inclusion in the study report. Samples additionalto 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 418-020 Page 5 This sample will be sent to: Kris J. Hansen, Ph.D. 3M EnvironmentalTechnology & Safety Services 935 Bush Avenue Building2-3E-09 St. Paul, Minnesota 55133-3331 Telephone: (651) 778-6018 Telefax: (651) 778-6176 The recipient will be notified in advance of sample shipment. Analyses of Prepared Formulations: Concentration: Concentration of the prepared formulationswill be verified during the course of this study. Duplicate samples will be taken from each concentrationon the first and last days of preparation. One sample of each duplicateset will be shipped for analysis;the remaining samples will be retained as backup samples. Backup samples will be stored under the previouslycited conditions and discarded at the Testing Facilityupon 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 concentrationwill 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 previouslycited conditions and discarded at the Testing Facility upon the request of the Sponsor. Shippin,q Instructions: Samples to be analyzed will be shipped (on cold packs, protected from light) to Kris J. Hansen, Ph.D., at the previouslycited address. The recipient will be notified in advance of sample shipment. Page 688 ARGUS 418-020 DISPOSITION: Protocol418-020 Page 6 Prepared formulationswill be discarded at the Testing Facility. All remaining bulk test substance will be retumed to: Nelda Marecki, Ph.D. 3M SMMG EHS&R 3M Center Building 236-1B-10 St. Paul, MN 55144-1000 TEST SYSTEM: Species/Strain and Reason for Selection: The Cd:CD_(SD)IGS BR VAF/Plus_ rat was selected as the Test System because: 1) this strain of rat has been demonstrated to be sensitiveto reproductiveand developmental toxins and has been widely used throughoutindustry for reproductive and developmental toxicityevaluations; 2) histoncaldata and experience exist at the Testing Facility(l"a);and 3) the test article is pharmacologicallyactive in the species and strain. Number: P Generation: Initial population acclimated: 165 virginmale rats and 165 virginfemale rats. Population selected for study: 150 virginmale rats and 150 virginfemale rats (30 per sex per group). F1 Generation: 150 male rats and 150 female rats, 30 rats per sex per group, will be selected for continued evaluation. An attempt will be made to select F1 generation rats to avoid over-representation of any P generation parental pair into the 1=2generation. Body Weiqht and A,qe: 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 claysof 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. Source: P Generation: Charles River Laboratories, Inc. Protoco4l18-020 Page7 The rats will be shipped in filtered cartons by air freight and/or truck from Charles River Laboratories, inc., to the Testing Facility. F1 and F2 Generations: Offspring will be delivered at the Testing Facility by the pregnant P or F1 generation clamsin this study. Identification: P Generation: Rats are permanently identified using Monel_ self-pieming ear tags (Gey Band and Tag Co., Inc., No. MSPT 20101 ). Male and female rats will be assigned temporary numbers at receipt and given unique permanent identificationnumbers when assigned to the study before administrationof the first dosage of the test substance. F1 and F2 Generations: Pups will not be individually identified during the postpartum period; all parameters will be evaluated in terms of the litter. At weaning, each F1 generation rat selected for continued observationwill be identified with a Monel_ self-piercing ear tag. ANIMAL HUSBANDRY: All cage sizes and housing conditions are in compliance withthe Guide for the Care and Use of Laboratory Animals (4). Page 690 ARGUS 418-020 Housin,q: P Generation Rats/F1 Generation Litters: Protoco4l18-020 Page8 P generation rats will be individually housed in stainless steel, wire-bottomed cages except dunng the cohabitation and postpartum periods. During cohabitation, each pair of rats will be housed in the male rat's cage. Beginning no later than day 20 of presumed gestation, female rats will be individuallyhoused in nesting boxes. Each clamand delivered litter will be housed in a common nestingbox during the postpartum period. F1 Generation RatslF2 Generation Litters: After weaning, the F1 generation rats will be individuallyhoused before cohabitation, housed in pairs (one male rat per female rat) during cohabitation,and individually housed after cohabitation. The same type of caging will be used as described for the P generation rats. Beginning no later than day 20 of presumed gestation,female rats will be individually housed in nestingboxes. Each dam and delivered litter will be housed in a common nesting box dunng the postpartum period. Nestinq 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 contaminationare conducted semi-annually and documented in the raw data. Room Air_Temperature and Humidity: The animal room is independently supplied with at least ten changes per hour of 100% fresh air that has been passed through 99.97% HEPA filters. Room temperature will be maintained at 64F to 79F (180C to 26C) and monitoredconstantly. Room humiditywill also be monitored constantly and maintained at 30% to 70%. Li,qht: 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 willbe given Certified Rodent Diet_ #5002 (PMI Nutrition International), available ad libitum from individual feeders. Page 691 ARGUS 418-020 Water: Protoco4l18-020 Pageg Water will be available ad libitum from individual bottlesattached to the cages or from an automatic watering access system. All water will be from a local 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 than 1.2 ppm chlorine at the time of analysis. Water is analyzed monthly for possible bacterial contaminationand twice annually for possible chemical contamination, Contaminants: Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the certified diet, the drinking water or the nesting material at levels that would interfere with the resultsof this study. Therefore, no analyses other than those routinelyperformed by the feed supplier or those mentioned in this protocol will be conducted. DAY NUMBERING SYSTEM: Gestation day 0 is defined as the day spermatozoa are observed in a smear of the vaginal contents and/or a copulatoryplug observed in situ. The day of birth is designated lactationday 0 (postpartum day 0) in the Health Effects Test Guidelines - Reproductionand Fertility Effects (Office of Prevention, Pesticides and Toxic Substances 870.3800, August, 1998). This same day is designated day 1 postpartum (day 1 of lactation) in the Standard Operating Procedures of the Testing Facility. Throughout this protocol,the day of birth will be designated day 1 postpartum (day 1 of lactation) and all subsequent ages of the F1 generation rats and days of the lactation period will be determined and cited accordingly. RANDOMIZATION AND COHABITATION: Upon arrival, P generation rats will be assigned to individualhousing on the basis of computer-generated random units. After acclimation, rats will be selected for study on the basis of physical appearance and body weight. The rats will be assigned to dosage groups based on computer-generated (weight-ordered) randomizationprocedures. 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 assignmentto cohabitation results in the pairing of F1 generation siblings,an altemate 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 Protoco4l18-020 Page10 gestation and assigned to individualhousing. If a female rat has not been mated after two weeks, the pair of rats will be separated withoutfurther opportunity for mating. Day 1 of lactation (postpartum) is defined as the day of birth and is also the first day on which all pups in a litter are individuallyweighed (pup body weights will be recorded after all pups in a litter are delivered and groomed by the dam). Litterswill not be culled duringthe lactation period, because random selection of. pups for cullingcould result in potential biases in pup viabilitiesand body weight gains dunng this period. All F1 generation rats will be weaned at the same age, based on observed growth and viabilityof these pups, on either day 22 postpartum, or if required,day 29 postpartum. Should it be necessary to extend the lactation period to day 29 postpartum, all affected observational intervalswill be adjusted accordingly. At weaning, a table of random units or a computer-generated randomization procedure will be used to select 30 male and 30 female F1 generation pups per group, resulting in a total of 300 rats (150 rats per sex) chosen for continued evaluation. At least one male pup and one female pup per litter, when possible, will be selected. If resultswarrant that the study be extended to include a third generation, the procedures previously described for the F1 generation will be used for selection of F2 generation pups continued on study. If study resultsshould warrant (e.g., poor reproductionperformance in the controlgroup or treatment-related alterations in litter size), parental pairs may be remated to produce Flb or F2b litters. If productionof a second litter is deemed necessary, the second cohabitationperiod will be scheduled approximately one to two weeks following weaning of the Fla or F2a litters. ADMINISTRATION: Route and Reason for Choice: The oral (gavage) route was selected for use because: 1) in comparisonwith the dietary route, the exact dosage can be accurately administered;and 2) it is one possible route of human exposure. Method and Frequency: P Generation: Male and female rats will be given the test substance once daily, beginning at approximatelysix weeks of age (at least 70 days before cohabitation)and continuing untilthe 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 Protoco4l18-020 Page11 F1 Generation: F1 generation pups may be exposed to the test substance during maternal gestation (in utero exposure) or via maternal milk duringthe 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 untilthe day before sacrifice. Dosages will be adjusted at least weekly for body weight changes andgiven at approximately the same time each day. F2 Generation: Pups may be exposed in utero duringgestation or via maternal milk duringthe lactation period. Rationale for Dosage Selection: Dosages were selected on the basis of prior dietary and gavage studies in rats performed by the Sponsor. Concentrationsmay be adjusted if toxicity observed in the P or F1 generation rats indicatesthat it is required. The highest dosage is expected to produce some toxicity. The intermediate dosage level is expected to produce minimal observable toxic effects, while the lowest dosage level is expected to produce no evidence of either systemic or reproductivetoxicity[noobservable-adverse-effect level (NOAEL)]. Dosage Levels_ Concentrations and Volumes: Dosage ,,, Group I Number of Rats oer Sex 30 Dosage (m_/k_/clav_ 0 _ Imcj/mL) 0 Dosage Volume (mL/k_ 5 II 30 1 0.2 5 III 30 3 0.6 5 IV 30 10 2 5 V 30 30 6 5 II The test substance wtll be cork_=clereO100_;. pure o! me purpose of __rJOS=_c_a_lcguelat,ons. Argus Batch Number B-418-020-A(Day.Month.Year) B-41B-020-B(Day.Monm.Year) B-418-020-C_Day.Monrn.Y ear) B-418-020-D(Day.Montn.Year) B-418-020-E(Day.Month.Year) I Page 694 ARGUS 418-020 TESTS_ ANALYSES AND MEASUREMENTS - P GENERATION: Protocol 418-020 Page 12 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: Daily before dosage. Postdosage observations will be recorded approximately 60 =10 minutes after administration. Maternal Behavior: Days 1, 5, 8, 15 and 22 postpartum. Observed abnormal behavior recorded daily. Clinical observations may be recorded more frequently than cited above if deemed appropriate by the Study Director and/or Study Monitor. Body Wei,qhts - Male Rats: Acclimation Period: Weekly. Dosage/Exposure Period: Day of Sacrifice: Weekly. Prior to sacrifice. Body Wei,qhts - 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 Protoco4l18-020 Page13 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 consumptionnot tabulated after day 15 postpartum, when it is expected that pups will begin to consume maternal feed. Feed Consumption Values - Male and Female Rats: Feed consumption values may be recorded more frequently than cited above if it is necessary to replenishthe feed. During cohabitation,when two rats occupy the same cage with one feed jar, replenishment of the feed jars will be documented. Individual values will not be recorded or tabulated. Estrous Cyclinq and Mating: Estrouscyclingwill be evaluated daily by examination of vaginal cytologybeginning 21 days before the scheduled cohabitation penod and continuing untilspermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug is observed in situ during the cohabitation period. On the day of scheduled sacrifice, an examination of vaginal cytology will be performed to determine the stage of estrous cycle. Duration of Gestation: The duration of gestation is calculated from day 0 of presumed gestation to the day the first pup is observed. Litter Observations: Litters will be examined after delivery to identify the number and sex of pups, stillbirths, live births and grossalterations. Fertility Parameters: Fertility Index (percentage of matings that resultin 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 Protoco4l18-020 Page14 Number of implantationsites. General conditionof dam and litter during the postpartum period. Litter Data: Litter size and viability [tabulated at birth (day 1) and on clays5, 8, 15 and 22 postpartum]. Viability Indices (percentages of pups born that surviveto days 1 and 5 postpartum. Lactation Index (percentage of pups that survive from clay8 to clay22 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: Viabilib/: Preweaning Period: Litters will be observed for dead pups at least twice daily. The pups in each litter will be counted once daily. Postweaning Period: Twice daily. Clinical Observations and/or General Appearance - Male and Female Rats: Preweaning Penod: Daily. Postweaning Period: Daily before dosage. Postdosage observations will be recorded approximately 60 10 minutes after administration. Maternal Behavior: Days 1, 5, 8, 15 and 22 postpartum. Observed abnormal behavior recorded daily. Clinical observations may be recorded more frequently than cited above if deemed appropriate by the Study Director and/or Study Monitor. Body Weights - Male and Female Rats: Preweaning Period: Days 1 (livebom pups), 5, 8, 15 and 22 postpartum. Postweaning Period: Weekly. Page 697 ARGUS 418-020 Protoco4l18-020 Page15 Presumed Gestation Period (Female Rats): Lactation Period (Female Rats): 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: Postcohabitation Period (Male Rats): Gestation Period (Female Rats): Lactation Period (Female Rats): Weekly. Weekly untilsacrifice. Days 0, 7, 10, 14, 18.21 and 25 (if required). Days 1,5, 8, 11 and 15. Feed consumptionvalues not tabulated after day 15 postpartum, when it is expected that pups will begin to consume maternal feed. Feed consumption values may be recorded more frequently than cited above if it is necessary to replenishthe feed. During cohabitation, when two rats occupy the same cage with one feed jar, replenishment of the feed will be documented. Individualvalues will not be recorded or tabulated. Postweaninq Developmental Observations: Sexual Maturation: Female rats will be evaluated for the age of vaginal patency, beginning on day 28 postpartum. Male rats will be evaluated for the age of preputial separation, beginning on day 39 postpartum. Estrous Cyclinq and Matin,q: Estrous cyclingwill be evaluated daily by examination of vaginal cytology beginning 21 days before the scheduled cohabitation period and continuinguntil spermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug is observed in situ during the cohabitation period. On the day of scheduled sacrifice, an examination of vaginal cytology will be performed Page 698 .= ARGUS 418-020 to determine the stage of estrous cycle. Duration of Gestation: Protocol 418-020 Page 16 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 observedfor dead pups at least twice daily. The pups in each litter will be counted once daily. Clinical Observations and/or General Appearance: Preweaning Period: Daily. Body Weights: Preweaning Period: Days 1, 5, 8, 15 and 22. Preweanin,q 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: i Rats and pups will be sacrificed by carbon dioxide asphyxiation. Page 699 ARGUS 418-020 GROSS NECROPSY AND HISTOPATHOLOGY: Protoco4l18-020 Page17 Adult P and F1 generation rats will be necropsied and examined for gross lesions. Gross lesionswill be retained in neutral buffered 10% formalin and examined histologically. Tissue trimmingand histopathology will be performed under the supervisionof or by a Board Certified Veterinary Pathologist. At scheduled sacrifice after completion of the cohabitation period (male rats) and on clay22 postpartum (female rats) blood samples (approximately4 mL per rat) wili be collected from the inferior vena cava into serum separator tubes and centrifuged. The resulting serum will be immediatelyfrozen on dry ice and maintained frozen (_<-70C) until shipment to the Sponsor for analysis. The liver will be excised, weighed, and a sample section (lateral lobe) frozen and retained at -<-70C until shipment to the Sponsor for analysis. After completion of sample collection,serum and liver section samples will be shipped (frozen on dry ice) to Kris J. Hansen, Ph.D., at the previouslycited address. Both the recipient and the Study Monitorwill be notified in advance of sample shipment. Gross necropsy will include an initial physicalexamination of external surfaces and all orifices,as well as an internal examination of tissues and organs in situ. The following will be examined: external and internal portions of all hollow organs; the external surfaces of the brain and spinal column, the nasal cavity and neck with associated organs and tissues; the thoracic, abdominal and pelviccavities with associated organs and tissues; and the musculo/skeletal carcass. The lungs will be perfused with neutral buffered 10% formalin. For all postweaning rats, the urinary bladder and lungs will be inflated with neutral buffered 10% formalin. See ATTACHMENT 4 for additional tissues to be weighed and retained, and histologicalevaluations to be conducted; all other tissues will be discarded. 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 conditionon the day the observation is made. The rats will be examined for gross lesions. Pregnancy status and uterine contents of female rats will be recorded (when appropriate). Aborted fetuses, delivered pups and/or concepti in uteri will be examined to the extent possible. Uteri of apparently nonpregnant rats will be examined while being pressed between glass plates to confirm the absence of implantation sites. See ATTACHMENT 4 for tissuesto be weighed and retained, and histological evaluations to be conducted; all other tissues will be discarded. P_e7_ ARGUS 418-020 Protoco4l 18-020 Page18 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: After completion of the cohabitation period, adult male rats will be sacrificed, and a grossnecropsy of the thoracic, abdominal and pelvic viscera will be performed. To assess the potential toxicity of the test substance on the male reproductive system, the following endpoints will be evaluated: Sperm Evaluations: A portion of the left cauda epididymis will be used for evaluation of cauda epididymal sperm concentration and motility using computer-assisted sperm analysis (CASA). Motility will be evaluated by the Hamilton Thome IVOS by collection of a sample from the left cauda epididymis. The remaining left cauda epididymis will be used to manually evaluate sperm morphologyand 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 will includethe 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. Or.qanWeiqhts: The following organs will be individually weighed: right testis, left testis, left epididymis (whole and cauda), right epididymis, seminal vesicles (with and without fluid) and prostate. Histopatholo.qy: The remaining portion of the left epididymis, the right epididymis, prostate and seminal vesicles will be fixed in neutral buffered 10% formalin for possible histopathological evaluation. The testes will be fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin for possible histopathological evaluation (see ATTACHMENT 4). Should a second litter be deemed necessary, male rats will not be sacrificed until after the cohabitation period for the second litter, extending the study by approximately 14 weeks. Scheduled Sacrifice - P and F1 Generation Female Rats: Female rats will be sacrificed after completion of the 22-day postpartum period (should a second litter not be required). The number and distributionof 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 Protoco4l18-020 Page19 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 Survivin,q Pups - P and F1 Generation Female Rats: Dams with no survivingpups 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. FI/F2 Generation Pups Found Dead on Day I Postpartum: Pups that die before examination of the litter for pup viabilitywill be evaluated for vital status at birth. The lungs will be removed and immersed in water. Pups with lungsthat sinkwill be identified as stillborn; pups with lungs that float will be identified as livebom, and to have dieclshortly after birth. Pups with gross lesionswill be preserved in Bouin's solutionfor possible future evaluation. Should postmortem autolysis preclude these evaluations, it will be noted in the necropsydata. FIlF2 Generation Pups Found Dead or Moribund on Days 2 to 22 Postpartum: Pups found dead or sacrificed due to moribund conditionwill be examined for gross lesionsand for the cause of the moribundcondition or death. Pups with gross lesions found on days 2 to 5 postpartum will be preserved in Bouin's solutionfor possible future evaluation; gross lesionsof pups found on days 6 to 22 postpartum will be preserved in neutral buffered 10% formalin. Should postmortem autolysis preclude these evaluations it will be noted in the necropsydata. FIlF2 Generation Pups Not Selected for Continued Observation: All pups culled on day 22 postpartum will be sacrificed, and three pups per sex per litter will be randomly selected and examined for gross lesions; gross lesionswill be preserved in neutral buffered 10% formalin. Necropsy will include a single crosssection of the head at the level of the frontal-parietal suture and examination of the cross-sectionedbrain for apparent hydrocephaly. Tissues (see A'I-FACHMENT 4) from the three selected pups per sex per litter will be weighed and retained in neutral buffered 10% formalin for possible histologicalevaluation. All remaining pups will be discardedwithoutfurther examination. Page 702 ARGUS 418-020 PROPOSED STATISTICAL METHODSCS'11): Protoco4l 18o020 Page20 Averages and percentages will be calculated. Litter values will be used where appropriate. Additional procedures and/or analyses may be performed, if appropnate. Type of Testa I. Parametric A. Bartlett'sTestc I II. Nonparametric A. KruskaI-Wallis Test f / (-<751% ties) Significant at p_<0.001 Nonparametric Not Significant Significantat'p<0.05 Analysis of Variance I t Dunn's Test Not Signilicant Significantat p_0.05 I Dunnett's Test Not Significant B. Fisher's Exact Test (>75% ties) III. Test for ProportionData Variance Test for Homogeneity of the Binomial Distribution a. Statistically significantprobabilities are reported as either p_0.05 or p_0.01. b. Proportiondata are not included in this category. c. Test for homogeneity of variance. Page 703 I ARGUS 418-020 DATA ACOUISITION_ VERIFICATION AND STORAGE: Protoco4l18-020 Page21 Data generated during the course of this study will be recorded either by hand or using the Primedica Argus Automated Data Collection and Management System, the Vivarium Temperature and Relative Humidity Monitoring System and the Ham#ton Thorne IVOS. All data will be tabulated, summanzed and/or statisticallyanalyzed using the Primedica 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). Records will be reviewed by the Study Director and/or appropriate management personnel within 21 days after generation. All original records will be stored in the archives of the Testing Facility. All original data will be bound and indexed. A copy of all raw data will be supplied to the Sponsor upon request. Preserved tissues will be stored at the Testing Facility at no charge for one year after mailing of the draft final report, after which time the Sponsor will be contacted to determine the disposition of these materials. RECORDS TO BE MAINTAINED: Protocol and Amendments. Test Substance, Vehicle and/or Reagent Receipt, Preparation and Use. Animal Acquisition. Randomization Schedules. Mating History. Treatment (if prescribed by Staff Veterinarian). General Comments. Clinical Observations and/or General Appearance. Blood Sample Collection, Processing and Shipment. Body Weights. Feed Consumption Values. Gestation Length. Litter Observations. Gross Necropsy Observations. Sperm Evaluation (motility, concentration and morphology). Organ Weights. HistologicalObservations. Study Maintenance (room and environmental records). Feed and Water Analyses. Packing and/or Shipment Lists. Page 704 ARGUS 418-020 KEY PERSONNEL: Protoco4l 18-020 Page22 Executive Director of Research: Mildred S. Christian, Ph.D., Fellow, ATS Director of Research: Alan M. Hoberrnan, Ph.D., DABT Associate Directorof Research and Study Director: Raymond G. York, Ph.D., DABT Director of Operations and Compliance: Barbara J. Patterson, B.A. Director of Laboratory Operations: John F. Barnett, B.S. Director of Study Management: Valerie A. Sharper, M.S. Manager of Animal Operations and Chairperson, InstitutionalAnimal Care and Use Committee: Dena C. Lebo, V.M.D. Consultant, Veterinary Pathology: W. Ray Brown, D.V.M., Ph.D., ACVP REPORTS: The Study Directorwill provide periodic updates of study progressto the Sponsor. Draft summary tables of unaudited computer-recorded data may accompany these updates. Statisticalanalyses will not be performed on these interim data. A comprehensive draft final report will be prepared on completion of the study and will be finalized following consultation with the Sponsor. The report will include the following: Summary and Conclusion. Experimental Design and Method. Evaluation of Test Results, Appendices: Figures, Summary and Individual Tables Summarizing the Above Data, Protocol and Associated Amendments and Deviations, Study Director's GLP Compliance Statement, Reports of Supporting Data (if appropriate) and QAU Statement. An interim summary report covering the period from initiation of test diet exposure through weaning of the F1 generation will also be issued. This report will be identical in format to the final report with the exception of inclusion of histopathological findings. The Sponsor will receive one copy of the draft report and two copies of the final report. INSTITUTIONAL ANIMAL CARE AND USE COMMI'I-rEE STATEMENT: The procedures described in this protocol have been reviewed by the Testing Facility's InstitutionalAnimal Care and Use Committee. All procedures described in this protocol that involve study animals will be conducted in a manner to avoid or minimize discomfort, distress or pain to the animals. PageT05 ARGUS 418-020 Protocol 418-020 Page 23 The Sponsor's signature below documents the fact that information concerning the necessity for conductingthis study and the fact that this is not an unnecessarily duplicative study may be obtained from the Sponsor. No altemative (in vitro) procedures were available for meeting the stated purposes of the study. REFERENCES: 1. Christian, M.S. and Voytek, P.E. (1982). In Vivo Reproductive and Mutagenicity Tests. Environmental Protection Agency, Washington, D.C. National Technical Information Service, U.S. Department of Commerce, Springfield, VA 22161. 2. Christian, M.S. (1984). Reproductive toxicity and teratology evaluations of. naltrexone (Proceedings of Naltrexone Symposium, New York Academy of Sciences, November 7, 1983), J. Clin. Psychiat. 45(9):7-10. 3. Lang, P.L. (1988). Embryo and Fetal Developmental Toxicity (Teratology) Control Data in the Charles River Crt:CD_BR Rat. Charles River Laboratories, Inc., Wilmington, MA 01887-0630. (Data base provided by Argus Research Laboratories, Inc.) 4. Institute of Laboratory Animal Resources (1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, D.C. 5. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 240-241. 6. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of variances. Biometry, W.H. Freeman and Co., San Francisco, pp. 370-371. 7. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275. 8. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121. 9. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Co., San Francisco, pp. 388-389. 10. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252. 11. Siegel, S. (1956). Nonparametric Statistics for the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104. Page 706 PROTOCOL APPROVAL: FOR THE TESTING FAClUTY ' AlanM. Hoberman, Ph.D.,DABT Directoorf Research Date Ra_d G."York_:__.D._,ABT AsSoc_te Director_amh Study Dim=or i/ ' Iv _De'_a C. Lebo, V.M.D. Chai_emon, Institutional Animal Cam and Use Committee FOR THE SPONSOR Date Date John Butenhoff, Ph.D., DABT, CIH Study Monitor Sponsor's Representative Date ARGUS 418-020 Protoco4l18-020 Page24 Page 707 ARGUS 418-020 ATTACHMENT 1 SCHEMATIC OF STUDY DESIGN AND STUDY SCHEDULE Page 708 ARGUS 418-020 ATTACHMENT 1 Protocol 418-020 Page 1 of 3 TWO-GENERATION REPRODUCTION STUDY a First Day of Test Substance Exposure P Generation Premating P Generation Male Rats 10 weeks P Generation Female Rats 10 weeks Cohabitation _ Last Day of Test Substance Exposure P Generation: 2 weeks Presumed Gestation Natural Delivery Lactation 3 weeks I I 3 weeks I F1 Generation Rats F1 GeRnaetsration _ I Postweaning I I Cohabitation = Presumed Gestation , _ I 10 weeks I 2 weeks 3 weeks F2 Generation Rats 3 weeks Day 22 Postpartum Weaning = Last Day of Test Substance Exposure F1 Generation = Lactation 3 weeks Postpartum Day 22 Postpartum = Dosage Period a. For additional details see "Tests, Analyses and Measurements" section of the protocol. b. Male rats sacrificed after determination of sufficient number of pregnancies; sperm evaluation. c. P generation female rats and F1 generation rats not selected for continuation on study sacrificed. d. F1 generation dams and F2 generation litters sacrificed. Page 709 ARGUS 418-020 ATTACHMENT1 SCHEDULE a'b'c Protoco4l 18-020 Page2 of 3 07 NOV 00 13 NOV 00 P Generation Animal Receipt - Acclimation Begins Start of Test Substance Exposure P Generation Rats 21 JAN 01 PM - 04 FEB 01 AM 22 JAN 01 04 FEB 01 12 FEB 01 01 MAR 01 16 FEB 01 01 MAR 01 12 FEB 01 P Generation Cohabitation Penod (After at least 70 days of test substance exposure). First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation. First Possible Delivery - F1 Generation Litters (Day 21 of presumed gestation). Last Possible Delivery - F1 Generation Litters (Day 25 of presumed gestation). First Possible Day 25 of Presumed Gestation Female Rat Sacrifice. Last Possible Day 25 of Presumed Gestation Female Rat Sacnfice. Scheduled Sacrifice - P Generation Male Rats (Earliest possible date). 05 MAR 01 22 MAR 01 First Possible Day-22 PostpartumWeaning (Sacrifice of P generation dams and F1 generation pups not selected for continued observation). Last Possible Day-22 Postpartum Weaning. 06 MAR 01 F1 Generation Postweaning Observations Begin (Details of tests cited in protocol). a. The study initiation date is the day the Study Director signs the protocol. b. The day of birth is designated postnatal day 0 (day 0 of lactation) in Addendum 10 to the Pesticide 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 Test Facility. Throughout this protocol,the day of birth will be designated day 1 postpartum (day 1 of lactation) and all subsequent ages of the F1 generation rats and days of the lactation period will be determined and cited accordingly. c. The in-life portion of the study will require approximately 42 weeks. If results warrant, this study may be extended to include a third generation; such a study extensionwould be conducted accordingto the procedures described previously for the F1 and F2 generations. Page 710 ARGUS 418-020 A'I-rACHMENT 1 Protocol 418-020 Page 3 of 3 31 JUL 01 Interim Status Report - Draft Mail Date. Estimated Datesa 06 MAR 01 Start of Test Substance ExposureF1 Generation Rats 28 MAY 01 PM - 18 JUN 01 AM F1 Generation Cohabitation Period (After at least 70 days of test substance exposure). 29 MAY 01 18 JUN 01 First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation. 19 JUN 01 13 JUL 01 23 JUN 01 13 JUL 01 First Possible Delivery - F2 Generation Litters (Day 21 of presumed gestation). Last Possible Delivery - F2 Generation Litters (Day 25 of presumed gestation). First Possible Day 25 of Presumed Gestation Female Rat Sacrifice. Last Possible Day 25 of Presumed Gestation Female Rat Sacrifice. 26 JUN 01 F1 Generation Male Rats Sacrificed after Day 21 of Cohabitation Period - Earliest Approximate Date. I0 JUL 01 03 AUG 01 First Possible Day 22 Postpartum (F1 generation dams and F2 generation litters sacrificed). Last Possible Day 22 Postpartum. 12 DEC 01 Draft Final Report (Includinghistopathoiogy). 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 littersare delivered and weaned. Page 711 ARGUS 418-020 ATTACHMENT 2 MATERIAL SAFETY DATA SHEET Page 712 31--0CT-2000 09:24 3m Fax me._sage ARGUS 418-020 Page 2/17 MATERIAL SAFETY DATA SHEET 3M 3M Centar St. Paul, Minnesota 55144- i000 1-800-364-3577 or (651) 737-6501 (24 hours) Copyright, 2000, Minnesota Mining and Manufacuurlng Company. All rights reserved. Copying and/or downloading of this information for the purpose of properly utilizing 3M products is allowed provided than: I) 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 disl;ributed with the intention of earning a profit thereon. DIVISION: 3M SPECIALTY TRADE NAME: MRTER_ FC-143 FLUORAD Brand Fluorochemical ID NUMBER/U. P. C. : 98-0211-0008-0 00-51135-09138-8 98-0211-5489-7 98-0211-7394-7 00-51135-02941-1 00-51135-10762-1 ISSUED: August 25, 2000 SUPERSEDES: DOCUMENT: July 28, 2000 10-3808-2 Surfactant 98-0211-0891-9 98-0211-6581-0 ZF-0002-0378-4 00-51135-09365-8 00-51135-10405-7 - - - i. INGREDIENT C.A.S. NO. PERCENT AMMONIUM AMMONIUM PERFLUOROOCTANOATE PERFLUOROHEXANOATE ............. ............. AMMONIUM PERFLUOROHEPTANOATE ............ HEPTADECAFLUORONONANOIC ACID, AMMONIUM SALT .................................. 3825-26-1 21615-47-4 6130-43-4 4149-60-4 96.5 0 0 0 - i00 - 1.5 -1 -1 The components of this product notification requiremants of ingredients in this material Existing monomers Chemical Substances are listed on EINECS. are in compliance with the chemical TSCA. All applicable chemical are listed on _he European Inven;ory of (EINECS), or are exempt polymers whose 2. PHYSICAL DATA BOILING POINT: ................. VAPOR VAPOR PRESSURE: ................ DENS ITY: ................. EVAPORATION RATE: .............. SOLUBILITY IN WATER: ........... SPECIFIC GRAVITY: .............. PERCENT VOLATILE: .............. pH: ............................ VISCOSITY: ..................... N/A N/& N/A N/A apprec. 0.4 - 0.5 Warer-i (Bulk) N/A 4 -7 (2_ aqueous solution) N/A Abbreviations: N/D - Not Determined N/A - Not Applicable Page 713 CA - Approximately 32-OCT-2DO0 09:24 3m Pax me.'_wage ARGUS 418-020 Page d/2) MSD5:FC-143 August 25, FLUORAD 2000 Brand Fluorochemical Surfactan% PAGE 2 2. PHYSICAL DATA (continued) Pn_r.TING POINT: ................. APPEARANCE Solid, AND Light ODOR: colored powder; N/A ..... slight odor. 3. FIRE AND EXPLOSION HAZARD DATA FLASH POINT: ................... FLAMMABLE LIMITS - LEL: ........ FLAMMABLE LIMITS - UEL: ........ AUTOIGNITION TEMPERATUP, E : ...... Non-flammable N/A N/A N/A EXTINGUISHING MEDIA: Waters Carbon dioxide s Dry chemical, Foam SPECIAL FIRE FIGHTING PROCEDURES: Wear full pro_ec%ive clothing, positive pressure and pants, bands or pressure around arms, protective covering for exposed including helmet, self-contalned, demand breathing apparatus, bunker waist and legs, face mask, and areas of the head. UNUSUAL FIRE AND EXPLOSION See Hazardous Decomposition HAZARDS: section for products of combustion. coat 4. REACTIVITY DATA STABILITY: ,%able INCOMPATIBILITY Not Applicable - MATERIALS/CONDITIONS TO AVOID: HAZARDOUS POLYMERIZATION: Hazardous poly_arlzatlon will not occur. HAZARDOUS DECOMPOSITION Carbon Monoxide and Fluoride, Ammonia. PRODUCTS: Carbon Dioxide, Oxldes of Nitrogen, Hydrogen 5. ENVIRONMENTAL INFORMATION SPILL RESPONSE: observe Use wet residue. precautions from o_her sections. Collec_ spilled macerlal. sweeping Place compound or water to avoid in a closed container. dusting. Clean up Abbreviations: N/D - Not Determined N/A - Not Applicable Page 714 CA - Approximately 31-0CT-2000 09:14 3m Fax message ARGUS 418-020 _age 4/2_ MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical Surfactant 5. ENVIRONMENTAL INFORMATION (continued) PAGE 3 RECOMMENDED DISPOSAL: Incinerate in an industrial or commercial facility in the presence a combustible material. Combustion products will include HF. Do dispose of in a sanitary landfill. Disposal alternative: Dispose waste product in a facility permitted to accept chemical waste. of not of ENVIRONMENTAL SUPPORTING DATA: DATA: BIODEGRADATION: Theoretical Oxygen Demand (ThOD): 0.320 g/g Chemical Oxygen Demand.(COD): 0.0007 g/g 20-Day Biochemical Oxygen Demand (BOD20): 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 (Lepomls macrochlrus) 96-hr EC50: 569 mg/L Green Algae (Selenastrum capricornutum) 14-Day EC50: >I000 mg/L Microtox (Photobacterium phosphoreum) 30-min EC50: 730 mg/L BIONCONCENTRATION: BCF - 1.8 REGWLATORY Volatile VOC Less INFORMATION: Organic Compounds: N/A. H20 & Exempt Solvents: N/A. Since regulations before disposal. EPA Hazardous). vary, consult applicable U.S. EPA Hazardous Waste regulations NumDer = or authorities None (Not U.$. The components of this product are in compliance with the chemical registration PICC5. requirements of TSCA, EINECS, CDSL, AICS, MITI, KECI and OTHER ENVIRONMENTAL INFORMATION: This substance has Lowest LCS0, EC50, minimal or ICSO toxicity < or - to i000 aquatic mg/L). organisms (I00 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 Page 715 CA - Approximately 31-0CT-2000 09:24 3B Pax BesRage ARGUS 418-020 Page 5/17 MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical Surfactant PAGE 4 5. ENVIRONMENTAL INFORMATION (continued) FIRE H_n: No PRESSURE: No _CTIVITY: No ACUTE: Yes CHRONIC: Yes 6. SUGGESTED FIRST AID EYE CONTACT: Immediately flush eyes mlnures. Get immediate with large amounts medical attention. of water for at leas_ 15 SKIN CONTACT: Flush skin with large amounts of water. 7f irritation persists, get mQdica I attQntion. INHALATION: If signs/symptoms slgns/symptoms occur, continue, remove person uo fresh air. If call a physician. IF SWALLOWED: 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 _terial. A pair of gloves _de from the following =_mterial(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 (Saranax) Use disposable is preferable shoe/boot covering for all protective or r_ber garments. boots. Disposable fabric RECOMMENDED Use with ventilation If exhaust protection. VENTILATION: appropriate local exhaust to maintain emissions ventilation. Provide sufficient below recommended exposure limits. ventilation is not adequate, use appropriate respiratory RESPIRATORY PROTECTION: Avoid breathing of airborne material. NIOSH approved respirators based on contaminants and in accordance wi_h Select one of the following airborne concentration of OSHA regulations: full-face high- Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 716 31--0C9"-2000 09:2# _m _axsessage ARGUS 418-020 _age .1_/ MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical 5urfactant 7. PRECAUTIONARY INFORMATION (continued) PAGE 5 efficiency filter respirator, full-face supplied air respirator. PREVENTION OF ACCIDENTAL INGESTION: Do not eat_ drink or smoke when using this product. Mash exposed areas thoroughly before eating. with soap and water. Wash hands after handling and RECOMMENDED STORAGE: Store away from areas where or pharmaceuticals. Store closed when not in use. product at room may come into contact with temperature. Keep container food ""PREVENT MOISTURE CONTAMINATION TO KEEP P0_DER FREE FLOWING."" FIRE AND EXPLOSION Nonflammable. AVOIDANCE: 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 dQcomposition products mantioned in the Reactivity Data section of this MSDS. clothing, food and tobacco Store work clothes separately products. Wash contaminated from other clothing thoroughly before re-use. Discard contaminated leather clothing. Decontaminate work surfaces frequently to avoid exposure by contact. HMI5 HAZARD RATINGS: HEALTH: PERSONAL 3 FLAMMABILITY: PROTECTION: X 0 (See REACTIVITY: precautions, 0 section EXPOSURE LIMITS INGREDIENT VALUE UNIT TYPE AUTH 7.) SKIN" AMMONIUM PERFLUOROOCTANOATE .......... AMMONIUM PERFLUOROHEXANOATE .......... AMMONIUM PERFLUOROHEPTANOATE ......... HEPTADECAFLUORONONANOIC ACID, AMMONIUM SALT ...................... 0.01 0.i 0.I NONE MG/M3 MG/M3 MG/M3 NONE T_A ACGIH Y TWA 3M Y TWA 3M Y NONE NONE " SKIN NOTATION: Listed substances indicated with "Y' under SKIN refer to the potential contribution including mucous membrane to the overall and eye, either exposure by the cutaneous route by airborne or, more particularly, by direct contact with the substance, vehicles can alter skin absorption. SOURCE OF EXPOSURE LIMIT DATA: - 3M: - ACGIH: 3M Recommended Exposure American Conference of Guidelines Governmental Industrial Hygienists - NONE: None Established Abbreviations: N/D - Not Determined N/_ - Not Applicable Page 717 CA - Approximately 31-0GT-2000 09:24 3m Pax ae._sage ARGUS 418-020 _age //_/ MSDS: August FC-143 FLOORAD 25, 2000 Brand Fluorochemical 8. HEALTH _ DATA Surfac_ant PAGE 6 EYE CONTACT : Moderate Eye pain, tearing, Irritation: and hazy siqns/s_nnptoms vision. can include redness, SKIN CONTACT : Mild Skin II-ritation (after signs/symptoms can include prolonged redness, or repeated swelling, and contact): itching. May be absorbed through the skin and produce those caused by inhalation and/or ingestion. effects similiar INHALATION: Illness requiring by inhalation to medical moderate attention quantities may result from a single of uhls material. swelling, to exposure May be absorbed time. by inhalation and persist in the body for an ex_ended Single overeXl:OSure, above recommended guidelines, may cause: I_ritation soreness (upper respiratory) : signs/symptoms of the nose and throat, coughing and can include sneezing. Prolonged cause: or repQated overexposure, above recommended guidelines, may Liver Effects: and tenderness slgns/symptoms can of upper abdomen. include yellow skln(_aundlce) IF S_ALLOWED: This product can porennially either through dissociation generate P_-fluorooctanoate anion, or meta_x)llsm. Animal studies conducted on Perfluorooctanoate anion indicate effects including liver disturbances, effects, and rats. Thee e_qDosure to instructed. weight loss, loss of appetite, adrenal and hematologic be_11gn tumors of the liver, pancreas and testes of male are no known human health effects from anticipated this Perfluoroocranoare anion when used as intended and Illness may result this material. from a single swallowlng of a moderate quantity of CANCER: A mixture of ammonium perfluoroheptanoa%e, perfluorohexanoate, (3825-26-1) was fed carclnogenlclty was significant compound two-year study there perfluorooctanoate, ammonium ammonium that was perfluoropentanoate 93 to 97% AMMONIUM and ammonium PERFLUOROOCT_OATE to albino rats for 2 years, no compound induced found in the study. There related benign testicular were sta%Istlcally tumors. In a second were statistically significant compound related Abbreviations: N/D - Not Determined N/A - Not Applicable Page 718 CA - Approximately 31-0CT-2000 09:24 3m P,axmemge ARGUS 418-020 _age _12_ MSDS: Aught FC-143 FLUORAD 25, 2000 Brand Fluorochemical 8. HEALTH HAZ_=_ DATA (continued) Surfactan% PAGE 7 benign tumors in the liver, pancreas, and testis when compared libitum and pair-fed conrl-ols. Based on the current knowledge, findings have no human health implications. (3825-26-1) (1983 1993 studies conducted jointly by 3M and DuPont). to ad these and MUTAGENICITY: Not mutagenic transformation in invitro mutagenicity assays. Did in a mammalian cell transformation not cause assay. cell REPRODUCTIVE/DEVELOPMENTAL TOXINS: Not teratogenic in rabbits by oral administration. rats by gavage or inhalation exposures. OTHER HEALTH R Product HAZARD Toxicity INFORMATION: S1_mm*ry Sheet is available. Not teratogenic to The presence of organic fluorochemicals in the population and subpopulations, such as workers, dating back to the 1970's. 3M's epldemiological workers indicates no adverse effects. blood of the general has been published study of its own 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 Perfluorooctanoate health effects anion when from used anticipated as intended exposure to this and instructed. SECTION CHANGE DATES INGREDIENTS SECTION CHANGED SINCE July 28, 2000 ISSUE Abbreviations: N/D - Not Determined N/A - Not Applicable Page 719 CA - Approximately 31--0CI'-2000 09:14 311FaxSessage MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical Surfactant ARGUS 418-020 _age _/_/ PAGE 8 The information in this Material Safety Data Sheet (MSDS) is believed to be correct as of the date issued. 3M MAKES NO _ANTIES, EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANY MERCHANTABILITY OR FITNESS FOR A PARTICULAR IMPLIED PURPOSE WARRARTY OF OR COURSE OF PERFORMANCE OR USAGE OF TRADE. User is responsible for deteFmining 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 datermlne whether it is fit for a particular purpose and suitable for user's method of use or application. 3)I provides information in electronic form as a service to its customers. Due to the remote possibility that in errors, omissions or alterations electronic in this transfer information, may have resulted 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 3_-0C'I"-2000 09:14 3tl Pax_es._age ARGUS 418-020 _age 10/1, MATERIAL SAFETY DATA SHEET 3M 3M Center St. Paul, 55144-i000 Minnesota 1-800-364-3577 or (651) 737-6501 (24 hours) Copyright, 2000, Minnesota Mining and Manufacturing Company. All rights information reserved. Copying and/or downloading for the purpose of properly utilizing of this 3M products is allowed provided that: i) the information is copied in full with no changes unless prior agreement is obtained from 2) neluher _he copy nor the original 3M, and is resold or ouherwise distributed with the intention of earning a profit thereon. DIVISION: 3M SPECIALTY TRADE NAME: FC-143 FLUORAD Brand MATERIALS Fluorochemlcal ID NUMBER/U. P. C. : 98-0211-0008-0 98-0211-5489-7 98-0211-7394-7 00-51135-09138-8 00-51135-02941-1 00-51135-10762-1 "r_suED: August 25, 2000 SUPERSEDES: July 28, 2000 DOCUMENT: 10-3808-2 Surfacuant 98-0211-0891-9 98-0211-6581-0 ZF-0002-0378-4 00-51135-09365-8 00-51135-10405-7 - - - i. INGREDIENT C.A.S. NO. PERCENT --w---- AMMONIUM PERFLUOROOCTANOATE ............. 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 - i00 - 1.5 -1 -1 The components of Uhis produc_ notification requiremenus of ingredients In thls materlal Existing monomers Chemlcal Substances are listed on EINECS. are in compliance wi_h the chemical TSCA. All applicable chemical are listed on _he European _nventory of (EINECS), or are exempt polymers whose 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 Wat_=l (Bulk) N/A 4 -7 (2_ aqueous N/A solution) Abbreviations: N/D - Not De_ermined N/A - Not Applicable Page 721 CA - Approximately 32-0CT-2000 09:24 3m Fax message ARGUS 418-020 _age _d/_/ MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical 2. PHYSICAL DATA (continued) Surfactant PAGE 2 MELTING POINT: ................. APPEARANCE Solid, AND Light ODOR: colored powder; N/A slight odor. 3. FIRE AND EXPLOSION HAZARD DATA FLASH POINT : ................... FLAMMABLE FLAMMABLE LIMITS LIMITS - LEL: ........ - UEL: ........ AUTOIGNITION TEMPERATURE: ...... Non-flammable N/A N/A N/A EXTINGUISHING MEDIA: Water, Carbon dioxides Dry chemical, Foam SPECIAL FIRE FIGHTING PROCEDURES: Wear full protective clothing, positive pressure and pants, bands or pressure around arms, protective covering for exposed including helmet, self-contalned, demand breathing waist and legs, apparatus, face mask, bunker and areas of the head. UNUSUAL FIRE AND EXPLOSION See Hazardous Decomposition HAZARDS: section for products of combustion. coat 4. REACTIVITY DATA STABILITY: Stable INCOMPATIBILITY Not Applicable - MATERIALS/CONDITIONS TO AVOID: HAZJIRDOUS POLYMERIZATION: Hazardous polymerization will not occur. HAZARDOUS DECOMPOSITION Carbon Monoxide and Fluoride, Ammonia. PRODUCTS: Carbon Dioxide, Oxides of Nitrogen, Hydrogen 5. ENVIRONMENTAL INFORMATION SPILL RESPONSE: Observe Use wet residue. precautions from other sections. Collect spilled material. sweeping Place compound or water to avoid in a closed container. dusting. Clean up Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 722 32-0C2"-2000 09:24 3M Pax Meemage ARGUS 418-020 Page 12/2> NSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical Surfactant 5. ENVIRONMENTAL INFORMATION (continued) PAGE 3 RECOMMENDED DISPOSAL: Incinerate in an industriai or commercial facility in the presence of a combustible material. Combustion products will include HF. Do no_ dispose of in a sanitary landfill. Disposal alternative: waste product in a facility permitted to accept chemical Dispose of waste. ENVIRONMENTAL SUPPORTING DATA: DATA: BIODEGRADATION: Theoretical Oxygen Demand Chemical Oxygen Demand 20-Day Biochemical Oxygen (ThOD): (COD): Demand 0.320 0.0007 (BOD20): g/g g/g 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 (Lepomls macrochirus) 96-hr EC50: 569 mg/L Green Algae (5elenastrum capricornutum) 14-Day EC50: >i000 mg/L Microtox (Photobacterium phosphoreum) 30-min EC50: 730 mg/L BIONCONCENTRATION: BCF - 1.8 REGULATORY Volatile VOC Less INFORMATION: Organic Compounds: N/A. H20 & Exempt Solvents: N/A. Since regulations before disposal. EPA Hazardous). vary, consult applicable U.5. EPA Hazardous Waste regulations Number = or authorities None (Not U.5. The components registration PICCS. of this product are requirements of TSCA, in compliance EINECS, CDSL, with the chemical AICS, MITI, KECI and OTHER ENVIRONMENTAL INFORMATION: This substance has Lowest LC50, ECSO, minimal or It50 toxicity < or - to I000 aquatic mg/L). organisms (I00 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 Page 723 CA - Approximately 32-0CT-2000 09:24 3m Pax message ARGUS 418-020 Page 2J/2_ MSDS: FC-143 FLUORAD August 25, 2000 Brand Fluorochemical Surfactant PAGE 4 5. ENVIRONMENTAL INFORMATION (continued) FIRE HAZARD: No PRESSURE: No REACTIVITY: NO ACUTE: Yes CHRONIC: Yes 6. SUGGESTED FIRST AID EYE CONTACT: Immadiately flush eyes minutes. Get immediate with large amounts medical attention. of water for at least 15 SKIN CONTACT: Flush skin with large amounts of water. If irritation persists, get medical attention. INHAI_T I0N: If signs/symptoms sigT_s/symptoms occur, continue, remove person Uo fresh call a physician. air. If IF SWALLOWED: 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 glove_ made from the following material(_) are recommended: butyl rubber. Use one or more of the following personal protection items as necessary ro prevent skin contact: head covering, coveralls. Protective garments (other than gloves) should be made of either of the following martials: polyethylene/polyvinylidene chloride (Saranex) Use disposable is preferable shoe/boot covering for all protective or rubber garmants. boots. Disposable fabric RECOMMENDED Use with ventilation If exhaust protection. VENTILATION: appropriate local exhaust ventilation. Provide sufficient to maintain emissions below recommended exposure limits. ventilation is not adequate, use appropriate respiratory RESPIRATORY PROTECTION: Avoid NIOSH breathing approved of airborne respirators material. based on contaminants and in accordance with Select one of the following airborne concentration of OSHA regulations: full-face high i Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately Page 724 ,.T1-0C3"-2000 09:24 3B P41.1 IJlemmage ARGUS 418-020 Page 14/1: MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical Surfactant 7. PRECAUTIONARY INFORMATION (continued) PAGE 5 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 earing. RECOMMENDED STORAGE: Store away from or pharmaceuticals. closed when not areas where Store in use. product at room may come into contact with temperature. Keep container food --PREVENT MOISTURE CONTAMINATION TO KEEP POWDER FREE FLOWING.-- F71_ AND EXPLOSION Nonflammable. AVOIDANCE: 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. HMI5 HAZ_n RATINGS: HEALTH: PERSONAL 3 FLAMMABILITY: PROTECTION: X 0 (See EXPOSURE LIMITS REACTIVITY: precautions, 0 section INGREDIENT VALUE UNIT TYPE AUTM 7.) SKIN" AMMONIUM PERFLUOROOCTANOATE .......... AMMONIUM PERFLUOROHEXANOATE .......... AMMONIUM PERFLUOROHEPTANOATE ......... H_PTADECAFLUORONONANOIC ACID, AMMONIUM SALT ...................... 0.01 0.i 0.I NONE MG/M3 MG/M3 MG/M3 NONE TNA ACGIH Y TNA 3M Y TNA 3M Y NONE NONE " SKIN NOTATION: Listed substances indicated with "Y" under SKIN refer to the potential contribution including mucous membrane to the overall and eye, either exposure by the by airborne or, cutaneous route more particularly, by direct contact with the substance. Vehlcles can alter skin absorption. SOURCE OF EXPOSURE LIMIT DATA: - 3M: - ACGIH: 3M Recommended Exposure American Conference of Guidelines Governmental Industrial Hygienists - NONE: None Established Abbreviations: N/D - Not Determined N/A - Not Applicable Page 725 CA - Approximately 31-0CT-2000 09:24 3H F_,r message ARGUS 418-020 Page 15/2: MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical Surfactant PAGE 6 8. HEALTH HAZARD DATA EYE CONTACT : Moderate Eye pain, tearing, Irritation: and hazy signs/symptoms vision. can include redness, swelling, SKIN CONTACT : Mild Skin Irritation (after prolonged or repeated contact) : signs/symptoms can include redness, swelling, and itching. May be absorbed those caused by through the skln inhalation and/or and produce ingestion. effects slmlllar IN_TION: Illness requiring by inhalation to medical moderate attention quantities may result from a single of this material. to exposure May be absorbed time. by inhalation and persist in the body for an ex_ended Single overexposure, above recommended guldQllnes, may cause: Irritation (upper respiratory) : signs/s_amptoms soreness of the nose and throat, coughing and can include sneezing. Prolonged cause: or repeated overexposure, above recommended guidelines, may Liver Effects: and tenderness slgns/symptoms can of upper abdomen. include yellow skln(JaundIce) IF S_4ALLOWED : This product can potentially either through dissociation generate Perfluorooc_anoate or metabolism. Animal studies anion, conducted on Perfluorooctanoate disturbances, weight effects, and benign anion loss, tumors indicate effects including liver loss of appetite, adrenal and hematologic 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 this material. from a single swallowing of a moderate quantity of CANCER: A mix1:ure of ammonium perfluoroheptanoate, perfluorohexanoate, (3825-26-1) was fed carclnogeniclty was significant compound two-year study there perfluorooctanoate, ammonium ammonium perfluoropen_anoate and ammonium that was 93 _o 97_ AMMONIUM PERFLUOROOCTANOATE to albino rats for 2 years, no compound induced found in the study. There were s;atls_Ically related benign testicular tumors. In a second were statistically significant compound related Abbreviations: N/D - Not Determined N/A - Not Applicable Page 726 CA - Approximately 32--0C2"-2000 09:24 311Faxme.q.._age ARGUS 418-020 Page 2b/17 MSDS: August FC-143 FLUORAD 25, 2000 Brand Fluorochemical 8. HEALTH HAZARD DATA (continued) Surfactanu PAGE 7 benign tumors in the liver, pancreas, and testis when compared libitum and pair-fed controls. Based on the current knowledge, findings have no human health implications. (3825-26-1) (1983 1993 studies conducted jointly by 3M and DuPont). to ad these and MUTAGENICITY: Not mutagenic transformation in invitro mutagenicity essays. Did not cause in a mammalian cell transformation assay. cell REPRODUCTIVE/DEVELOPMENTAL TOXINS: Not te_atogenic in rabbits by oral administration. rats by garage or inhalatlon exposures. Not reratogenic to OT}_T_ HEALTH R Product HAZARD Toxicity INFORMATION: S-mmary Sheet is available. The presence of organic fluorochemicals in the population and subpopulations, such as workers, da_Ing back _o the 1970"s. 3M*s epldemlological workers indicates no adverse effects. blood of the general has been published s_udy of Its own This product can potentially generate Perfluorooctanoate anion, either through dissociation or metabolism. Perfluorooctanoete 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 Perfluorooctanoate health effects anion when from used anticipated as intended exposure to this and instructed. SECTION CHANGE DATES INGREDIENTS SECTION CHANGED SINCE July 28, 2000 ISSUE Abbreviations: ----6--, N/D - Not Determined N/A - Not Applicable Page 727 CA - Approximately 32-0CT-2000 09:14 3M Pax IJe_age MSDS : FC-143 I_.,UORAD August 25, 2000 Brand Fluorochemical Surfactent ARGUS 418-020 *'age .L/i.t/ PAGE 8 The information in this Material Safety Data be correct as of the date issued. 3M MAKES IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANY MERCHANTABILITY OR FITNESS FOR A PARTICULAR Sheet (MSDS) is believed NO WARRANTIES, EXPRESSED IMPLIED WA==ANTY OF PURPOSE OR COURSE OF to OR PERFORMANCE OR USAGE OF TRADE. User is responsible for determining whether the 3M product is fit for a paz-Sicular 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 par_cicular 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 in errors, remote possibility that omissions or alterations electronic transfer in this information, may have resulted 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 ATTACHMENT4 ARGUS 418-020 Protoco4l18-020 Version:418-020(04NOV00) Page1 of 2 TEST SUBSTANCE PREPARATION PROCEDURE 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 solutionsof APFO for oral (gavage) administrationto rats on Pnmedica Argus Research Laboratories, Inc., Study number 418-020. B. General Information: 1. All solutioncontainers will be labeled and color coded. Each label will specify the protocolnumber, test substance identification,Argus batch number, concentration, dosage level, preparation date, expiration date and storage conditions. 2. Solutions will be prepared: Daily X Weekly Once prior to dosing B For_ days of use __ By Sponsor 3. Solutions will be administered at a final dosage volume of __5mL/kg/day. 4. Safety: X Gloves, uniform/lab coat, goggles or safety glasses and faceshield X Dust-Mist Respirator (for solution preparation and dosing) Half-Face Respirator Full-Face Respirator/Positive Pressure Hood X Tyvek sleeves (when usingthe bulk material) X Work in a chemical fume hood and use a half-face respiratorwhen using the bulk TAgS only 5. Dosage solutions adjusted for % Activity/Purityor Correction Factor Yes X No (Calculations based on 100%) Activity % Purity Correction Factor 6. Sampling requirements: Cited in protocol. 7. Storage: Cited in protocol. Page 730 ATTACHMENT4 ARGUS 418-020 Protoco4l18-020 Version:418-020(04NOV00) Page2 of 2 TEST SUBSTANCE PREPARATION PROCEDURE 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 and mix with a stir bar and magnetic stir plate (see PREPARATION CALCULATIONS). 3. Once the test substance is completely dissolved, transfer the solutionto an appropriately sized graduated cylinder. QS ad with vehicle to the requiredvolume (see PREPARATION CALCULATIONS). 4. Stopper the graduated cylinderor cover with parafilm and mix by inversion several times to ensure proper mixing. Return the solution to the labeled container with the stir bar. Place on a magnetic stir plate and agitate prior to and during aliquotting,dosage administrationand/or sampling. 5. Repeat steps (1) through (4) for each concentration. Written By: _(_._-- (_' _ ' Clarification: _J-_/_"_"J)-_N'YNeos (See attached clarification form.) Initials/Date: (-_,__ _. 0/' Page 731 ARGUS 418-020 ATTACHMENT 4 NECROPSY, ORGAN WEIGHTS AND HISTOPATHOLOGICAL EVALUATION Page 732 ATI'ACHMENT4 ARGUS 418-020 Protocol418-020 Page 1 of 2 NECROPSY, ORGAN WEIGHTS AND HISTOPATHOLOGICAL EVALUATION Orqan wei,qhts The following organs willbe individuallyweighed and organ-to-body weight and organqo-brain weight ratioswill 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 oviductsand cervix epididymides prostate seminal vesicles (with coagulating glands and fluid) For F1 and 1=2generation weanlings, the following organs will be weighed from one randomly selected pup per sex per litter: brain spleen Tissue Retention thymus 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) Female Rats adrenal glands gross lesions (includingtissue masses) vagina Male Rats uterus with oviducts, cervix and ovaries testis (right) seminal vesicles (with coagulating gland) epididymis (right) prostate Note: Testes will be fixed in Bouin's solutionfor 48 to 96 hours before being retained in neutral buffered 10% formalin. Page 733 ATTACHMENT4 ARGUS 418-020 Protocol418-020 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 histologicalevaluation: target organs (if identified by amendment) gross lesions (including tissue masses) Histoloqical 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 histologically a. 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 longitudinalsection) 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. Histopathologicalexamination should detect qualitative depletion of the primordialfollicle 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 statisticallyappropriate 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 histologicalevaluationa. 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 ARGUS 418-020 _" _R_'_DIG'_ Arg9u0s5RSehseaerhcyh DLraibvoe.ratBoruields.ingI hAe. Horsham. PA 19044 Telephone: (215) 443-8710 Telefax: (215)443-$587 PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LI'I-I'ER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS SPONSOR'S STUDY NUMBER: %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 Chanae: 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 F 1 generation pups per sex per litter per group (60 male and 60 female pups per group), resulting in a total of 600 rats (300 rats per sex) chosen for continued evaluation, rather than 30 male and 30 female (1 per sex per litter) F 1 generation 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 F 1 generation rat per litter per group for continuation through mating to produce the F2 generation. If results warrant that the study be extended to include a third generation, the procedures previously described for the F 1 generation will be used for selection ofF2 generation pups continued on study. ANY REVISIONS TO THIS FINALIZED AMENDMENT SUBSEQUENT AMENDMENT. MUST BE MADE BY -Page 735 Reason for Change: ARGUS 418-020 Protocol418-020 Amendment1 Page 2 The Sponsor requested that sexual maturation be measured for two pups per sex per litter per group. 3. Rationale for Dosage Selection (page 11 of the protocol): The intermediate dosage levels are expected to produce minimal observable toxic effects, rather than the intermediate dosage level is expected to produce minimal observable toxic effects. Reason for Change: This change corrects the protocol because there are two intermediate dosage levels rather than one intermediate dosage level. 4. Postweaning 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 sperrnatid concentration using computer-assisted sperm analysis (CASA). The left testis will be weighed (both before and after removal of the tuniea albuginea) and then homogenized. A sample from the resulting homogermte will be stained with an IDENT Stain Kit from Hamilton Thome Research and a slide will be prepared for analysis by the Hamilton Thorne IVOS. Ten fields will be analyzed to detcmfine testicular spc:fftatid 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 SUBSEQUENT AMENDMENT. MUST BE MADE BY Page 736 ARGUS 418-020 Protocol 41 g-020 Amendment 1 Page 3 6. F 1/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 !0% formalin for possible histological evaluation. Reason for Chan_;e: This change clarifies the protocol. 7. F 1/F2 Generation Pups Not Selected for Continued Observation (page 19 of the protocol): All pups not selected for continued observation following continued observations for sexual maturation will be sacrificed and a limited necropsy will be performed. The thoracic, abdominal and pelvic cavities will be examined for moss lesions: -moss lesions will be preserved in neutral buffered 10% formalin. All other tissues and the carcass will be discarded. Reason for Chanqe: 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 1 and 2 of ATTACHMENT 4 to the protocol): The following tissues will be collected from the three selected F I and F2 generation weanling rats per sex per litter, rather than from all F 1 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 4114-020 Amendment 1 Page 4 AlanM.Hob_. Ph.DD.,_r Director of Research Date Ray__,q_GY. ork, P_.. D_BT Date Ass_.c 7_eDireetor o_ch Study'Director :_LJc_,._,a /-DZ-na C. Lebo, V.M.D. Date Chairperson, Institutional Animal Care and Use Committee John Butenhoff. Ph.D., DABT, CIH Date Study Monitor Sponsor's Representative ANY REVISIONS TO THIS FINALIZED AMENDMENT MUST BE MADE BY SUBSEQUENT AMENDMENT. Page 738 ARGUS 418-020 905 Sheehy Drive. Building A Horsham. PA 1904,1 Telephone: (215) 443-8710 Telefax: (215) 443-85g'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 Amendment 2 - 8 February 2001 I. Nipple Examination (page 2 of Amendment 1): [Effective Date: 1 February 2001] On day 12 postpartum, all male pups will be examined for the presence of nipples. The criterion of passing is met when no nipples are present. Reason for Change: This change clarifies the criterion and sex of pups to be examined. Alan M. Hoberman, Ph.D., DABT Director of Research Date R_. York, Ph,Q., I_ABT Date Associate Director of RL_se_ch and Study Direetor Theresa H. Woodard, D.V.M. Date Chairperson, Institutional Animal Care and Use Committee John Butenhoff, Ph.D., DABT, CIH Date Study Monitor and Sponsor's Representative Any revisions to this finalized amendment must be made by subsequent amendment. Page 739 ARGUS 418-020 905 Sheehv Drive. Building A Horsh_n. PA 19044 Telephone: (215) 4-43-8710 Telefax: (215)a43-8587 i PROTOCOL 418-020 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: Fax: (215) 345-7070 (215) 345-4326 The recipient will be notified in advance of sample shipment. Reason for Chan_e: This change adds the address for tissue shipment to the protocol. _-/-//'2'_7._.' "_-....._ _Alan M. Hoberman. -" Director of Research Ph.D., DABT l --_ " _ ......-.- . Date Valerie A. Sharper, M.S. Date Director of Study Management for Raymond G. York, Ph.D., DABT Associate Director of Research and Study Director ., Theresa H. Woodard, D.V.M. ,-" Date John Butenhoff, Ph.D., DABT, CIH Date Chairperson. Institutional Animal Care and Use Committee Study Monitor Any revisions to this f'malized amendment must be made by subsequent amendment. Page 740 ARGUS 418-020 905 SheehyDrive_Bldg.A Hor_=nP. AI_ Telel:hon_(215) 443-8710 TelefaK:(215)443-8587 ARGUS R_ARCH Chcrles RiverLct:x_ctories Discoveryand Devel_t Serving__ PROTOCOL 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITI'ER 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 acc.ount for survival of pups for entire period following the calculation of viability index (percentage of pups born that survive to days 1 and 5 postpartum). ADliarnecMt.oHorofbReersmeaanr,cPhh.D.,DABT De,, Date Askoc_te Directdl_ of Res_'ch and Study'Director Theresa H. Woodard, D.V.M. Date Chairperson, Institutional Animal Care and Use Committee John Butenhoff, Study Monitor , ClI-I Date Any revisions to this rmalized 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 PROCEDURES OF THE TESTING FACILITY OPERATING 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 I II III (mg/k_/day) 0 1 3 Studya DL 8 DL 11 DG 18 DL 8 DL 11 DL 8 DL 11 Rat Numbers 13814, 13817, 13818, 13830 13806, 13808 13809 13831, 13849, 13859, 13860 13837, 13850, 13853, 13858 13868, 13874, 13877, 13882 13889 IV 10 DL 8 13892, 13899, 13913, 13914, 13916, 13917, 13919, 13920 DL 21 13907 V 30 DL 5 13945 DL 8 DL 11 13931, 13932, 13950 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 F1 Dosage Group V Dosage (mg/kg/day) 30 Date 08 MAR O1 08 MAR O1 Day of Study DS 1 DS I 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), F1 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 (0.08mL). 5. On 15 April 2001, F1 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 HI 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 1 Female Rats 0 0 4 0 2 1 0 5 0 0 1 0 1 I 0 14 0 0 1 14 0 0 1 2 0 16 0 0 3 2 14 0 3 0 1 17 0 4 0 0 2 0 1 0 1 2 0 2 0 0 1 0 2 17 0 1 0 0 2 0 1 10 0 0 11 0 2 0 1 Range of Time Deviated (minutes) +1 +1 to +3 +1 +1 +1 to+2 +4 +14 +52 +1 to +10 +329 + 1 to +6 +I +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 Dosage (mg/kg/day) 0 II 1 III 3 IV 10 Date 09 MAR 01 15 MAR 01 25 MAR 01 10 APR 01 15 APR 01 17 APR 01 21 APR O1 23 APR O1 23 JUN 01 02 JUL 01 12 MAR 01 13 MAR O1 15 MAR 01 24 MAR O1 27 MAR 01 02 APR O1 05 APR 01 09 APR 01 12 APR 01 29 APR O1 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 JUN01 29 JUN 01 07 JUL O1 14 MAR 01 25 MAR 01 02 APR 01 09 APR O1 12 APR 01 19 APR 01 06 JUN 01 18 JUN 01 Number of F I Generation Rats Male Rats 3 Female Rats 0 36 0 4 0 0 11 2 0 1 0 12 0 4 0 0 1 1 0 0 2 0 22 0 1 0 2 0 3 21 0 1 0 10 0 42 0 0 1 0 3 0 2 0 3 0 28 0 5 57 0 1 0 4 0 0 2 0 2 0 1 0 2 0 1 O 3 0 2 0 1 10 0 0 1 42 0 0 1 13 0 0 9 Range of Time Deviated (minutes) +1 +1 to +17 +1 to +3 +1 to +6 +1 +5 +1 to +3 +1 to +3 +1 +1 -1 -4 to -1 -2 +1 +1 +1 to +3 -1 -5 to -1 +1 to +10 +1 +1 +1 +1 to +2 +26 to +40 +1 to +2 +8 to +16 -1 +1 +1 to +2 +1 +63 +1 +1 +1 -1 +1 +4 to +7 -1 +8 to +15 -1 +1 to +4 +1 to +3 Page 746 ARGUS 418-020 Dosage Group V Dosage (mg/kg/day) 30 Date 08 MAR 01 15 MAR 01 17 MAR 01 19 MAR 01 30 MAR 01 02 APR 01 03 APR 01 08 APR 01 10 APR 01 12 APR 01 20 APR 01 16 MAY 01 09 JUN 01 12 JUN 01 01 JUL 01 Number of FI Generation Rats Male Rats 2 Female Rats 1 1 0 6 0 55 0 0 1 2 0 5 0 3 0 1 0 54 0 0 15 0 10 0 3 0 1 0 6 Range of Time Deviated (minutes) -1 to +5 +41 +1 to +2 +67 to +79 +29 +1 to +12 -1 +1 -I +5 to +20 +1 to +5 -2 to -1 -2 to -1 +1 +1 to +3 These deviations did not adversely affect study because, except for fifteen incidents, minutes or less. the outcome the extent or interpretation of the deviation of the was ten 7. Postdosage observations were not recorded for the following rats. Generation P F1 Dosage Group II IV V I III Dosage (mg/kg/day) 1 10 30 0 3 IV 10 V 30 Date 18 JAN 01 18 JAN 01 15 DEC 00 22 MAR 01 26 MAR 01 21 MAY 01 05 JUL 01 31 MAR01 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 DS25 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 study because sufficient data were available to evaluate this parameter. of the 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 19JAN 01 Day of Study DS 68 Sex Female Rat Number 13882 This deviation did not adversely affect the outcome or interpretation because sufficient data were available to evaluate this parameter. of the study Page 748 ARGUS 418-020 9. Observations for maternal behavior were not recorded for the following P generation female rats. Dosage Group I Dosage (mg/kg/day) 0 Day of Study DL 1 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 DL 22 Date 16 FEB 01 05 MAR 01 06 MAR 01 07 MAR 01 08 MAR 01 09 MAR 01 10 MAR 01 13 MAR 01 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 O1 DL1 16FEB 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 Recorded a 1, 2, 3, 4, 5 4, 5 4, 5 4, 5 4, 5 4, 5 4, 5 4, 5 4, 5 I, 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 lmale 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 F1 Dosage Group III V Dosage (mg/kg/day) 3 30 Date 10MAR 01 I0 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 F1 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 because sufficient data were available to evaluate this parameter. of the study 12. Predosage observations, dosage volumes and postdosage observations were not recorded for the following rats. Generation F1 Dosage Group III IV Dosage (mg./k_/day) 3 10 Date 12APR 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 study because sufficient observations were available to evaluate theses parameters. There was no discrepancy in the chemistry data, therefore presumed that the rats were dosed appropriately. of the it is 13. Terminal body weights were not recorded for the following rat. Generation F1 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 because sufficient data were available to evaluate this parameter. of the study Page 750 ARGUS 418-020 14. On 29 May 2001, DG 0, F1 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 F1 Dosage Group II III IV Dosage (mg/kg/day) 1 3 I0 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 F1 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 Dosage (mg/kg/day) 0 IV 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 F1 Dosage Group I IV V Dosage (mg/kg/day) 0 I0 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 study because sufficient data were available to evaluate this parameter. of the 20. Clinical observations were not recorded for the following pups. Generation F1 Dosage Group V Dosage (m_/k_/day) 30 Date 25 JUN 01 26 JUN 01 Day of Study DL 3 DL 4 Litter Number 1568 1568 Number of Pups 12 12 These deviations did not adversely affect the outcome or interpretation study because sufficient data were available to evaluate this parameter. of the 21. Anogenital distance measurements were not recorded for the following rat. Generation F1 Dosage Group II Dosage (mffkg/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 because sufficient data were available to evaluate this parameter. of the study Page 752 ARGUS 418-020 22. The terminal blood sample was not taken for the following rat. Generation P Dosage Group I Dosage (m_/kgJday) 0 Date 19MAR 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 14JUL 01 Day of Study DL 22 Sex Female. Rat Number 1362 This deviation did not adversely affect the outcome or interpretation because it was a single event. of the study 24. The pituitary was not retained for the following rat. Generation P Dosage Group I Dosage (m_/k_/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 F1 Dosage Group V Dosage (m_/k_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 because sufficient data were available to evaluate this parameter. of the study 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 F1 Dosage Group I II HI IV V Dosage (mg/kg/day) 0 1 3 10 30 Date 08 MAR 01 08 MAR Ol 09 MAR 01 26 APR 01 13MAR 01 09 MAR 01 09 MAR 01 09 MAR 01 11 MAR 01 11MAR 01 13MAR 01 14MAR 01 Day of Study DS I DS l 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 ,i 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 F1 Dosage Group I Dosage (mg/kg/day) 0 II 1 III 3 IV 10 V 30 a. Uterus and cervix were retained. Date 23 JUNO1 06 JUL 01 25 JUN O1 23 JUN 01 26 JUN O1 23 JUN 01 29 JUN 01 25 JUN O1 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. Date and Study Director Page 754 ARGUS 418-020 APPENDIX H CERTIFICATE OF ANALYSIS Page 755 ARGUS 418-020 Centre Analgflcal Laboratories. inc. V''_'_k'_IL Phone: (814) 231-8032 Fax: (814) 231-1253 or (814) 231-1580 Purity _ INTERIM CERTIFICATE OF ANAL YSIS Centre Analytical Laboratories COA Reference #: 023-033 3M Product: Ammonium Pertluorooctauoate Test Control Reference #: TCR-99131-37, Lot #: 332 Test Name Purity: 95.2% Specifications Result 95.2% Appearance Identification Metals (ICP/MS) 1. Calcium 2. Magnesium 3. Sodium 4. Potassium 5. Nickel 6. Iron 7. Manganese Total % ImpunW (NMR) Total % Impm'tty (LC/MS) Total % ImpunW (GC/MS) Residual Solvents (TGA) Purity by DSC Inorganic Anions (IC) 1. Chloride 2. Fluoride 3. Bromide 4. Nitrate 5. Nin'ite 6. Phosphate 7. Sulfate Organic Acids: (IC) 1. TFA 2. PFPA 3. HFBA 4. NFPA Elem.-mal Analysts_: 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. Fluorine Ammonium Analysis' Ion Selective Electrode White, erystalhne solid Theoretical Theoretical Theoretical Theoretical Theoretical Value Value Value Value Value = 22.3% = 0.935% -- 3.25% = 0% = 66.1% Theoretical Value = 4.18% Conforms Positive I. 0.001 wt./wt.% 2. <0.00I 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 w_Jwt% 4.49 wL/w_.% None Quantified None Detected 99.7% 1. <0.015wt./wt.% 2. <0.005vct./wt.% 3. <0.040 wt./wt.% 4. <0.009wt./wt.% 5. <0.006wtJwt.% 6. <0.006wtJwt.% 7. <0.040 wtJwt.% 1. <0.1 wt./wt.% 2. <0.I wt./wt.% 3. <0.1 wt./wt.% 4. <0.25wt./wt.% 1. 18.9 wt./wt.% 2. 1.31 wt./wt.% 3. 3.75 wt./wt.% 4. 4.34 wt./wt.% 5. 63.2 wt./wt.% 3.49 wt./wt. % COA023033-37.doc Page 756 Page 1 of 2 ARGUS 418-020 CEntrG Analytical laboratories. Inc. r V _'_k_ Phone: (814) 231-8032 Fax: (814) 231-1253 or (8141 23%1580 INTERIM CER TIFICA TE OF ANAL YSIS Centre Analytical Laboratories COA Reference #: 02_t-033 3M Product: Ammonium Perfluorooctanoate Test Control Reference #: TCR-99131-37, Lot #: 332 Date of Last Analysis: 12/15/00 Expiration Date: 12/15/01 Storage Conditions: < -10 *C Re-assessment Date: 12/15/01 tPurity ffi100% - (Total Metal impurities, 0.006% + Total NMR impurities, 0.34% + Total LCJMS impurities, 4.49%) Total impurity fxom all tests ffi4.84% Purity = 100% - 4.84% = 95.2% 2TFA HFBA NFPA PFPA Trifluoroacetic acid Heptafluorobutyric acid Nonafluoropentanoic acid Pentafluoropropanoic acid 3Theoreticalvalue calculationsbasedon the empirical formula, CsFIsO:(')NI'I4(+) (MW=43].1) LC/MS Purity Profile: PeakI # 2 3' Tmal Retention12.T14im0 e (rain) 13.504 14.099 Ma2s6s9(s) 331,319 369' IdeCntbity C_ homologuc/Ft_ PFOA 1A67r5ea96 860991 21861700 22890287 %0A.7r3ea 3.76 4.49 This work was conducted under EPA Good Laboratory Practice Standards (40 CFR 160). PreparedBy: /_,,,_If_d__ D_vid S. Bell Sc_ltist. Ce_t/ _ua_boratories _../,,_6r Date ./ /,"_ohn Flaherty uate " Laboratory Manager, Centre Analytical Laboratories COAO23033-37.doc Page 2 of 2 Page 757 ARGUS 418-020 APPENDIX I ANALYTICAL REPORT Page 758 3M Medical Department Study: T-6889.6 3M Medical Department Stu0y: T-6889.6 .... -:,-=........ --_ --: ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analytical Report: FACT "fOX-164 LIMSE00-2738 Study Title Oral(Garage) Two-Generation(One Utter perGeneration)ReproductionStudyof AmmoniumPerfluorooctanoat(eAPFO/PFOA)in Rats q | _ -L'_-_ Analytical Laboratory Report Title Determinationofthe Presenceand Concentrationof PFOA Fluorochemicainl RatSera Samples Data Requirement January 7, 2002 Author 3M EnvironmentaLlaboratory Study Completion Date At signing Performing Sere Analyses 3M Environmental Laboratory Building 2-3E-09, 935 Bush Avenue SL Paul, MN 55106 Laboratories Sera Extractions Pace Anahttical Se_ices, Inc_Tier2 Facility 1700 Elm Street SE, Suite 100 Minneapolis, MN 55414 Project Identification 3M MedicalDepartmentStudy:T-6889.6 ArgusIn-LifeStudy:418-020 Analytical Report: FACT TOX-164 3M LIMS No. E00-2783 Total Number of Pages 110 ._M/:nvirnnrr_ntal I ahnmlntv 3M Environmentai Laboratory Page 759 P:n_ 1 Page ] 3M Medical Department Study: T-6889.6 3M MedicalDepartmenSt tudy:".!"-6889.6 - "-"........ - ARGUS 418-020 Analvncal Report: FACT TOX-104 LIMS E00-2738 AnalyticaRl eportF: ACTTOX-164 UMS E00-2738 This pagehas beenreservedforspecificcountryrequirements. 3M Environmental Laborato_. Page 760 Page2 3M Medical Depalu.entStudy: T-6889.6 3M Medical DepartmentStudy:T-6889.6 Analytical AD:Z_rIO A1 o t'_t-t R_p_: _._C'_ _']_-u164 LIMS E00-2738 AnalyticalReport:FACT TOX-164 LIMS E00-2738 GLP Compliance Statement Analytical Laboratory Report Title: Determination of the Presence and Concentration of PFOA Fluorochemical in Rat Sere Samples Study Identification Numbers: T-6889.6, FACT TOX-164, LIMS E00-2738 This study was conducted in compliance with United States Environmental Protection Agency (EPA) Good Laboratory Practice (GLP) Standards 40 CFR Part 792, with the exceptions in the bulleted list below. Exceptions to GLP compliance: There were two study directors in this study. This study was designed as two separate studies. The in-life phase (Argus #418-020) was considered to end at the generation and shipment of specimens. The analytical study (3M FACT-TCX164) was considered to start at the receipt of these specimens for analysis. This resulted in having two separate study directors, one for each phase of the same study. However, since the technical pedorrnance of each phase was entirely separate, no effect is expected from this exception. Dose confirmation end stability samples were not analyzed according to the GLPs. The purity and stability of the surrogate THPFOS standard is not included in this report, it is not known at this time. John Butenhoff, Ph.D., Study Director David Sanck_, Ph.D., Sponsor Representative Li._ Clemen, Principal Analytical Investigator William Reagen, Ph.D., Laboratory Mana_ Date Date Date " ..x Date 3M Environmental Laboratory 3M Environmental Laboratory . Page 761 Pa0e 3 Page 3 3M Medical Department Study: T-6889.6 3M Medical Department Stucly:T-6889.6 -- -:'=- ........... ARGUS 418-020 Analytical Report: FACT TOX-161 LIMS E00-2738 AnalyticalReport: FACT TOX-164 LIMS E00-2738 GLP Study--Quallty Assurance Statement Analytical Laboratory Report Title: Determination of the Presence and Concentration, of PFOA Fiuorochemical in Rat Sora Samples Study identification Numbers: T-6889.6, FACT TOX-164, LIMS E00-2738 This study has been inspected by the 3M Environmental Laboratory Quality Assurance Unit (QAU) as indicated in the following table. The findings were reported to the study , director and laboratory management. Inspection Dates I 5/30/01 Phase Protocol Date Reported to Management Study Director 05/30/01 ;J 05/30/01 6/27/01 6/26/01 09/25/01-09/28/01 and 10/01/01-10/02/01 11/07/01-11/08/01 Analysis Sample Dilutions Data Draf_report 06/27/01 06/26/01 10/03/01 11/09/01 i 06/27/01 06/26/01 _ 10/03/01 ; 11/09/01 QA U Repredentative Date 3/VlEnvironrr_ntal La/x3ratorv 3M Environmental Laborato_ Page 762 Paoe 4 Page 4 3M Medical Department Study: T-6889.6 3M MedicalDepartmentStu0y:T-6889.6 Table of Contents - "--'-.......... -' _ Analytical ARGUS 418-020 Report: FACT TOX-164 LIMS E00-2738 Analy'dcalReport: FACT TOX-164 LIMS E00-2738 GLP Compliance Statement................................................................................................... 3 GLP Study - Quality Assurance Statement ............................................................................ 4 List of Tables .......................................................................................................................... 6 Study Personnal and Contributors......................................................................................... 7 Locationof Archives............................................................................................................ -.7 Introductionand Purpose ....................................................................................................... 8 Speciment Receipt and Maintenance ..................................................................................... 8 Chemical Characterization of the Reference Substance ..................................................... .:10 Sample Preparation and Analysis.......................................................................................... 11 Dose Confirmation and StabilityAnalyses ........................................................................ 11 Sera Analyses.................................................................................................................... 11 Method Summaries ........................................................................................................... 12 Preparatory Method .................................................................................................... 12 Analytical Method ....................................................................................................... 12 Analytical EQuipment.................................................................................................. 13 Deviations/Amendments ................................................................................................... 14 Data Quality Objectives and Data Integrity ............................................................................ 14 Data Summery, Analyses, and Results.................................................................................. 14 Summary of Quality Control Analyses Results.................................................................. 15 Statement of Data Quality ................................................................................................. 16 Summary of Sample Results ............................................................................................. 16 Statistical Methods and Calculations ..................................................................................... 17 Statement of Conclusion ........................................................................................................ 17 References ............................................................................................................................. 17 Appendix A: Chemical Characterization and Control Matrices .............................................. 18 Appendix B: Protocol, Amendments, and Deviation(s) .......................................................... 19 Appendix C: Extraction and Analytical Methods .................................................................... 36 ETS-8-4.1, Extraction of Perfluorooctanesulfonate or Other Fluorochemical Compounds from Serum for Analysis Using HPLC-Electrospray/Mass Spectrometry, (14 pages) .......... 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 Fluorochemicais in Serum Extracts Using HPLC-Eiectrospray/Mass Spectrometry, (9 pages) .......................... 66 ETS-8-5.2, Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry, (11 pages) ........................ 76 Appendix D: Dose Confirmation Analyses and Data Summary Tables ................................ 87 Appendix E: Data Spreadsheets ........................................................................................... 90 3M Environt_ental Laboratory 3M Environmental Laboratory Page 763 Page 5 Page 5 3M Medical Depa_ u.ent Study: T-6889.6 - . .......... -_ - - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-273S 3M MedicalDepartment Study:T-6889.6 AnalyticalReport:.FACT TOX-164 LIMS E00-2738 Appendix F: Example Calculations........................................................................................ Appendix G: Interim Certificate(s) of Analysis ....................................................................... Appendix H: Report Signature Page ...................................................................................... 106 10"1 110 List of Tables Table 1. Specimens received from Argus Research Laboratory Study (418-020) on 14 November, 2000 ............................................................................................ :..... 8 Table 2. Specimens received from Argus Research Laboratory Study (418-020) on 18 April, 2001 ............................................................................................................ 9 Table 3. Specimens received from Argus Research Laboratory Study (418-020) on 13 July, 2001 ......................................................................................................... _...9 Table 4. Specimens received from Argus Research Laboratory Study (418-020) on 09 August, 2001 ........................................................................................................ 9 Table 5. Characterization of the Analytical Reference Substance in Study FACT-TOX-164 ................................................................................................ ......... 10 Table 6. P Generation Rat Samples Analyzed in Study FACT-TOX-164 ............................. 11 Table 7. Target Ions Monitored in 3M Laboratory Analyses.................................................. 13 Tabel 8. Determination of the LOQ in the Analyses of Rat Sara Extracts ............................ 15 Table 9. Matrix Spike Recoveries in the Analyses of Rat Sara Extracts............................... 16 Table 10. Characterization of the Control Matrices Used for Sara Analyses in Study FACT-TOX-164 ......................................................................................................... 18 Table 11. Characterization of Test Substance in Study FACT TOX-164 .............................. 18 Table 12. Dose Confirmation Analyses - Extracted 11/17/00, Analyzed 11/27/00 ............... 87 Table 13. Dose Confirmation Analyses - Extracted 11/27/00, Analyzed 11/28/00 ............... 88 Table 14. Dose Confirmation Analyses - Extracted 01/17/01, Analyzed 01/23/01 ............... 89 Table 15. TOX 164 Data Summary of PFOA Concentration---Rat Serum (pg/mL) .............. 89 .':lk_g'nv/mnm_nt_lI Dhnratnrv 3M Environmental Laboratory Page 764 Daem Page 6 3M Medical Depa_tuient Study: T-6889.6 3M Medical Department Study:T-6889.6 .... - .............. ARGUS 418-020 Anal_ical Report: FACT TOX-164 LIARS E00-2738 AnalyticalReport:FACT TOX-164 LIMS E00-2738 Study Personnel and Contributors StudyDirector John Butenhoff, Ph.D. 3M Corporate Toxicology 3M Medical Department Building 220-2E-02 St. Paul, MN 55144 Analytical Chemistry Laboratories Sera Analyses 3M EnvironmentalLaboratory(3M Lab) Lisa Clemen, Principal Analytical Investigator Sponsor 3161Corporate Toxicology 3161Medical Department Building 220-2E-02 ST. Paul, MN 55144 David Sanders, Ph.D., Sponsor Representative Sera Extractions Pace AnalyticalServices,Inc.--Tier2 Facility 3M Lab Contributing Personnel Rhonda Dick" Kristen J. Hansen, Ph.D. Madena M. Heying" Harold O. Johnson "Contract _ Drofes_or_ service employees Kelly J. Kuehlwein Sally A. Linda Bob W. Wynne" Location of Archiv_ 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. 3M Environmental Laborato_ Page 765 Page 7 3M Medical Department Study: 3"-6889.6 3M Medical Department8tuOyT:-6889.6 - -- "--- Analytical ARGUS 418-020 Report: FACT TOX- 104 LIMS E00-2738 AnalyticalReport:.FACT TOX.164 LIMS E00-2738 Introduction and Purpose The purpose of the study is to determine the presence end concentration of PFOA fluorochemical in rat sara samples taken from the 3M study "Oral (Gavage) TwoGeneration (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO/PFOA) in Rats." The sara samples are the product of the in-life study completed by Argus Research Laboratories under study number 418-020 ('T6889.6). Analyses of sara samples were completed by the 3M Environmental Laboratory under study number FACT-TOX-164 (E00-2738), and the results of these analyses are. presented in this report. The analytical portion of this study was initiated on 07 June, 2001. Specimen Receipt and Maintenance The 3M Environmental Laboratory received dosage solution/suspension specimens collected at the end of the m-lifestudy #418-020 on 14 November, 2000, and sera specimens collected on 18 Apdl 2001 from Argus Research Laboratones. All dosage solution/suspension specimens were received cold in good condition on ice packs while all seraAiver specimens were received frozen in good conditionon dry ice. All specimens were immediately transferred to storage at -20"C = 10C. Specimens that were extracted at Pace Tier2 were shipped frozen on dry ice. Table 1. Specimens received from Argus Research Laboratory Study (418-020) on 14 November, 2000 Specimer_ Dosage SoluboNSuspension Timepolm Day0 Stability Day 10 Stability ConcencalJon Total # II 5 5 5 RM Envimnrr_mtal Laboratory 31t4 Environmental Laborator3. , Page 766 Paoe 8 Page 8 3M Medical Department Study: T-6889.6 3M MedicalDepartmentStuclyT: -6889.6 .... ---_- ........ -- _ ----- ARGUS 418-020 Anal_ical Report: FACT TOX-164 LIMS E00-2738 AnalyticalReport: FACT TOX-164 UMS E00-2738 Table 2. Specimens received from Argus Flmmarch Laboratory Study (418-020) on 18 A _dl, 2001 Specimens Serumand Liver Gender Female Male Group I II III IV V I II III W V Total # 26 26 29 29 28 30 30 30 3O 29 Table 3. Specimens received from Argus Research Laboratory Study (418-020) on 13 July, 2001 ,Specimens DosageSolution/Suspension Tinmpoint Concentralion Totml# 5 Table 4. Specimen=; received from Argus Research Laboratory Study (418-020) on 09 August. 2001 Specimens Serum and Liver Gendmr Female Male ' Group I II III IV V I II III IV V Total 28 28 27/28 28 29 3O 29 30 30 29 ."4M_'n_,irnnm_nPaIl mhnnllPnrv JM Environmental Laboratory Page 767 Paoe 9 Page 9 3M Medical Department Study: T-6889.6 3M MedicaDl epartmenSt tudyT: -6889.6 .... .--........ ---_ _ - ARGUS 418-020 Asaai.vticalRepon: FACT TOX-164 LIMS E00-2738 AnalybcaRl eportF:.ACTTOX-164 LIMSE00-2738 Controlmatricesusedin sereanalysesperformedduringFACT-TOX-164were obtained fromcommerciasl ourcesand are presentedin AppendixA. Samplesanalyzedat the3M EnvironmentaLl aboratorywillbe storedand maintainedat the laboratoryaccordingto GLP requirements. Chemical Characterization of the Reference Substance Ammonium perlluorooctanoate CAS Number:3825-26-1 ChemicalFormula:CTFlsCOO'NI-6" MolecularWeight:430.9 Chemicalcharacterizationinformationonthereferencesubstanceammonium perfluorooctanoatuesedin thisstudyis presentedin tabularformbelow, Table5, Characterizationof the AnalyticalReferenceSubstancein Study FACT TOX-164 I.ocatlon Sub_mrme 3M lab III THPFOS PFOA TcR-gg030-030 (Surrogate Sta_) TCFI-00017- O55 Seuml m SynOumt t.alxxi=_ m SCta=mralagme m llm_al IJ= Om='N_k_ 1NU_,,-Nm _ "S_a_ otAna_sfromC,_m_,_BM_W_ -20"C 10"C 332 w_ powoe" gS.0"o/, __mml_ G. _ 10"C Q75-gl wPae_ NA RM F.nvirnn_ntal Laboratory 3M Environmental Laboratory Page 768 Paoe 10 Page lO .... 3M Medical Department Study: %6889.6 3M Medical Department StuclyT: -6889.6 Sample Preparation and Analysis ----'= ....... --_- "---'-'-Analytical ARGUS 418-020 Report: FACT TOX-164 LIMS E00-2738 AnalylJcaRl eport:.FACT TOX-164 UMS E00-2738 oo,e md Stabny Dose confirmation and stability analyses were performed on test substance dose samples (concentration, Day 0 Stability,and Day 10 Stability) collected on 10 November 2000 during the in-life phase of the study:,the results are presented in Appendix D. Dose confirmation and stability samples were not analyzed according to the GLPs (analyses occurred prior to study initiation). Dose confirmation and stability extractions were performed on 17 November, 2000, 27 November, 2000, and one re-extraction performed on 17 January, 2001 by diluting these samples with Milli-Q water, then extracting the samples using the ion pair procedure, ETS-8-4.1. For one dose solution concentration sample, a matrix spike was prepared (approximately 100 ng/mL) by diluting the concentraion sample then spiking the diluted solution. In all cases, samples were analyzed versus an unextracted curve using HPLC-ES/MS/MS. The instrumental parameters and analytical conditions described in ETS-8-5.1 were used for dose solution analyses. Detailed descriptions of the methods used are located in Appendix C. lk,mk,aly= As per the study protocol, only serum samples from the P Generation Group I, Group IV, and Group V were analyzed in this phase study (See Table 6 for more information). An equal number of male and female rat sera samples were randomly selected for analysis. Sera samples were extracted beginning on 14 June, 2001 using an ion pairing reagent and methyl-ten-butyl ether (MtBE). Sample extracts were analyzed using highperformance liquid chromatography-electrospray/tandem mass spectrometry (HPLCESMSMS) in the multiple reaction mode versus an extracted sera curve. PFOA levels were quantitated by external calibration. Table 6. P GenemUon Rat Samples Analyzed in Study FACT-TOX-164 DmmgeGroup GroupI GroupIV GroupV Gender Male Female Male Female Male Female Total # 3 3 10 10 10 10 .'MAEnvinSnrn_nt_lI_boratotv 3M Environmental Laboratory Page 769 Pass 11 Page 1l 3M Medical Department Study: T-6889.6 3M MedicalDepartmenSt tudy":1"-6889.6 Method Summaries ..... -==.......... " -'--- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-273g AnalyticaRl eport:FACTTOX-164 LIMSE00-2738 Followingis a briefdescriptionofthe methodsusedduringthis analyticalstudyby the3M EnvironmentaLl aboratory.Detaileddescriptionsof themethodsusedin thisstudyare locatedin AppendixC. 311E+m1 4mmentlmI.dabmatmy PREPARATORY METHOD ETS-8-4.1,"Extractionof PotassiumPerfluorooctanesulfonaoterOther FluorochemicaCl ompoundsfrom SerumforAnalysisusingHPLC-Electrosprey/Mass Spectrometry" ETS-8-4.2, "Extractionof FluorochemicaCl ompoundsfrom Serumfor Analysisusing HPLC-Electrosprey/MasSspectrometry" Analyticasl ampleswareextractedusingan ion-pairingextractionprocedure.An ionpairingreagentwas addedto a laboratorysampleandtheanalyteionpairwas partitionedintomethyl-ter_butyl-ethe(rMtBE), The MtBEphasewas removedand put intoa nitrogenevaporatoruntildry. Eachextractedlaboratorysamplewas reconstitutedin 1.0 mLof methanolandfilteredusinga 3 mLplasticsyringeattached to a 0.2/zm nylonfilterintoglassautovials. ANALt'llCALMETHOD ETS-8-5.1,"Analysisof PotassiumPerfluorooctanesulfonaoterOther Fluorochemicals in Serum ExtractsUsingHPLC-Electrospray/MasSspectrometry" ETS-8-5.2,"Analysisof PotassiumPerfluorooctanesulfonaoterOther Ruorochemicals in SerumExtractsUsingHPLC.,-Eiectrospray/MaSspsectrometry" Analyseswareperformedby monitoringone ormoreproductionsselectedfroma singlepnmaryion crmractertsticofa particularfluorochemicaul singHPLC/ES/MS/MS. For example, molecular ion 413, selected as the primary ion for PFOA (CTFlsCOO') analysis,wasfragmentedfurtherto produceion 169 (CaF7").The characteristicion 169 wasmonitoredforquantitativeanalysis. qAJ _nu_rn_ntml I JD_ 3M Environmental Laborato_. Page 770 P_i'Im 1 _) Page 12 3M Medical Department Study: T=6889.6 3M MedicalDepartmenSttudy:T-6889.6 -- ------_-......... - -- ARGUS 418-020 Anal_ical Report: FACT TOX-164 LIMS E00=2738 AnalyticaRl eportF: ACT'TOX-164 UMS E00-2738 ANALYTlCALOUII_ENT The followingis representativeof these_ngs usedduringtheanalyticalphaseof this study. Uquid Chromatograph:Hewtett-PackaredSeries1100 LiquidChromatographsystem Analyticacl olumn:Keystone BetasiTlM Cle 2x50 mm (5 pm) Columntemperature3: 0C Mobilephasecomponents: ComponentA: 2rnMammoniumacetate ComponentB: methanol Flowrate:300 pL/min Injectionvolume:10 pL SolventGradient:8.0 minutes Time (minutes) 0.0 1.0 5.5 7.5 8.0 %B 10% 10% 95% 95% 10% Maim Spectrometer:Microrness API/MassSpectrometerQuattroI1" TripleQuadrupole system Software:Mass Lynx"3.4 ConeVoltage:15-60 V CollisionGas Energy:2.0-50 eV Mode:Electro,spraNy egative SourceBlockTemperature:150=C4-10C Electrode:Z-spray AnalysisType:MultipleReactionMonitoring(MRM) Tabk)7. TargetIons Monitoredin 3M LaboratoryAnalym TargetAnalym PrimaryIon(JUUU)I ProductIon (_Au) u PFOA f 413.0 THPFOS I 427.0 I 169.0 80.0 3M Environmentatl ==hor4toly 3M EnvironmentaLlaboratory Page 771 Page13 Page13 3M Medical Department Study: T-6889.6 3M Medical DepartmentStudy:T. -6889.6 ..... -_= ....... =-_ ----Analytical ARGUS 418-020 Report: FACT TOX-164 LIMS E00-2738 AnalyticalReport: FACT TOX.164 LIMS E00-2738 Devlation_Amendlmmts There were three deviations and one amendment from the original protocol. Deviations and amendments from the original protocoland methods are included in the AppendzxB. Data Quality Objectives and Data Integrity The following data quality objectives (DQOs) were indicated in the protocol for this study: Unearity: The coefficient of determination (r2) equal to or greater than 0,990 using 1/)< weighting. Limits of Ouantltation (LOCi): The LOQ is equal to the lowest acceptable standard in the calibration curve, defined as the lowest standard that is both 2 times the matrix blank and is calculated within :_.30%of the expected concentration. Acceptable Accuracy: Quality control samples are required to meet _-P.25%accuracy, provided they are quantitated within the selected calibrationrange. Confirmatory Methods: If a confirmatorymethod is used, an amendment to the protocol will be written. Demonatration of Specificity: PFOA identification will be substantiated by chromatographic retention time (approximately 7 minutes), by the characteristic primary ion (413) and the characteristic product ion (169). Data Summary, Analyses, and Results Data quality objectives for the analytical phase of this study outlined above and in the 3M Environmental Laboratory protocol for FACT TOX-164 (see Appendix B) were met with the exceptions noted in this reDort. .Rta_l nvimnrn_nmlI _hnmtnrv 3M Environmental Laboratory Page 772 PA_ 14 Page 14 3M Medical Department Study: T-6889.6 3M Medical DepartmentStudy:T-6889.6 .... -='= ....... ---: -'-'-- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-273g AnalyticalReport: FACT TOX-164 UMS E00-2738 =um==,w=a=aatycomma nh== Lineadty: 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 most appropriate to the data. Low curve points with peak areas tess than two times that of the extraction blanks were deactivated to disqualify a data range that may have been significantlyaffected by background levels of the analyte. Occasionally, a single mid-range curve point that was an obviousoutlier may have been deactivated. Quantitation of each analyte was based on the response of one specific product ion using the multiple response-monitoring mode of the instrument (see Appendix C, Analytical Methods). Umita of Quantitation (LOQ): The LOQ is equal to the lowest acceptable standard in the calibration curve (defined as a standard within +30% of the theoretical value), and is at least two times the analyte peak area detected in the extraction blanks. (see Table # 8 below). Table 8. Determination= of the LOQ in the Analy,ses of Rat _ _mlym Me_md LOQ Sara I Dose Solution ! PFOA PFOA 5.28 ng/mL I 10.0 nghnL Extracts Blank=: AJlblanks ware below the lower limit of quantitation for the compounds of interest. Accuracy: Accuracy was determined by analysis of CCVs and was reproducible to within 25%. - Matrix Spikos: Although matrix spikes were not a quality controlcomponent of this Stucly,because the extracted matrix curves were prepared in the same matrix as the samples (rat serum); two matrix spike tests were performed. The first test was performed prior to the start of sample extraction/analysis to determine extraction efficiency while the second test was performed after sample extmctiorVanalysis 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 =_?..5%of the theoretical concentration versus extracted matrix curves. (see Table # 9 below). 3M Environmental Laboratory 3M Environmental Laboratory Page 773 Paae 15 Page ] 5 3M Medical Deparmaent Study: T-6889.6 3M MedicalDepartmentStudy:.T-6889.6 - - ,-- .......... ---_-_ Analytical ARGUS 418-020 Report: FACT TOX-164 LIMS E00-2738 AnalyticalReport:FACT TOX-164 LIMS E00-2738 Table 9. Matrix Spike Recoveries in the Analymm of Rat Sera Extracts Concenuatlon Recovery _ an Unexlmct_ Curm Recovery remus an Exlracl_l Matrix Curve SParimorptloe j Analyses i 25 ng/mL 500 ng/mL 64% II NA 67% I NA _nah_es t 1500 ng/mL i 87% t j 50000ng/mL t 75% I 86% 89*/. Spike Recovorie=: Spike recoveries of +95% of expected values were achieved for all continuing calibrationverifications spiked in the control matrix. = Surrogate=: The surrogate (THPFOS) was added to all samples and standards. THPFOS was not used for quantitation, but was used to monitor for gross instrument failure. The surrogate response of each analytical run was verified to determine that it did not vary more than +50% from the mean within each analytical run. Extracts which were diluted 1:50 or 1:1000 showed surrogate deviations lower than 50%. Since these ware consistently low, these outliers will not affect tim outcome of this study. smte..mt or am,aty 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, calibrationcurve verification recoveries and matrix spike recoveries, indicate that these data are quantitative to 25% or greater. Summary o_ sumpae Re=umt= PFOA results (those obtained using lot # 332) have been corrected for purity of the analytical reference matenal. Dose Confirmation and Stability 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. Sample= from Control Animals: Low levels of PFOA were detected in the male sere of the control animals. Samples from DomKI Animals: In general, PFOA levels found in female sere of the test animals increased from dose group 4 to group 5. PFOA levels found in male sere remained the same between dose group 4 and 5. Significant differences between male and female PFOA levels were observed in these data. Detailed sample data tables are presented in Appendices D and E. 3M Environmental Laboratory 3M Environmental Laboratory Page 774 PAn_ IR Page 16 3M Medical Department Study: T-6889.6 - -= ........... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 3M MedicalDepartmenSt tuOyT:-6889.6 AnalyticaRl eportF: ACTTOX-164 LIMSE00-2738 Statistical Methods and Calculations Statisticalmethodswerelimitedtothecalculationof meansand standarddeviations.See AppendixF forexamplecalculationsusedto generatethe serumsampledata in FACT TOX-164. Statement of Conclusion Underthe conditionsof the presentstudies,the fluorochemicaPl FOA wasobservedin the sera of all ratsdosedwith the testsubstanceduhngthein-life phaseof thestudy. References None ._lLll _nvirr_rr_ntDI I Rhnnllbvv 3M Environmental Laboratory Page 775 I::)_ 17 " Page 17 3M Medical Depazu.ent Study: T-6889.6 3M MedicalDepartment Study:T-6889.6 ..... -=_="........ = _ ----'- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analyl]calReport:FACT TOX-164 UMS E00-2738 Appendix A: Chemical Characterization, and Control Matrices Table 10. Characterization of the Control Matrices Used for SMa Analyses in Study FACT-TOX-164 Control Matrix Rat Serum TN-A-4516 Source S_ma-/_ch St0cage _ Chem_ Lot # Frozen -20_C 019H89291 Table 11. Charactmbation of Test Substance in Study FACT-TOX164 Test Substance Chemical Name Sounm Ammonium Per_xxooclanoate APFO/PFOA TCR-g9030-030 NA Expiration DeW Storage Conditions Chemical Lot # 10r3V2006 -20_ 10_ 332 I_hylJcII Oel4=rtl_Jon Wl'blo powder Pumy _S.OY." ovlulao_e See 1heCenJr=al ol suWym Imm Cen_ ._1a__ _ Jn,N_endix G. 3M Environmental I..aboratorv 3M Environmental Laborato_ Page 776 Pa.ae18 Page 18 3M Medical Department Study: T-6889.6 3MMedicalDepartmenSt tu0yT: -6889.6 -- ""': ........... -_- -'"--- ARGUS 418-020 Analytical Report: FACT TOX- 164 LIMS E00-_ ._,8 Analy*dcRael portF: AC'I:TOX-164 LIMSE00-2738 Appendix B: Protocol, Amendments, and Deviation(s) RM I_nvimnrr_nt_l I ahnnltnrv 3M Environmental Laborato_. Page 777 PaoA 19 Page ]9 3M Medical Department Study: T=6889.6 ..... "== ........ = =-- - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 ProtocolFACT.TOg-164 Phage TRIo Oral(Gavage) Two-Generation (One Liner per Generation) Reproduction Study of Ammonium Perfiuorooctanoate(APFO/PFOA) in Rats PHASE PROTOCOL Performing Laboratories 3M EnvironmentalTechnology & Safety Services 3M EnvironmentLaalboratory 935BushAvenue St.PaulMN 55106 Pace Analytical ServicesI,nc. 1700 Elm Street SE, Suite 100 Minneapolis, MN 55414 Laboratory Project Identification FACT-TOX NumberTOX- 164 3M Toxicology Study Number T-6889.6 Argus In-life Study Number 418-020 LIMS E00-2738 3M EnvironmentaLl aboratory 3M Environmental Laborato_ Page 778 PageI of _10 Page 20 3M Medical Department Study: T-6889.6 .... -:_ ........... ARGUS 418-020 -Analytical Report: FACT TOX-164 LIMS E00-2738 Protocol FACT- TO)(. 164 Study Identification Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammomum Perfluorooctanoate (APFO/PFOA) m Rats Sponsor Sponsor Representative Study Director Phase Locations Principal Analytical Investigator (PAl) Analytical Testing Laboratories Proposed Phase Timetable Analyses Start Date Analyses Termination Date 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-ZE-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 Buildin2g-3E-09 935BushAvenue St.Paul,MN 55106 Telephone: (651 ) 778-6176 Pace Analytical Services, Inc. 1700 Elm Street SE, Suite 100 Minneapolis, MN 55414 May 28, 2001 November 30, 2001 3M EnvironmentalLaboratory 3M Environmental Laboratory Page 779 Page 2 of _, ,, ^.j^=/,_ Page 21 3M Medical Department Study: T-6889.6 Analytical port: A -164 LIMS E00-2738 Protocol FACT- TOX- 164 1. 9"ruor Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooetanoate (APFO/PFOA) in Rats 2. PURPOSE The analytical phase of this study is designed to evaluate levels of PFOA in scra specimens of F0 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 11. 3. REGULA TORY COMPLIANCE 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. QUAUTYASSURANCE 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. REFERENCESUBSTANCEFORFACT-TOX-164 Ammonium Pertluorooctanoate (APFO/PFOA), CTF_sCOO'NI_*, CAS 3825-26- l The target analyte is perfiuorooctanoate (PFOA), CTFIsCOO'. 6. TESTSUBSTANCE Ammonium Perfluorooctanoate (APFO/PFOA), C_FtsCOO'NI'_*, CAS 3825-26-1 7. TEST SYSTEM 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 (garage) route. After cohabitation of the P Generation, five groups of male and female rats (301sex/group for a total of 300) will be selected from FI Generation pups for cominuexl 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 EnvironmdntaLl aboratory 3M Environmental Laboratory Page 780 Page3 of_1o.... !_ I Pa_ 22 3M Medical Department Study: T-6889.6 .... --'-......... =_ _ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Protocol FACT.TOX. 164 Number of S )ectrnensper Dosage group and Dosage Levels i Dosa_leGroup I Number of Rats per Sex 30 Dosage (m_k_/day) 0 Concentration (m_ltL) 0 . 30 1 0.2 I. I 30 IV I 3O i v I 30 3 0.6 10 2 30 _ 6 For this phase study, 40---100 sera samples from Group IV (10 mg/kg/day) and GroulbV (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. SPECIMENRECEIPT Seraspecimenswere receivedfrom ArgusResearchLaboratoriesI,nc. at theendof the inlife phaseonApril 18, 2001. Seraspecimenswereshippedbyovernightcourierand were received frozen on dry ice. Speeimeus 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. PREPARATORYMETHODS ETS-8--4, "Extraction of Fiuoroehemical Compounds from Serum for Analysis using l-IPLC-Eiectrospray/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 methylten-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 ern3plastic syringe attached to a 0.2 lma nylon filter into glass autovials. 10. ANALY'rlCALMETHODS ETS-8-5, "Analysis of Potassium Perfluorooctanesulfonate or other Fluorochemicals in Serum Extracts using HPLC-El=:trospray/Mass Spectrometry" 3M EnwronrnentalLaboratory 3M Environmental Laboratory Page 781 Page 4 of _FI0 ..... I.. !. Page 23 3M Medical Department Study: T-6889.6 ..... ---_-......... -----: ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Protocol FACT- TO)(- 164 Analysis is performed by monitoring one or more product ions selected from a single primary, ion characteristic of a particular fluorochcmical using HPLC-ESMSMS. For example, molecular ion 413, selected as the primary ion for PFOA (C_Fz5COO) analysis, is fragmented further to produce ion 169 (C_%').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 OUALITYOBJECTIVES 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 Ouantitation (LDQ) 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 _approx/mately 7 minutes), by the characteristic primary ion (413) and the characteristic product ion (169). Minor modifications to the Data Quality Objectives may be implemented at the discretion of the PAl. 12. SuB-CONTRACTEDANALYSIS 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 Enviro_tal 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 PSS-Admm-04 PSS-Admin-06 PSS-ARC-02 Quality System Laboratory Facilities Training Record Fries Maintained by QAU Disposition of Archive Materials 3M EnvironmentaLl .agoratory 31t4Environmental Laboratory Page 782 Page5 of 9'_ .... f , Page 24 3M Medical Department Study: %6889.6 - -'-'- .......... :_-_ RGU 4 - Analytical _clpon: _A_ _)_)_'-164 LIMS E00.2738 ProtocolFACT.TOg.164 PSS-ARC-04 PSS-DC-05 PSS-DM-03 PSS-OPS-01 PSS-OPS-02 PSS-OPS-03 PSS-OPS-04 PSS-OPS-05 PSS-OPS-06 PSS-OPS-07 PSS-OPS-08 PSS-OPS-09 PSS-OPS- 10 PSS-OPS- 11 PSS-OPS-13 PSS-OPS-]4 PSS-OPS- 15 PSs-oPS-16 P$S-OPS- 17 PSS-OPS-18 PSS-OPS-24 PSS-OPS-31 PSS-OPS-32 PSS-OPS-37 PSS-MC-01 PSS-MC-02 PSS-MTR-01 PSS-MTR-02 PSS-MTR-05 PSS-MTR-06 PSS-MTR-07 PSS-MTR-08 PSS-MTR-09 PSS-Safety-01 PSS-Safety-02 PSS-Safety-04 PSS-Safety-05 PSS-TS-01 ArchivinDgata,SpecimenandLogbooks Lab NotebooksL.ogbooks,andPhoneLogs StatistiEcvaalluationfData UseandMaintenancoefUltra-TurrTa2x5 Homogenizer Raw Data HazardousWasteDisposal Use andMaintenance of N-Evap Analytical Evaporator Use of Compressed Gases in the Laboratory Use and Maintenanceof NANOpurc II Water Purification System Cleaning Non-disposable Volumetric Pipettes Laboratory Calculations Deviations fromEstablished Procedures AnalyticalDefinitions Use and Cah'brationof a Bottle-Top Dispenser Use and Maintenanceof Lab Refrigerators, Freezers, and Ovens Use and Cah3_-ationof Syringes with a Hamilton Chancy Adapter Glassware Cleaning Use and Maintenance of the FL_berScientific Isotemp Freezer Use and Maintenance of Ultrasonic Water Baths (Sonicators) Use and Maintenanceof Vortex Shakers Use and Maintenance of a Desiccator Use and Maintenance of Shakers Operation, Maintenance and Calibrationof Laboratory Operation,Maintenance, and Calibration of pH Meters and pH Electrodes Purchasing of Laboratory Supplies Receipt of Laboratory Supplies Calibration of CertifiedWeight Set Calibration of Certified Thermomcters/Thermocouples Calibration of EppendorfPipenes Verification of Calibrationof the Eppendoff Pipcttor New Equipment Qualification (IQ. PQ, OQ) Verification of Calibrationand Use of Analytical Balances Use and Maintenance of F'_r Scientific Electronic Temperature Monitoring Devices General Laboratory S_ety Use and Maintenance of Biological Safety Cabinets Emergency Evacuation Procedures Use and Maintenance of Laboratory Fume Hoods Training Procedures 13. STATISTICALANALYSIS Statistical methods will be limi_=dto the calculation of means and standard deviations. Examples of the calculations used in the analyses will be included in the phase report. 3M EnvironmentaLl aboratory 3M Environmental Laboratory Page 783 Page 6 of V to Page 25 3M Medical Department Study: T-6889.6 ..... -_'- ........ : -=-- ARGUS 418-09-.0 Analytical Report: FACT TOX-164 LIMS E00-2738 Protocol FACT-TOX. 164 14. REPORT A report of the analyte results will be prepared by 3M Enviromnental Laboratory'. The reportwill include,but notbe limitedto, thefollowing,whenapplicable: 14.1 Nameandaddressof thefacilityperformingthephase. 14.2 Datesuponwhichthe phasewas initiatedandcompleted. 14.3 A statementof complianceby the PAI addressinganyexceptionsto Good Laboratory PracticeStandards. 14.4 Objectivesandproceduresasstatedin the approvedphaseprotocol,includingany amendmentsto theoriginalphaseprotocol. 14.5 Identity, purity, stabilityandthe solubilityof the referencestandardunderthe conditionsof use. 14.6 A descriptionof the methodsusedto conducthe test(s). 14.7 A descriptionof the specirncns. 14.8 A descriptionof anycircumstancetshat mayhaveaffectedthequalityor the integrity of thedata. 14.9 The nang of the Phi and the nan.s of other scientists, professionals, and supervisory personnel involved in the phase. 14.10 A description of the transformations, calculations, or operations performed on the data, a summary and analysis of the analytical chemistry data, and a statement of the conclusions drawn from the analyses. 14.11 Statisticamlethods used to evaluatethedata,if applicable. 14.'/2 The signed and dated reportsof each of the individualscientistosr other professionianlvsolveidnthephase,ifapplicable. 14.13The locatiownhererawdataandthephasereporatrctobestored. 14.14A statemenptreparebdytheQualitAyssurancUenitlistitnhgedatesthatstudy inspectioannsdauditwseremadeandthedatesofanyf'mdingrseportetdothe StudyDirectoarndManagement. 14.15Ifitisnecessartyomakecorrectioonrsadditiotnosafinarleporatfteirthasbeen accepted, the changes will be madP in the form of an angndment issued by the Study Director. The angndment will clearly identify the part of the final report that is being angnded, the reasons for the amendment, and will be signed by the Study Director. 3M EnvironmentaLl aboratory 3M Environmental Laboratory Page 784 Page7 of 91_ Page26 3M Medical Department Study: T-6889.6 -- - "---.'.-...... ---_ ----- ARGUS 418-020 Analytical Report: FACT TOX- 164 LIMS E00-2738 ProtocolFACT.TOX-164 15. LOCATIONOFRAW DATA, RECORDSA, NDFINALREPORT Originaldata or copiesthereof,will be availableat 3M EnvironmentalLaboratoryto facilitateauditsof the studyduringitsprogressandbeforeacceptanceof thephasereport. When the phase report is completed, all original paper data, including those items listed below will be retained in the archives of 3M Enviromrental Iahoratory. All corresponding training records, cahq_rationrecords, 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 Shippingrecords 15.1.4 Raw data 15.1.5 Approved final report (original signed copy) 15.1.6 Electroniccopiesof data 15.2 The following supportingrecordswill be retainedseparatelyfrom the studyfolder in the archivesaccordingto 3M EnvironmentaLl aboratory StandardOperating Procedures: 15.2.1 15.2.2 Training records Cah'brationrecords 15.2.3 Instrument maintenance logs 15.2,4 StandardOperating ProceduresE, quipmentProcedures,andMethod._ 16. DATA/SAMPLE RETENTION All sera specimens remaining after the analytical phase is completed will be sent to and maintained by: Lisa Ciemen 3M Environmental Laboratory Building 2-3E-09 935 BushAvenue St. Paul, MN55106 Telephone: (651) 778-6t_ _;sld 3M EnvironmentaLl aboratory 3M Environmental Laborato_ Page 785 Page8 of 1tIt> Page 27 3M Medical Department Study: T_889.6 - ""= ............ --- - ARGUS418-020 Amalvtical Report: FACTTOX-16.1 LIMS E00-2738 ProtocolFACT-TO)(-164 17. PROTOCOLAMENDMENTSANDDEVIATIONS Planned changes to the protocol will bc in the form of written amendments signed by the Study Director and the Sponsor's Representative. Amendments wm be considered as part of the protocol and will be attached to the final protocol. All changes to the protocol will be indicatexl m the phase report. Any other changes wfl] be in the form of written deviations, signed by the Study Director and filed with the raw data. 18. ATTACHMENTS 18.1 Attachment A: Material Safety Data Sheets (MSDS) for Reference Standard 3M EnvironmentaLl aboratory 3M Environmental Laboratory Page 786 Page9 of _10 Page 28 3M Medical Department Study: T-6889.6 19. SIGNATURES - -.= ............. ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 ProtocolFACT.TO)(-164 David Sanders, Ph.D., Sponsor Rel_csentativ Date John Butenhoff, Ph.D., Study Director Lisa Clemen., Principal Analytical Investigator Date Date 3M Environment.at _horatory 3M Environmental Laboratory Page 787 Page 10of @10. Page 29 3M Medical Department Study: T-6889.6 .... -- ............ -- ARGUS 418-020 Analytical Report: FACT TOX- 164 LIMS E00-2738 J Study Title Oral (Gavage) Two-Generation (One Utter per Generation) Reproductaon Study of Ammonium Perfluorooetanoate (APFO/PFOA) in Rats PROTOCOL AMENDMENT NO. 1 Amendment Date: November 17, 2000 Performing Laboratory 3M EnvironmentaTl echnology& Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 Laboratory Project Identification 3M Medical Depa_ia,,enSt tudy: T-6889.6 Argus In-Life Study: 418-020 Analytical ReIxxt: FACT TOX- 164 3M LIMS No. E00-2738 ._M Fnvirnnn_nt_l Laboratory 3M Environmental Laborator), Page 788 Paoe 1 of 3 Page 30 3M Medical Department Study" T-6889.6 ..... ---............ RGU 4 _ o -Analytical _eIport: _A_I_ _)_'- 164 LIMS E00-2738 Protocol FACT TOX-O01 Amen'Oment No. 1 This amendment modifies the following portion(s) of the protocol: 1. PROTOCOLREADS: Doseconfn'rnalwJaosnnotdiscusseidntheEnvironmentaLlaboratoraynalyticpahlaseprotocol. AMENDTOREAD: 2.Thedoseconf'n'marainodnstabilistaympleswereprepareadndanalyzepdriortothestarotf theanalyticpahlaseofthisstudy.Thesesampleswerenotprepareodranalyzeadccordintgothe GLPs. MethodsETS-8-.4.a1ndETS-8-5.1werelooselfyollowedT.he resultwsillbereporteidn the final analytical report. REASON: From the protocol for the Primedica study: Analyses of Pr_ared Formulations: Concentration: Concenwation of the preparedformulations will be verified during the course of this study. Duplicate samples will be taken from each concentration on the t-n'stand last days of preparation. One sample of each duplicate set will be shipped for analysis; the remaining samples will be retained as backup samples. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor. Stabili_: Stability of the preparedformulations will be documented during this study. Two sets of duplicate samples (2 mL each) from each concenlration will be taken on the first clayof preparation. One sample of each duplicate set will be shipped on the day of preparation. These samples will be analyzed at the following tLmepoints: 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 Facilitupyon the request of the Sponsor. Stability measurements demonstrate that the preparedtest ar_cle will be stable for ten days. It is best to perform this priorto the analytical phase study imtiation to ensure that prepareddosing mixtures will remain stable and thus avoid the cost and potential errorof preparingdoses each day. Also. no approved/validated methods were in place for dose confirmation analysis. RIL4I_nvimnrr_nt_l I slhnnltnrv 3M Environmental Laboratoo, Page 789 Pao_ 2 of 3 Page 31 3M Medical Department Study: T=6889.6 .... -=_-......... ---=--- ARGUS 418-020 Analytical Report: FACT TOX-lb.; LIMS E00=2738 Protocol FACT TOX-O01 Amendment No. 1 Amendment Approval David Sanders, Sponsor Representative Date John L Butenhoff, Ph.D., Study Director Date 3M EnvironmentaLl aboralorv 3M Environmental Laborato_ Page ?90 Paoe3 of3 Page 32 3M Medical Depamnent Study: T-6889.6 ..... ---_-........ ":"-- ARG S - ')0 Analyucai Report:I_AS_'8"l:_)'_-164 LIMS E00-2738 Record of Deviation L Identification Study / Project No. FACT-TOX-104 Argus 418-020 LIMS E00-2738 Deviation Ty_ (Check one) - 17SOP .....X MC_hod [']Equipment Procedure _ Protocol [7Other: Document Number(s): ETS-8-4.2, ETS-8-5.2 Dam(s) of occurrence: 06/14/01, 06/15/01 8. Description: Required Procedure/process: Method ETS-8-4.2 does not list matrix spikes as a QC parameterif the curve is prepared in the same malrix as the samples (i.e. rat serum e,alibration curves and rat serum samples). Method ETS-8-5.2 states five points, at a minimum, arc to be used to generate the calibration curveandthe-curver_must be > 0.990. Actual Proccdm_Jprocess: Mau'ix spikes-werepr_ar_l (06/]4/01) prior to thestartof thesampleexu'acdonin orderto determine exn'action efficiency and to det_mine the endogenous level of target analy_epresent in the commercially available serum. For this commercially available serum, endogenous levels werebelow 1.00ppb for the targetanalyte.This serumwasthen usedto preparethe exn'acmd matrix calibrationcurveandcontinuingcalibrationverificationsfor this study. _ _ These sample extracts were analyzed on 06/I5/01. For this analysis, not all stated QC criteria wcrc followed. Only four points wcrc used for the calibration curve instead of five points and the r_ value was 0.9831 instead of 0.9900. Since these data are screening quality only and additional matrix spikes will be Cx_-actedat the end of the study these data are OK as entered. These sampie-extracts-wea:_not reanaly-zecl. III. Actions Taken: "........... (such as amendment issued. SOP revision, etc.) This deviation-was written. Recorded By IV. Impact on Study l Project No adverseimpacton theoutcomeof this study. Date ' Authorized By (Study Director/Project lead) . - Date 3MEnvironmentaLal boratory Form L"J_-_.O 3M Environmental Laborato_ DeviationNo. 1 (amllncdbyStudyDiRctororProleerl.cadattheendofstudyorp_jcct) Page33 Page 791 3M Medical Depamnent Study: T-6889.6 -- -:_- -......... ARGUS 418-020 Analytical Report: FACT TOX-16,* LIMS E00-2738 Record of Deviation L Identification Study / ProjectNo. FACT-TOX-164 Argus 418-020 LIMS E00-2738 -Deviation Ty_ (Check one) D SOP -- 17Method-D Equiptuent Procedure X Protocol D Other: Document Number(s): FACT-TOX- 164 Date(s) of occurrence: 06/19/01 IL Description: 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 tug/kg/day and group V - 30 mg/kg/day) " Actual Procedure/process: An equal number oftuale and female samples were randotuly selected from the two P generation dose groups (group IV - 10 tug/ks/day and group V - 30 tug/kg/day.) In addition, 3 male and 3 female samples were randomly selected from the P generation control group (group 1 - 0 tug&g/day) IlL Actions (such as amendment issued, SOP revision, etc.) This de_ation was written. Taken: Recorded By .................... Date Lisa A. Cletuen J_ _ _ IV. Impact on Study / Project These samples' results will add useful reformation concerning endogenous control group. -No adverse impact on this study. 08/10/o01/,Aol levels present in the Authorized By (Study Director Project Lead) Date JM Envwonmental Laboratory Form 12T$-4..8.0 3M Environmental Laboratory Deviation No. (m,p_ byStudyDirtetoror ProjectLeadat the,ridof studyor Imojtet) Page 34 Page 792 3M Medical Dcpa_u.ent Study: T-6889.6 - " "-=........ Recordof Deviation I. Identification ----------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study / Project N__ FACT-TOX-I_ _Lrg_ 418-020 LIMS E00-2738 Deviation Type (Check one) SOP XMeth0d Protocol Other: Equipment Procedure Document Numl_cr(s): ETs_-I,ETS-8-5.-f -Dat--e(s)of occurrence: 01/17/01, 01,'23/01 Ii. Description: Required Procedure/process: Meiho--dsstate-A matrix spike and matrix sp;ke duplicate will be extracted and analyzed per. _i for_j samples, 7wi-t-ah-minimum 0(2 per batch. ...... Actual Procedure/process: On the dose confimtation extraction performed 0i/f7/01 no matrix spike or matrix spike dupli_te_were prepared_d .s.ubs._uentlwyerenot _al3;z_l on 01,'23/01. ................................... IlL Actions (such as amendment _ssued. SOP reviJton, etc.) This-deviation was written. " ................... Taken: ..................... i Recorded By ................ Date LisaA. Clemen "/_i_. )_ _ 10/05/01 IV. Impact on Study / Project This omission Will not havean adverseimpacton this study,otherq-ualitycontrol aspectsof the analysis wereincluded-(b|_.s, continuingcalibrationverificatio_i which met methodcriteria. Authorized By (Stu_.g,_or/Projectffead)., , ;e,a;_r _,._'e.re,,l,.,,k.,bra.'v. _6 Jane's 3M Environmental Laboratory Form ETS-4-8.0 3M Environmental Laboratory .... / Date - Deviation No. (m_lln_lbySt.ayDir_tor orProjecLt r.adattheendof..dy orproject) Page 793 Page35 3M MedicalDepartmentStudy:T-6889.6 3M Medical DepartmentStudy:T. -6889.6 .... -"_ .......:."_" ARGU_S 418-0")0 Analv_cal_eport:FACT T_X- 164 LIMS E00-273_ AnalyticalReport:FACT TOX-164 LIMS E00-2738 Appendix C: Extraction and Analytical Methods This appendix includes the following methods: _.1, Extractionof PotassiumPerfluorocx_nesulfonate or Other FiuorochemicalCompounds from Serum for Analysisusing HPLC-Electrospray/Mass Spectrometr(y1,4pages) _.2, Extractionof FluorochemicalCompoundsfrom Serum for Analysis Using HPLC-Electrospray/M__ Spectrometry,(15 pages) _.1, Analysisof PotassiumPerfluorooctanesulfonateor Other Fluorochemicals in Serum ExtractsUsing HPLC-Electrospray/MassSpectrometry,(9 pages) _, Analysisof PotassiumPerfluorooctanesulfonateor Other Ruorochemicals in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry,(11 pages) 3M Env#onment,=!La_ratorv 3M Environmental Laboratory Page 794 PaOli20 Page 36 3M Medical Department Study: T-6889.6 .... -:--- ......... -_ -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 3M ENVIRONMENTALLABORATORY i t METHOD EXTRACTION OF POTASSIUM _UOROOCTANESULFONATE OR OTHER FLUOROCHEMICAL COMPOUNDS FROM SERUM FOR ANALYSIS USING I:rPLC- ELECTROSPRAY/b_#.SS SPECTROMETRY Method Number: ETS-8-4.1 Adoption Date: 03/01/99 Author. Lisa Clemcn, Glenn Laugenburg RevisionDate: q/971qQ Approved By: Laboratory Manager 7.,. Group Leader Date qlz, ls9 Date Tcch-ic_l Reviewer Date l_t C_/_ 0_nJ 1.0 SCOPE AND APPLICATION 1.1 Scope: This method is for the extra.on of potassium perfluorooctanesulfonate (PFOS) or other fluorochemieal compounds from serum. 1.2 Applicable compounds: Fluorochemical mufactants or other fluorinated compounds. 1.3 Matrices: Rabbit, rat, bovine, monkey, madhuman serum or other fluids as designated in the validation repo_ Word 6/95 3M Environmental Laborato_ ETa8-4.1 Page 795 Page I of 14 Page 37 3M Medical Department Study: T=6889.6 ..... -:_ ........... ARGUS 418-020 Analytical Report: FACT TOX-16.* LIMS E00-273_ 2.0 SUMMARY OF METHOD ._ 2.1 2.2 This method describes the procedure for _g potassium perfluorooctanesulfonate ('PFOS) or other fluorochemical sta-factants from serum, or other fluids, using an ion pairing reagent and methyl-ten-butyl ether (MtBE). In this method, seven fluorochemicawlesreextractePdF:OS, PFOSA, PFOSAA, EtFOSE-0H, PFOSEA, M556, andsurrogatsetandar(dsee3.0 DefinitionsA)n.ionpairinrgeagenitsaddedto thesampleandtheanalymionpairispartitioniendtoMtBE. TheMtBE extracits removedandputontoa nitrogeenvaporatourntidlry.Eachextracitsreconstituitned1.0 mL ofmethanolt,henfiltertehdrougha 3 ccplastiscyringaettachetdoa0_.tunnylon filteirntoglassautovials. ThesesampleextractasreanalyzedfollowinmgethodETS-8-5.1orotherappropriate methods. 3.0 DEF_rrIoNs 3.1 PFOS: per/]uorooctanesulf(oannaitoenofpotassiumsaltC),F,_SO/ 3.2 PFOSA: perfiuorooctasnuelfonylamidCe__FtTSO_q]-I, 33 PFOSAA: perfluorooctane sulfonylamid(eothyl)acetate C,Ft_SO_N(CH2CH,)CH_CO," 3.4 EtFOSE-OH: 2(N-ethylperiluorooctune sulfonamido)-ethyl alcohol C,Ft_SO,N(CHC,H,)CH,CI_OH 3.5 PFOSEA: pcrfluorooctane sulfonyl ethylamide CtF,TSO2N(CH,CHx)I-I 3.6 M556: C,Ft_OS,N(H)(CH,COOH) 3.7 Surrogate mandard: 1H-1H-2H-2H perfluorooctane sulfonic acid 4.0 WARNINGS AND CAUTIONS 4.1 Health ud sm_ret), warnings 4.1.1 Use universal precautions, zspezially laboratory coats, goggles, handling I.imal tissue,whir.h may contain pathogens. and gloves when - S.0 INTERFERENCES 5.1 There are no interferences known at this time. 6.0 EoUrPMEWr 6.1 The following equipment is used while performing this method. Equivalent equipment is acceptable. 6.1.1 Vortex mixer, VWR, Vortex _e 2 6.1.2 CentrifugMei,stral I000orIEC 6.1.3 Shaker,EberbachorVWR 3M Env_ronmemal Laboratory ETS-8.-4.I Page 796 Page 2 of 14 Page 38 3M Medical Department Study: T-6889.6 .... -:_ ........ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 6.1.4 Nitrogen evaporator, Organomation 6.1.5 Balance ( 0.100 g) t 7.0 SUPPLIES AND MATERIALS 7.1 Gloves 7.2 Eppendorf or disposable pipettes 7.3 Nalgene bottles, capable of 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 ofmeasm'ing 5 gL to 50 gL 7.10 Graduated pipettes 7.11 Syringes, diaposable plastic, 3 cc 7.12 Syringe filters, nylon, 0.2 gin, 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-Qra water, l_in_e syringes a mlnim_lm of 9 times with meth_ol, 3 rinses fi'om 3 separate vials. 8.0 RExc_r_ ANDSTANDARDS 8.1 Type ] reage_lt grade water, Milli-Q TM or eqllivalent_ all water used in this method should be Milli-Q TM water and may be provided by a MiIfi-Q TOC PlusTM system 8.2 Sodium hydroxide (lqaOI-I), J.T Baker or equivalent 8.3 Tetrabutylammonium hydrogen sulfate(TBA), Kodak or equivalent 8.4 Sodium carbonate (Na2CO_),LT. Baker or equivalent 8.5 Sodium bicarbonate (NaI-ICO_),J.T. Baker or equivalent 8.6 Methyl-T-Butyl Ether, Omrdsolv, glass distilled or HPLC grade E7 Methanol,Omnisolv,glassdistilloerdHPLC grade 8.8 Serum orblood,frozenfromsupplier 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 F._,aefitm ETS.&4.1 nfPl=t_.q from .q_m_ Page3 of 14 Page 39 Page 797 3M Medical Department Study: T-6889.6 .... .--_-......... _ - ARGUS 418-020 Aaaalytical Report: FACT TOX-164 LIMS E00-2738 ,; t 8.10 8.11 - 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), moleeuiar weight = 527 8.9.6 M556 (3M Specialty Chemical Division), moleettlar weight -- 557 8.9.7 Surrogate standard: _H, perfluorooctane mflfonic acid (1-H,1-H, 2-H, 2-H CIFt3SOjH) molecular weight -- 428 8.9.8 Other fluomchemieals, as appropriate Reagent preparation NOTE: Wh=n preparing larger volume= than listed in reagent, standard, or surrogate preparation, adjust accordingly. 8.10.1 8.10.2 10 N+sc_ium hydroxide (lqa0I-I): Weigh npproximmely 200 g NaOH. Pour into a 1000 mr. beaker containing 500 mL Milli.Q TM water, mix until all solids are dissolved. Store in a 1 L Nalgene bottle. 1N sodium hydroxide (NaOH'): Dilute 10NNaOH 1:10. Measure 10 mL oflO N NaOH solution into a 100 ml.,volumetric flask and dilute to volume using MiUi-QTMwater. Store in a 125 mL Nalgene bottle. 8.10.3 0.5 M tetrabutylammouium hydrogen walfate (TBA): Weigh approximately 169 g of TBA into a 1 L volumetric c_ntaining 500 mL Milli-Q TM water. Adjust to pH I0 using approximately 44 to 54 mr of 10 N NaOH (While adding the last mL of NaOH, add slowly because the pH changes abruptly). Dilute to volume with Milli-Q TM water. Store in a 1 L Nalgene bottle. 8.10.3.1 TBA requires a cheek prior to each use to ensure pH = 10. Adjust+as needed using 1 N NaOH solution. 8.10.4 025 M sodium carbonate/sodium bicarbonate buffer (Na=COJNaHC03): Weigh approximately 26.5 g of sodium carbonate (Na=CO_)and 21.0 g of sodium bicarbonate (NaI-ICO3)into a 1 L volumetric flask and bring to volume with MilllQm water. Store in a 1 L Nalgene bottle. Standards preparation 8.11.1 Prepare PFOS standards for the standardcurve. 8.11.2 Prepare other fluomehemieal st=mdards,as appropriate. Multieomponent fluorochemieal 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 nag of PFOS into a 100 mL volumetric flask and record the actual weight. 8.11.4 Bring to volume with methanol for a stock standard of approximately 1000 ppm 8.11.5 Dilute the stock solution with methanol for a working standard 1 solution of approximately 50 ppm. 8.11.6 Dilute working standard I with methanol for a working standard 2 solution of approx. 5.0 ppm. 3M Environmental Laboratory ETS-8-4.1 Pase 4 of 14 Page 40 Page 798 3M Medical Department Study: T-6889.6 - ""----_.-.......... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 8.12 ' 8.11.7 Dilute working standard 1 with methanol fora working standard 3 solution of approx. 0.50 ppm. Surrogate stock standard preparation 8.12.1 Weigh approximately 50-60 nagofsur_gate standard 1-H,1-H, 2-H, 2-H, C,F.SO_H into a 50 mL volumeuicflaskandrecordtheactualwei_t. 8.12.2 Bringto volumewith methanolfor a surrogatestockof approximately1000-1200 ppm. 8.12.3 Prepare a surrogate working standard. Transfer approximately 1 mr. of surrogate stock to a 10 mL volumetric flask andbring to volume with methanol for a working standard of 100 ppm. Record the actual volume namferred. 9.0 SAMPLE I_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 priorto extraction. 10.0 QUALITY CONTROL 10.1 Solvent Blanks, Method blanks and matrix blanks 10.1.1 An aliquot of 1.0 rnT methanol is used as a solvent blank. 10.1.2 Extracttwo 1.0 mL aliquots ofMilli-Q TMwater following this procedure and use as method blanks. 10.1.3 Extract two 1.0 r,T. aliquots of the serum following this procedure and use as matrix blanks. See 11.1.4. 10.2 Matrix spikes 10.2.1 Prepare andanalyze matrix spike and matrix spike duplicate samples to determi-e the accuracy of the _xtraetion. 10.2,2 Prepare each spike t,cinS a sample chosen by the analyst, usually the control matrix received with eachsample set. 10.2.3 Expected concentrations will fall in the mid-range of the ini_al cah'bration crave. Additional spikes may be included and may fall in the low-range of the initial cah'brationcurve. 10.2.4 Prepare one matrix spike and matrix spike duplicate per 40 samples, with a minimum of 2 matrix spikes per batch. 10.3 Continuing calibration checks 10.3.1 Prepare continuing calibration check samples to ensure the accuracyof the initial calibration curve. 10.3.2 Prepare, at a minimm_n;one _ cheek per group of 10 samples. For example,ff a sampleset= 34, fourchecksarepreparedandextz_ted. 10.3.3 Prepare each continuing calibration cheek from the same matrix used to prepare the initial curve. 3M Environmental Laboratory ETS-8-4.1 Page 799 Page 5 of 14 Page 41 3M Medical Department Study: T-6889.6 .... -_.-.......... _ ARGUS 418-020 Analytical Report: FACT TOX-16._ LIMS E00-2738 I0.3.4 The c::pected concentrations will fall within the mid-range oft,he initial calibration curve. Additional spikes may be included thatfall in the low-range of the initial calibration curve. This is necessary if the analyst must quanritate using only the low end of the calibration curve (for example, 5 ppb - 100 ppb, rather than 5 ppb - 1000 ppb). I1.0CALmRATION AND STAm)ARDrzA'nON 11.1 Preparematrixcafibratiosntandards II.I.ITransfeIrmJ.,ofserumtoa 15roT. centrifutguebe. 11.1.2Ifmostsamplevolumesarelessthan1.0mL, extracsttandardwsithmatrix volumes equal to the sample volumes. Do not extract less than 0.50 mI. of matrix. Record each sample volume on the extraction sheet. 11.1.3Whilepreparinagtotaolftwentyaliquotisn15mL centrifugteubesm,ix orshake between aliquots. 11.1.4Two l mI.,aliquotosr,otherappropriavtoelume,serveasmatrixblanks. Typically use the standm-dconcentrations and spiking amounts listed in Table 1, at the end ofth_ section, to spike, in duplicate, two standard curves, for a total of eighteen standards, two matrLxblanks, and two method blanks. 11.1.5 Refer to validation report ETS-8-4.0 & ETS-8-S.0-V-1, which lists the wor_ng ranges and the Linear Calibration Range (LCR) for cah'bration curves. 11.1.6 Use Attachment D as an aid in calculating the concentrations of the working standards. See Section 13.0 to calculate actual concenla'ations of PFOS in calibration standards. 11.2 To each standard, blank, or continuing check, add appropriate amount of surrogate working standard for the concentration to fall within the calibration curve range 5 ppb 1000ppb. 11.3 Extracstpikedmatrixstandardfsollowin1g2.6-12.1o6fthismethod.Use thesestandards to e,stablish each initial curve on the mass apect_'omete_r. 3M Environmental Laborato_ ETS-8..4.1 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 L Using 1.0 mL of matrix Working standard IJ.L Approx. final cone. of (approx. conc.) analyte in matrix - Blank 0.500 ppm 0.500 ppm 5.00 ppm 5.00 ppm 5.00 ppm 50.0 ppm 10 0.005 ppm 20 0.010 ppm 5 0.025 ppm I0 0.050 ppm 20 0.I00 ppm 5 0.250 ppm 50.0 ppm 50.0 ppm 50.0 ppm I0 0.500 ppm 15 0.750 ppm 20 1.00 ppm 12.0 PROCEDURE 12.1 Obtain fi'ozen 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 rnL 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 worksheeL 12.5 Label the tube with the study number, sample ID, date and _-_lyst initials. See attached worksheet for documenting the remaining steps. 12.6 Spikeallsamplesi,ncludinbglanksandstandardrse,adyforcxtractiwointhsurrogate standard a.sdescribed in I1.2. 12.7 Spike each matrix with the appropriate amount of standard as described in 11.1, or Table 1 in that section, for the cah'brationcurve standards. Also prepare matrix spikes and continuincgalibratisotnandards. 12.8 Vortexmix thestandarcdurvesamplesm,atrixspikesamplesa,ndcontinuincgalibration samplesfor15seconds. 12.9 Checktoensm_the0.5M TBA reagentisatpH 10.I.fnota,djusatccordingly. 12.10 To eachsample,addI mL 0.5M TBA and2 mL of0.25M sodiumcarbonate/sodium bicarbonatbeuffer. 12.11 UsinganOxfordDispensera,dd5 mL methyl-tert-buettyhler. 12.12 Cap each sample and put on the shaker at a setting of 300 rpm, for 20 minute,s. 12.13 Centrifuge for 20 to 25 minutes at a setting of 3500 rpm, or until layers are well separated. 3M Environmental Laboratory ETS-8-4.1 Page7 of 14 Page 43 Page 801 3M Medical Deparu.ent Study: T-6889.6 ..... --_--........ =- -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 w 12.14 Labela fresh15rn.Lcen_fugetubewiththesameinformatioansin12.5. 12.15 Remove 4.0rn.Loftheorganilcayertoth/sclean15mL cen_fugctube. 12.16 Puteachsampleon theanalyticna/ltrogeenvaporatourndldry,approximatelIyto2 ';" hours. 12.17 Add 1.0 mL ofrnethanol to each centrifuge tube using a graduated pipette. 12.18 Vortex mix for 30 seconds. 12.19 12.20 12.21 12.22 Attach a 0.2 j.trnnylon 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. Label the autovial with the study number, animal number and gender, sample timepoint, matrix, final solvent, extraction date, and amflyst(s) performing the extraction. Cap and store extracts at room tempm-atm_or at approximately 4 C until analysis. Complete the exlraction worksheet, attached to this document, and tape in the study notebook or include in study binder, as appropriate. 13.0 DATAANALYSISANDCALCULATIONS 13.1 Calculations 13.1.1 Calculataectuacloncentrations of PFOS, or other applicable fluorochcmical, in calibration standards using the followinegquation: mL ofstandarxdconcentration ofstandar(d,-,/mL) = n,.oJf.s,tandsr+dmI.,ofsun-oga_standar+dinitimaaltrixvolume(re.L) Final Conccnlration _g/mL) of PFOS in matrix 14.0 METHODPERFORMANCE 14.1 14.2 The method detection limit (MDL) is analyte and matrix specific. Refer to MDL report for eeific lVDLand limit ofquantitation ('LOQ)values (see Attachments B and C). The following quality control samples are extracted with each batch of samples to evaluate the quality of the exUaxdon 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 of the extraction. 14.2.3 Continuincgalibration check samples to determi-e the continued accuracy of the initial calibration curve. 14.3 Refer to section 14 of ETS-8-5.1 for method performance criteria. _5.0 POLLUTIONPREVENTIONANDWASTEMANAGEMENT 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 Laborato_. ETS-g-4.1 I_..o.._,,.*.;._l_lffie'tC' _ __ Cm.m Page8all4 Page 44 Page 802 3M Medical Department Study: T=6889.6 ..... ------......... =.... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 16.0 RECORDS 16.1 't Complete the extraction work_eet att_htd to this tr,tho6, and tape in the study notebook or include in the 3-ring study binder, as appropriate. 17.0 ATTACHMENTS 17.1 Atta_hmtmt A, Extraction worksh_t 17.2 Attachmvat B, MDI_OQ values and mrmm_ry 17.3 Attachment C, Calibration standard conccmtrationworkshvct 18.0 I_FEmgNCES 18.1 The validation report a._ociated with this method is ETS-8..4.0 & 5.0-V-1. 18.2 FACT-M-3.1, "Analysis of Serum or Othtr Fluid Extracts for Fluorochemicals u_g HPLC-Electrospray Mass $pectromctDr" 19.0 AFFECTEDDOCUMENTS 19.1 ETS-8-5.1, "Analysis of Seru_ or Other Fluid _ HPLC-Electrospray Mass Spectrometry" 20.0 REVlSlONS for Fluomchemicals using Revision Number I Reason For Revision Section 12=21Changed to include sample mota, ge at morn temperature. Section 12.13 Adde_l the shaker spctxL Section 12.17 Final volume is 1.0 mL; not adjusted for initial volumes less than 1.0 mL. Revision Date 04/02/99 3M Environmental Laboratory Ers-8.4.1 'l::.wt'mctionafPFOS from Fro'urn Page 803 Page 9 of 14 Page 45 3M Medical Department Study: T-6889.6 .... -- .......... Extraction Workahcet ET$'-8-4. I -----"----- ARGUS 418-020 Anal_ical Report: FACT TOX-164 LIMS E00-2738 Study# Surroga_S_ FC-Mix FC-Mzx FC-MLx Comments Matrix approx, ppm approx0...5pm approx5.ppm approx5.0ppm Box# actual ppm acu_ ppm actual ppm -,cu_ ppm Wk/Day, # # # # DateSp/ked/Analyst "t CCV MS MSD 1 '" . . . . . . . Blank S_J# _erum F,_tru_ou Method Vortex 15 sec. Pipeue Mamx P_, 1rid..of 0.5 M "I'BA.,pH 10. 'pn" P_ae_e 2 m]. 0f0.25 Na2CO'ff0.25M N_-/CO_ I_ffa, ': Volume , ,i amount- mL Std.# Ssd. # Dispense 5 _ of methyI-t-butTlether Shake 20 rain. Ce_mfuge 20-2S,nun. Removea a mL aliquot of orIgantclayer Put on NitrogenEvaponttorm dr_r_:ss Add methanol Volume TN-AShakerspeed: , Cem_ifugespeed: m]_ ,m, ,, Tm'_qlure: TN-A- Vorte3x0 sec. Filteursmea 3ccB-D synneewith 00._tfmilmi"nto IJ end=.._e_m_levial ConLCalV.erificatuisoendssamemau'iuxforstd F . mL Dste dkintttsiJ A_.L...,..._o 3M Environmental Laboratory _ 0I Page 804 lrt 1/% .,.4_1A Page46 3M Medical Department Study: T-6889.6 - -- ......... --_ _ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 MDL/LOQ values for rabbit serum Compound MDL LOQ Linear Calibration Range (LCR) (ppb) (ppb) Approximate concentrations to be used for preparing the Standard Cah'bralion Curve PFOS 1.74 5.55 5 ppb - 1000 ppb PFOSA 1.51 4.79 5 ppb - 1000 l_b PFOSAA 3.46 20.5 5 ppb - 1000 ppb EtFOSE-OH 11.4 36.2 5 ppb - 1000 ppb M556 6.03 19.2 5 ppb - 1000 ppb PFOSEA 5.71 18.2 5 ppb - 1000 ppb MDL/LO_ values m mr, bovine,monkey, andhumanserum,andmonkey plasmawere not sta_tically determined. Two curves m each of thesemalriceswere e_u:ted andanalyzedwith therabbitserum curvesto det_zmineequivalence. Responses in the mr, bovine, monkey, andhumanwere equi.valentto the rabbitresponses,therefore,theirMDL andLOQw_11be the same values as deI_n_ed m rabbit PleasseeeLOQ SummaryandIPIDLstudyinETS-8-4.&0 5.0-V-fIorfurtheirnformation. AttachmentB: MDL/LOQ Summary 3M Environmental Laborato_ ETS-[t-4.1 Page 805 Page 11 of 14 Page 47 3M Medical Department Study: T-6889.6 ..... ._- ........ --_ ------ ARGUS 418-020 Anal.vrieal Report: FACT TOX-164 LIMS E00-_, 38 Compound: PFOS 1_. ared range Rabbit Senma of standzr_ i (_pb) (ng/mL) Full Range Low Cm've High era-re 1/X 0.995- 978 4.94 - 248 97.8 - 978 0.995.978 LCR from curve (ppb) (u_aI.) 24.8- 978 4.94- 248 97.8 - 978 4.94 - 978 % R_ov_y Range g3-108 85.104 85-106 94-111 Compound: PFOSA Prepared range Rabbit Serum of standards (ppb)(n_mZ.) Full Range 0.993 - 976 LCR from curve (ppb) (ng/ml.) 4.93 - 976 Low Curve 4.93 - 97.6 4.93 - 97.6 % Reeaavery Range 88-103 g'/-105 High curve 1/X 24.8 - 976 0.993 - 976 24.8 - 978 4.93 - 976 93-102 94-103 Compound: PFOSAA Prepared range RabbitSerum of staudards (ppb)(ug/_..) Full Range Low Curve High curve 1/X 0.991 - 974 4.92 - 247 49.2 - 974 0.991 - 974 L(_L fi_n curve (ppb) (ng/mL) 24.7- 974 9.74 - 247 97.4 - 974 9.74 - 974 % Recovery Range 8l-lll 97-107 85-108 95-115 RSD Range 4.67-I 1.0 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 Amchment B: MDL/LOQ Sunm_ 3M Environmental Laborato_ ETS-8-4.1 Page 806 Page 12'of 14 Page 48 3M Medical Depmtment Study: T=6889.6 ..... -.--_-....... --, --'-=-- ARGUS 418-020 Analvucal Report: FACT TOX-164 LIMS E00-2738 m Compound: _.tFOSE-OH Preparedrange RabbitSerum of standards _' (ppb) (ng/mL) Full Range Low Cm've High curve 0.993 - 976 4.93 - 97.6 49.3 - 976 LCR from curve (ppb) (n#xx_) 49.3 - 976 9.76- 97.6 97.6 - 976 %Recovery Range 77-110 97-107 90-109 I/X 0.993 * 493 I 9.76 - 976 Compound: PFOSEA Preparedrange Rabbit Serm.n of standards (._b) (ng/mL) Full Range 0.993 - 976 LCR from cm"vc (._b) (ng/mL) 24.8 - 976 Low Curve 4_03 - 248 9.76 - 248 High ran're 1/X 49.3 - 976 0.993 - 976 49.3 - 976 9.76 - 976 86-111 %Recovery Range 96-106 91-110 86-106 95-117 Compound: M$56 Preparedrange RabbitSerum of standards (ppb) (ng/mL) ]:u_l Range Low Curve High cm've i/X 0.993 - 976 4.93- 97.6 97.6- 976 0.993- 976 Leg from curve (ppb) (n#mL) 24.8 - 976 9.76- 97.6 97.6 - 976 9.76- 976 %Recovery Range 88-106 100-105 81-111 97-110 P..SD Range ,, 11.2-25.5 14.1-21.3 11.5.19.6 I 1.1-21.2 RSD Range 10.1-16.2 11.8-19.5 105.-18.2 10.1-19.1 RSD Range 4.82-17.9 5.95-18.2 5.11-9.74 4.7%19.5 AttachmentB:MDL_OQ Summary 3M Environmental Laboratory ,, , _ _.._. _.. .. ___.._..,,,,.L... ETS-g-4.1 Page 807 Page 13of 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): Analyte(s): "t Sample matrix: Method/revision: Target analyte(s): FC mi_ std approx. 0.500 ppm: FC mi_ std approx. 5.00 ppm: FC miYstd approx. 50.0 ppm: Surrogate std approx. I00 ppm: Standard number: Equipment number: F'mal solvent and TN: Blank fluid/Identifier: Actual concentrations of standards in the PFOS PFOSA . PFOSAA EtFOSE Std cone Std coac Std coac Std _ ug/mL ug/mL ug/mL ug/mL 0.500 0.507 0.532 0.501 0.500 0.507 0.532 0-501 5.00 5.07 5.32 5.01 FC miT PFOSF.,A Std cone us/mL 0-521 I 0.521 5.21 M._6 Std cone ug/mL 0.501 0.501 5.01 5.00 5.07 5.32 5.01 5.21 5.01 5.00 5.07 5.32 5.01 5.21 5.01 50.0 50.1 53.2 50.1 52.1 50.1 50.0 50.1 53-2 50.1 52.1 50.1 50.0 50.1 53.2 50.1 52.1 50.1 50.0 50.1 53.2 I 50.1 52.1 50.1 All Am_ spikedmL 0.010' ! 0.020 i 0.005 j All Final vol mL 1.0 l 5 1.025 1.010 0.010 0.020 0.005 0.010 0.015 0.020 ! 1_015 [ 1.025 t 1.010 I 1.015 1.020 1.025 Calculated eoncentrat/ons of standards in the sample mtrix PFOS PFOSA PFOSAA EtFOSE PFOSEA M356 Surrogate Final tone Final _e Final cone Final cone Final_m Finalcone S_ eonc ALl Ain't spEced 4.93 5.00 9.76 9.89 24..8 2.5.I 4.9.3 50.0 97.6 98.9 5.24 10.4. 26.3 52.4 104 4.94 j 5.01 9.78 9.93 24.g 25.2 4.9.4 50. ! 97.8 t 99.3 5.13 10.2 2.5.8 $1.3 102 100 Surrel_tte Finatgone ng/mL 0.005 429438 I 255010 -735 I 746 976 I 989 256234 249448 I 520512 255183 SO0 782 737 " 749 766 1038 978 993 I ,017 Validated ranges - approTimate concentrations Serum PFOS PFOSA PFOSAA EtFOSE-OH PFOSEA IV1S$6 Rabbit Bovine 5.00-1000 ] 5.00-1000 I 5.00-1000 I 5.00-1000 1 5.00-1000 I $.00-1000 _ only. Use v_ues forrabbit. Rat j F.atima_ rally. Use values for Mb/L Monkey & Plasma ,_stimatesonly. Use valu_ for rabbiL Hunum Esmna_ only. Use vzlu_ for rabbit. 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 .... .---_-........ --,- ------ ARGUS 418-020 Analyucal Report: FACT TOX-164 LIMS E00-2738 3M ENVIRONMENTALALBORATORY i METHOD EXTRACTION OF FLUOROCHEMICAL COMPOUNDS FROM SERUM FOR ANALYSIS USING H]DLC-FJ._-CTROSPRAY/MAss SPECTROMETRY Method Number:. ETS-8-4.2 Adoption Date: 03/01/99 Approved By:. Effective Date: __q. I D[ Laboratory Manager g_'/7l,.,- 7'_-_ ' _ Group Leader Date o _-/,z./,, Date 1.0 SCOPEANDAPPLICATION m 1.1 Scope: This method is for the extraction of fluorochemical compounds from scrun_ 1.2 Applicable compounds: Huorochemica] surfactants or other fluorinated compounds. 1.3 Matrices: Rabbit, rat, bovine, monkey, and humanscram or other flul___ the validation report, f_,_) _/_ / 2.0 SUMMARYOF METHOD 2.1 This performance-based method descn'bes the procedure for extracting perfluorooctane- sulfonate (PFOS) or other fluorochemical _ts from scram, or other fluids, using an ion pairing reagent and methyl-ten-butyl ether (MtBE). An ion pairing reagent is added to the sample and the analyte-ion pair h 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 gm nylon filter using a 3-mL plastic Word6/95 3M Environmental Laborato_, ETS-84.2 Extra_cmofFluorochemicaJfsromSerum Page 809 Page l.of 15 Page 51 3M Medical Department Study: %6889.6 _-.-- -- _ .ARGUS 41_20 Analytical Kepon: FACT TOX- 164 LIMS E00-2738 ( 2.2 syringientoglassautovial(sA.pplicatioofnthismethodtosevenfluorochernicwaiss demonstrated: PFOS, PFOSA, PFOSAA, EtFOSE-OH, PFOSEA, M556, and a surrogate standard { see 3.0 Definitions }). These sample extracts are analyzed following method ETS-8-5.2 or other appropriate method. 3.0 DEFINITIONS 3.1 PFOS: perfluorooctanesulfonate (anion of potassium salt) C,F,_SOf 3.2 PFOSA: perfluorooctasnuelfonylamiCdteFnSChNH2 3.3 PFOSAA: perfluorooctane sulfonylamido (ethyl)acetate C,FnSO2N(CH2CH3)CH2CO2" 3.4 EtFOSE-OH: 2(N-ethylpeffluorooctanc sulfonamido)-ethyl alcohol C_,TSO2N(CI-I2CH_)CH2CH2OH 3.5 PFOSEA: perfluorooctane sulfonyetlhylamide CsFI_SO2N(CH2CH3)H 3.6 M556: C_=,7OS2NCH)(CH2COOH) 3.7 Surrogate standard THPFOS: 1H-IH-2H-2H perfluorooctane sulfonic acid 4.0 WARNINGS AND CAUTIONS 4.1 Health and safety warnings 4.1.1 Use universal precautions, especially laboratory coats, goggles, and gloveswhen handling animal tissue, whichmay contain pathogens. 5.0 I_'E_NC_ 5.1 There are no interferences known at this time. 6.O EQIJrp_fgwr 6.1 The following equipment is used wiu'leperforming 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 6.1.4 Nitrogen evaporator, Organomation 6.1.5 Balance (_+0.100 g) 7.0 Su ANDMATERIALS 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 810 Page 2 of 15 Page 52 3M Medical Department Study: T-6889.6 ..... ---_-......... --_ -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 7.4 Volumetric flasks, glass, type A 7.5 ; 7.6 I. 7.7 40 mL glass vials (I-CHEM or equivalent) Centrifuge tubes, polypropylene, 15 mL Labels 7.8 Bottle-top Dispenser - 3.0 to I0.0 mL or a 5-10 mL graduated pipette, glass 7.9 Syringes, capable of measuring 5 laL to 50 laL 7.10 Graduated pipettes 7.11 Syringes, disposable plastic, 3 m/., (B&D or equivalent) 7.12 Syringefilters, nylon, 0.2 l.tm,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 I_AGEN'rS AI_ STArC0An_S 8.1 Reagent grade water, Milli-QTM, Nanopure H 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 (NazCO_), J.T. Baker or equivalent 8.5 Sodium bicarbonate fNaHCO3), J.T. Baker or equivalent 8.6 Methyl-T-Butyl Ether, Onmisolv, glass distilled or HPLC grade 8.7 Methanol, Onmisolv, glass distilled or HPLC grade 8.8 Serum or blood, frozen from supplier 8.9 Fiuoroehemical 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, perflnomoctane sulfomc acid (I-H,I-H, 2-H, 2-H C4FI3SO3H,[THPFOS]), molecular weight = 428 8.9.8 Other fluorochemicals, as appropriate 3M Environmental Laboratory ETS-8-4.2 Page 811 Page3 of15 Page 53 3M Medical Department Study: "1"-6889.6 .... ------........ =---- ARGUS 418-020 Analytical Report: FACT TOX- 164 LIMS E00-2738 8.10 8.11 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 a100 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 thepH 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 (Na2CO_/NaI-ICO3):Weigh approximately 26.5 g of sodium carbonate (Na2CO3) and 21.0 g of sodium bicarbonate (NaHCO3) into a I L volumetric flask and bring to volume with water. Store in a 1L polypropylene (or equivalent) bottle. Standards preparation 8.11.1 Prepare PFOS standards for the standard curve. 8.11.2 Prepare other fluorocl_mical standards, as appropriate. Mnlticomponent fluorochcmical standards are acceptable (for example, one working standard solution containing approximately 1.00 pg/mL of PFOS, PFOSA, PFOSAA, PFOSEA, M556 andEtFOSE-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: molecular wt. PFOS (499) molecular wt. KPFO$ (538) ffi 0.927S ( Correcdon facwr ) 8.11.4 Bring to volume with methanol for a stock standard of approximately 1000 btg/mL. 8.11.5 Dilute the stock solution with methanol for a working standard 1 solution of approximately 50 pg/mL. 8.11.6 1000Ug/mLx5 m/.'] 100m/. ) =50_1n" Dilute working standard I with methanol for a working standard2 solution of approx. 5.0 pg/mL. 3M Environmental Laboratory ETS-8-4.2 Page 812 Page 4 of 15 Page 54 3M Medical Depa1_m,cntStudy: T-6889.6 ..... -'-............ -_" ARGUS 18.4 -02O Anal.vncal Report:FACT TOX-164 LIMS E00-2738 50/4_ImLx lOmL 1 =5.0_ImL 100m/. J 8.11.7 Dilute working standard 1 with methanol for a working standard 3 solution of approx. 0.50 pg/mL. I _opt/1_0_0m_x/.._l.,o,d..) = OJO0/_r imL 8.12 Surrogate THPFOS stock standard preparation 8.12.1 Weigh approximately 50-60 mg of surrogate standard 1-H.1-H. 2-H. 2-H, CsFl3SOsH crHPFOS) into a 50 mL volurr_tric flask and record the actual weight. 8.12.2 Bring to volun_ with methanol for a surrogate stock of approximately 10001200pg/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 I00 pg/mL. Record the actual volume transferred. 9.0 SAMPItEHANDLING 9.1 All samples are received frozen and must be kept frozen until the extraction is performed. 9.2 Mow samples to thaw at room temperature or in lukewarm water prior to extraction. 10.0 OuALrrv CONTROL 10.1 Solvent Blanks, Method Blanks and Matrix 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 methodblanks. 10.1.3 Matrix Blanks: Matrix blanks are prepared from one of three sources: 1) a study control matrix from a study control animalreceived 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 Cornrmrciallyobtained (same species) matrix curve--If the curve is prepared using commercially obtained matrixin the same species as the study animal,prepare two man-ixblanks using this same connmrcially availablematrix. 3M Environmental Laboratory ETS-8-4.2 Extraction of FluorochemicaJsfrom Serum __ -. - .... --_.-_.e-- ._ Page 813 Page5 of 15 Page 55 3M Medical Depa_unent Study: T-6889.6 ..... ---_-............ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 ' 10.2 10.3 10.1.3.3 Surrogate matrix curveml.f a surrogate matrix is used for the curve and continuing cah'brationverification samples: a) prepare two (2) matrix blanks using the surrogate matrix. b) Also, prepare a matrixblank with each set of matrix spikes (a set is a matrix spike/matrix spike duplicate at one level) using a commercially available maI_ of the same species as the study animals. Matrix spikes 10.2.1 Study Control Matrix Curve No marxix spikes are prepared. 10.2.2 Comn_rcia_y obtained matrix curve (same species) No matrix spikes are prepared. 10.2.3 Surrogate matrix curve Matrix spikes are necessary ff matrix is not availablein 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 rece_,,ed with each sample set. 10.2.4.1 If there is not sufficient sera availablefrom the control group, prepare matrix spikes using commercially availablematrix 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 sampk.s, with a minimumof 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 <)OQ, 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. Continuing calibration verifications (CCVs) 10.3.1 Prepare continuing cah'brafionverifit:ationsamples 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 (Le., either the study control matrix, commercial matrix of same species, or surrogate matrix). 331Environmental Laboratory v'-___ ...._ ETS.8-4.2 __*s_i ...... )p Page 814 Page6of 15 Page 56 3M Medical Department Study" T-6889.6 -- - "-_---........... ARGUS 418-020 Analy_cal 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 I0 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 Addkional continuing c_'bration verifications may be included at the same, low, mid or high-range concentration. 11.0 CALIBRATIONANDSTANDAP.,D_.ATNIO ILl Prepare matrix eal;bration standards 11.1.1 Transfer 1 mL of appropriateserum 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, rabbitsera 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 robes, 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 blank.s,and two method blanks. 11.1.5 11.1.6 Refer to validation report ETS-8-4.0 & ETS-S-5.0-V-1, which fists the working ranges andthe Linear Cah_rationRange (Lg_) for calibration curves. 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 curverange 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 foUowing 12.6-12.16 of this method. Use these standards to establish each initial curve on the rr_ spectrometer. 3M Environmental aboraton., 'I_ 0...,..) ETS-8-4.2 tL"I I C,=,,..O... Page 815 Page7of 15 Page 57 3M Medical Department Study: T-6889.6 "-_ ......... -" "---"-- ARGUS 418-020 Analytical Report: FACT TOX- 164 LIMS E00-2738 Table I Appro_dmate spiking amounts for standards and spikes Usin_ 1.0 ml. of matrix Working standard (approx. conc.) - Approx. final conc. of gL analyte in matrix - Blank 0.500 pFm 0.500 pprn 5.0O pprn . 5.00pprn 5.00 ]:_rn 50.0pprn 50.0pprn 50.0ppm 50.0 ppm 10 20 5 I0 20 5 I0 15 . 20 0.005 ppm 0.010 pprn 0.025 pprn 0.050ppm O.100 pprn 0.250_m 0.500ppm 0.750pprn 1.00 pprn 12.0 PROCEDtraE 12.1 Obtain frozen samples and allow to thaw at morn 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 work.sheet) for documentintgheremaininsgteps. 12.3 Vortexmixfor15secondst,hentransfe1r.0mL orotherappropriavtoelumetothe 15 mL polypropylene centrifuge tube. 12.4 Return unused samples to heezer 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 extract/on with surrogate standaradsde_cn_d m 11.2. 12.7 12.8 12.9 12.10 Spike each calibrationstandard matrix with the appropriate amount of standard as described in 11.1, or Table I in that section, for the cab'brat/oncurve standards. Also prepare rnat_ spikes if necessary andcontinuing calibration standards. Vortex mix the standard curve samples, nmtrix spike samples, and continuing calibration samples for 15 seconds. Check to ensure the 0.5 M TBA reagent is at pH 10. If not, adjustaccordingly. To each sample, add l mL 0.5 M TBA and 2 rnLof 0.25M sodium carbonate/sodium bicarbonate buffer. 12.11 12.12 Usinganbottlteopdispenseorr5-10mL graduategdlasspipettaed,d5mL methyl-tenbutyl ether. Cap each sample and put on the shaker at a setting of 300 rprn for 20 minutes. 3M Environmental Laborato_ ETS-8.4.2 Page 8 of 15 Page 58 Page 816 3M MedicalDepartmenSttudy:T-6889.6 .... ---_.-.....-.-._--- ARGUS 418-020 AnalyticRaelportF:ACT TOX- 16.1 LIMS E00-273_ 12.13 Centrifuge for 20 to 25 rrfinutesat 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 15mLcentrifJgetube. 12.16 Put each sample on the analytical nitrogen evaporator until dry, approximately 1 to 2 hours. 12.17 Add 1.0 nil of methanol to each centrifuge robe using a graduated pipette. 12.18 Vortex mix for 30 seconds, or longer if needed. 12.19 Labela I.5mL glassautovia(lorlow-volumeamovialwhen necessarwyi)ththestudy number,animalnumberandgenders,ampletimepoinmta,trixf,inaslolvente,xtraction date,andanalyst(pse)rformintgheextraction. 12.20 Attacha 25 ram.0.2IJmnylonmeshfiltteora3 mL syringaendtransftehresan_lefrom step 12.18 tot his syringe. Filter into the labeled antovial, 12.21 Cap andstor_extra_atroom temperaturoeratapproximate4lyC untialnalysis. 12.22 Completetheextractiwoonrkshee(tAttachmenAtorsimilawrorksheeta)ndincludien thestudybinder. 13.0 DATAANALYSISANDCALCULATIOSN 13.1 Calculations 13.1.1 Calculate actual concentrations of PFOS, or other applicable fluorochemical, in calibration standards using the following equation: mLof atd xconcentra_n of std (_ / rrd). = Finalconcentr_on ( llgI rid.)of PFOSin matrix mL of std + mL of aurrogmaetd+ ini6almaa_ volume(ml, ) 14.0METHOD PERFORMANCE 14.1 The method detection limit (MDL) is analyte and reaL'ixspecific, Refer to MDL report for specific M:DLand limit of quantitation (IX)Q) values (see Attachments B and C). At the discretion of the PAl, 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 of ETS-8-5.2 for method performance criteria. 3M Environmental Laboratory WTfrlteticm ETS-8-4.2 nf b"hwcw'tw.hpmlr.ai_ frnrn ._"vnm Page 817 Page9 of 15 Page 59 3M MedicalDepartmentStudy:T-6889.6 .... --'-.'.-.-.-.-....- ARGUS 418-020 Anal_icalReport:FACT TOX- 16.4 LIMS E00-2735 15.0 POLLUTION PREVENTION AND WASTE MANAGEI_H_NT 15.1 Disposeof samplewaste,fian-anabsloelventwasteand usedglasspi_ttewaste using proper methods and by placing each in their designated waste container. 16.0 RECORI_ 16.1 Complete the extraction worksheet attached to this method (or a similar worksheet), and includeinthestudybinder. 17.0 A'rrA_ 17.1 Attachn_ntA, Extractiownorksh_t (asimilawrorkshcctmay bc substitutefdor AttachmentA) 17.2 Attachment B, MDL/LOQ values and summary 17.3 AttachmentC, IonPairStandardCurvesworksheet(asimilawrorksheetmay bc substitutefdorAttachmentC) 18.0 REFERENCFeq 18.1 The validation report associated with this method is ETS-8-4.0 & 5.0-V-1. 18.2 FACT-M-3. I,"'Analysoifs Serum or OtherFluidExtractsforFluorochemicalussing HPLC-E]ectrvspray Mass Spectrometry" 18.3 ETS-8-5.2,"Analysiosf Potassium PerfluorooctanesulfonoartOetherFIuorochemicalisn Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" 19.0 AFFECTEV DQCVME_TS 19.1 ETS-8-5.2, "Anadysiosf PotassiumPerfluorooctanesulfonate or OtherFluorochemicalisn Serum Extracts Using HPLC-Electmspray/Mass Spectrometry" 20.0 R_vlSlONS Revision Number 1 2 Reason For Revision Sectim 12.21 Changed to include sample Smile it tM, mmlneratum. Se._on 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_ Se_tiea 1.1, 2.1 Rliminate "potassium' from perfium'ooclanesulfonam 8.9.1 Add K toPFOS 8.9.3 Add H to PFOSAA Revision Date 04402h99 10.2-10.2.414,.2.2 Add informatioanboutusing mu'roSme mau'ix, clarifcyontromlatrixand spiking the curve, changc spikesto evo_ 20 samples 10.3 Clarify purpose of cmtinuiali calibration ! 1.1 Added wording about control animal sent. using and net using cmmn_:ially available ,issue in general, make less specific for eqnipmeatnsupplies. equivalent bottle may be used. Substitute water for Miili-Q. Nalsan or 3.44 Environmental Laboratory ETS-8.4.2 gvtr.w_;tWt af ]l_tvC'_v_vvt;e_| 4Fr_ttv_tlm-ttm Page 818 Page!0 of 15 Page 60 3M Medical Deparunent Study: T-6889.6 .... -'-_- ......... A"_n-a_lytical _-e-e_o',Gft..Ur_A_,__Bl-_1__("._,__-O-164 Extraction Work.sheetETS-8-4.2 LIMS E00-2738 Study_ Matrix Box# WE/Day Date Spiked/ Analyst: 5 SurrogateS_ actuall_g/mL # FC-Mix approx0..5 gg/ml. # FC-Mix approx5. _g/mL # F-C-Mix approx5.0 _g/mL # Comments Verified by MS MSD o ! Blank ID _ Set,ram lgsqraetinn Metbml Vortex | 5 Ilb'_. amount = : mL Date & Initials Pinette Ma_'iX. snike with amm_nriaze surromlte ca" FC-'Mix VOItIII_ mL Pivene ! mL of 0.5 M TBA. pH 10. pH =, $td. # Pivette 2 mL of 0.25 NaICO)/0.25M NaHCO?buffer , Dismmse/vioette5 mL of metl_l.-t.-Imrvetther DismmserID #: Std. # TN-A- Shake 20 rain. Shak_ ID #:. Sh=tn'rspeed: Centrif_ 20-25 min. Centrifat,e _ C_mf_ sneed: Remove a 4 mL alimmt of oct,'anicla_-r Put on NimmmnEvazmcatotro drsmess Add methan_o! Volume mL TN.A- Voqcx _O s, ,, Filter usintt a 3mL B-D s',mn_e with a O.2um filter into a ! .5 mL autoxamnievial Cont. Cal. Verifications gsed same malrix as for $td cur_. Appendix A: Exwacticc Wotkshc_t 3M Environmental Laboratory _'S-8-4.2 Page 819 Page. 11 of 15 Page 61 3M MedicalDepartmentStudy:T-6889.6 ....---_.-.....-.--.-=- ARGUS 418-020 AnalyticRaelportF:ACT TON-164 LIMS E00-273_ MDL/LOQ values for rabbit serum Compound MDL LOQ Linear Calibration Range (LCR) (ng/mL) (ng/mL) Approximate concentrations to be used for preparing t. the Standard Calibration Curve PFOS 1.74 5.55 5 ng/m_1000 n_mL PFOSA 1.51 4.79 5 ng/nd.,-10n0s0/mL PFOSAA 3.46 EtFOSE-OH 11.4 20.5 5 n_/ml_1000 nB/mL 36.2 5 ng_._-1000 n_/mL M556 6.03 19.2 5 ng/mI.,-10n0s0/mL PFOSEA 5.71 18.2 5 nf/rnI.,-1n0g0/m0L MDL/LOQ values m rat, bovine,monkey,andhumanserum,andmonkeyplasmawerenot statistically de_,,.;.,ed. Two curves ineach of thesemamceswere extractedandanalyzedwith the rabbit serum curvetsodetermienqeuivalenRcees.ponseisntheratb,ovinem,onkeya,ndhumanwereequivaltetnot,he rabbirtesponses,therefotrhee,iMrDL andLOQ wilblethesamevalueassdeterminiendrabbisterum. PleasseeeLOQ SummaryandMDL studyinETS-8-4.&05.0-V-fIorfurthienrformation. AppendixB:MDL/LOQValuesandSummary ETS-8-4.2 g.xtrnetitwl nf ]_hlcwr_h_it_l_ 3M Environmental Laboratory freml ._t_qtm Page 820 Page 12of 15 Page 62 3M Medical Department Study: T=6889.6 - - "-:_- ......... ' _ - ARGUS 418-020 Analytical Report: FACT TOX-16. LIMS E00-2738 Compound: PFOS Preparedrange Rabbit Serum of standards (n$/mI.,) Full Range ),, Low Curve 0.995 - 978 4.94 - 248 High curve I/X 97.8 - 978 0.995 - 978 LCR from curve (ne./mI..,) 24.8 - 978 4.94 - 248 % Recovery Range 83-108 85-104 97.8- 978 4.94 - 978 85-106 94-111 RSD Range 4.67-11.0 5.34-12.0 4.84.9.80 4.60-10.5 Compound: PFOSA Preparedrange RabbitSerum of Standards (nf/mL) Full Range 0.993 - 976 Low Curve 4.93 - 97.6 High curve 1/X 24.8 - 976 0.993 - 976 LCR from curve (nt'/mL) 4.93 - 976 4.93 - 97.6 24.8 - 978 4.93 - 976 % Recovery Range .. 88-103 87-105 93-102 94-103 RSD Range 5.10-14.7 9.85-14.7 5.08-13.9 5. !O-14.5 Compound: PFOSAA Prepared range Rabbit Serum of standards {ng/mL) Full Range 0.991 -974 Low Curve 4.92 - 247 High curve 1/X 49.2 - 974 0.991 - 974 LCR from curve (,g/mL,) 24.7 - 974 9.74 - 247 97.4- 974 9.74 - 974 % R_overy Range RSD Range 81-I 11 97-107 85-108 95-115 4.18-10.6 i= 6.38-21.8 4.33-12.5 4.11-23.2 Appendix B: MDL/LOQ 3M Environmental Laborato_ Values and Summary ErS.8-4.2 F.xtra_tion of Fluorochemical$ from Serum Page 821 Page 13 of 15 Page 63 3MMedDiceaplarStmtue%dnyt6: 889.6 Anal iRcaelport:ll8164 Compound: EtFOSE_H Preparedran_ Rabbit Serum , of sm.ndm'_ (,$/mL) Full Range 0.993 - 976 Low Curve 4.93 - 97.6 High curve 1/X 49.3 - 976 0.993 - 493 Compound: PFOSEA Prepared range Rabbit Serum _ of standards (ns/n_) Full Range 0.993 - 976 Low Curve 4.93 - 248 High curve l/'X 49.3 - 976 0.993 - 976 Compound: M_556 Prepared range Rabbit Serum of standards (._/mL) Full Range 0.993 - 976 Low Curve 4.93 - 97.6 High curve I/X 97.6 - 976 0.993 - 976 LCR from curve (n$/mk) 49.3 - 976 9.76 - 97.6 % Recovery Range RSD Range 7%110 97-107 11.2-2.5.5 14.1-21.3 97.6 -976 9.76 - 976 90-109 86-111 11.5-19.6 11.I-21.2 LCR from carve (._/mL) 24.8 - 976 9.76 - 248 49.3 - 976 9.76 - 976 % Recovery Range 96-106 91-110 86-106 95-117 RSD Range I0.1-16.2 11.8-19.5 10.2-18.2 10.1-19.1 LCR from curve (ns/mL) 24.8 - 976 9.76-97.6 97.6 - 976 9.76 - 976 % Recovery Range 88-106 lOO-lO5 81-111 97-110 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 Laborato_ ETS-8-4.2 Page 822 Page 14 of 15 Page 64 3M Medical Department Study: T-6889.6 .... -=.......... _ _ ARGUS 418-020 Analytical Report: FACT TOX-Ib4 LIMS E00-2738 EXAMPLE Ion Pair Standard Curves - Fluids Amdyst(s) _ Prep date(s): Analyte(s): Study Animal Matrix : Method/revision: Target analyte(s): FC mix std approx. 0.500 pprm Studynumber.. Final solvent and TN: Blank fluid/ideulilien ;Record,namxu._d,, pr.-rar." curv,:., (e.g., 'Rabbit.' ID #XXX) I FC mixstd approx. 5.00 ppm: FC m_ s',adpprox. 50.0 ppm: Surrogate std approx. I00 ppm: !Recordtilest..mdardusedtoprepmt'ieleex_ac_edcar'.es). Actual concentrations of standards in the FC mix in methanol PFOS PFOSA PFOSAA EtFOSE PFOSEA MSS6 Std cone Std cone Std _c Std coxte Std _ac Std cone _g/ml. o.soo 0.500 5.00 [t[/mL 0.507 0.507 5.0"7 _t[_LI, 0.532 0.532 5.32 l_g/mI., o.5oi 0.501 5.01 _I, o.521 0.521 5.21 _[/mL o.5oi 0.501 s.o_ All Ain't _iked mL O.OLO 0.020 o.oos All Final vol mL 1.o15 1.025 t.010 55..o0o0, _to_ F" 5_.32 -l;5,.,0"1Jl__ _5.21- _5.01 550o..0_o _'I Il3k k.5_Mk_all4g1,5_._1,.a1t_.IjIld! JL _' 50.0 50.1 53.2 50.1 !j 52.1 50.1 50.0 50.1 53.2 50.1 t 52-1 50.1 0o.0o120o oO..oOoL5O 0.015 0.020 11..o02515 11..oloo 15 1.020 1.025 Calculated concentrations of standards in the sera mtrix: Rabbit PFOS PFOSA PFOSAA EtFOSE PFOSEA _ Surropte Finaclonc Final coru: Final a_c Final conc Final omc Finaclonc Stdomc 4.93 4.94 .5.01 9.'/6 9.78 9.93 24.8 24.8 25.2 49.3 Final cone 9"7.6 248 493 735 t 746 782 737 ng/mL 500 766 976 t 9119 ! 038 978 993 I0 !7 All Ain't sp____ 0.005 Validated range; - appro_dnmteconcentralions Serum PFOS PFOSA PFOSAA Rabbit 5.00-1000 ng/mL $.00-1000 ng/mL 5.00-1000 nf/mL Bov3ne Rat Monkey & Plasma Human Estimates only. Use values f_"_t. Estim_,___r_ely. Use values for rabbit. Estimates only. Use values forrabbit. Egimates only.Use valuefs_-rabbit F..tFOSE-OH $.00-1000 nlgml, PFOSEA $.00-1OO0 [ ng/mL [ MS.f_ 5.00-1000 ng/mL AttachmentC:Ion PairStandardCurves ETS-8-4.2 Extractionof Fluorochern/calfsromSerum 3M Environmental Laboratory Page 823 Page!5 of 15 Page 65 3M Medical Department Study: T-6889.6 .... -- ........... -"---- ARGUS 418-020 Anal_ical Report: FACT TOX- 164 LIMS E00-2738 3M ENVIRONMENTAL LABORATORY ' METHOD ANALYSIS OF POTASSIUM PERFLUOROOCTANESULFONATE OR OT_R FLUOROfn_MICAL_ IN SERUM EXTRACTS USING E_LC-ELECTROSPRAY/MASs SPECTROMETRY Method Number: ETS-8-5.1 Author:LisaClemcn,RobertWynne Approved By: Laboratory Manager !%_ Adoption Date: 03/01/99 Revision Date: _//_/_ Date Group Leader Date TechnicaRleviewer " Date emoewe_p_t_ 1.0 SCOPE AND APPLICATION _ Dm 1.1Scope:Thismethoddescribetsheanalysiosfserumextractfsorfluomchcrnicsaulrfactants usingHPLC-electrospray/msapsesctrometry. 1.2ApplicableCompounds: Fluorochemicaslu:factanotrsotherfluorinatceodmpounds,or otherionizablceompounds. 1.3Matrices:Rabbitr,atb,ovinem,onkey,andhuman serum,orotherfluidassdesignateidn the validation report Word 6/95 3M Environmental Laboratory ErS-g.5.1 Analysis of Serum _ Using F.S/MS Page 824 Page 1 of 9 Page 66 3M Medical Department Study: T=6889.6 .... -=........ =, _ ARGUS 418-020 Analytical Report: FACT TOX-I LIMS E00-2738 2.0 SUMMARY OFMETHOD 2.1 "i This method describes the analysis offluorochemical surfacmuts exu'acted from serum or otherfluidsu,singHPLC-electrospmy/masspsecU'omeuTo,rsimilasrystcransappropriate. The analysiissperformedbymonitorinagsinglieoncharacterisotfaicparticular fluorochemicsaulc,h as theperfluomoctanesulfo(nPaFlOeS)anion, m/z= 499 Additionallsya,mplesmay beanalyzeudsinga tandemmassspectrometteorfurthevrerify theidenfiWofacompoundby detectindgaughteironsoftheparention. 3.0 DEFINITIONS 3.1 Atmospheric Pressure Ionization (API): The Micromass Quam-o H n-iple quadrupole systemsallowforvarioumsethodsofionizatiboyntltilhdnvg arioussourcesp,robes,and interfaceTsh.eseincludbeutarenotlimi_dto:Elec_spraylon_7_ti(oEnSI)A,_nospheric PressurcehemicaIlonizati(oAnPcI)T,h_-.ospraye,tc.The ioni_,_opnrocessm these techniqueosccursatannosphm'ipcressur(ei.en,o.t,underavacuum). 3.2ElectrospraIyonizatio0nES,ESI):amethodofionizatipoenrformedata1_nospheric pressm'w,herebyionsinsolutioanretransferrteodthegasphaseviatinychargeddroplets. These chargeddropletasreproducedby theapplicatioofnastrongelectricfaileld. 3.3Mass SpectrometryM,ass Spectromete(rMS),Tandem Mass Spectrometer(MS/MS): The API Quat_ ]I triple quadrupole systems are equipped with quadrupole mass selective detecwrs. Ions are select/rely discriminated by mass to charge ratio (m/z) and subsequently detect_:d. A single MS may be employed for ion detection or a series (MS/MS) for more specific fi-agmenmtion information. 3.4 Conventional vs. Z-spray probe interface: The latest models ofMicromass Quam_ H triple quadrupole systems (pod 1998) utilize a "Z-spray" conformation. The spray emitted from a probe is orthogonalto the cone aperture. In the conventional conformation it is aimed directly at the cone aperture, afterpassing through a tortuous pathway in the counter .electrodTeh.oughtheconfiguratiiosndifferentth,emethodsofoperatiocnl,eaninga,nd maintenance are the same. However, Z-spray componenm and conventional components are not compatible with one another, but only with similar systems (i.e., Z-spray components arc compatible with some other Z-spray _ e_.) 3.5 Mass Lynx Software: System software designed for the specific operation of these Quatlro I] triple quadrupole systems. Currently MassLynx has Windows 95 and Windows_1"4.0 - versions. All versions are similarF.or more details seethe manual specific to the insmm_ent (Micromass Quatu_ II triple quadrupole MassLynx or MassLynxNT User's Guide). 4.0 WARNINGS AND CAUTIONS 4.1 Health and Safety Warnings: 4.1.1 Use caution with the voltage cables for the probe. Wh_ engaged, the probe employs a voltage of_oximately 5000 Volts. 4.1.2 When handling samples or solvents wear appropriate protective gloves, eyewear, and clothing. 3M Environmental Laboratory 4 Mk_" ETS-8-5.1 _(N,q._,_ l_q_,.,_,_'S T Tl-_" _ "_/&A_ Page 825 Page2 of 9 Page 67 3M Medical Department Study: T-6889.6 -- -"---'_-.......... --- ARGUS 418-020 h-nulytical Report: FACT TOX-164 LIMS E00-2738 4.2 ' Cautions: 4.2.1 Do not operatesolvent pumps above capacity of 400 bar (5800 psi) back pressure. If the back pressure exceeds 400 bar, the HP1100 will initiate automa_c shutdown. 4.2.2 Do not run solvent pumps to dryness. 5.0I_'IZRF_RENCES S.1 To r-inffniizneterferenwcheesnanalyzinsgamplest,eflosnhouldnotbeusedforsample storagoeranypartofiusmm_entatitohnatcomesincontacwtiththesampleorextract. 6.0 Egtm, ME_rr 6.1 Equipmentlistebdelowmay bemodifieidnorderto oplSrniTethe system. Documentany modific.atiionnthse rawdl,,asmethoddeviations. 6.1.1 Micmmass Quam_ H tripl_eole electrospray io,,intlon source Mass Spectrometerqni'ppewdithan 6.1.2 HPll00 lowpulse solvent pumping system, solvent degasser, column compartmenta,ndautosampler 7.0 SUPPLIES AND MATERIALS 7.1 Supplies 7.1.1 High purity grade nitrogen gas regulated to approximately 100 psi (House air system) 7.1.2 HPLC analytical COIL"; specificS to be det_,,,ined by the analyst and documented in the raw data. 7.1.3 Capped autovials or capped 15 mL centrifuge tubes 8.0 RZACZN'rsAb_ STOmARD_; 8.1 Reagents 8.1.1 Methanol, HPLC grade or equivalent 8.1.2 Milli-Q TM water, al] water used in thi.qmethod should be Milli-Q TM water or equivalent, and may be provided by a Mini-Q TOC Plus system or other vendor 8.1.3 Ammonimn acetate, reagent grade or equivalent 8.2 Standards 8.2.1 Typically two method blanks, two matrix blanks, and eighteen matrix standards are preparedduring the extra,on procedure. See ETS-8-4.1. 9.0 SAMPLE_KNDLIN(_ 9.1 Fresh matrix standardsare preparedwith each analysis. Extracted standards and samples are stored in capped autovials or capped 15 mid cenUifuge tubes until analysis. 3M Environmental Labora_ ............ ETS-8-$.I Aualymof Serum_uact UsingES/MS _.=-. .... Page 826 Page3 of 9 Page 68 3M Medical Department Study: T-6889.6 .... --_ .......... - ARGUS 418-020 ,_-:alytieal Report: FACT TOX-164 a LIMS E00-2738 9.2 If analysis will be delayed, extracted standards and samples can be refrigerated at approximately 4* C, or at morn temperatta'e, until analysis can be performed. t !0.0 I_UALITY CONTROL 10.1 Solvent Blanks, Method Blanks and Matrix Blanks 10.1.1 Solvent blanks, method blanks and matrix blanks are printed and analyzed with each batch to determine contamination or carryover. 10.1.2 Analyze a method blank and a man_ blank prior to each calibration curve. 10.2 Matrix Spikes 10.2.1 Matrix spikes are prepared and analyzed to determine the matrix effect on the recov.ery efficiency. 10.2.2 Matrix spike duplicates are preparedand analyzed to measure the precision and the recovery for each analyte. 10.2.3 Analyze a man-ixspike andmalrix spike duplicate per forty samples, with a mi.imum of 2 spikes pet 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 of the initial calibration curve. 10.3 Continuing Calibration Verifications 10.3.1 Continuing cah'brationverifications are _-_yzedto verify the continued accuracy of the calibration curve. 10.3.2 Analyze amid-range cah'brationstandard after every tenth sample, with a mi-lmem of one per batch. l 1.0 CAI,II_it-aTIONANDSTANDARDIZATION 11.1 Analyze the extracted matrix standan_ prior to and following each set ofextrants. The average of two standard curves will be plotted by linear regression (y =.my + b), weighted I/x, not forced through zero, using MasaLynx or other suitable software. - 11.2 If the curve does not meet requirements, perform routine maintenance or reextra_:tthe standard curve (if nece_V) and reanalyze. 11.3 For purposes of accuracy when quantitating low levels of a-=lyre, it may be necessary to use the low end of the cah'brationcurve rather than the full range of the standard curve. Example: when attempting to quantitate approximately 10 ppb of analyte, generate a calibration curve consisting of the standanh from 5 ppb to 100 ppb rather than the full range of the curve (5 ppb to lOOOppb). This will reduce inaccuracy attn'buted to linear regression weighting of high concenlration standards. 3MEnvironmentalLaboratagt_._ ..: ........ Annlv_im _=..._ EI'S_5.1 nf._r_nw l_-zt.met _ l l_'_na T:_'_ Page 827 .Page 4 of 9 Page69 3M Medical Department Study: T-6889.6 -- "-=........... -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 12.0 PROCEDURES 12.1 Acquisition Set up .: 12.1.1 Click on start button in the Acquisition Control Panel. Set up a sample list. Assign t a filename using MO-DAY-Iast digit of year-sample number, assign a method (MS) for acquh-ing, and type in sample descriptions. 12.1.2 To create a method click on scan bu_on in the Acquisition control panel and select SIR (Single Ion Recording) or MRM. Set Ionization Mode as appropriateand mass to 499 or other appropriate masses. A full scan is usually collected along with the SIRs. Save acqui_tion method. I.fMS/MS iusu-tnnentsare employed, additional product ion fi-agmentation 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 of exw_ted standards and ends with a set of_ 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 Autosampler 12.2.1 Set up sample tray at,cording to the sample llst prepared in Section 12.1.1. 12.22 Set-up the I-IP1100/autosampler at the following conditions or at conditions the analyst considers appropriate for optimal response. Record actual conditions in the insmnnent logbook: 12.2.2.1 Sample size = 10 pJ..injection 12.2.2.2 Inject/sample = 1 12.2.2.3 Cycle time = 13.5 minutes 17..2.2.4 Solvent ramp -. Time 0.00 rain 8.50 ml, 11.0,.in 12.0 mi. McOH 40% 90% 90% 40% 2.0 mM ._mmonium acetate 60% 10% 10% 60% 12.2.2.5 Press the "Start"button. 12.3 Instrument Set-np 12.3.1 Refer to ETS-9-M.0 for more details. 12.3.2 Check the solvent level in reservoirs and refill if necessary. 3MEn_ronmenml Luboratcx_--_ _ -........ _S-8-5.1 Anslv_, nf .u_n_ i:.xtme*l |_inp F.OJI_._ _,:-, .... Page 828 Page S 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 enclof the probe. Use an eyepiece to cheek the tip. The tip should be fiat with no jagged edges. If the tip is found to be unsa_factory, disassemble the probe andreplace the stainless steel capillary. 12.3.4 Set HPLC pump to "On". Set the flow to lO - 500 uJ../min or as appropriate. Observe droplets comi-g out of the tip of the probe. Allow to equih'lyratefor approximately 1Ominutes. 12.3.5 Turn on the nilrogen. A fine mist should be expelled with no nitrogen leaking around the tip of the probe. Readjustthe 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 neb_li_ng gas 10-15 lit_our 12.3.6.3 HPLC constant flow mode, flow rate I0 - 500 pJ./rnln 12.3.6.4 Pressure <400 bar (This parameter is not set, it is a guide to ensure the HPLC is operating correctly.) " 12.3.7 Carefully guide the probeinto 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 st_dybinder with a copy taped into the instrument log. 12.3.9 Using the eross-flow counter electrode in the F.S/MS source is recommended for the analysis of biological matrices. 12.3.10Click on :Jt_ button in the Acquisition Conlrol Panel (this may vary among MassLynx versions, see appropriate MassLynx USER'S GUIDE). Press the start button. _-qn, e start and end sample number includes all samples to be analyzed. 13.0 DATAANALYSISANDCALCtnLATION_; 13.1 Calculations: 13.1.4 Calculate matrix spike percent recoveries using the following equation: % Recovery = Observed Result - Backm-oundResult x 100 rpeae Result 13.1.5 Calculate pement difference using the following equation: %Difference - Exeected Cone. - Calculated Conc. x 100 Expected Cone. 13.1.6 Calculate actual concentration of PFOS, or other finorochemical, in matrix (_ ofPFOS talcf.zomst&Curve x DilutioFnactor) x 1 ue (Initial Volume 0fmatrix (mL_+ mL ofSurrot, ate Standard_ 1000 ng Final Volume (mL) 3M Environmental Labor_ ------......... ETS-8-5.1 Anilvm of Smum F._ Usina E.e_vfS _ ..... Page 829 Page 6 of 9 Page 71 3M Medical Department Study: T-6889.6 .... -:_ .......... ------- ARGUS 418-020 Analytical Report:FACT TOX-164 LIMS E00-2738 14.0 MVrHOD PERFORMANI_ 14.1 Method Detection Limit 0VID].)and Limit ofQuantitation (LOQ) are method, ana]yte, and t matrix specific. Please see ETS-8-4.1, Attachment B, for a listing of cm'r_t validated lVIDLand LOQ values. 14.2 Solvent Blanks, Method Blanks, and Matrix Blanks 14.2.1 Solvent blanks, method blanks, and mm_ blanks values are must be below the lowest standard in the cah_orationcurve 14.3 Calibration Curves 14.3.1 The r_value for the calibrationcurve must be 0.980 or better. 14.4 Matrix Spikes 14.4.1 Ma_ix spike _ concentration. recoveries are must be within 30% of the spiked 14.5 Continuing Ciflibration Verifications 14.5.1 Continuing calibration verification percentrecoveries must be 30% of 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 res_yzed or other actions as det_,u_ined by the analysL Document all actionsin theappropriate logbook. 14.7 If'data arc to be reportedwhen performance criteriahave not been met, the data must be foomoted on tables and discussed in the text of the report, _5.0. POLLUTIONPI_VENTIONANDWASTEMANAGEMENT 15.1 Sample extract waste and flammable solvent is disposed in high BTU containers, and glass pipeUe waste is disposedin broken glass containerslocated in the laboratory. 16.0 I_coR_s 16.1 Each page genera_ for a study must have the following information included either in the header or hand wril_m on the page: study or project number, acquisition method, integr'_ion method, sample name, e_'tion date, dilution factor (if applicable), and analysL 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 iusm_ent runlog. 16.3 Plot the calibration curve by lineffirregression, weighted l/x, thenprint these graphs and store in the study folder. 16.4 Print data integration summmT, _on and store in the study folder. method, andchromatograms, from MassLynx, 3M Environmental Laborato_ .............. EI'S-8.$.I Analysisof Su'am_ UsingES/MS _.,:. .... Page 830 Page7 of 9 Page 72 3M Medical Deparanent Study: T-6889.6 - --.=_......... _-_ _ ARGUS 418-020 An_|ytieal Report: FACT TOX- 164 LIMS E00-2738 16.5 Summarize data using suitable so_vare (Excel 5.0) and store in t._esvady folder, see Attachment A for an example of a summary spreadsheeL 16.6 Back up electronic d_,= to appropriate medium. Record in study notebook the file name .t_ and location ofbackup electronic data. .17.0 TABLES. DIAGRAMS. FLOWCHARTS. AND VALIDATION DATA 17.1 Attachment A: ETS-8-5.1 Data summary spreadsheet. 18.0 REFeReNCES 18.1 FACT-M-4.1, "Extraction ofPotassium Perlluorooctanesuffonateor OtherFluorochemleal compounds from Serum for Analysis Using HPLC-Electrospray/MassSpectrometry 18.2 ETS-9-24.0, "_)pm-alionmadMaintenance of the Micromass Atmospheric Pressure Ionization/Mass Spectrometer QuattroII triple quadrupoleSystems" 18.3 The validation report associated with this method is ETS-8-4.0 & 5.0-V-1. 19.0 AF_CrED Do_rrs 19.1 ETS-8-4.1, '_.xlmction of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds fi_m Serum for Analysis Using HPLC-Electrospray/MassSpecU'omelry" 20.0 Rrctstoss Revision Number. 1 Reason For Revision Section 6.12 Clarification of I-IP1100 s3_tem components. Section 11.1 Average of two curves, not standardvalues, are used for plotting linearregremion and added the 1/x weighting of the curve_ Section 12.2.2.4 Clarification of solvent ramp. Section 17.1 Clumged from _-_chment B to A. Revision Date 04!02/99 3M Environmental Laborato_._._, =......... E1"S.8-$.1 Amlym ofSerumExw_ UsingES/MS ,_---=-. _ . Page 831 Page 8 of 9 Page 73 3M Medical Dep_,hucnt Study: T-6889.6 -- - "_ ........ : _---"----- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Laboratory Study # t Study:. Test Material: _inzl Solvcnc Method/Revision: Amly_csl Equi_-_ SystemNumbs. ha_t Softw=_.Nnou: R-SquaredValue: Slope: Y Iutcrccpc Dan: ofExuscfion//mtl,ysc DateofXntysh/_. ysc Group Dose Sample_ Concentration . ughnL Initial VoL mL Dilution Factor Final Couc. ug/mL Slope: Taken:humlinearregnnsiou equm_n. Group/Dose: Takm _ the study folder. Sample#: Talum_, the study folder. Concentration (ug/mL): T-t'*',,from the ]_-t.tT-yl_.integrafioD IZWml_ry. Initial Volume (mL): T-_,'- from the study folder. Dnuflou Factor. Taken fromthe study foklmc. Final Cone- (ug/mL): Ctlculatedby divl,4i,,_the initial volume fromthe conc=m=iou Attachment A: SummarySpreadsheet ETS-8-5.1 Analysis of SerumExtra= Using F.S/MS 3M Environmental I.aboratolZ._ __........ -._.-. _ Page 832 Page 9 of 9 Page 74 3M Medical Department Study: T-6889.6 ........... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Method Modification Methods: Sectionmodified: ETS-8-7.0, ETS-8-5. ], ETS-8-97.0 add section14.3.2 Methodreads: NA Modify method to _ 143.2 The second(bracketing) ath'lmldon _ The first _ tnd seczptable _ea " tnlty be dmm'tivtted, if imlnlmental drift tffee_ the data. hec,_ shall bracket _utble data. EffeCtive date ofmodificalion ETS-8"7.0: 7/22/99 Effective date of modification ETS-8-5.1: 4/26/99 Effective date ofmodi.fieation ETS-8-97.0:7/28/99 SignaturoefPAl maddam ,,/o:,,ov E:_.,:tC,_! of Original u';z.. _tl:/L_ .'? 3M Environmental Laboratory ............... -:.. .... Page 833 Page 75 3M Medical DeparmaenSt tudy: T-6889.6 - - ----_-........ :, _ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 3M ENVIRONMENTALLABORATORY METHOD ANALYSIS OF POTASSIUM PERFLUOROOCTANRSULFONATOEROTHER FLUOROCHEMtC_T-_IN SERUMEXTRACTSUSING HPLC-ELECTROSt_Y/MASs SPECTROMETRY Method Number:. ETS-8-5.2 Author: Lisa Clemen,KrisHansen ApprovedBy. Adoption Date: 03/01/99 Revision Date: _ }/- / O! Laboratory Manager Date _-'F_- Group Leader ozlole/ Date TechnicalReviewer oz-oI.,,t Date emt Co_dO_l DID 1.0 ScQI'EAl_lA>rrbXCTATXON 1.1 Scope: This rr_tboddesen'besthe analysisof serumextractsfor fluorochemicaslurfactants using l-IPLC-electrospray/massspectrometry. 1.2 Applicable Compounds: Fluorochemicalmrfaetantsor other fluorinatedcompounds,or other ion/zablecompounds. 1.3 Matrices: Rabbit,rat,bovine,monkey,andhumanserum,orotherfluidsas designatedin the validationreport. Word 6/95 3M EnvironmentalLaboratosg_...___.,-....... A alqNnP_e _ .-._.=-.._. ETS-8-5.2 _ _ome_ _ Page 834 _Cl_l_dre Page I of 11 Page 76 3M Medical Department Study: T-6889.6 .... -=........... -_ -'---- ARGUS 418-020 Analytical Report: FACT TOX- 164 LIMS E00-2738 2.0 SUMM4nY 0r METHOD 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 _ the analysisof fluomchemicalsurf_tants extracted from serum or other fluids, using HPLC-electrospray/mass spectrometry, or similarsystem as appropriate. The analysis is performedby monitoring a single ion characteristic of a particular fluorocbemical, sm:has the perfluorooctanesuifonate (PFOS) anion, m/z= 499. Additionally, samples may be analyzed using a tandem mass spectrometer to further verify the identitT of a compound by detecting daughter ions of the parent ion. 3.0 DEFINITION_ 3.1 Atmospheric Pressure Ionization (API): The Micromass Quattro 11and Ultima .t,,'iple quadrupolc systeim allow for various methods of ionization by urillrivlg various sources, probes, and interfaces. These include but are not limited to: Electro@ray Ionization (F_.SI), Atmospheric Pressure chemical Ionization (APcl), Thermospray, etc. The ionization process in these techniques occurs at azmospberic pressure (Le., not under a vacuum). 3.2 Electrospray Ionization ('F._,ESI): a method of ionization performed at atmospheric pressure, whereby ions in solution are transferredto the gas phase via tiny charged droplets. These charged droplets are produced by the application of a strong electrical field. 3.3 Mass Spectrometry, Mass Spectrometer (MS), Tandem Mass Spectrometer (MS/MS): The API Quattro H and Ulfima 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 b directly at the cone aperture, after passing through a tortuous pathway in the counter electrode. Though _ configuration is d/ffer_ the methods of operation, cleaning, and maintenance arc 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 Mass Lynx Software: System software designed for the specific operation of these Quattm TItriple quadrupolc systems. Currently MassLynx has Windows 95 and W'mdowsNT 4.0 versions. All versions are similar. For more details see the manual specific to the instrument (Micromass Quattro II or Ultima triple quadrupole MassLyr_ or MassLynx NT User's Guide). 4.O W^_G_ ^vm CAVIIQNE 4.1 Health and Safety Warnings: 4.1.1 Use caution with the volUtgn cables for the probe. When engaged, the probe employs a voltage of approximately 5000 Volts. Word 6/95 3MEnvironmental Laborata_.._ EI'S-8-5.2 Analwis of Serum Extract Usin_ ES/MS , -......... ._:-. .... Page 835 Page 2 of I 1 Page 77 3M Medical Department Study: %6889.6 ..... ---_-.......... - -- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 4.1.2 When handling samples or solvents wear aFpropriate 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 INTERFERENCES 5.1 To _ interferences when analyzingsamples, Teflon should not be used for sample storage or any part of instrummatation that comes in contact with the sample or extract. 6.0 EQtr_MENT 6.1 Equipment listed below may be modified in order to optimize the system. Document any modifications in the raw dAt_as method deviations. 6.1.1 Micromass Quattro H or Ultima triple quadrupole Mass Spectrometer equipped with an elec_tospray ioni_atlon source 6.1.2 HP1100 or Agilent low pulse solvent pumping system, solvent degasser, column corrtpamnent, and autosampler 7.0 SUPPLIEi$ AND MATERIALS 7.1 Supplies 7.1.1 High purity grade nitrogen gas regulated to approximately 100 psi (House air or nitrogen system) 7.1.2 HPLC analytical column, specifies to be determined by the analyst and documented in the raw data. 7.1.3 Capped autovials and capp_ 15 mL centrifuge tubes 8.0 REAGENT S AND STANDARDS 8.1 Reagents 8.1.1 Methanol. HPLC grade or equivalent 8.1.2 Milli-QTM water, all water used in thLmethod should be Mt_Q TM water or equivalent, and may be provided by a Mtqli-QTOC 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 Laborato2iK___........... ETS-8-5.2 _..:.-.. _ Page 836 Page3 of I 1 Page 78 3M Medical Department Study: T-6889.6 ..... --:_- ......... - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 9.0 SAMPL_ HANDI_G 9.1 FreshmatrixstandardasrepreparewditheachanalysiEsx.tractesdtandardasndsamples arestoredincappedautoviaolrscapped15mL centrifutguebesuntialnalysis. 9.2 Ifanalysiwsillbedelayede,xtractesdtandardasndsamplescanberefrigeraatted approximate4lyC,oratroom temperatunu:n,tialnalysciasnbeperformed. 10.0 QUALrrYCONTIROL 10.1 Solvent Blanks, Method Blanks and Matrix Blanks 10.1.1 Solvem blanks, method blanks and matrix blanks are prepared and analyzed at least once during the course of the study to determine ff contamination occurred during sample prep. 10.1.2 Analyze at least one solvent blank priorto each calibrationcurve. 10.1.3 Matrix blanks should be analyzed with each sample list that includes undiluted exffat:ts. 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 ate monkey sera), matrix spikes and matrix spike duplicates are prepared in blank sample matrix (e.g., monkey sera) and analyzed to verify extraction efficiency. 10.2.2IfcurvesandmethodQC areprepareidnthesamematrixassamplesn,o additional matrixspikeasrerequired. 10.3 Continuing Calibration Verifications (CCVs) 10.3.1Continuincgalibrativoenrificatiaorneasnalyzetdoveriftyhecontinueadccuracoyf thecal_ratiocnurve. 10.3.2Analyzetwocab-marisotnandard(soneateachof2 levelsa)fteerveryonetoten samplesw,itha mininmmoftwoperbatchandalwaysfinishiannginjection sequencewithatleasttwo_n standards. II.0 CALIBRATION8ND STANpARDIZATION 11.1 Analyze the extracted matrix cah'brationstandards prior to each set of extracts. The curve will be plotted by linear regression, weighted l/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 reanaly'_ the standardcurve. 11.3 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 full range of the standard curve. Example: when attempting to quantitate approximately 10 ppb of analyte, it may be beneficial to generate a cah'brationcurve consisting of the standards from 5 ppb to 100 ppb ratherthan the furl range of the curve (5 ppb to 1000 ppb). This will reduce inaccuracy attributed to linear regression weighting of 3MEnvironmentalLaborat_ty__ ETS-8-5.2 Analysis of Serum Extract Usin_ E..q/MS ............_..-:_-. Page 837 Page4 of 11 Page79 3M Medical Depa.r_ent 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 m common between the curves. ]:or example, the low curve may inchide the following points: I, 5, 25, I00, 250 ppb and the high curve may include the points: 250, 500, 750, 1000, 1250 ppb. t 12.0 Plt0cl_OR_ , 12.1 Acquisition Set up 12.1.1 On the MassLynx _in page, set up a sample list name. Save the list as ir_trument designator letter, last 2 digits of test year-too-day, and a letter that will increase through the alphabet with each additional list for that day. Example Sample List: IYYldMDDa or D010712a I=ins_t name (D for "Davey") YY--year of test (01) MM=month of test (07) DI_y of test (12) a--first sample list (run) of the day (the next sample list will end with 'b,' the next 'c' and soon.) 12.1.2 Assign a filenarneusing the instrument designator letter, the last 2 digits of year-tooday, and a 3-digit sequential file numberthat starts with I and increases by one for each filename. Example F'fleName: IYYMMDD..'?_..or D010712001 I--instrument name (D for "Davey'_) YY=year of test (01) MM---monthof test (07) DD=day of test(12) ###=3-digit sequential file number starting with 1 through 999 (001) 12.1.3 Also, aspart of the sample list, assign a method (MS) for acquiring, an inlet file, a bottlneumber,aninjectivoonlumeandsamp_ descriptions. 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 appropriateand mass to 499 or other appropriate masses. Also set the acquisition start and stop _v_. Save acquisition method. If MS/MS instruments are employed, additionalproduct ion fragmentation information may be collected. See Mi_'om._ Mas_ynx 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 extr_ted raat_ 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. 3MEnvironmental Laboramo/__ Analysis __-........ _.-:.. ETS-8-5.2 nf.ca-Jr_nn I:;.xtraet l lxln g.q/M.q _ Page 838 Page5 of 11 Page 80 3M Medical Department Study: "1"-6889.6 ..... ---_-.......... - - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 12.9. 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 HPI.,Cto the following condiu'onsor 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 = I 12.2.2.3 Cycle time = I0.0 minutes 12.2.2.4 Flow rate = 300 pI./mm 12.2.2.5 Mobile Phase (program) Time MeOH 0.00m 1.00 ,,,;,,. 5.50 rain. 7.50 mill. 8.00 mill. 10% 10% 95% 95% 10% 2.0 m/VlAmmonium acetate (in H20) 90% 90% 5% 5% 90% Instnnnent Set-up 17..3.1 Refer to ETS-9-?A for more details. 12.3.2Checkthesolvenlteveilnreservoiarnsdrefiilflnecessary. 12.3.3Cheekthestainlesstseeclapillaartytheendoftheprobe.Use aneyepiecteocheck thetip.Thetipshouldbeflawtithnojaggededges.Ifthetipisfoundtobe 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 I0 - 500 p.I./minor as appropriate. Obscrw droplcm coming out of the tip of the probe. 12.3.5 Turn on the nitrogen. A fine mist should be exl=nedwith 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 paramemrsat the following settings. These settings may changein order to optimizetheresponse: 12.3.6.1 Dryinggas250-400liters/hour 12.3.6.2 ESI neb-l_ing gas 10-15 liters/hour 12..3.6.3 HPLC constant flow mode, flow ram I0- 500 pL/min 12.3.6.4 Pressure <400 bar (This parameter is not set, it is a guide to ensure the I-IPLCis operating correctly.) 12.3.7 Carefully guide the probe into the opening. Insert probe until it will not go any furdaer.Connect the voltage cables to the probe. 3M Environmental Laboratory-.._ ETS-8-5.2 AnalysoifsSerumExtractUsingES/MS __-.. , .... =_..--.... Page 839 Page6ofII Page 81 3M Medical DeparmsentStudy: T-6889.6 -- ""-:......... --------- ARGUS 418-020 Analytical Report: FACT TOX-164 LEVISE00-2738 12.3.8 Print the tune page, MS file, HPLC parameters, sa.-z_le list and the Microsofz 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 MassLyv.x versions, see appropriateMasaLynx USER'S GUIDE). Ensure start and end sample number includes all samples to be analyzed. 13.0 DATAANALYSISANDCALCULATIONS 13.1 Calculations: 13.1.1 Calculate matrix spike percent recoveries using the following equation: ObserveRdesul-tMatriBxlankResult % Recove_ = Sp_.ingl._el x I00 13.1.2 Calculate percent difference using the following equation: %Difference = ExpectedCone.- C._u_ed Con_ x 100 _pected Con_ 13.1.4 Calculate actual concentration of PFOS, or other fluorochemical, in matrix (ttg/mL): .(Conc.ofPFO,,VCak. fromStd.Curve(nsInt), x DiiutionFactor) "_(InigalVolumeof Matriz(mL,) + mL,of 5urrogate Standard) x 1148 lO00 n g 14.0 MKTE[ODPI_pZORMANCE 14.1 Method Detection Lirait(MDL) and Limit of Quantitation (LOQ) are method, analyze, and matrix specific. Please see ETS-84.2, Attachment B, for a listing of current validated MDL and LOQ values. 14.2 Solvent Blanks, Method Blanks, and Matrix Blanks 14.2.1 Solvent blanks, method blanks, and matrix blanks values must be below the lowest active standard in the cah2ntion curve. 14.3 Calibration Cm'ves 14.3.1 The coefficient of determination value for the calibration curve must be 0.990 or better. 3MEnvironmenta! Laborat_ ETS-8-5.2 Annlwi _F'._ntm F.Trra_ lTine lg__?tA'._ __=........ =_,=-, - Page 840 Page 7 of I1 Page 82 3M Medical Deparmaent Study: T-6889.6 ..... -=_ ........... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 14.3.2 All active cah'brationcurve point nmst be within 25% of the theoretical value with the exception of the LOQ point, which may deviate up to 30%. 14.3.3 Cah'brationstandards with peak areas less than two times the curve mar_ blank _ mustbedea-+tivattoeddisqualiafdyatarangethatmay beaffectebdybackground levels oftheanalyte. 14.3.4Low or highcurvepoints may bedeactivatteodoptimize a linearrangeappropriate to the d_t_ 14.3.5Not includilnogworhighpointdsroppedtooptimiztehelinearrangec,urvepoints may be deactivated if they devi_t+emore than 25% from the theoretical value when the curve isevaluatedover a linear range appropriateto thedata. 14.3,6 One point below the LOQ may remainactive even flit deviates more than -*-30%or has a peak Lea less than two times the matrix blank;however, the LOQ will be defined at the lowest point with acceptable deviation. 14.3.7 A vullrlcah3ration curve must contain at least 5 active points above and including the LOQ. 14.4 Matrix Spikes 14.4,1 The average matrix spike pert,eat recoveries should be within __3. 0% of the spiked concentratiRoenc.overieosutsidoef this rangeshouldbediscusseidnthereport. 14.5 Continuing Calibration Verifications (CCVs) 14-5.1 Continuing calibration samples within the linearrange of the run mast show a percent recovery within a:25% of the spiked concentration. If a CC'V is outside of this recovery, subsequent data should not be accepted. Acceptable data must be bracketed by the curve and passing CCVs. 14.6Ifcriterliiasteidnthimsethodperformancseection isn'mtet,maintenancmeay be performeodn thesystemandsamplesre.analyzoerdotheractionassdeterminebdythe analystD.ocumentallactionisntheapproprialtoegbook. 14.7 Ifdataan:tobereportewdhen performancceriterhiaavenotbeenmet,thedatamustbe foomotext on tables and discussed in the text oft.he.report. IS.0 POLLUTIONPREVENTIONANDWAST]_MANAGEMENT 15.1 Sample extra_ waste and flaaumablesolvent is disposed in high BTU containers, and glass pipette waste is disposed in broken glass containers located in the laboratory. 16.0 RTC'_R_ ..... 16.1 The first page of each aAt_packet generated for a study must have the following information included either in the header, in the footer or hand written on the page: study or project number, instrument, sample matrix and time point, date, and analyst. 16.2 A data packet includes the following: d_t_ review summary form, MassLynx quantify compoundsummaryreport for eachtarget analyte,quantifcyah'bratrieopnorftoreach targeatnalyt(ecurve)m,ethodreportW,ord documentlistisnegt-upparametertsu,ne ET$.8.5.2 Analysisof SerumF.xtracUt singES/MS 3M Environmental Laboraaagz.._ ..: ........ .-._.-:-. _ Page 841 Page 8 of 11 Page 83 3M Medical Department Study: T-6889.6 .... -_ ......... --_ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 method report, MassLynx scanning method report, HPLC n_thod report, sample list, and quantity sample report (chronmtogram). 16.3 For eachanalysis, af-_r printing the tune n_thod reportW,ord dc_.-mrlleismting, set-up pm-an_ters, MassLynx scanning method report, and sample list, copy and tape into the instrun'_runntiog. Tl_ original is maintained in the datapacket. 16.4On eachpageofthequantifcyompoundreportq,uantifcyalibratiroenport(curve)a.nd quantifsyamplerepor(tchromatogramt)h,efollowinignformatimoanstbeincludeedither intheheadert,hefootaro,rhandwritteonn thepage:studyorprojecntumber,instrument, method,cah'brati(otnhemethodandcah'brafairocnusuallayssigned _ sam= nard), analystan,d dat_. 16.5 The analyst must date and _ the first page in a packet as long as their initials and date are electronically included on each page. If initials and date arc not electronically included, they must date.and initial each page. 16.6 Summarize data using suitable software (e.g., Excel) for inclusion in the final report. See Attachment A for an example of a summary spreadsheet. 16.7 Back up electronic d_t_to appropriate medium. Record the file name and location of backup electronic data in instmn_nt log book. 17.0TABLES.DL_ORAMS,FLOWCHARTS, AND VALmAT[ON DATA 17.1 AttachrncAn:t Datasuaa_arsypreadsheeL 18.0 _I_RV-_c_ , 18.1FACT-M-4.I,"ExtractioofnPotassiuPmerfluorooctancsulfoornOattheerFluorochemical compoundsfromSerumforAnalysiUssingHPLC-Electrospray/MSapsesctrormtry 18.2 ETS-9-24.0, "Operatioand Maintenancoef the MicromassAtmospheric Pressure Ionization/Mass Spectrometer Quattro II triple quadrupole System,s" 18.3 The validation report associated with this method is ETS-8-4.0 & $.0-V-1. , 19.0 AFFEC'rl_ DOCUMENTS 19.1ETS-8-4.2",ExtractioofnPotassiuPmcrfinorooctanesulfoornOattheerFluorochcmical Compounds from Serum for Analysis Using HFLC-Electrospray/Mass Spectrometry" Er$-g-$.2 Anal_is of Serum Extract Usinf ES/MS 3M Environmental Laboratar;g__ ............ ___. _ Page 842 Page 9 of 1 ! Page 84 3M Medical DcpaJm_ent Study: T-6889.6 .... -_= ....... - _- _ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 20.0 REvisiONS Revision ; Number. lte._on For Revision 1 Section 6.1.2 Clarifcation of HP1100 system components. Section 11.1 Average of two curves, not standard values, are used for plotting linear regression and added the l/x weighting of the curve. Section 12.2.2.4 Clarification of solvent ramp. Section 17.1 Changed from attachn_nt B to A. 2 10.1 Clarified when blanksaremm 10.2 A_-'v_-in,_'ucdons for when surrcqla_matrix is used. 10.3Speci_ru_uixem_tsfor CC1/s. I I.I Requiresonly a calibrafioacurvebeforethe samples. 11.2 ClKify whaXtodo ffcurvc do_ nocm_ requinmcnL_. 11.3 Allow to mmca the curve,. 12.1.1 Citify Lxmpicfin ID. 12.1.3 Clarifytypical run. 12.2.Changes to mobile phasegradientand specifyflowrate. 14.3Change8ccpt,lblllmi_. Addspecificfsor t_,_pr_nc_of calibrationcurve. 14.3.3 When to ,_,'tiva_ mlibrallon standardsbased on blankresponse. 14.3.5 When m ,t_,etivate mlibzafionstandardswithinthe linearrange. 14.4 Modifies evaluationanduse of matzixspik_. 14.5 Describes evaluationand useoF_"Vs. 14..5.1Evaluationof _*"Vs. 16.0Addrequircm_tsforrecords8riddocumentation. Revision Date 04/02/99 Attachment A: SummarySpreadsheet E1"S-8-5.2 Anal]ntisofSerumExtracUtsing ES/MS 3M Environmental Labora_ _._._........ -_.-:-. _ . Page 843 Page 10 ofi 1 Page 85 3M Medical Dcparm_ent Study: T-6889.6 ..... --'-'_ .......... -- ------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Laboratory Study # Study: TestMaterial: Ma_x/F'inalSolvent: Method/Revision: Aaaly_caElquipmenStystemNttmb_. Insu_ment SoftwasTYVetsion: Filename: R-_luzr_ Value: Slope: Y Intercept Damof Extraction/Analyst: Date of AnalvsirdAnalvst: Group Do_e Sample# Conomlzzlton up/mL Initial VoL mY. Dilution FaL_or Final Conc. u_/mL Slosme:Takenfromlimffirrc_ffision cauation. Grouu/Dose: Talmnfrom dz study folder. Sample#: Talccnfrom tim studyfolder. Concentration (nzlmL_: Tslmn from thz l_ssLvnx incesa'gionsummary. Initial Volume (mL): Takenfrom the study folder. Dilution Factor: Takenfrom the study folda. F'malConc. (uzlmL_: Calculata4by dividinltthe initial volume from the conccamuion AttachmentA: SummarySpradshemt ETS-8-5.2 Analysis of SerumExtractUsing ESIMS 3MEnvironmental Laborat.ory .... _........ =_.-. _ Page 844 Pagel I of ! 1 Page 86 3M Medical Dcpa_h.cnt Study: T-6889.6 3M MedicaDl epamnenSt tudyT:.-6889.6 - -- -"---_- ......... ----------- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 AnalyticaRl eport:FACTTOX-164 LIMSE00-2738 Appendix D: DoseConfirmation AnalysesandDataSummaryTables Table 12. Do_ Group Dole ConflrmaUonAnalyMs- Extracted11/17/00,Analyzed11/27/00 Simple# Concm,lUsti_ of PFOA F.xpecl_ CoN: of PI:OAuB/mL" '%Recover 1.?0o.w._._ I <Loo(lo,m_.) ,A ,.od k I ,, ., J PFOA i PFOA -------- Idean _ RPD ! .. L ,. iB-418.020-A-C-100_Dt ' SternlyOr/o s4__,o.A-c-o.smL 11110/00 B-418-_A-AO.5 niL B-418-020-A-D10-0.5 mL B..41S.020_-A-1 B-418-020-A_-2 B-418-020-B-A-1 B-418-020-B-A-2 _llblily Dey 0 11110/(X) B.418-02G.C-_l B.418-020_2 B.418-C20-D-A-1 B..418-020-D-_2 0.0855 (LOQ(_on0_L) <LOO (10 ng/mL) <LOO 10 d.OO (10 nffmL) <LOQ 10 191 189 485 438 1809 1119_ 0.0979 NA NA NA NA NA 200 200 600 600 2000 2000 B-418-020-E-A-1 13-418-020-E-A-2 5579 6,350 6000 6000 ; liability Day lO 11/10/00 COrlCenlnltlOn_ B-41_I0-I B-418-G20-A-D10-2 B-418.C2O-B-D10-1 B-418-020-B-D10-2 B_I11_D10-1 B-418-020-C_D10-2 0,-418-020,-[}-[:)10,-1 B.418..020-D-D10-2 , B.418-,020-E-D10-1 B-418-020-E-D10-2 ; B.411_020-A.C-I e-41_2 B..4111-Q20-B-G-1 B-4111-0_1_..,_ B-418-020-C-C-I _ (10 n_l,,) <LOQ 10 L 177 175 441 451 11'32 1085 5825 5614 <1.O(2(10 r_mL) <LOO (10 no_.) 179 I"/0 484 NA NA 200 200 600 600 2000 2000 6000 (KX)0 NA NA 200 200 600 11110/00 i B-.418-0Q0-C-C-2 B-418-020-D.C-1 B-418-020-D-C-2 478 1820 1800 600 2000 2000 B-418-C20-E-C-1 8140 6000 B-418-0_0-E-C-2 80_8 (m00 Intormal_n was omained from cr1_n of custoo_ forms accompanying Sanlples. .',IJL_4'nv/rnnrrmnt_l i _hnnltnrv 3MEnvironmental Laborato_.___.....- ........_..:-. _ Page 845 87% _ r ! NA NA NA _ NA NA NA 95% 95% 81% 73% 90% 95% 93% 106% NA )5% 1% '7% 13% 10% 5% )9% 13% h11A I 88% 1% 88% J 7714' I ?_,_ 2% 75._..%% 87% 86186%' 2% 85% 97% 4% 94% NA NA NA _ 85% 87% 5% 82% 81% 3% 80% 91% 90% 102"/, 100% 90% 1% 101% 2% PAOe 21 Page 87 3M Medical Department Study: T-6889.6 3M MedicalDepartmenSt tudy:T.-6889.6 .... --_:-......... "_ _ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 AnalyticaRl eportF: ACTTOX.164 LIMSE00-2738 Table 13. DoN ConfirmationAnmly_s-ExtmctN111/27/00, Analyzed11/2W00 c,,o.p I o=_ . ' sarape# i__r,_PFOA = uj/mL or % Re _Concm PFOA ug/mL" I% Rermvety PFOA P_-OA Mean RPD M,,_uxJ.kJ 1127oo-w=-, I 127oo.w_k.3 ; QC B.41e-020-A-C,-100pp_MS IB-418-020-A-C-100_I_MSD! St_ay Oey 0 B-41S-020-A.C,-0.SmL 11110/00 BB.4-1481-10__))2-0A--AD-1A0--00.._5mmLL B.41S-020 ;. :. 1 I B-418-020_A-2 s.41_=o.s._l B-418-020-B-A-2 lllblllty _y 0 11110/00 B-418-020-C-_1 B-418-Q20-C_-2 [ B-418-(_0-D-A-1 B-418-020-D-A-2 B-418-020-E-A*l* _'418-020-E-A-2 A Slmbil/tyDay 10 11110/00 i i Conl_mUon 11110f00 S-41e-020_DI0-1 B-411_Q0-A-DI0-2 B-41_10-.1 B.418-Q20-B-D10-2 i B..,418-020-C-D10-1 ,, B-418-020-C-D10-2 i B-418-020-D-D10-1 B-418-Q20-D-010-2 B,,418,,,020-E-D 10,, 1 B-418-020-E.D10-2 B-418.020-A-C-I B-41_20-A-C-2 S-41S-020-B-G-_ B-418-020-B-C-2 B..411k020-G,C-1 B-41&020-C-C-2 N18-020-D-_1 B-418-020.D.C-2 _OQ(,OnWmL) ,d.OQ (10 nffmL) 0.0M4 0.0856 <LOQ (10 ngm) <<LLOOQQ ((1100 nng_//mmLL)) <LOO (10 ngm) <LOQ (10 ng/mL) 155 147 4_ 488 1788 17g_ I 11183 11256 <LOQ (10 _mL) j <J.OO(10 fl_/mL) i 138 15'7 464 496 1560 1758 __=__3 5e57 <LOO (10 ng/rnL) <LOQ (10 nlVmL) 1M 185 452 443 1741 188_ NA NA 0.0979 0.0979 NA NNAA NA NA 2o0 200 600 600 2000 2000 6000 6000 NA NA 200 200 600 600 20(X) 2000 6000 6000 NA NA 2O0 200 600 600 2000 2000 NA 88% 87% NA NA 7e_ 73% 82% 78% 89% g0% 186%* 188%* NA _ 78% 77% 83% 78% 88%. I _ 99% NA 79% 75% 74% 87% 94% = =I = U% 1% i NA i NA NA NA 7_ 80% 4% 90% 0% 187%A 1% NA NA 74% 13% 8O% m 96% NA 1_ 12% 7% NA 81% 4% 75% 2% T 91% ] 8% B-418-020-E-C-2 5441 8000 _ 91% , = Sample _ outlier. on 01Q3/01 to confirm mcoven/. Recovery wa= not confirmed, considered an tnforma_n was ot_minsd from emin of custody forms seeomp_'qing sarnptes. RM Fnvimnrr_nt_l LaboralDrv 3M EnvironmenzaLlaborauz_z._._:_.-..... _1 =_'.. -Page 846 Paae 22 Page88 3M Medical DepartxnentStudy: T-6889.6 3M MedicalDeparlmenSt tudyT:.-6889.6 .... .-__-._........ _-_ - ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analy_caRl eport:FACTTOX-164 I.JMSE00-2738 Table 14. Dole Conflrmatk_ Analymm- Extmclld 01/17/01,Analy-Jm0d1/23/01 -.IDole _ IdemodB_ ;_ Samlde o117oI-wI_-1.1 _ of PFOA ExpeclmJCon of ucjtmLor % P.e PFOAug/mL" ,c.LOO(I0 ngmu.) NA 011701-WBk.l.2 <LOQ(10ng/mL) NA I_al_llltyI_y 01 B.418-0Q0-E.A.1 5466 6000 11/10/00 I B.418-020-E-A-2 5014 6000 lnforrnal]onwas ot)_B_ tramcnmnof custodytonnssccompan_ngsaml_eS. % Reoowwy NA ' 91% I 84% PFOA Mean NA !17% !PFOA , RPD NA 9% Table 15. TOX 164 Data Summary of PFOAConcentmUon_Rat Serum(pg/mL) Gendmff PFOAConc. Timepoint Average = SD Oroup I 0.0 mgdlq_lay Female _ Day22 Male End ofcO"Ull_Wk_ <LOQ (0.00528ug/mL) r.-3 0.0344.,.0.0148 n=3 Group 4 FenWe _ Day22 0.370 -,.0.0805 n-10 10 mg/kg/dw Group5 30 _ Male EndofcohaJodatO'1 Female t.aClalmnDay22 MaJe EnclofconaJ=_amon 51.1 = g.30 rml0 1.02_ 0.425 n=lO 45.3 * 12.6 n-10 ,IM Environmentatl=hoc_orv 3MEnvironmentaLlaboratmgL_........_...=-.._ Page 847 Paae23 Page89 3M Medical Dcpamnent Study: T-6889.6 3M Medical DepartmentStudy:T. -6889.6 Appendix E: Data Spreadsheets - --- ARGUS 418 020 Analytical Report: FACT TOX- 164 LIMS E00-2738 AnalyticalReport:.FACT TOX-164 LIMS E00-2738 .?MEnvironmental/.aboratorv 3M EnvironmentaI LaboratooL...__ _-.. _..... _.:... _ Page 848 Paoe 24 Page 90 3M Medical Department Study: %6889.6 Study: tmdua Nmulm<'li 1_8_: t_m_'l_,v_. _ km_mt Sdmm_j: $_m m_m,_ Ibl,m_d Vdmr,; Y,.kimm: b i_ i_li+/lff. rl,m.d Dim _Aml/lrll i,=m_, DOSZ VERIFICATION S/IJ_IPLF.,S FACT-T'G_I4d. ,,mira4I_ P------.-- Smldm [I'$44.t rrs.41.is, _ o'mTw e..l-l,a,l_ t,.. c.. I lilTS0 IIIk_lM I I_11_o Ill&iN .... -= ......... F.CT-TOX-n. _q_m4, ns.o2o 4_1W_,Xlel T.o.CJ_mnm* ll4w_uml _m' _ APFOm I,m : "_-'--'-- ARGUS 418-020 AnalyticRaleport: FACT TOX- 164 LIMS E00-2738 .a I I I'_O'Wllk-2 I idNlN-I__,A10-_0-11_SlI__#_MS i 1I II/IOP_00_ NIN0-A-A,-0.SmL Jllbl411yDly @ II-4 tI.OIO-A+&I- I II, lOqO_O i-61I+020-A-A-2 I B_I III4_O-II-A-I l ll-ll I ll-I_0-11-A2* I I..4111-I_O._-A.2 I B-_l I_4_-_- l i 1.4111+0_0-D-A.2 I IJ.4tII-i_0-E-A*I I I..411-O20-E-A-2 I _lll_14y D41y10 114,It-0_0-A-D.... lI/lll_l_0 II_II_+DIO-/ I D41114_O41-D10_ I I_III-_O._-DI&.I B.41___@_'_-DIO-2 'I I _411-4_".O-2 I "' D,411_Q_O-E-DIO-I I _ NV 1141 N /_IA mA NA NA _ NA N_ NA _ NA NA I_LA+ NA NA _ Irmmr I._.5 F_,tw _ I _11_$6 _t. u _, _ Ii ct OQ(10IqpI_] lI..l__-_ tI 6&410 D_0__1l1ll2'_1l0__S , 000+1018255 1-25 1+,11.1 I t+25 1 1.25 |.25 20101 _oJ _11 0.110 D00llr_19 I <l_ll0q_ll_l 0.00 I I_O11Z?OZ$ <I.I_ l tOllFml., o_ I omH2"_2+' <LO+10.ym_l ?|+.p_ _1121_16 + 1141 I_._ l_ I..25 1.2_ 1.25 l._l 1.25 1.2._ I =I I..15 DI _O01 _0001 _k_OI IOIDOI [ _001 [ XIOI _1 I +"IO01 5001 ?O.O1 _II_)O_I i 7115 DOOII2?III.... 75._J I DOOI_'P0_ 41111 1141_ 19.27 lOl.l_ _ Ik00 I_J01127059 i _I12_ i JD_112_P ID_0112_0_0I 55_9 63|0 'v-I.(X_',,Oq .... _1._llOl_,n_++ H.II ITS ""?._,10 T_.t3 '_001121_I$ + _00112'_46 I '"411 451 1.2.1 1 I_II)I l?.?llI _II_ I.I,I + I_01 13.10 I IDO011271_II 16+$ $1LI_ _ NA O0{O__1?mgl I_A N^ _^ _ _ 2000 2_0 _ 41_O_ NA 20e _ IO_ 2_C _ % Tm1_ Cm. 1I'4P%_ , p i II% i! 1 +,A t ++, ttA 95,. iS% I% 71% t0% 'I_% 9$% I_I,*,, NA _ ] IIW, L, 41'I".- ] 5% i_ I i II_ i NA _ NA ,, I " l IP+ ll_, I% ?5% 71% 1$% l_l_ _ I IUll B._I+L____-_+.2 t I I-+III_II-C-2 l B.4 t +_..+..._-_'+_-_. 2 I B._II_II_J_-I_C-I I iPlrOA/pO+4kll,p, m_maml B-4,I_O-E_-, Ib4 i $.02G.I.t_.2 ! l 'I i_t i_mMl_ D_e VIs_m_ By" 0t;lS_01 _ 01114_0k1)_ NA I_ NA NA 14A i c--i-.-..NiA A-- 0mill I- 0.2 mlmL C - ILl,mired. D" 2 mi_k II - t II_lW_ 1.25 2_1 1.21 2101 1.25 _! I.ZI 1_I.4 |+iS ] 20001 t SO00I 5G00! 000 O00112TI_4 _I.I_ flO_I/ml.) 61.SI D_OII_'_2 I"_ I 16#1 I_O1127010 '12.10[ D0011=_I_'# 1120 I;I.14 I ll)OO112"_o_, .... i _t_4l I_ I l_/_'Jl t02t , NA 200 +ms 311_0 _ i 6_00 NA 11% _ 91% 11o% 100_ Nl 11% I% 01% , 101+/ K 3M Environmental Laboramoz.... ., ..-.....-....:--_.. Page 849 Page 91 ..... .--_-_........ _-- _ ARGUS 418-020 3M Medical Depat tment Study: T-6889.6 FACr.TOX-n_ _, 4n_z0 Analytical Report: FACT TOX-164 LIMS E00-2738 laamL I_mmim01"em Sin): MulIIdllq_lli PA_-_ _ A,III_ 41 i_0. flml (_IINlll) ")'lNl'_ml_lm_ IlawIhglllm bRIY d AI_O m IdI 1" " 17I "44-1 & kI'l_=_$.l _ I,a_im: .t_.m1_mm, MaiIWm,1L4 II u-_'I" r_.. elf_,,,nallmt _d_ i_lI iI" Illl I-_....-_AII_I: _RIF'ICATI_ SAA4i"s'_ Il_Ir_qlIWW IIt271gDi I I_I_0 MMM Mi B '_" Solu1o1_11QD_ , 0 SUII_ W DIy 0 I I/lll_O I I 171_-wIIk-t It l_00-_llk-.1 I I Ill_Illk-3 II.II_A.(_. l0_Hli,il_ 1.411.4)20-A-I_I0-O_b.qlSD II_.0.4I[1lI.mO*-4-C4LS'I-La. l_,411._0.A.D IO.0.S.ml _41 _-4_-_ I _41 _A_lk. ] I_l i1.4D0.I-A*I -_I_2 I,.4li-I_l_._b-I I-41 il-_l_-A-_ 1.4111.(120.D-A-_ II_l_ GW oo0 611.4 _(10 _J <i.4_ (10 qllL) 'CI.O_ ( 10 II4BIL) It011,1 I 0.01ll I_ ILl GGG Ii nn ?6-2 ?S.? 77.S 70.0 s_lI.L__l_((Il0l)anlln__)l.) _11._ ( IG q_ll.) q._) ( l0 IIVIL) i 4_ (10 II_l lll0Ji_l] 119.1147 _LU.7*1_9 4.1'/M '_J.? IIS) J447 I01 4150.1l'/ IIII0_0 _ _lIl0"l ?0*I ! 17_*I k_ _.or/! A0rll) N_A NA _LA _L_ 200 _ t00 44G 2OOO _ _ NA 14".. 17% _,A NA 11% etl% 111% 7)% 9l*.. I_% _A : 14% NA I _. ! _A ' NA NA i I 95",. I i "_',. I hA I'. 10% i19-. ', % I1_.. _ I 1% _ 118% ,m_'_e I..411L420*_..D 10-I I_IIII0-_ NIN-I n_.t._m,_ca 6?.ll 1014.11147 n.l I o.oo 161441173 'c_ ( l0 Ill.ILl , <t,c_90 ,,i,..t ! pFOA/PO_A 8 P_m_la_e_ I,_lH_I_0-D-C.I I1,,_I II_D.,_-2 1-41ll-G_Ikll-l_-I I_t iIIII_VI? 0111_1 L.AC 72.1 17-0 g44 IIl_l.O_|O I'J_..1_ l_II Cam*---., _ - I)ilFIL C m (U_ Illl'l/l- I* ll_ImlL 2000 6000 N .A I_0 _ _000 15_1 e4% "% ,,, I_*/. 2% , 95% 4% "NA'1J,,N,"A1 91% S_w. I_,_ SO'.. I I I I% I01% 3M Environmental LaboratmgL__ _ -.. . . . . . . . 1 . 1 1 - - Page 850 Page92 ..... ----_-...... -: ----- ARGUS 418-020 3M Medical 13_partmentStudy: T-6889.6 rAer-Tox.t_ _4J_m Axmlytieal Report: FACT TOX- 164 LIMS E00-2738 ill_" llACT"IIID_* I IA * MII_ 4 |l'li_ _ll ICl_llt l_ ll_lmdl_ll IQIY d A/ql_ I Ill _,/_i _ Imm/llimll'vlllil i',sFmm llmmr II,-Squmd Vlf Y-/ill_ iruI d imlmj _ i_.. d MIhIIAIW_C sH,_ u,m VlJUF/CATION SAMPLES r I ;' L'l_.t.4. I. A Lff$4-s J ii',,_ _ lli_lI i.I r"' Ill|w, Sire r'm I UI?A0 I I/Jim0 IIWW NIIa II1_ 1 I J;l'l_-Wlllk-I 1127gO-WI_.2 112?00-Wllk-3 11llal i fllll* of PI1DA almlL er *A llec d PFOA _ _ ar % 5_1m Cl i RP1D l I_ i.ZI I t.00 I_l 12W15 _..OQ I I0 _l_l- I NA i IqA 1.2J I CLan I_O11_101t <LO0 (IO q;iL t NA I NA I ..?._ I O_ I_01120017 <LC_ r 10 el, ai.I NA i N'A _ Na NA ll_ll.l_0-A-C-I_.'-_--$_ "1 HA 1._ I M.14 l_lll1001 t 0._l.Si Ol_l.) i'P,. ( U_, I I% ll.411_O_N)-i-A- I I-IlI-OL'_- _ ;. _ i.4 114_0-1D*A-2 _I_E-_* I l I_ 1._ Jl01 lllO IP_l I_ I$_ I _ 1.1_ inl II.T) II_l Imu* 147 li 111,,11 Ellll lllil4_ 419 1 NA t35 I NA I*)S i_01 71,7.1 I_011]'ll0S_ I_) I _ I t4 _ll m_ _ll_ ! iii1.1 210 100 _ _ _ ?l_t,' 73% _ I0% t_% NA NA 1q_% li_. _ _ 4_ _ A! O_ 1 ivan: _lllli _111112 idl OI0.;I iIl-.Idlll-_10*A-C-I 2 li-i I l li II 1' lilll t I_0 I NA 115 II "/_J2 1111_ I I?11 i I k_4 1.115 _001 0.00 _liZll_ I (l'_(1OllmM'J "1_" Olll_OI _ I I NA I I_ I II sli"OI .I,.S_ S3'i I 0 1 ml_uL I)" 1 II'lltL _ . ?i% 1 1 NA /4A I -- i I_ I I_ NA NA 3M Environmental LaboratooL.._ .._-......_..:.-. _ Page 851 Page 93 3M Environmental Laborataw__ _-_........ -;.:-.. _ Page 852 Page 94 .... .- ........... -+ --. _ ARGUS Anr_,.Q.r,ro,_,.,,_v 3M Medical Deparma_at Study: T-6889.6 FAer-Tox.i_ ,tn_ 4n_ Silly: IlUACT.'TI__X. Almm411-m_ Gla](_) T_ IlalmWU_m _ d APFOm _ Immm_R ._ln_ R-.Sq_mdVdw_ Y-immMB i_ d IIIIIi_AII_ Lr11"4-4I.4 rlTpIl-|. I Ida_J J.4 S_ r" Ammmmm c.. 011|IUOIIIWW Analytical Report: FACT TOX-164 LIMS E00-2738 s_m_ DOS_ VIWUlr/CATION f_blPL.F_ n._ VoL _llld _ _ Cam. el pIro_ ef PIr_t lU_e IIPD _011 _I -Wi|k*l ._ _dll-_CMbA-I i e' I t_ 1 [_ / A-OmlI_L |_ I G00 _lOl_16 C_ll0_'_b 1.3J _001 17+45 S_lOllal017 t_ _ NA NA , NA NA _ _l_- 3MEnvironmentaLlaboratm____..._.-.:..._...:..._ Page 853 Page95 .... -= ............ ARGUS 418-020 3M Medical Department Study: T-6889.6 rAer-Tox-n6, ,mp_4n_:o S_lly: i_aam I_mdmCtlmSmmu_ I IA_'_r111_x'li4"Aqlm411-1DIL0mli_lls)l r--------- Smpm "-_r- "' '' r__:- ,,llvaml tumwma .r_mal I,_mlm" m _amw: Dmm,_ I_mllm U It_ vdr.. _ Analytical Report: FACT TOX- 164 LIMS E00-2738 _eLAPIOmlIIII Dram mt_um_awAlallm: r/--- m(Alslyll/,4811m dOou Imlm:mwJ_l_71t 01/T_I 0_I MMN 0144Nll IdMH DOSE VERIFICATION Dml S.4_IPI..I_ f_ml_m _._,_ eo,_,,_,.w--.,., IIOAA0| 170l-Wllll -1.2 1.411kC_D-l.A-2 _ Caw. =,= _ 1O _ d Iq_DA all_L, er % k a.oo.o.l,._.) I '_X_l (IQ llrllll. 1 S014 1_C_ _ IqWOA m_mL _A NA I tlll_V_" l)_e vm6mv By I_$/OI I.AC 0 A- II_lnaL Ce G& D" 3 miln_ E" t mlpm_ % ill.w? _ % Taqm Cmt. I Ilia , 14% P_OA I 14ram J I NA I PIrOA IIPD NA IT',_ , O_. 3M F.nvironmenml Laboratarg._ _,.-......... _:-. I - - Page 854 Pag_ 96 3M Medical Deparunent Study: T-6889.6 -- -. ........ FACT-TOX-104 Arg_ 4]S-OlO _> _ ARGUS418-020 .Analytical Report: FACT TOX-164 LIMS E00-2738 Study: Pm_k_t Ntmtbee('Test Sumtm_) Mau'_ M_: t,mmm_ SoltwaaCVmma: FACT.TOX-IM. _ ERDA Cemlanmeof_ _'$4-4.1 L_'_lb$.l 411-020, OmJ (Cuwlq_} Ttm-Gt, elemlmn Repmduclmn Sludy ofAPFO m Ra_ .smpm ),am_aut3.4 Sample Data DOSE VERIFICATION SAMPLES Gmp SlmlNe _xu.m_t I 1/17t00. Amtly_d I 1/27/U0 _ % PJ_DA PJFOA 11/2?/00. Analyzed I U211_0 % PFOA PFOA Extracted 01,'17/9l. % Al_tiv'_d 01 _3._1 _ PFOA PFOA Dm_ Mem_:l Elk QC Sml_ly Day O | 1/10_O .ft41d_li_ Day 0 11/| 0/00 WBlk-) WBik-2 V4BIk.3 B.418-020-,,,.C-I ooppe-MS ]_411_020-A-C- 1(X)ppb-M SD B-411-020-A-C-0.5 mL B-411-020-A-A-0.S mJ,. I_d I |4)2G-A-D I 0-0.$ mL I_t I Ib020-A-A- I B4 J_020*A-A-2 _11_020-B-A-I B-411bO20-B-A-2 B-41 g-02G.C-A-I B.41 It-020-C-A-2 I Ib020-D-A- I B.4111-020-D-A-2 % _Tm'lff( C_In. " NA 14% 87% NA NA 95% 95% I1% "/3% 90% 9S% ll4mm NA |(#A, NA NA 95% "_P/_ 93% B_I I _020-1:-A-I 93% B-41 $-020-E-A-2 106% 99% Stab_ly Day 10 11110/100 Cmnllms " I Ill 0300 1_411-O20-A-DIO-I IE_4111-020-A.D10-2 B-418-020-B-DI 0-1 B-411.02G-_*D10-2 B.41 IbO20-C-DI0-I B-41 B-020-C-D I 0-2 B-41 $.020-D-D IG.1 ]_.411_020-D.DI0-2 B-411t-010-E-DI 0-1 B*4111-020-EoD 10-2 B.411t-020-A-C- 1 B-411_020-A-C-2 B-41 It-020-B-C- I 1_411k020-11-C-2 B.-4111-020-C-C- I B-4111-020...C-C-2 _..4 | 8-020-_-C- l B-q 111-020-I)-C-2 _41 |-020-E-C- I B-41B-O20-E..C-2 NA 118% II1% 7"PA 75% I7% IS% 9"/% 94% NA 90"/. 115% 12% 80% 91% 90% 102% 100",6 NA I1% 76% 16% 95% NA I'PYt 81% 90% 101% - S_mpleee-e_tnct_lee01/l?,'01 tocoef_m lUlth mcovt_. Rm_eve_ wasemlemtfmmd, IU_ NA 4% NA NA I% IOtfi, $% 13% NA !% 2% 2% 4% NA _1% 3% !% 2% cemidemdm % _Targtq CNm". NA |$% |?l,. NA NA ?IP_. 73% |2% ?lle/. |9% 90'/. i16% ^ I|r/. ^ NA 69"/. "/1P/. 77% 113"/. 7rY, liP/. 93% 99% NA 79% 112% 75% 74"/. 117% IM% 90*,; 91% om_rr Meaa NA II1% RPD NA I% NA NA NA NA 76% 6% 80% 4% 90% 0% 1117%^ I% NA NA 74% 13"/. SO',; "P/. $3% 12% 96% "PA NA NA 11% 4% 75% 2% 91% IP/. 90"/. I% % IRTesreleove_Csenrc. I M_qls RPD NA NA NA NA NA NA NA NA NA NA NA 91% 84% HA NA NA NA NA HA NA HA NA NA NA NA NA NA NA NA NA NA NA NA |7% 9% NA NA NA lqA NA NA NA NA NA NA NA NA NA NA NA HA NA NA NA NA 3MEnvironmentalLaboratm__._..._ ........ -_.-.- _ Page 855 Page 97 __ - -._-_ .......... - -,--_____ARGUS 418-020 3M Medical Dcpa_l_.ent Study: T=6889.6 FACI'-TOXo164 AIIUI_ 418020 Study: FAC'T-TOX-164. E_-27,11 I._dl_ NmWm_'_ Sul_xn_ I P_ln=. MimIVll_,vmm _)_aad EquJp_mSyumNembe_ Sol_tw_emm F/_: It.,_iml v-u.,,': S_ Y . llm_IK I_111 of Elllall_ ha/yl I_lm Of Aludyl_Aaldyst: ofDma p "_ _qalyil: SampleData _ (Cmvllle) T_ T.ulg.6 IIm_ E1"5-8.4.2 A IE'i_4-$.2 _,lm Am_1062_t _ 3.4 Smli_ c,,. S_ #muwm_u c.._ 0t/IlJl_ 1 R_i" (_r_ i _ 1.06/_/01.0"/'117._ I 06/=_2d01,O6/zt/q01.07/11/01 Box:oi-O29 ((_s i,m' m miami lit Oummwm ) _ nl mlm cite Analytical Report: FACT TOX-164 LIMS E00-2738 S_dv of PFOA m RJ_ RAT SERUM Groep O_e MelNd Bl_ ._atl_ I RT_062101 -H20 Blk-I Illlll Vii. mL I BI_ RTS061101-_I Bikol I RRTTS_O06622110011--SHm2OIBBIkL-k2-2 II o.o._w.,-y P1.o_._Lo_xo._ ] Grmlp I PPII$3111i0016FF,.GGqqllII,.00MMKKDDJ.L..OD222.Z II PI3601M.GIIPl.0MKD. PDI06 I P 13607M,Cd_ 1,0MKD. PD I07 I PI3613M,Grpl.0MKD. PDIWI I Gmp4 PI,1891F.Gq_,IOMKD,LD22 I 10 mllk'k_day P 13It92F.G_l14.I 0MKD.kD22 I p 13t93F.Gfl14.10MKD t r122, 1 p i 319,1F._. 10MK.D.I..D22 I p131196F._4.10MK,D,I.D22 I P13B96F.C_q_4.10MKJD.LD22 I I_I $89'TF.G_4. I 0MII_D.LD22 I p13191F.G_4. IOMKD,LD22 1 pI ] li99_._I14. I 0M I_DJ,,O2_ 1 p13901F.Gir_4.I OMK,J_;LI_:_ I p 13691M._I4. I_. PD106 I p13692_._, 101vlKD, It'D106 I p 13697M,C_qI4.IOMK_, PDI07 I p 13MIIIM.Gflp4. 1061KD. PD 107 1 p 13'703M.C_q_4.10MJI_DP. D I 0_ 1 P 1370aM.Gl_4.101dKD. PD I I_" I P 13709M.C_I_. I 0MKD. PD 109 1 p 137101vI,Grp4.10._D. PD 109 I p 137 ISM,Ca_4,10MK_, PD I I0 I p13716M.Gr_. 10M0_D, PD110 I Gmp$ P 13921F.OII_ -1OMKJ[)._D_ J 30 mll/kl/Ihly P 13922_._$.30MKD.I._2 I p 13923F.Ca_S.30MK,D_ ! p 13924F.Grp$ .110_IrJ, 0.LJ$Z2 1 P 1392JF.G_rls5..1OMK.D.I./)22 I p 139261_.CmpS.30MK_.LD2-_ I P 1,1927F.GrpS.30k_ICD.I.D22 I P 139211F,_5.$0MI_) I r_22 I P 13930F.GmS.,10MKD.LD22 I p I J9.11F,Ol'p5.30MI(D.I.,I_I_ I P1,1721M.Gm$ .3OMK.D, PD I 0_ ; ] P 1,172-1M.Grl_,._k41g._, M)I_ 1 PI3_2?M._.,_gMI_D, PDI0? ! I p 1,1721M.G_p$.lOM]Ir,D. P_ 107 I p 13733M._p$.30MIKD. PDI01 I p 13734Id.GI_$.30MKD. PD I_ I v,7_4._$Jowo,.VOlO_ i e,7,_.c_.a_,,w. _n_ 1 p I 3?_LGaI_K,D, PD 110 I PI3747M._,_,____In_IKO. PDII0 I I PFOA - I_flmmmmimle Dine _,,mmd/By: Dlle Vmfi_l/By: 07/10/01, 0_J06/01 L.AC 0_/13/01 SIIInmll_e Vo_mmll _M AI/ylns Oil. PFOA DillliNi FIx_or I PFOA C.c. l el/mL i 1.63 Fdcnsme A01_27016 ] CoecellCrllllon I of PFOA I uwmL or % I_: _/OQ (0"0_$28 uWlld') i MeJ,ilt I PFOA I _ ul/mL i NA 2_l1lld_Al/lil__OieK_ N_ NNAA NA NA NA NA NA NA NA NA NA NA NA NA NA NA C_,_il I.mv _ Low NA _...,ll_ i.ow Cme_l_l i,,o_ C_l_ud _ NA c'Mfmlmd Low NA NA NA _La_ _ NA NA NA NA _ C_II _li_l Io_, _mfm_ _ _ _ _l,m_ C_m_lil NA c_.., _t_ NA _ i.4_ u,. Law _ I I.'/7 AOiOb2701B <LCX;I(0.0032& w;_mJ.) j I1 [ 11.4219 AA0001602672071091_' c<LLOO_O(fOO.O.0O05$228Julu_tu_m'mLL_l 1_0 ,<cLLOC__ i ,.11 Aoio_-.,o(L:OIOI|0.00.'q2tvi_/m],..) I II lJ 23.62641 I AA0011006622770022021 ! <<LLOO_Oq0(0.0000552281t1quymi:,'Lm) L_ 'I <1.OO S0.14 A01062702_, I 0.0501 20.,11 37..17 A0 I062'7024 I A010627025 ! 0.0208 0.0,12" 0 0344 5 65.|4 _ A01_)_7029 0,320 $ 79.15 A010627030 $ 411.13 A01_627031 0.390 0.241 3 15.45 A0 I0627032 I 3 q0.1.1 A0106270.13 0.427 0.451 2J 16.73 MO107170.?.,1 $ _0.11 A0106270_3 04111 0.,2.,31 $ 77.67 A010627036 2_ 111,94 M010717024 0.311 0.4'74 3 1000 66.15 36.12 A01062703t I M010717031 0.331 36.8 0.370 1000 I000 $6.7,1 61.41 M0107170,121 M0107170M, $6.'7 68.4 1000 1000 $0.1t ,14_I M010717057 M0107170311 $0.2 $,1,4 I_Q0 3946 M010717069 39.5 I000 $9.00 M010717040 $9.0 10_ 51.711 M010717041 $1.8 I000 4t.04 M0107I?0&2 48.0 I000 46.__9 M010717043 46.3 $1.1 $0 22.04 _0107 l?02.q |.10 SO 16.q16 M010717026 0.1_| SO 27.60 M0 I071?02"/ 1-111 SO 37.63 MOI0?S?02I l.lll 50 11,21 M010717029 I0 57.45 A01062,706_ 0.910 0.$74 10 q0.11 A010_a270_1 10 92..70 AOI_?70G2 10 .19.07 A010_7063 0.901 0.927 0.391 SO 26.45 MOI0?I?0J0 1.32 1.02 101N) _.92 M010717044 50._ I000 29.94 M010717046 29.9 I_00 10_0 39.57 61.12 M0107170dq MOIO?I?OSO ,19.6 61 1 I_0 33.44 M010717051 .13.4 1000 i=o, _,_ 42.17 M010717052 42.2 _46 M010717o$$ s,,.4 z_.42MO1_1_, =7.4 Ira0 J0.0? IV10107170S5 _0.1 Innn 61.53 MOI0?I?0S6 61.6 45..1 iLSD E_I. DI_ MS_MSD IU_D NNAA NA NA 4.10 0.014_ 2|.? 0.01106 18..2 9.30 41.5 0425 2%9 12.6 3M Environmental Laborato____ . . . . . . . . . _ --.-. _ Page 856 Page 98 3M Medical Dcparuncnt Study: T-6889.6 Study: FAC_J'.TOX-IIJ,I. EDO-Z'J31 Pmd_t h;emlJeffTat .Tmls_m_): i_mx: P_m_/ll_mmu: .,_d3m_at e.mmmm Sy'mm N_ Jwmmmn Sotv,mWVerm_ F_: R-Sqemwl Vsl_: I_el of Exg_ml/_ Dills of/_llylm/AlWtyI_ DlJe of D_I R.J_lmmo_Aally_: Sample Data -- - -_--_ - ......... ARGUS 418-020 FACr-TOX_-t Arps_ 418-020 Analy6cal Report: FACT TOX-164 LIMS E00-2738 (]md(Gmqp)T_.C_mlmm(Omei,,.-,im'C,_mme)lbe_-,_ T-6109.6 ILJ Smm Le'ITMI_.I E1T_-$.2 _ M eJ_-'_ m _m: _rve .4m/m,_m Idmlym 3.4 See Amakmms See/umcl_nm .Tm_lvafPFOAmKlm WVHI_I RWW 06_ Jaq01.0&"_|. 06ra_ 1. 0d_l/01. 07117/501 MMH 0711IV01 MMH RAT SERUM Group Dwe MmNd B_L s_tmx Blk Gmep I 0.0 mg,/k_day Grcmp4 10 mK/kl_day Gmlmp _ 30 mllflLffdly PFOA Die P:lefed/_y: Dine vmfimIV By:. .Saml_ s RTS062 I01-H20 BI-2 ItTS0_101-Sms Blbi KTS062101-Sen IIIk-2 PI311OJF.GalJlN p 13802F.OqJ 1.01dgD.LD22 ,I,01dKD. fDt06 P i_ I,,0Mg.D. PDIff7 PI)6DM.GoI.01dX, D. PDI01 P 13491F.CBle4.I_ p l _I_J.F.GIIs4.10&IXD.LL.D22 P I _19) F.G_4. I 0MgD, L.D_ f 131194F.,dIN,.I W,4D_DJJ322 p 13195F.Grp4. I_ P 1385MF.Gqu4.10MKD,L,I_.2 p 13419"fl:,L13e_1. 01tOCD,,I,,,131_ p t311geF.GqJ4. t0Mg, DJJ)_ p 13899F,,Ge_4. I0AOCO.LI_2 IOMIC_.LD22 p 13691M.CnlS,4. IOMKD. pD 10 _. p I_IOMICD, It_10_ p 136971_GaI_. 10MICD. PDI0? PI36glM_.i0MKD. P_IOT p 137051_LGdp4.I 0Mg.D, PD 101 p 1370414.Grp4. IOM](J_. Iq)104 p I3"/091dr+Gele4I.OkO(J_. P'DI00 PI3TIOM.GIp4.IOMKD, PDI0_ P 137 ISM,Gq_4.IOMK,D. PDII0 P 13716M.GsV4.I0+. PD110 P139_11F-GII_ P 13922J=.Gel5k-10MK rt.L,D22 PI3923F.GIpS_ p13924F.G_pS.10A4rI(DJ..D22 p 13925F.Ge,p.5.30MX.D&D_ pi _F.GqkS..10Mg.D.L.DZ2 eI lm2_.n.5..L_dlC.D.I.D_ p13921F.C_,30MI_D.I.DZ2 pI _mF.CXl_ .._21_C.D.LJ[322 p 1322 IM,G_I_$.3_4K_. PDI06 p 1372_jIOMKD. P'D IGli P t3?2_k4._KD. PDI07 plyPAIM.GepS..101,LK_. PDI0_ pI$';3)M.Gq_.10MKD, lq)101 PD734M,GoS,3m4KD. PDIOe r I y'rJM.Gq_,34Nd]CJ_ p i 3"/401_.34M4KO. PDI0_ PDIOD p 1374014.OI11S.10MI(,D.PDI l0 pI 374";M.Gqt,5..lOIdKD. lq)110 0"/110_ll. OI,/_OOI Olll$/Ol _tJoe _ Iq.SD uffmdl, IoPrFO%A Reg _ (0.00528 Iqvml.) <:LOQ (0.00521 <LOQ (o.oo5211qVml,.) <1.,_ (0.00521 wVmL) <LOQ (0.00521 vffmL) <1.130 (0.nnS21 upmL) 0.o.501 0.0201 0.0322 0.126 0.396 0.241 0.427 0,451 0.418 0.251 0.311 0.474 0.331 36+8 M.? M.4 50 :e 544 39.$ 59.0 51.1 41.0 46.3 1.10 0.841 1038 l.Jll 0.010 0.574 0._o 1 0.92"7 o.391 1.32 S0.9 29.9 39.6 01.1 33.4 42.2 56.4 27.4 50.1 61.6 ] :WFOm_ ] I NA ] O.0'M4 0.37__0 5 I+I 1.02 45.3 MSS._I,dtS. D_. RPD N^ _,A NA NA d3.0 00148 21.7 00105 18.2 930 4 J._ 0+42_1 27.9 12.e 3M Environmental Laboram_ _ _......... _,:.- _ Page 857 Page 99 _ ..: .......... +_- ---__ ARGUS 41 _n'mu_,,.v 3M Medical Department Study: T-6889.6 FACr-TOX-16+ Argus 418020 Analytical Report: FACT TOX-164 LIMS E00-2738 Silly: FACT-TOX-1+,4. E00-2731 I,__,-,,t_+m"mlri_nSt almmm_ ) Mlmz: laee..-,._ Fa-,.---: R-sei._l _.Slmwm l_muecr: Sollwmt/Vemmm: v.a,-': Y4mm'mm: DIllS of _tlllCl_AlUlJySl: DlesofAaa_aAulyst Dllmof rt,.,,,, ll+t,,ducttoa/A.l_ly.st: Sample Data Oral (Om'ql*) T_ T.6119.4t ilal Smsm E'I"S41.4L2& EI'$4-$.2 _IS9 _ J.4 _ Ilei_, .Tin .al_mmmm r.-- ,tllllimml t... 06/14/01 " 06/15/01 _l/II/01 IIWW I_MH MMH B_: 01.,021 (Oi i,m,,, _ Gmwmom) l_m 't_mm m m_mmml ogre S_y of PFO^ m RAT SERUM GrlNIp _41_Blaak _ktBla_k QC POA - SI _11_1 R'rS0I401-H3OBUt-I RTS0b1401-H2OBIk-2 RTS_I4OI-Sc_BIk-I RTS061401-SlmlIIIk-2 .q+'l_061401 -M_2,_ pl_ RT_O614OI.VISD-_ I_b RTS0I401-MS-$001_I4+ RTS0I401-MSD-50OI_eb JIIICI_I V,.eI l. I I I l ]t Il _ _irl_m" l "t4 1.25 L.Z$ I 74 1..25 1,25 L..?Jr 1.25 _v: Verig_l/By; o(d22/01 LAC 01/13,'01 _ Vlrlilild 4_IIHIIJI OIIIHl_lJl O_iiJlJI OIIH_ll O11 H_It O_ Hillt NA NA PFOA PFOA Fmlemlme COnl_ltl rlllell I Mill R_D _Fl_r I I 1 I C_m_,L 0.00 000 0.00 0.00 $010150111 S010615019 $01015020 S010615021 uf/mol,r PoFr OVA* Me<. I uPvFmOLA <LOQ(0.00107_,/n ,t } * <LO_10.00107ug'ml I + <L(_ <LOQIO.0OI07uI_mL) i j <LOO(000107Ul_.mLI } <LO(_) _ MSS/MIdS.DDe'Rv+PD NA NA i 12+67 S0n06 u$022 I I 14..]6 _l_lS0_ rj blP'_ 6S", _ m'+ 13 ++ I i 2117.30 S0t_bl$024 I 6g'.. 1 1, 276.16 S010bi$025 + 65b. I " 6P,_ 4% 3M EnvironmentLaalborau_ ..... -........ .__... _ Page 858 PageI00 3M Medical Department Study: T-6889.6 Study: FACT-TOX-16,1. E00.2_II N_eu SuWWa} Idama Mmlaml4te_mm &m_lyvmd E4ml_UU lamnm_l So_fmm: F_Mnw: Sylnn I_m_n: _v_. Y4mm'ce_: D_ of E.Irac_.'_saJ)qL Dems of AlmdyswAJmdys_ Di of/_ul D,_.,,,_/_alysc Sample Data -- - -. ........... FACT-TOX-]_ Argus 418-020 -+ ------ ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Ond (Oivqp) T_mum T,,Mn._ Itm ,_'lm E'rs.41.4.3 A ETS-I-5_ _pO)0HI9 _ .IL4 Sm Amalmrm .-_ _mm (Ow Lm pn _nmume) as mcsmmmS _ Repmdeamm Sm4y ofPFOA m Rm_ Sm A,lu_mmmo 06/14_I RW'W 06,'15'91 O6/IIV01k4MH RAT SERUM Group &ample II Mellm3d Bl.,t_t Blank PFOA - Pcrfluoro_na_ RT,S061401-H20 Blk.l R_I401@ BM(-2 RTS4_I401- .'. Blk-l RTS06140 I+.SmuBI,k-2 R"I_06140 I-M+_25 lqm R_ l_ I-klISD.2_5 R'r'so61101 - M,_-q0 lq_ RT_6 LdlOI .MS_SOG _eb i_a_ Ema_l_y DaCeVtmfted/By: _"_ I LAC 01/13/01 PFOA CO_. 0+420 O.tO 0+00 0.00 117 14.4 217 276 _ll_llrlt m @(PI_A IW _l or % P-_ ',_ (0.0010"7 vWn_) <,L.OO(O.COI07 upmJ.) <L_C_ (O.GOI07 qlmd,.) _ 100010"7 up_,L ) _% 61% 61% 6S% Ml.sn PFOA vWmL <LOQ <LOQ 64% 6_% 14_D Std. I)ev+ MS/MSD RPD NA I_+_ 13% 4% 3M Environmental Laborat_ ........... __:... _ Page 859 PagelOl -- - ..-+........... ARGUS 4 18-020 3M Medical Depaxtment Study: T-6889.6 FACT-TOX-164 xn_,_4]s-o2o Analytical Report: FACT TOX-164 LIMS E00-2738 Study: FACT-TOX. 164. E00-2"rJli N*nlafl'.,.. _) l_md/Rm,mmn A.mllyu_ _ Symmm I_l: iwmmmm Solh,mmNa'uan; F,lmame: Lt._lsmml Slope: Y.4-..,.-',... V-k-,: Droll lit F.,m.-_,,_a Aml,lnn: DII_ of Aml_m/Anmlyl: I_m of I_m II_mmo_Am_Imc Sample Dill _ (C.m_qlC)T_m_amm'mm (OI T.II_.6 Lain' IX_ Camm'mu) _ _.Z &ETS._-_ _mm maummmml msmom_ S_I_J _ 3.4 _-. Iklmv .T_ Amci_mm .,--,_m_mmu $_ Amml_ 0WI_01 RWW 0WI_91 MMH 01/20P01 Boxl: 01-011 saJy of PIFOAm Ra_ RAT SERUM Grip i sam" I_ ] Ml_od BLink B_Lk RTSOI I_OI.H20 Blb-l RTSOEI301-H2OBI*2 RTSOI I_01-,._o'I B u,*I RTSM 1301-.,_ BIk-2 (_ R_ 130I.kf..S.$O iSl_ RTS0_ 130I-kl[_D-$0 p_ PFOA " _e RT_01130 I.MS- 1500 i_b R'_011301 -MSD- I _00 I_b RTS0111_01 .MS-SC_00 i_b R'I_011301 .k(SD-S0000 ins_ A o l'_ak wss mm m_-imm_ nm _I_o_ .'... _mq,_bold limiL Dine _y: Dill Vm_ml/By: 01/_ I L,AC _47Ol _ VmMl . I I I I I I I I I I P,.,,l_llle Vlltlmlll NA NA HA _HiI_ NA NA NA NA NA NA riroA _Irll4_r I I I I I I _0 SO 1000 1000 PFOA Fdllllllll t COllltqtl rl, 1e4t Mill I_I1,,,I ] Iwmlo. f PoFr O%A RIt PmFwOmAL 0"00 14010115030 _LOQ |0.0Q$36 uwmL ) 0.00 I M01011S031 ] <LOOf0,00536uc.,mL_ <LOQ 0.00 M010115032 <LOQ (0.0053o _wmL} A [ ( 0.00 M010115033 <LOQ 10.0053b up,mL'_ I <LO0 i $$.111 M0 I01150"_1 $1_4 M0101115035 iO_'y, 110% j I 105% 21.414 24.111 46.19 43.410 M0101115036 M010115037 M01011_0311 M01011_0.39 92",, 80% 9_,. le% i I 16',, t + 19% _D kl.YS_ilMl. SD RPD NA _ NA 4% 13% I% 3M Environmental Laboratoa_z_._ __:.......... .--.... Page 860 Page 102 3M Medical Department Study: T-6889.6 Sl_ly: FACT*TOX- I_. 1:00-27311 Proem .*,,,_ ct"l Suimtmm_, Mamx: MeUmd/_w_ Aml_l Immm_t Fikma_: R-Scla=_l _ut_Eat Sy_em k--..,_ So4_w_m_,: v,m,. Stole= Y- i nle't'_*_ Dat_ of E.xmct mevAaaiyu: O( _IVSW_Iy=I DIne ofD'ata Redtcuem.'A,"ugysl: Sample Data - .: .-__....... ARGUS 41 _,q,')n,.,_v.,.v FACT-TOX=I64 Artus41s=o2o Analytical Report: FACT TOX-164 LIMS _-uu-:..;_ Ond (r.*vN_) ")'_ T..6Ug.6 Itm_ b'Wra*$.4.2 b=1['_8-$.2 _ _HI9 _ 3.4 r_ S_ See Alm:bmma .ftm Allackm_B N/13,_I RWW Qm/I$_DI MMH 0_'20_1 MMH (O1_ _ pCf Gmcrtlmn) _uCX)On Shady of PFOA m _&t$ am esnaea rm m-re, cu_c RAT SERUM Groep DeR MethOd BMuU Mlwrm BL"k i *"ml_ B f (, RTSO1130I-H20 ialk. i RTS01130 I-H20 Bn,.2 RTS01 I_10I-_rlerl Bit,. I R'F$_ 1301-_,tll lal_.2 0C R'rs_ _301-_S@ _ RTe'_ 1301*M_D'$O p R_OI I$0 | *MS- i _00 p_ RT$0_ 1301 -MSD- I$00 _pb R"rS08130 t-M.,_O000 _ PFOA - PerCum_ R'r$01130I-MSD-_0_0p_ A - peak w.s not m_ .t:nued. nec *bore ",," _ Ina. DramEram'By: Da_e Venf,_ By: O_t29tOI LAC _.,t.'Ol mmh PFOA Clmc. mlfJmL 0.00 0.00 0.00 0.00 ._$.l[t 31.2 21.4 24.9 46.9 43.4 Cmmmwalmn Iff PFOA mf,/mL or e,_Rec <LO0 (0.005.3b ug,mL ) <LO_ (0.00530 uF.,mL) <LO_ (0.r_$,36 Ult'nd,) A <[..O_ (0.005_b ug,mL ) 106% 110% 92% 110% 92% 86% I Me=. i PFOA ulbm[. ) ,_LOO <LO0 l 1011% ] [ 86% I I gg'/, [, _l) SId. De'*. MY_'qI_;O RPD '_A _A 4".. 13% _t',. 3M Environmental Laborateo_._ ......... -Page 861 Page 103 3M Medical Department Study: T-6889.6 -- FACT-TOX-i 64 ._ms 4ttm2o -.--+_ .......... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Study: FACT-TOX-IM. E00-273S Pmdu_ N_mbmrfTmuSoimma_): Main'u: Mmdmd/R_vmm: ._ml_l F._mmmt System Ntwnber F/Itmmt: R-Sqimd V_me: Slope: Y Immtqx Dmtt of _/uudytr _ of _a_y_: Dm of Dam Redtm_WAttlytt: Slln_e Dlltl CnJ (Gavae) Tw_C,ammlmoo (Ore _ T-41n.6 J_ S_m_ I1'rGam'momb Rc,,p_odq_on bm0y of PFOA m Kau E'1_1.42 & _T_i*$-I SmlU m mmr_ml om_ Madtlme04 I0_ .$a _.- AmdmnmB .r,_ Sel/umtt_u 08/13/01 RWW D8127101MMH 0W2_'01 MMH Box W: 01,031 RAT SERUM GDP_OeIp 'M_.os,os,_..- :illmpJe _RTTSSO0II3s0t1_-Hm2-OXBZIkO-2mk-n It4au'_ B4aJ RTIS0_8, 13,00l1--SS4__IrBaBIkJ-2k-I - _" RRT'I_'S0O11, 113300I,.M-._S.D_--_50 lq!__b RT.50111301.I_- 15QOpl_ R'I'SOI 1301-_1 _00 ppb RRI'S'r_I_0111_3001-,M-.MSDS--__O10401.0_plb PFOA - I_lkaemlx)aanoau ImYadl"l_. J lI lI ,I I 1 II F_..Ii;r|cJtSor'I_tlN iI..,_?.5 _nV'mOrpll*_d __Hm_hi_ ]0PFdIFlm_OemAr n nPCwFomOmL,c4.. o0.0.o0 o F_aam* ;1 uCg/omnocLremPorFraOt_"Au,_Rec i u&rlw:l_emaArLn ,M._01u0,8o2t?:_01mSTt';<,L_OL0O(t0o0.0.o2Mo2, 6uzr.t_m.L__ i <LOO I, M_.I_St(D1I1. 2iDRPD N^ 1.275,$ Ca.._,_maafmmlmm,llH'iJil__ I I 0.f0l0 MMO01lO0$12?70O2lg0l<iLO,_QLtO_OO(02.0b0lu2__nI_dw.,mi" LI _, <LOO i NA l1...2.__ l.._ 1.2_ t1,.._2.$ CC__mefm'mmmdmlHHqi__h NA NA NNAA I '! i 4319..341"/ MM0O1I0g__227;'002212 ], 50 20.83 MO101_27023 50 2._.d"/ M010_2"/024 I 1II+_0 j 322._.74,o MM0O1I.t2_"2;0";2'0, 26 i 9983%% 1_4.,. 9LP/. ,7,0%"/. i [ 96% ii I |.p_ ) 73% i 5% I% 1.1% DI_ Eaiemd/By: Vmf,_V By: 0_/O,UOI LAC W,U0! mm_ 3MEnvironmentalLaborataoz__ ......... ._.:. _ Page 862 Page104 3M Medical Department Study: T-6889.6 ._. Mm_ FAC'I'-TOX-IM. El_t-2731 ._umm_Tcu SU_MqjCE_ AALI_tJ_I _l_t Syua_ l_.w,.,_-- lmman_ Filmla_ ,_hwalw_/mm: R-,_l_d V-_..: Sk_: Y*lh_,.,.d4.t D,l_-s of ExulcuomvhJlal_t: I_de,$ oI AIllltvl I_/U_II _11: D*te orData Redua_/A_l_ Ssmple Dztz - -. ............... ARGUS 418-020 FACT-TOX-164 A_us4ns-o2o Analytical Report: FACT TOX-164 LIMS r..uu-._, _ (_vllc) T.4U9.6 I_ Salm Tw_-,lT._a_ntmm ((_ Limit I_' G_nw_n ) Kammauctma .$_1y el' PFOA m MMebu_ll0gl P_mymt !1.4 _/Umaina Sm .4umdmmm ,T_e/um=r_u See Amdjmm 01/I.!/01 IIW_/ 01/27/01 III/"_'W01 MMH RAT SERUM _. Group PFOA - Pt,.rfl_ E.nmred/By: ve_f_[t By. _*mld_ IP _ i_-. WI _wmL .,,,oA ColJrelulrll_ *q_ml. or % Rec RTSOII3Ol-l'[2Olalk*2 _ _ R'l_130l-._n Blk*2 _ _ RTS_ J_oI.M._O m_ I 41.3 RT_OII 130 I-MSD-50 R'lr_OI I _01 -M_ 1500 ppb 39.$ ] 20.11 RT$_I 130 I-MSI_- ISO0 22.S x_somo,.______._i 32.'; Rl_'_81301 _000 nb _ (0.00268 _..m,L_ 98'/, 93% 14% qo% 81% "/0% Mean PFOA ut.'mL <LOQ <LO0 _t',., 8"_.. ?S'/. _O SRd. De_. _.I$,_SD KPD _,A N _, S% 8% 14% 09/04/01 ]._C _t4/OI 3MEnvironmental Laboratory.._ . .......... _ Page 863 Page 105 3M Medical Depaa'tment Study: "I"-6889.6 3M MedicalDeparlmenSt tuo_%. 6889.6 - _........... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 Analy_caRl eport:FACTTOX-164 LIMSE00-2738 Appendix F: Example Calculations Formula Used for SeraAnalym in Study FACTTOX-164 AR (ng/mL) x DF x FV (mL) x 1.0 IJg = Reported Concentration (pg/mL) Ev (mL) Calculation Used for Group 4, LD22,Animal ID P13891F 65.14ng/mLx5x 1 mL x 1.0pg = 0.326pg/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 "411.4_nuimmrttml I Dl-,nmtnnl 3M Environmental Laboratm_._. ......... -_ Page 864 I:)'Af1_ _R Page 106 3M Medical Department Study: T-6889.6 3M MedicalDeparlmenSl tudyT: -6889.6 _ _-........... ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 AnalyticaRl eport:FACTTOX-164 LIMSE00-2738 Appendix G: Interim Certificate(s) of Analysis .':IU _nv/rnnmntml I Dhnr_tnrv 3M Environmental Laboratark_._............. Page 865 PArsA Page 107 3M Medical Department Study: T-6889.6 .... _-......... _ _. _ ARGUS 418-020 Analytical Report: FACT TOX-164 LLMS E00-2738 O'kkptmne: 3048 _rm Drive (m4) StateCoUegeP, A16801 w_v.clmlmlal_.com m14)1.1z. or(014) Purity I INTERIM CERTIFICATE OF ANAL YSIS Centre Revlsios 2 (1@/17/01) Analyl/cal Laboratm'/m COA Reference #: 3M Product:. PFOA, Primary Standard Test Control Reference #: TCR-99030-30 023-034 TestNsume Purity: 9$.0% Specfllcatious Rmult 95.0% Appcm'an_ IdcnUficauon NMR Metals (ICP/MS) 1. Calcitma 2. Magnesimn 3. Sodium 4. Pomsmum 5. Nickel 6. Iron 7. Manganese Total % h.purity (NMR) Total% Im_ty (LC/MS) Total % ImpunW (GCJMS) Residual Solvents(TGA) Purityby DSC t.org_c Anions I. Chloride 2. Fluoride 3. Bromide 4. Nilrale 5. Nimm 6. Phospha= 7. Sulfate | Ors_(IC) I. TFA 2. PFPA 3. HEBA 4. NFPA White, crystalline solid Conforms Positive 1. 0.001 wtJ_% 2. <0.001 wtJwt.% 3. 0.001wtJwt.% 4. <0.001 wt./wl.% 5. _0.001wt./wt.% 6. <0.001 wtJwt.% 7. <0.001wt./wt.% 0.36 vn./wr.% 4.68wtJwt.% None _hmntificd.% None Detected 99.8% I. <O.015wtJwt.% 2. <0.00$wtJwt./. 3. <O.040wtJwt.% 4. <O.O09wt../wt.% 5. <:0.006_'t.% 6. <O.006wU,wt.% 7. <O.040 _% I. <0.Iwl./w_.% 2. <0.1wt./wt% 3. <0.1wt./wt.% 4. <0.25 wtdwt.% 1. Carbon 2. Hydrogen 3. Nitrogen 4. Sulfur 5. _uorm ,_',,omum Analys_"r" laa Selective Electrode I. Tlceretica] Value = 22.3% 2. Theon_a] Valwe= 0.935% 3. Theon_a] Vah - 3.25% 4. 'rncorcticalValue = 0% $. TheoretiealValue=66.1% I. 18.9 wtJwt.% 2. 1.27 wtJwt.% 3. 3.76 wt./wL% 4. 4.38 wtJ_% .5. 62.1wtYwt.% Them_d Value = 4.18%_.._% 2.94 wtJwt. % COA023034REVISIONZdo 3M Environmental Laborato_.._._. ; .-....... :- _ Page 866 ]PN_i of 2 Page 108 3M Medical Deparmaent Study: T-6889.6 - ......... -----__ ARGUS 418-020 Analytical Report: FACT TOX-]64 LIM3 _-UU-_' ,'j_ '_vO'Nk_k_i_..: 3048 Ro:ma;_ Drive State College, PA 16801 www.cemmtao.com (814)zs',-eo_ Fax(8: ',4_)-nm or_e_4m)',-',seo INTERIM CERTIFICATE OF ANAL YSIS Rt,wi._n 2 Clarl 7/01) Centre Analytical Laboratmdes COA Reference #: 023-034 3M Product: PPOA, Primary Standard Test Control Reference #: TCR-99030-30 Date of Last Analysis: 10/31/00 ExpL-ationDate: 10/31106 Storage Conditions:< -I0 "C Re-assesmnent Date: 10/31106 IPurity= 100%- (total metal impurities,0.002%+ TotalNMR impu.fides,0.36 _-TotaJ LC/MS impurities,4.68 %) Total impurityfromall tests = 5.042% Purity = 100% - 5.042%= 95.0/o 2TFA HFBA I_FPA PFPA Trifluorow_ic acid Heptafluombutyricacid Nonafluoropentanoicacid Peutafluoropropanoicacid _'heore_icavl aluecalcut_onsbasedontheempiricaflormeb.,C,,F_:_3.2(')N(+I-)14 (MW=431.1) This work was conducted underEPA Good ;*horatoPrryacticeStandards(40 CFR 160). LC/MS Pur/ty Profile: Rl_.mtltonTime (mill) Aru 1 12.144 269.0 C6 205859 0.87 2 13.533 331,319 Ft_/C'7 903329 3.81 3 14.238 369 PFOA 22630600 Total - 23739788 4.68 Pr=pm_! By: . _. r Reviewed By: COA023034 REVISION _ 3M Environmental Laborat_ .......... _ Page 867 Page 2 of 2 Page 109 .... 3M Medical Department Study: T-6889.6 3M MedicaDl eparlmenSt tudyT:.-6889.6 Appendix H: Report Signature Page .._. ........ : .--- ARGUS 418-020 Analytical Report: FACT TOX-164 LIMS E00-2738 An_ ReportF: ACTTOX-164 UMS E00-2738 John Butenhoff, Ph.D., Study Director Date David San_m, Ph.D., Sponsor Repmsemasve Date l.JsaClemen,Principal AnalylJcalInves#gator Date WilliamReagen,Ph.D., Laboratory Managemem Date RL4 _'mt/m_l i ahnnltnnt 3MEnvironmental Laborato_L____ :_.-.......... =___.. _ Page 868 pena 27 Page110 ARGUS 418-020 APPENDIX J ENVIRONMENTAL AND HUSBANDRY REPORTS Page 869 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 05 Protocol Number: 418-020 Range of Dates: 07-Nov-2000 14:11 to 13-Nov-2000 08:59 Target Range: Species: Rat Total Numberof Days: Total Number of Hours: Total Number of Data Points: Temperature 64F to 79F 7 138.5 139 Relative Humidity 30%to 70% 7 138.5 139 Mean (:!:SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Number of Points Low(%): 68.5 ( 1.4) 51.9 ( 4.0) 71.1 63.9 68.0 50.8 66.6 44.1 139 (100.0) 139 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Report Generated: 18-Jul-2001at 11:07 COMMENTS: 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 Target Range: Species: Rat Total Numberof Days: Total Numberof Hours: Total Number of Data Points: Temperature 64F to 79F 129 3080.75 3078 Relative Humidity 30% to70% 129 3080.75 3078 Mean (+ SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Number of PointsLow (%): ReportGenerated: 18-Jut-2001at 14:06 COMMENTS: 67.4 70.1 67.3 65.9 3078 0 0 (_+0.6) (100.0) (0.0) (0.0) 45.8 62.4 46.7 30.8 3078 0 0 (_+6.2) (100.0) (0.0) (0.0) REVIEWEDBY: _) _.__. _'_Tk DATE: 7 2-,_O/ 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 Target Range: Species: Rat Total Number of Days: Total Number of Hours: Total Number of Data Points: Temperature 64"F to 79"F 22 502.25 501 Relative Humidity 30% to 70% 22 502.25 501 Mean ( SD): Maximum: Median: Minimum: Numberof Points in Range (%): Number of Points High (%): Numberof Points Low(%): Report Generated: 18-Jui-2001at 14:11 COMMENTS: 70.3 ( 0.8) 46.5 72.1 63.1 70.2 45.8 68.3 27.7 501 (100.0) 498 0 (0.0) 0 0 (0.0) 3 ( 5.6) (99.4) (0.0) (0.6) REVIEBWyE: D D,TE: Page 872 ARGUS 418-020 ARGUS Relative Humidity Deviations Report Location: Room 16 Protocol Number: 418-020 Range of Dates: 09-Feb-2001 14:30 to 02-Mar-2001 12:59 Humidity Target Range: Species: Rat Date 25-Feb-2001 25-Feb-2001 25-Fe_2001 Time 06:00 07:00 08:00 R.H. 29.0 L 27.7 L 28.5 L 30% to 70% Date Time R.H. H : Value out of range - High L : Value out of range - Low R.H. : Relative Humidity (%) Report Generated: 18-Jul-2001at 14:16 _hese deviationsdidnotadverselyaffectthe outcomeor interpretationof thestudy. The followingdeviation(s)impactedon the outcomeof the studyas described: Page 873 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 01 Protocol Number: 418-020 Range of Dates: 05-Mar-2001 11:30 to 21-Mar-2001 16:59 Target Range: Species: Rat Total Numberof Days: Total Numberof Hours: Total Numberof Data Points: Temperature 64F to 79F 17 389.25 390 Relative Humidity 30% to 70% 17 389.25 390 Mean (+ SD): Maximum: Median: Minimum: Number of Points in Range(%): Number of Points High (%): Number of Points Low (%): ReportGenerated: 18-Jul-2001at 11:13 COMMENTS: 70.0 70.9 70.1 67.1 390 0 0 (+-0.5) (100.0) (0.0) (0.0) 55.2 63.2 55.3 39.3 390 0 0 (+_2.0) (100.0) (0.0) (0.0) Page 874 ARGUS 418-020 ARGUS 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 Target Range: Species: Rat Total Number Total Number Total Number of Days: of Hours: of Data Points: Temperature 64"F to 79F 4 64.75 65 Relative Humidity 30% to 70% 4 64.75 65 Mean (_+SD): Maximum: Median: Minimum: Number Number Number of Points of Points of Points in Range (%): High (%): Low (%): Report Generated: 18-Jul-2001 at 14:01 COMMENTS: 70.5 74.1 72.2 64.6 65 0 0 (-+ 3.3) (100.0) (0.0) (0.0) 51.4 67.9 48.9 43.0 65 0 0 (_+6.7) (100.0) (0.0) (0.0) REVIEWED BY: __ DATE: _ _/-c/ 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 Target Range: Species: Rat Total Number of Days: Total Number of Hours: Total Number of Data Points: Temperature 64F to79F 4 64.75 65 RelativeHumidity 30%to 70% 4 64.75 65 Mean (:!:SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Number of Points Low (%): 72.0 ( 1.7) 57.8 (+_2.8) 74.2 63.4 72,6 57.8 68.6 50.5 65 (100.0) 65 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Report Generated: 18-Jul-2001at 11:32 COMMENTS: REVIEWEDBY: L/_ _ -_ "C"k_ DATE: 7 7 _t)l Page 876 ARGUS 418-020 ARGUS Temperature and Relative Humidity Report Location: Room 01 Protocol Number: 418-020 Range of Dates: 24-Mar-200108:30 to 25-Mar-2001 15:59 Target Range: Species: Rat Total Number of Days: Total Number of Hours: Total Number of Data Points: Temperature 64F to 79F 2 31.25 32 Relative Humidity 30% to 70% 2 31.25 32 Mean (+ SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Number of Points Low (%): 70.7 (_+0.4) 52.0 (_+1.7) 71.2 55.8 70.8 51.7 69.9 48.8 32 (100.0) 32 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) ReportGenerated: 18-Jul-2001at 14:08 COMMENTS: REVIEWEDBY: /-_) _.._/ .."/I. DATE: "72 _ 0/ 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 Target Range: Species: Rat Total Number of Days: Total Number of Hours: Total Number of Data Points: Temperature' 64F to 79F 2 31.25 32 Relative Humidity 30% to 70% 2 31.25 32 Mean (_ SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Numberof Points Low (%): 69.7 ( 0.5) 42.1 ( 1.6) 70.5 45.3 69.6 41.7 68.8 39.2 32 (100.0) 32 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) ReportGenerated: 18-Jul-2001at 14:09 COMMENTS: Page 878 ARGUS ARGUS 4 ! 8-020 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 Target Range: Species: Rat Total Number of Days: Total Number of Hours: Total Number of Data Points: Temperature 640F to 79F 22 504.0 504 Relative Humidity 30% to 70% 22 504.0 504 Mean ( SD): Maximum: Median: Minimum: Number of Points in Range (%): Number of Points High (%): Number of Points Low (%): 72.6 (+ 1.0) 50.5 75.4 71.5 72.7 50.5 70.1 33.3 504 (100.0) 503 0 (0.0) 1 0 (0.0) 0 Report Generated: 15-Aug-2001at 09:30 COMMENTS: (+ 5.0) (99.8) (0.2) (0.0) 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 Target Range: Species: Rat Date 06-Apr-2001 Time 06:00 R.H. 71.5 H 30% to 70% Date Time R.H. H = Value out of range - High L = Value out of range - Low R.H. = Relative Humidity (%) Report Generated: 15-Aug-2001at 09:34 ./ These deviationsdidnotadverselyaffecttheoutcomeor interpretationof thestudy. The followingdeviation(s)impactedon theoutcomeof the studyas described: StudyDirect,o,,r_".n._]_ J(__/'_--__/'- Date: f,_-7_L]t_-(.2/ 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 Target Range: Species: Rat Total Number of Days: Total Numberof Hours: Total Numberof Data Points: Temperature 64"F to 79"F 22 504.01 504 Relative Humidity 30% to70% 22 504.01 504 Mean (-+SD): Maximum: Median: Minimum: Number of Points in Range(%): Number of Points High(%): Number of Points Low (%): Report Generated: 18-Jul-2001at 11:15 COMMENTS: 73.2 (+ 0.9) 59.3 75.8 76.0 73.3 59.1 70.4 43.0 504 (100.0) 495 0 (0.0) 9 0 (0.0) 0 (+_4.8) (98.2) (1.8) (0.0) REVIEWED BY: L/]- _ ,_4"1 _ DATE: "7 2 _" Page 881 ARGUS 418-020 ARGUS Relative Humidity Location: Deviations Room 41 Report Protocol Number: 418-020 Range of Dates: 25-Mar-2001 15:35 to 15-Apr-2001 15:59 Humidity Species: Target Rat Range: Date 07-A _r-2001 09-A _r-2001 09-A _r-2001 12-A :)r-2001 12oA}r-2001 12-A _r-2001 12-A)r-2001 13-A _r-2001 13-A _r-2001 Time 06:00 06:00 11:00 07:00 08:00 09:00 10:00 06:00 11:00 R.H. 72.8 H 72.3 H 72.3 H 71.6 H 72.2 H 70.7 H 76.0 H 71.6 H 70.8 H 30% to 70% Date Time R.H. H = Value out of range - High L = Value out of range - Low R.H. = Relative Humidity (%) Report Generated: 18-Jul-2001 at 11:29 v_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 _ PMI NUTRITION I | N T E | NAT I0 NAt ARGUS 418-020 Page Iof 2 SampleNo.:L0022289-3 Received0:8/03100 Reported0:8/16/00 CERTIFIED RODENT DIET MEAL LOTNUMBER AUG 01 00 2C Assay /Analvte ProteinK,jeldah(lN x 6.25) Protein Fat Fat Fiber, crude Fiber, Crude Arsenic Arsenic Cadmium Cadmium Calcium Calcium Lead Lead Mercury Mercury Phosphorus Phosphorus Selenium Selenium PRKR FTEE/FTAH FIBR ASF CDF CAF PB HGSP PF SE Site:Rill Locator5.002 ProjectC:ERT. Result 20.9 6.01 4.25 <0.200 0.056 0.788 0.187 <0.025 0.560 0.362 U'nits % % % ppm ppm % ppm ppm % ppm Foradditionianlformatiopnl,easceontact= (I) Forassaymethodolog-yCustomerService3s1,4-982-1310 (2) ForNutritionIanlterpreta-tDiro.nDorrancIe-laugh3t1,4-768-4362 (3)Allotherquestion-sRichmondI,N ManufacturiPnlgant7,65-962-9561. Theterm"LesTshan"isusedtosiiptifythelowelrimitof qmmtitatioofnthepmcdcu, reundetrheconditionesmployeTd.heuseof thetcfm=LesTshand" oensotimplythaUt 'ac_ofAnalytwe enp: resenSt.amplessubmittetodRalstoAnnal)tic.Laa] boratorfioers routineanalysiswillberetainedforItminimumofthirty(30)daysafterthereporotfanalysisis issued.Extendesdtorage requirememntussbt ebrougthottheattentioonfRalstoAnnalytiiuLtal boratorpierisotrooratthetimeofsampsleubmission. REVIEWBEYD: II 1401S.HanleRyind'* St.LouisM.O65144 Phone3:14-768.410"0_FaxM: 4-76S-4765 DATE _i'=E- XAC -- Page 883 __e_ |1 "._.7.. " ARGUS 418-020 PMI NUTRITI( : ,oo I N T E R N A T I 0 NF,u_. CERT. CERTIFIED RODENT DIET MEAL LOTNUMBER AUG 01 00 2C Assay / Analyte Result Units Orgattophosphate pesticides Diazitton Disulfoton Ethion Malathion Methyl Parathion Parathion Thimet Thiodan Trithion Organochlorine pest.&PCB's Heptachlor Epoxide Heptachlor DDE Lindan Endrin Mircx Alpha-BHC Delta-BHC Aldrin Dieldrin DDT Chlordane Methoxychlor Beta-BHC HCB PCB Aflatoxin screen Aflatoxitts 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 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, 3 !4-982-1310 (2) For Nutritional Interpretation - Dr. Dorrance Haught, 314-768-4362 (3) All other questions - Richmond, IN Manufacturing Plant, 765-962-9561. Theterm"LessThani"susedtosigniftyhelowelrimitofquantitatioofntheproceduurnedetrheconditionesmployeTdh. euseof the term"LessThan"doesnotimplythattraceosfAnalytewerepresentS. amplesubmittetdo RalstonAnalyticaLl aboratorifeosr routineanalysiwsillbe retainefodr minimuomfthirty(30)daysaftetrhereporotfanalysisissuedE. xtendesdtorage mquiremenm_ustbsbroughtottheattentioonfRalstoAnnalyticaLlaboratorpierisotrooratthetimeofsamplseubmission. AA,A REVIEWBEYD: DATE 1401S.Hank7Road_ St.LouisM, O 63144 Phone3:1. 4-768-410*0 Fax3: 14-768-4765 i Ii=_^AC;T L;_r' _,:- ' Page884 --[/__ //t/_ _/__/.Q.L. i t.enlnca Papers _emevai LD/et ,,,+;,5+, ,, Return to CertifiedAnalysis Retrieval I Product Code: Product Desc: Lab Number: Lot Code: Entered: 5002M CERTIFIED RODENT L0025623-1 OCT 03 00 3A 1015100 DIET MEAL ARGUS 418-020 Assay , PROTEIN FAT (ACID HYDRO.) I FIBER (CRUDE) ARSENIC I[ CADMIUM CALCIUM LEAD II MERCURY II PHOSPHORUS II SELENIUM II Analysis Units 21.5 % 5.64 % 5% LESS THAN 0.2 PPM 0,083 PPM 1.07 % 0147PPM LESS THAN 0.025 PPM 0.7,6oh 0.361 PPM IORGANOPHOSPHATESlIPPM Diazinon Ethion LESS THAN 0.02 ILESS THAN ,0.02 Methyl Parathion L'0E.S0S2THAN ORGANOPHOSPHATES Disulfoton Malathion PPM LESS THAN 0.02 LESS THAN 0.02 Parathion L0.E0S2S THAN IThimet !Trithion +s++,, :0L.0E2SSTHAN Thiodan 0.02 II 0L.E0S2 S THAN Aldrin Beta-BHC DDE, Delta-BHC Endrin Heptachlor Lindane Mirex jtp,,,,, ][LESS THAN 0.02 ][Alpha-BHC J LESS THAN 0.02 ] ][LESS THAN 0.02 IILESTHSAN 0.02 llC'hlordane I[DDT LESS THAN 0.02 LESS THAN 0.02 IILESS THAN 0.02 IILESTSHAN 0.02 IIDieldrin HCB LESS THAN 0.02 I LESS THAN 0.02 I[LESS THAN 0.02 IIHeptachlor Epoxide LESS THAN 0.02 IILESS THAN 0.02 Methoxychlor ,LESS THAN 0.02 llLESS THAN 0.02 PCB LESS THAN 0.15 LL! _ C03C G_ " " t"-% _: LJ.J http :I/www. [abdiet.comlcenified/pwa spc002.asp _ ......... ._ PageS85. _ EXACT CO,_-,, . " ',4.'N/-k?l /#_j_.. 12120/2000 .. ARGUS 418-020 IIA.atoxin IIAflatoxins IILESTSHA5NPPB II No notes. Foradditionalinformationp,lease contact: 1) MichaelJ. Murphyat (314)982-2383- for assaymethodology 2) Dr. DorranceHaughtat (314) 768-4362- for nutritionainl terpretation 3) Richmond,IN ManufacturingPlantat (765) 962-9561- allotherquestions The term "Less Than" is used to signify the lower limit of quuntitation of the procedure under the conditions employed. The use of the teml "Le$$ Than" does not imply that traces of analyte were present. ,,_,,r'_v_EWBYE:D DATE Pas_.e886 i'EXACTCO-:'-:" I____ff7/fglo.L. " ARGUS 418-020 Pip Iof2 Samplelqo.:L0028475-2 lte_ved: 11/30/00 Rzported:12/14400 Sire: RI_ Locmor:5002 Pro.)eccCERT. CI_TIFIED_ DIL_ bfEAL I._Th'UMBBR.DFC, 01 00 IB _"T I,Jmttw_e Prom_ K),mshl (N _ Prom_, Fit Fiber,e_sde F_r, _ _k An_dc Cadmium Cadmium Caldum Calcium Lead IAed Mercury Phmphorm fkd,miam Selenium FIYJUFTAH Rmmlt 2o.s _F CDF CAF PB RG_ PF .SE 3.99 <0.200 0.0_3 0.97"/ 0.139 c0.025 0.6S9 0.159 Unin '_ % ppm ppm % ppm ppm % ppm ForKldifimImnlfnnmaipol_zmocontact: (I)Forumay_Iosy. Ctm_r Sm'vic3_l,L.gr_-13"10 (2)ForNz_timml]n_. Dr. Dms'm:z_ 314,.7_,,4362 (3) Allo_" qm_om - RJduuouIdN. _ _ 765-9_.-9561. "I_tam"LmTsI_"tsm_ m_ th tmqrltmnot'qmattmMors_ _ m_ _ _ _. 'rhcmoof mqubmmmmisntmtmm#mz tk minimotl_mn _ L.msmmmlsiarmora _ e,- ot_ m_ REVIEWEDBY: DATE , i EXACT' Page 887 f CKR.TIFIII_U3_nqT DIET MEAL LOT_ DKCO!O0IB ._,.,..,I,rS-,.,h_ Oqpum_t/_ _ _hyZ _ Pmlhion Thhwt "rhtodlm Trlflllou or_moqa_ _ _ H_tnchior DDE I_ Endrln ldlrmt AIp_.BHC I_lm.BHC AJdrtn DDT _hx'dmm l_or Bet_BI.IC H(_ P(_ .,Lah, l_l:lmmee_m Project:a_.T. ARGUS 418-020 ohm, _ 4.020G 4.0200 ,:0.O2OO ,,:O.O2OO 4.0_00 4.0200 4.t_O0 4.O200 4.0200 _.o2oo .,:O.O2OO 4.02OO 4.0200 .:O.O2OO 4.O2OO 4.0200 4.O200 4.0200 4.0200 4.0200 4._00 4.o200 4.0200 4.0200 4<:0.150 _.oo uuns ppm ppm ppm ppm ppm ppm ppm ppm ppm ppm Ppm _v,,, ppal prm ppm ppm ppm ppm ppm ppm ppm ppm For _ _l_mm_ou,pinto (1) For_m7 men.lake. Cmmu_ ServimL314-982o1310 (2) ProN" ulr/lto_/nSwpmtttm - Dr._ _ 314.768.4.M2 (3) .Anothmq"uemtom-_ n_ _ Phmt,76S,._-gS61. 'r_m'm",mTma"terealm_ tk,kswaIk_aCqmnztmd_'tt__ mskrtb_maditio_m 'r_ umOf t_ rosa"l.a_Tree"_ommt_mp_,_-mmma_t_tc wa_pmmt kmplmmul_UatfoP.dmmAmbUml.i._am_ _ mu_mmd_ w__em_m_tr tuk_mm_ 00)_ 8a_ mpoaofmd3_ b im_ Xlxen_mnp JuleHnmnmum_ IJme_et nnmm_im_Rmlmm,kml3_LJ,_edmn._ miortoerettt_ti_ _ _ REVIEWEBDY: DATE Page 888 ARGUS 418-020 Lanr er Laboratories Wherequalityisa science. Lancaster Laboragorxes Colle_tec:06/20/200! Submiz_ed: Reported: Dlscard: 06/20/2001 06/23/2001 07/29/20_! Poinz #2 Formulation Wa_er Sample Sample No. WW 3634413 i0:40 by EA Accoun_ N_n_Der: 02423 16:30 a_ 14:25 Lab 905 Sheehy Dr B!eu F Grab Primedica 5? Unzon Worcester Argus Streez MA 0160E Page I of 2 CAT No. 00224 00226 0022. Q 00368 01504 C!506 01505 Analysls Nal_ Chlor1_e Ortho-Phcsphate as P Sulfate Nitrate Fluorlde _:izro.uen Nl_rlte t]l_roqen Brom1_e 0017_ Pes_Icl_es/PC_'s In Water 00453 00454 00455 00469 00477 00478 00638 0190_ 01903 01904 01905 01906 01907 Cl90g _1909 01910 01911 6191. _ 01913 01914 01915 01916 0191" 0191B 01919 GanTaa BHC - LlnOane Hep_achlor Aldrln D1el_.rln Endrln DDT Endrln Alcehyde Alpha BHC Beta BHC Del_a BH-Heptacnior Epoxl_e DDE DDD Chlordane Toxapnene En_osulfan I Endosulfan En_osu!fan PCBI016 PCB-12ZI PCB- 123-PCB-1242 FC5-I-_4S FC-_-IZ54 ?C_1760 il SulSate 31956 HerD_claes :n ;';ate: CAS l_Z 16887-00-6 14265-44-2 14808-79-8 14797-55-B 16984-48-8 14797-65-0 n.a. AS Recelwed ReSult < 2.0 < 0.020 < 5.0 < 0.50 < 0.50 < 0.50 < 2.5 58--_9-9 76-44-S 309-00-2 60-57-I T2-20-_ 50-29-3 7421-93-4 319-84-6 319-85-7 319-46-@ 1024-57-3 72-55-9 T2-54-8 57-74-9 0001-35-2 959-98-_ 33213-65-9 i031-0_-6 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12 _72-29-6 ! I09_-69-I 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 < 0.2B < 3.8 < 0.0094 < 0.0094 < 0.029 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 < 0.94 AS Remex_d Ll_t of Q%lan_tatlon =.0 0.020 5.0 0.50 C.50 0.50 Z.5 Unitl mgll mg/l m u/l mq/l mo/l m=/! mg/l 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 0.02-3 0.94 0.94 0.94 0.94 0.94 0.94 0.94 ug/l u /1 u9/l u /l ug/l ug/l ug/l ug/l ug/l ug/l uq/l u_/l ug/l ug/l ug/! ug/l ug/l ug/l ug/l ug/l ug/l u /l ug/l ug/l ug/l Dilution Factor 5 l 5 5 5 5 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 MEMB ER La__slef i.&Dor;llof_es. Irl. 24Z$New_na_i_e 1.3ncaster. PA 17605-2.';.5 PO B_x 12425 '"""'= / / 7/5/_i E) ACT C'.i' I Z/r/l<> Page 889 """"'" ARGUS 418-020 LancastLear boratories _ science. _casnQr _orauorxes S_ple No. _ 3634413 _oiieccec:06/20,'2001 I0:40 by EA Account Number: 22423 SuDmitted: 06/20/2001 Repcrted: 06,'28/2001 Discard: 07/29/2001 Point #2 Formulatlon Water Sample 16:30 at 14:28 Lab 905 Sheehy Dr Bld9 F Grad Primedlca 5 _ Unzon Worcester Arzus Street M_. 01603 Page 2 of 2 CAT No. _ysaa Hi 01857 01858 05286 05287 05288 05289 05290 05291 J5_9-C5293 08103 2,4-D -_,4,5-TP 2,4,5-T Dalapon DlnoseD Dlca_a MCPP MCPA 2,4-DP {Dlchlorprop) 2, _-DB _entachlcr_Dnenol _ _r 94-_5-" 93-72-! 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 _el_ _S_C < 0.49 < 0.04_ < 0.049 < 1.2 < 0.25 < 0.30 < Z00. < ZOO. < _'.49 < 0.49 < 0.05 C_mmonwealth of Pennsylvania LaD Cer=lflcat,-on No. 36-03" As Recezved L_t of _c_Caon C.49 _.04- _ 0.Q49 1.2 C.25 2.30 200. ZOO. 0.49 5.49 0.05 UnaCs ug.l u_,'i u: ug, i ug/i ug/i ug,'i ug/i ug/i u_,l ug/l Dllu_on Factor 1 1 1 1 1 l ". ! 1 ! CAT No. 00224 00226 00228 00368 01504 01506 01505 00178 01856 00816 00817 _ym_m N_ Chlor1_e OrTho-Phosphate Sulfate tlITrate Nitrogen Fluor1_e _:itrlTe NiTrogen Bromaae PesTlc1Oes/PCB's as P In WaTer HerD1c:Ses an WaTer WaTer Sample ExTract MerDicide WaTer Sample ExTracTlon Pesu. Laboratory _ EPA 300.0 EPA 365.3 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 EPA 608 SW-846 SW-846 8151A 8151A EPA 609 Chronicle _ys_s TEMPI Date R i 06/21/2001 1 06/21/200! 1 06/21/2001 _ 06/2172001 I 06,'2!/2001 1 06/Zl/Z001 1 06/21/2001 1 06/21/2001 1 06/25/2001 ! 06/22/2001 TI_ 14:25 _!:00 14:25 14:25 14:25 14;25 14:25 19:45 16:12 09:00 1 06/21/2001 09:45 _alymt Mark A. Bu=kwalter Danlel S. Smith Mark A. Buckwalter Mark A. BuckwalTer Mark A. Buckwalter Mark A. BuckwaIter Mark A. BuckwalTer Anita M. Dale Tiffany DeDoran A. Ley_a M. Z1_aerman Amanda E. Wa_e Dilu_ Fa=_z 5 1 5 5 5 5 5 1 1 1 1 M E M BE R Larlcastef I.JDotalOtl('$, Inc. 2-125 New Holland _ke [ ,' tt Page 890 ARGUS 418-020 LancastLear b0mt0ries r, _ soence. Lancaster T_orator_es Sample No. _ 3634414 Co!!ec:ec:06/20/2001 I0:30 by _% Acaoun= Number: 02422 SuDmittec: 06/20/2001 16:30 Reported: 06/25/2001 Discard: 07/29/200! a_ 14:25 Poin_ #_ Anaiy_ical Wa_er Sample LaD 905 Sheehy Dr Bldg B Grab Primedica 5T Union Worcester Argus S=ree= _ 01608 Page 1 of 2 CAT No. 00224 0022_ 00228 00368 01504 01506 01505 00178 Analys_s Name Chloczde Ortho-Phosphate Sulfate t_itra:e NICrogen Fluor1_e N1_rlte Nitrogen BromlOe as P Pes_icides/PCB'$ in Water 00453 00454 00455 00469 00477 00478 00638 GIg0Z 01903 01904 01905 01906 01907 01908 01909 01910 01911 01912 01913 01914 01915 01916 C1917 01919 01919 01_56 Gamma BMC - Lan_ane Hep_achlcr Al_rln Diei_rln En_rln DOT Endrln Aldehyde Alpha BHC Beta BHC Delta BHC Heptachlcr Epoxlde DDE _DD Chlordane Toxaphene En_osulfan I Endosulfan II En_osulfan Sulfate PCB-1016 PCB-12_I PCB-1232 PCB-1242 PCB-1248 PCB-1254 PCB-I260 HerD1c:_e$ _n Water CAS Numbez 16887-00-6 14265-44-2 14808-79-B 14797-55-8 16984-48-8 14797-65-0 n.a. 58-99-9 76-44-8 309-00-2 60-53-I 72-20-8 50-29-3 7421-93-4 31_-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 i031-0_-8 12674-11-2 11104-28-2 11141-16-5 53469-21-9 12672-29-6 11097-69-1 11096-82-5 M E M BE R L._rtcasler Laboralone$. Inc. 2-_25 New HOlLand Pike Lancaster. PA 17505-2425 717-656-2100 Fax: 717-65_-2681 Am Re=e_ved Result < 2.0 < 0.020 < 5.0 < 0.50 < 0.50 < C.50 < 2.5 < 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 As Received :-i_t of _ta_on 2.0 0.020 5.0 0.50 0.50 0.50 =.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 '' --_" " _-_ Units mg;1 mg/! mg,'! mg/l mg/l mg/l mg/l Dilu_on Factoz 5 l 5 5 5 5 5 ug/l 1 ug/l 1 ug/l 1 ug/l 1 ug/l 1 ug/l 1 ug/l 1 ug/l 1 u_/l 1 ug/l 1 ug/l 1 ug/l 1 u_/l 1 ug/l 1 ug/l 1 ug/l 1 ug/l 1 ug/l I ug/l 1 ug/l i ug/l 1 ug/l 1 ug/l 1 ug/l i uo/l 1 2216 Rev. 9t11100 Page 891 ARGUS 418-020 It. LWnaernequcaaliTsytsatLseciaernbceo. ratories Lancaster Laboratorzes Sample No. WW 3634414 Coiie=:e::06,'10/2222 1_:2_ :5" L:.. SuDmi:tea: _6/2612001 16:39 Reported: 06/2_,'2001 a: 14:2_ Dascard: 97/29/2C_1 Poin= #3 Anai3"=ical La_ 905 Sheehy Water Sample Dr Bldg B Grab Ac:=u== Nu_er: _24Z3 Prime_ica 5 r Union Worcester Arcus Stree: _L% _!60_ Page 2 of 2 CAT No. 01857 01858 05286 05287 05288 052_9 05290 05291 05292 05293 0_I03 Ana/ysaa Name =,4-D =.4,5-TP =,4,5-T Dalap0n D_nosen D_camma MCP? MCPA :,4-DP _D_:hlcrp_op_ =.4-D_ Pen_achlorcpnenol CJ_ )humber 94-n5-7 93-72-1 93-76-5 ?5-99-0 88-85-7 1918-00-9 93-65-2 94-_4-6 120-36-5 94-82-6 87-86-5 AS Reci_.ved Result < 0.48 < 0.048 < 0.048 < I.Z < 0.24 < 0.29 < 190. < 190. < 6.48 < 0.48 < 0.05 Com2nonwealth of Fennsylvanla Lab CerzIflcarlon No. 36-037 AS Recel%_l*d _-'_'t of Quantl_aZ,%on 0.48 0.048 _.048 i.= 9.24 0.29 190. 190. _.48 0.48 0.05 Units ug.! u_/! u=/l ug.i uq/1 ug/i ug/! ug/l ug,'l ug/l ug/l D_lu_%on FaCtOr 1 i 1 1 1 1 1 1 ! 1 1 CAT NO. 00224 ,_C7.16 00-2_ _036_ 01504 01506 01505 00178 01856 00616 0081". Analye_.a :hlcrl_e Na_m 0rt.'.c-P._csphate Sul.;a_e as P t_itrate _trogen Fluor'-_e N1trlte Bro_tlae Nltroqen Pestic1_es/PCB'$ zn Her_c:des _n Water Water Wa_er Sample EK_rac= Herbzcide Water Sal_le Extract _.on Pest. Laboratory Met:hod EPA 300.0 EPA 365.3 EPA 300.0 EPA 300.0 EPA 300.0 EPA 300.0 E?A 300.0 EPA 608 SW-846 8151A SW-846 8151A EPA 608 Chronicle Am_IMs_a Tz_.a/| 1 DaCe _ 06/21/2001 1 06/21/2001 1 06/21/2001 1 06/21/2001 1 06/21/2001 1 06/21/2001 I 06/21/2001 1 06/21/2001 1 06/25/2001 i 06/22/2001 T_ i_:39 21:00 14:39 14:39 14:39 14:39 14:39 20:05 16:49 09:00 1 06/21/2001 09:45 An_ymt Hark A. Bucxwal_er Danxel S. smith Mark A. Buckwalter Hark Mark A. Buckwalter A. auckwalter Mark Mark A. Buckwalter A. Buckwalter Anita M. Dale Tiffany A. Ley_a Deborah M. Zl_erman Amanda E. Wade D._.u ,_o_ Fa=_z 5 1 5 5 5 5 5 1 I 1 I_1 E M B E _ L_llcastel' Laboratories, Irl& _25 _lew Hohanl= Pike Lancas:e. ;A 17_$-...-,_25 .PO Ii0_ _2425 Page 892 1 " I EXACT COI -PY--! B ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. BOx 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsh_m, PA 19044 Attn. D_-_ Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8197-00A Date sampled : 11/28/00 Time sampled : 1400 Date received: 11/28/00 Sampled by : EM Sample source: Formalation ,*_a7/oa L_bor_-_r_ I ANALYTICAL RESgLTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of s_mDling, meets the EPA and DEP drinking water st_-_vds for this parameter. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 < 0.1 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than 'rNTC - too numerous to count mg/l -milligram/liter PA DEP #09-332 (> 200) _,_,_____..%f_ Ma_'_nn E. Fedock/ President _. Page 893 _$/0 t _. ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. Box 319 C_, PA 18914 (215} 723-6466 INC. SAMPLE ANALYSIS REPORT Customer : Argus Research, Inc. 905 Sheehy Dr., Building A Hors_, PA 19044 Attn. D_n_ Lebo Attn: 215-443-8710 FAX # : 215-443-858 Sample source: Rm. 39 ixo.,,.. ,a/_7/00 ANALYTICAL Sample number: Date sampled : Time sampled : Date received: 8197-00B 11/28/00 1400 11/28/00 Sampled by : EM RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, che water supply, at the time of sa_ling, _ts standards for this parameter. the EPA and DEP drinking water MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <i <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) PA DEP #09-332 Ma_a_n''_'_-_-F'eEd.ock/ President Page 894 ' - .._.-..U.. 7-'_' _.___._: ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. Box 319 C_%LPORT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsh_m, PA 19044 Attn. D_-_ Lebo Attn: 215-443-8710 FAX # : 215-443-858 Sample number: 8197-00C Date Time Date sampled : 11/28/00 sampled : 1400 received: 11/28/00 Sampled by : EM Sample source: Rm. 15 '_ r/Oo ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, th_ water supply, at the time of sampling, standards for this parameter. meets the EPA and DEP drinking water MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <I <1 <1 < 0.I All results which are outside the "Maximum Contaminant Level" (MCL) establishec under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous mg/l -milligram/liter PA DEP #09-332 to count ( 200) _z,__-_//_ Mary_ E. Fedock/ President Page 895 t_ 7/_! .. 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 Horsh=m, PA 19044 Attn. D_-__ Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8197-00D Date Time Date sampled : 11/28/00 sampled : 1400 received: 11/28/00 Sampled by : EM Sample source : Jxr,_l ytical L_or_.'+'=.-_ J&/-_7/_ ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of s_ling, meets the EPA and DEP drinking water standards for tb_s parameter. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 < 0.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 mg/l - milligram/liter PA DEP #09-332 (> 200) ____J._/_ Maryami E. Fedock/ President Page 896 ! EXACf: ........ _//- 7//9._. ANALYTICAL LABORATORIES, P.O. Box 319 CWALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT ARGUS 418-020 Customer: Argus Research, Inc. 905 Sheehy Dr., Building A Horsh_m, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: Date sampled : Time sampled : Date received: Sampled by : 8331-00A 12/18/00 1315 12/18/00 EM Sample source: Analytical %-_Aor_ory _ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sa_ling, standards for this parameter. meets the EPA and DEP drinking water MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 < 0.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 mg/l - milligram/liter PA DEP #09-332 (> 200) _w__J_ _. 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 HorshRm, PA 19044 Attn. D_n_ Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8331-00B Date sampled : 12/18/00 Time sampled : 1315 Date received: 12/18/00 Sampled by : EM Sample source : Chem. Lab ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. 'Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <I <I <1 < 0.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/l - milligram/liter PA DEP #09-332 z"/"_"_/_/_;y_z_'--_z_-_/_ Maryan_. Fedock/ President Page 898 [_H "_/l_Z6.,-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., 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. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 < 0.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/l - milligram/liter PA DEP #09-332 /-t--_--_z/_/'__z_-_/_ Maryan_. Fedock/ President Page899 i LC.--"- _Oi_ 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., Building A Horsham, PA 19044 Attn. D_n_ Lebo Attn: 215-443-8710 FAX #: 215-443-858 Sample number: 8331-00D Date sampled : 12/18/00 Time sampled : 1315 Date received: 12/18/00 Sampled by : EM Sample source: Rm. 20 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sa_ling, meets the EPA and DEP drinking water standards for this parameter. MCL Resul_ Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 0.4 .. l_.Z._,- 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) PA DEP #09-332 Marya_. Fedockl President ARGUS 418-020 vLVa/'nmomcuaa/sdaytsLeoarenbceo.ratories Lancaster L,ltboratories SampXe No. WW 3842380 Collected:OX/26/2001 08:50 by EA Submitted: Repor=ed: 01/26/2001 02/06/01 Discard: 3/9/01 905 Analytical Lab Semi-Annual 16:00 at 05:22 Poin: #i AM Grab Water Sample Account Number: 02423 Pr_medica 57 Unxon worcesuer Argus Street HA 01608 905_ CAT No. 00224 00228 00358 01S04 01506 07322 01SOS 00178 An&lysLs Naae Chloride Sula_e Ni_ra_e Fluor lde Nxurogen NL=rlCt N_u.':gen Oruho-phosp_laue B_om_ de Pes_2c_des/PCB's _n waker 00453 00454 30455 O0469 00477 00435 OOG311 01902 01903 01904 _1905 01906 C!gC_ 01908 01909 01910 01911 _1912 01913 C1914 019!_ 01916 01_1_ _'-91| Dl)l_ Gamma BHC * L_nc_ne Mep_ac,_lor Aldrln Dleldr'-n Endrln DDT Endr_n Aldehyde Alpha IHC Beta BHC Del_a RHC Mepuacnlor pox_e DDE Z:_D Chlordane Toxapnene [ndosul,'an Endosulfan Endosul_an P_'B* 101G ,_ 2_ S_l_a_e PCS- 1221 _C_- 1232 _B- 1242 PL'B- 1248 _CB- I754 P-_B - 1260 CAS N_et 16187- 00-& 14808-79-8 14797-SS-8 16S84-48- e 14797-GS-0 14205-44-2 n.a. A8 Recexwod Result 2.0 5.0 0.50 0.S0 0.S0 S. 0 2.5 58-8)-9 7644-8 309-00-2 60o57-1 72-20- @ 50-29-3 7421-93-4 319*|4_ 319-08-7 219-85-8 1024-57-3 72-S5-9 72-54-8 57-74- 9 |001-38-2 959-98-8 33213-G$-9 i031*07-8 12_74- II-2 IiI04 28- _ II141- I&*S 53469-21- 9 12072-29*_ II097-5_* 1 II_95-_2-_ ;.0098 0.0098 0.0098 0.0090 0.009 :.@396 < C.098 00098 0.0098 0.0098 ( 0.00_8 0.009| 0.0098 0.29 .1.9 0.009% ( 0.0098 < 0.029 _ 1.3 1.0 _ 1.0 !.3 -.0 _ ".2 I.D As Received _XlUC of 0uan_k_aC_oD 2-0 5.0 0.$0 Q.SO 0.S0 5. D 2.5 0.0098 0.0098 0.0098 0.0095 0.0098 0.0098 0.098 0.0098 0.0098 0.0098 g.0098 0.0098 0. D098 0.29 3.9 _.0098 0.0098 0.02g 1.0 1.0 1.0 1.0 1.0 1.0 l._ Unito mg/! mg/1 mg/1 mg/1 mg/l rag/1 mg/l ug/1 ug/1 ug/l ug/l ug/1 ug/l ug/l ug/l ug/l u_/l _g/1 uS1 ug/l ug/1 ug/1 ug/1 ugll ugll ug/l ug/l ug/l ug/l ug/l ug/l "_g/l Paslof2 DAlucA_ Factor 5 5 5 5 S 5 S 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l 1 1 1 1 1 1 1 1 i L_irlcilstffr l,SOoratDr_s, Irl[ ......,o,.w_,.iExAo_TooPl Lancaster. PL 17_05-142S 717.SSS-2J00 F3x: 717-656-_tJI1 2216 R_'. _111_0 Page 90I ARGUS 418-020 - VLVahennmucaa/_saLsteOaer,b'o_-reatories Lanc:ail:.e: Collected: LaboEito:iee 01/26/2001 Sample 08 :S0 No. WW by EA 3542350 Submitted: 01/26/2001 16:00 Reported: Discard: 02/06/01 3/9/01 at 05-22 905 Analytical Semi -Annual T=h Point #I AM Grab Water Sample Account Number: 02423 Primedica 57 Union Worcester Argus Street MA 01608 Pqp: 2 of 2 90SAP CAT No. OXOSG Am&lylJm Name HeElD_C_dtl _n water 015S7 01858 0528G 05287 05288 05289 05290 05291 05292 05293 08103 2,4-D 2,4,5-TP 2.4,5-T Dalapon D_oseb n J.cambl MCPF HCPA 2,4-DP 2,4-DB (Dichlorprop) Pentachlorophenol LS lh_beE 94-75-7 9)-72-i g3-?i;- S 75-99-0 811-85-7 1918-00-9 93-65-2 94- 74-G 120-36-5 94-82-G 87- 88- S AS Re=ewed Itomu_Lt < 0.48 < 0.048 < 0.048 1.2 < 0.24 ( 0.29 < 190. < 190. < 0.48 < 0.48 < 0.05 Co_luonwealth of Pennsylvania Lab Certification No. 3G-037 As Itece_ed LLa/t of _?.ltatton 0.48 0.048 0.048 1.2 0.24 0.29 190. 190. 0.48 0.48 0.0S DD_Ltm ug/l ug/l ug/1 ug/l ug/1 ug/1 _g/1 ug/l ug/l ug/l ug/1 Dilution Psc_or 1 1 1 1 1 1 1 1 1 1 1 / M E M B ER LancasterLal:ormne_ inc. 2425New*.w_a_l_e PA 17105-2425 7174S6-2300 Far 7174JS&.2J11 Page 902 i I EXAC_TCOPY 221S ll_. 9/11100 ARGUS 418-020 Anal/sis Repo "" LancasatLseoarenbcoe ratories Lancamcer LaboraCoriem Sample No. WW 35423S1 Collecced:01/26/2001 08:40 by EA SIQ_miCued: 01/26/2001 16000 Reported: Discard: Q2/06/01 3/9/01 a_ 05-22 AM 905 Formulation Lab Point #2 Grab Sem_ -Annual Wa_er Sample Account Number: 02423 Primedica ST Unlon Worcester Argus ScreeC MA 01608 905-2 CAT No. 00224 00221 00268 01S04 0ZS0& 07322 01505 A_&lymis Chlorxde $ul_ace N'--" NLurace Fluor_de N1c.-ogen N1_:l_e Nicrogen Crcho-p_ospl_lLce Bromide O01?i _s_icl_es/PCB's In Wiutr 00453 004S4 O04SS 0046_ 0047" 004?| 00631 01902 O1_O3 31904 3190S 01_0; 01937 0190_ _190% 01910 _!_11 :1912 01913 01914 _191S ;191S 01917 01919 _I_I_ Gaf_m& IHC - L_nd&ne Hepuachlor Al_rln _el_r_n Ert_=l_ =:T Endr_n AldehYde Alpha BHC Beua BHC D_lUa _MC H_pUa:_lo: :D_ _DD Epoxl_e Chlordane T=xaphene _:_:sulfan _ [n_osulfan Endosulfan I; $_ifa:e P,-'B-IOI& ;_-1221 P_3-1232 _03-1242 _-124_ _-'3-I_4 _-I_ CAS Number IG||?-00-G 14808-79-8 14797-SS-8 i&98448o8 14797-6S-0 14265-44-2 n.a. Am Received Result 2.0 S.0 < 0.$0 0.50 0.50 5.0 _.S 58-8%-9 7_-44-8 309-00-2 6053-! 72-208 50-29*3 7421-93-4 31_-84"E 319-85-? _I_-|6-_ 1_4-_7*3 72-S_-9 72-54-8 $7-74-9 8001-3S-2 9S9-91-i 33213-GS-9 I031-0_-1 126_4-II-2 11104-29-2 11141-16-_ S_469-21-9 i_72-2_*_ 2109T-69-I II09_-_'_ C.0096 0.0096 c O._09& ;.3096 0.00_6 3._096 0.396 0.009_ O.OO%& 0.0096 0.00%6 < 0.0096 0.009_ 0.29 3.1 0.009E :.:09S =.029 I.C 1.3 I._ 1.3 1.3 i._ 1.5 All Re=e_ved Lmit of Q'umnckCac_on 2.0 S.0 0.So 0.50 0.$0 S.O 2.5 0.0096 3.0096 0.0096 0.0096 0.0096 0.0096 _.096 0.0096 O.OO96 0.009_ 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 Units mg/1 mg/l mg/l mg/l _/I mg/l mcj/_ ug/l ug/l ug/l ug/l ug/l ug/l u_/l ug/1 ug/l u_/L u_/1 ug/1 ug/l ug/l ug/1 ug/l ug/1 ug/l ug/l ug/l ug/l ug/l ug/_ ug/l _/i PageI of 2 DLluc,am ractoE S 5 5 S S 5 S 1 1 1 1 i 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 .. 1 1 1 ,_.t_.e,_,oo,mo.,...-,c. Page 903 --_//_,,/_ / 9/11_ '-"/ - ARGUS 418-020 Analysis Repo LancastLer :x a ries _l r w__/sasmr_ Zdnc:astmr Collec_ed: Laboratories 01/26/2001 Sample 08:40 Ho. WW by EA 3S423S1 Su_minted: 01/26/2001 16:00 Reported: Discard: 02/06/01 3/9/01 at 05:22 AM 905 Formulation Lab Poinu #2 Grab Semi-Annual Water Sample Accoun_ Number: 02423 Primedica 57 Union Worcester Argus S_ree_ MA 01608 l_g 2 of 2 905-2 CAT No. O18SG ,t,._alyoAx Name Herbicides _n _&_er 0185_ 011S8 05280 05287 05288 05289 05290 05291 05292 05293 08103 2.4-D 2,4.S*TP 2.4.S-T Dalapon D_noseD DICiI_DI MC'PP HCPA 2.4-DP (DIchlor_rop) 2,4-DB Penuachlor:pnenol _ Number Am Recoiwed Reault 94-75-7 93-72-i 93-76-S 75-99-0 08-05-7 191|-00-9 92-65-2 94-?4-6 120-30-S 94-82-6 87-8&-5 < 0.48 0.048 < 0.048 1.2 0.24 < 0.29 190. ( 190. 048 0.48 o.0S Commonveal_h of Pennsylvanxa Lab Cer:ificatlon No. 26-03_ AS RecaAved L.u_Lt of QuantA:atA=a 0.48 0.048 0.048 1.2 0.24 @.29 190. 190. 0.41 0.48 0.0S _A_s ug/l ug/l ug/l ug/l ug/l ug/l ug/l ug/l ugll ug/l ug/l DAlutAcm Fat:o: 1 1 1 1 1 1 1 1 1 1 1 MEMBER 242S I_w w,olta_cl P,ke Lancamer.I_ 1710S-2425 717-IS6.2]00 Faa: 7174_-21181 Page 904 i EXACT COPY I /_/ 2216 Ile_. S111/00 ANALYTICAL LABORATORIES, P.O. E_x 319 c_raT.WONT, PA 18914 (215} 723-6466 INC. ARGUS 418-020 S_LE A_IALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A HorshRm, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: Date Time Date sampled : sampled : received: Sampled by : 2018-01A 01/03/01 1430 01/03/01 EM Sample source : Chem-Lab ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. T_erefore, the water supply, at the time of sa_ling, meets the EPA and DEP drinking water standards for this parameter. Lmlm_/mx MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <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 mg/l - milligram/liter PA DEP #09-332 (> 200) ____j_ Maryafn% E. Fedock/ President Page 905 [ _/_ 7//_.Z_oI i .... ARGUS 418-020 ANALYTICAL I_ORATOR_ES, P.O. BOX 319 CHALPONT, PA 18914 (215} 723-6466 INC. SAMPLR ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: Date sampled : Time sampled : Date received: Sampled by : 2018-01B 01/03/01 1430 01/03/01 EM Sample source: '/zlo Rm. 38 7 ANALYTI CAL 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. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 I.i '/el,,, 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/l - milligram/liter PA DEP #09-332 _________ Marya_ E. Fedock/ President Page 906 / _q._'a.l_tT/?__C. _ i::- ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. Box 319 C_rAT.WONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsh_m, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: Date Time Date sampled : sampled : received: Sampled by : 2018-01C 01/03/01 1430 01/03/01 EM Sample source : Analytical I,,, [-.aJ_orn._-I or_ 7 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of s_mDling, stam_a_ds for this parameter. meets the EPA and DEP drinking water Parameter MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 < 0.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 mTgN/TlC- mtiololingurmaemr/oluister to count PA DEP #09-332 (> 200) __ __/_7__ Mary_nn E. Fedock/ President Page 907 I C,-:i.i. _../ ANALYTICAL LABORATORIES, P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT ARGUS 418-020 Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Borsh_m, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample source: Vv/o, Rm. 14 ANALYTICAL Sample number: 2018-01D Date Time Date sampled : 01/03/01 sampled : 1430 received: 01/03/01 Sampled by : EM RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sa_ling, standards for this parameter. meets the EPA and DEP drinking water amams/_x MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 0.6 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 mg/1 too numerous - milligramliter PA DEP #09-332 _o count (> 200) _ ___._W_'__ fl Hat,ann E. _ Fedock/ President Pag9O8 ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. Box 319 C_%LFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsh_m, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: 2337-01A Date Time Date sampled : 02/14/01 sampled : 1515 received: 02/14/01 Sampled by : EM Sample source : Chem. Lab r _ D_ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of s_mpling, meets the EPA and DEP drinking water standards for this parameter. MCL Resul_ Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <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 mg/l TNTC PA DEP milligram/liter too numerous to #09-332 count (> 200) ____ Maryann __ j_,_ . E. Fedock/ President Page 909 I X,tt i ,'GC.-.. ANALYTICAL LABORATORIES, P.O. BOx 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT ARGUS 418-020 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 _J f) b _ ,.3,_,,.,%/.3,, v,. z_/.,o/_, ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of samDling, meets the EPA and DEP drinking water standards for this parameter. Ea_ama_ax MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/1 <1 <1 <1 0.5 / All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to count (> 200) mg/l - milligram/liter PA DEP #09-332 _-,---_----_/-_o_"_2"2'_z_w_-_&_. Maryan_ E. Fedock/ President Page910 [ /_ ]P "7/[_-/.'_- [- "." .. ANALYTICAL LABORATORIES, P.O. BOx 319 Cw_ONT, PA 18914 (215) 723-6466 INC. ARGUS e 4 ! 8-020 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsh_m, 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 _- _O_J ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the tim of sampling, meets the EPA and DEP drinking water standards for this parameter. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <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/l - milligram/liter PA DEP #09-332 _._4_J________ Mary_nn E. Fedock/ President Page 911 .... ANALYTICAL LABORATORIES, P.0. BOX 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE ANALYSIS REPORT ARGUS 418-020 Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. D_n_ 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 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the waner supply, at the time of sam_ling, meets the EPA and DEP drinking water standards for this parameter. MCL Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <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/l - milligram/liter PA DEP #09-332 ___ Sary_nn _. _ _sident Page 912 L i zx I_# 7/(_ i .... ARGUS 418-020 A.-%Ia_YTICAL IdklBOI_'I'OI_L_, INC. P.O. Box 319 _, PA 18914 (215) 723-6466 SAMPLE % Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. D_n Lebo Attn: 215-443-8710 FAX #: ANALYSIS REPORT Sample number: Date sampled : Time sampled : Date received: Sampled by : 4135-01A 03/07/01 1430 03/08/01 FO Sample source: Room #39 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sa_ling, standards for this paramener. meets the EPAandDEP drinking water MCL _esuZt Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 0.6 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbolkey: < - less than TNTC - too numerous to count mg/l - milligram/liter PA DEP #09-332 (> 200) ,,,fj_____,_./___/ j EXACT u_py, 1 Page 9 ] 3 ! . ARGUS 418-020 ANALYTICAL LABORATORIES, P:O. BOx 319 CHALPONT, PA 18914 (215) 723-6466 INC. S_/_PLE AMALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsh_m, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: 4135-01B Date Time Date sampled : 03/07/01 sampled : 1430 received: 03/08/01 Sampled by : FO Sample source : Chem. Lab _- ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sampling, meets the EPA and DEP drinking water standards for this parameter. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 < 0.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 mg/I milli gram/lit er PA DEP #09-332 (> 200) _-_---_--_-J-_-_--<_Y_--__''/_ Marya/_n E. Fedock/ President Page 914 _i ARGUS 418-020 ANALYTICAL LABORATORIES, INC. P.O. BQX 319 c;rAT._ONT, PA 18914 (215) 723-6466 SAMPLE ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsh_m, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: Date Time Date sampled : sampled : received: Sampled by : 4135-01C 03/07/01 1430 03/08/01 FO Sample source: Analytical _-_or_r_r_J _7/_/0i I ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the waner supply, at the time of sampling, standards for this parameter. meets the EPA and DEP drinking water armma_ MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <i <1 <1 < 0.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 TmNgT/Cl- - mtiololingurmaemr/oluister to count PA DEP #09-332 (> 200) _/__o_w Maryann __/_ .___ E. Fedock/ President Page 915 0 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: 4135-01D 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 sa_ling, meets the EPA and DEP drinking water standards for this parameter. MCL Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/I/'-D <i <1 <1 1.5 All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (*_). Symbol key: < - less than TNTC - too numerous to count (> 200) mPgA/lDEP- m#i0l9l-i3g3r2am/liter M____E._ Fedock/ President Page 916 " ?lll _f .. ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. BOX 319 CHALFONT, PA 18914 (215) 723-6466 INC. SAMPLE A_YSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsham, PA 19044 Attn. Dena Lebo Attn: 215-443-8710 FAX #: Sample number: Date sampled : Time sampled : Date received: Sampled by : 4266-01A 04/02/01 1400 04/02/01 FO Sample source : Analytical ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of samDling , meets the EPA and DEP drinking water standards for this parameter. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <I <1 <1 < 0.I All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol < - TNTC - mg/l key: less than too numerous PA DEP #09-332 to count (> 200) .f Maryann E. Fedock/ President ! 7/'Z/o' ,_ ., -_-.-. I XAC C,,.:,. Page917 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 : 4266-01B Date Time Date sampled : 04/02/01 sampled : 1400 received: 04/02/01 "Sampled by : F0 Sample source: Rm. 16 Rack 027 ANALYTICAL RESULTS Water Safety Classification: No Coliform bacteria were detected. Therefore, the water supply, at the time of sa_ling, meets the EPA and DEP drinking water standards for this parameter. MCL Result Coliform Bacteria, counts/100 ml Noncoliform Bacteria, cou/%ts/100 ml Total Chlorine, mg/l <1 <1 <1 0.6 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/l milligram/liter PA DEP #09-332 ___J_ Ma_Cann E. Fedock/ President Page 918 _| +t_-j[__,-i__,:_'.: , %.,%.q' .:....i ?!_n.fo,_; ARGUS 418-020 ANALYTICAL LABORATORIES, P.O. Box 319 C_,_ONT, PA 18914 (215) 723-6466 INC. SAMPLR ANALYSIS REPORT Customer: Argus Research, Inc. 905 Sheehy Dr., Bldg. A Horsh_m, 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. axama_ MCL Resul_ Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l <1 <1 <1 0.3 q- - 9-,o/ All results which are outside the "Maximum Contaminant Level" (MCL) established under the "Safe Drinking Water Act" are marked by asterisks (**). Symbol key: < - less than TNTC - too numerous to mg/l - milligram/liter PA DEP #09-332 count (> 200) ___ d Mary_n z_/_7 E. Fedock/ President l:3age919 EXACT CCr /! "" 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 source : PoLmulations Sample number: 4266-01]) Date Time Date sampled : 04/02/01 sampled : 1400 received: 04/02/01 Sampled by - F0 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. ___ Coliform Bacteria, counts/100 ml Noncoliform Bacteria, counts/100 ml Total Chlorine, mg/l MCL <1 Result <1 <1 < 0.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 mg/l milligram/liter PA DEP #09-332 (> 200) _____/_ M_yann E. Fedock/ President -- Page 920 ARGUS 418-020 l i-an er ratories Wtx_rec_ta//ty/assc/ence Lancaster Laboratories Sample No. GS Collec_ed:01/26/2001 09:S0 by EA Submi_ued: 01/26/2001 16:00 ReporTed: 02/06/01 au 05:22 AM Discard: 3/9/01 Bedding: Lot # MJI600 Sample 3542353 Account Nkunber: 02423 Primedica 57 Union Worcesuer Argus Sgreeg MA 01608 Page I of 2 CAT No. 00159 01646 01649 01651 01655 01666 0693S 06936 01224 Ju_al_a_a Nale Mercury Barlum Cadmlum Chrc_nl u_ Lead SAlver AEsenlc _ Selenium TR Peauicides/PC3s An solids CJLS Number 7439-97-6 7440-39-3 7440-43-9 7440-472 7439-92-i 7440-22-; 7440-32 7782-49-2 AS Received ReaU.lt < 0.096 < 9.9 < 2.0 4.D 9.9 2.0 0.99 1.2 _ AS Recai_d LilLit of QuangkEat;on 0.096 9.9 2.0 4.0 9.9 2.0 0.99 0.99 Unig8 mg/kg n_J/ kg mg/kg mg/_g mg/kg mg/k= m_/K_ mg/k_ D1ucxon Factor 1 1 1 1 1 1 1 I 01218 01219 01220 01221 01222 01223 01859 01981 01982 01983 01984 01985 01986 01987 01988 31989 01990 01991 01992 :1993 31994 31995 01996 01997 _199_ Gan_a BHC - Lindane Hep_achlo-- A1 d."ln DDT DAeldrln Endrln Hethox.v. chlor Alpha BH_ Beta BHC De1_a BH_ Hep_achlor Epoxide DDE DDD Chlordane Toxaphene Endoaulfan "- --ndosul-aan --_ Endosu!Zan Sulfate --ndrln Al_ehvde .=CB- 1016 ?CB- 122! P_B- 1232 P_B- 1242 P_" 1248 PC'B* 1254 __:__._._,...-,.-, .... _...... 58-89-9 76-44-8 309-00-2 50-29-3 60-57-i 72-20-8 72-43- _ 319-84-6 319-85-7 318-86-8 I024-57-3 72-55- 9 72-54-8 $7-74-8 8001-35-2 959-98-8 33213-65-9 I031-07-8 7421-93-4 12674-11-2 11104-28-2 11141-16-5 53469"21"9 12672- 29-6 II097-69-1 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. !7. 17. 17. < 17. 17. __r_-,_._ _; , _ _::},'_ _ 0.33 0.33 0.33 0.67 0.67 0.67 3.3 0.33 0.33 0.33 0.33 0.67 0.67 17. 33. 0.33 0.67 0.67 0.67 17. 17. 17. 17. 17. 17. ug/kg 1 ug/kg 1 ug/kg 1 Ug/kg 1 ug/kg 1 ug/kg 1 ug/kg 1 ug/_g I ug/kg 1 ug/k_ 1 ug/kg 1 ug/k_ 1 ug/k_ 1 ug/kg 1 ug/kg 1 ug/kg 1 ug/kg 1 ug/kg 1 ug/kg 1 ug/kg I ug/kg 1 ug/k_ 1 ug/kg I ug/kg 1 ug/kg ! / -_/_ ;_.:/.... _._ ._ _-i_,.... _-_.:_3_/J'=L .......... ,',1 --- .81 _t *a .":1 _._= _zew _ollane _lte " kqa_.J - -_r _. _t**_ _.,_/_, 7t7-i._-:301} ._,_x:."_.7-_$6-;_;_ _AoCT COPY /,r/ol J Page 921 2215 ,_sv. 'YlliO0 ARGUS 418-020 ii LWhaerneqcuaa//rsnytaeL_ernacbe. oratories Lau,,caster LaJDorat'.o_ies Sample No. GS Collected:01/26/2001 09:50 by EA Submigted: 01/26/2001 Reported: 02/06/01 at Discard: 3/9/01 Bedding: Lot # HJI600 16:00 05:22 AM Sample 3542353 Account Number: 02423 Primedica 57 Urxlon Worcester A_gus S_reeu HA 01608 Pag_ 2 of 2 CAT No. 01999 01863 04174 04176 Analysis PCB-1260 Namm Appendlx IX Herblclde/ 2,4-D 2.4.5-TP in soil CAS Number 11096-82-5 %4-75-7 %3-72-1 As leceived Result ( 17. c 17. < 1.7 Am Rece_wed Llatc of Qua.nccacion 17, 17. 1.7 Units ug/kg DLluCLaa. Paccor 1 ug/kg 1 ug/kg 1 l EXA..CTCOPY M EM B E R IJmCaS_ Lab_atones, Inc. 2425NlwHo_landP_ IJncasmr, IDA1710S-142S P?lOr7I4oKz-23102042S F4x: 7'174U-2UI Page 922 221i RoY. 9111/00 ARGUS 418-020 Explanation of Symbols and Abbreviations The following defines common symbols and abDreviabons used in reporbng tecnntcadlata. N.D. TNTC lU nhosicm C C..11 meq g ug ml m3 none detected Too Numerous To Count International Units micromhoslcm degrees Celsius (diet) calories milliequNalents gram(s) microgram(s) milliliter(s) cubic meter(s) BMQL MPN CP Units NTU F lb. kg rng I ul fib > um/ml Below Mimmum Quantitation Level Most Probable Number cobalt-chloropiatinate units nephelomemc tumidity units degrees Fahrenl_eit pound(s) kilogram(s) milligram(s) liter(s) microliter(s) fibers greater than 5 microns in length per ml < > ppm ppb Dry weight basis less than - The number following the sign is the limitof auantitation, the smallest amount of analyte which can be reliably determined using this specific tesL greater than parts per million - One ppm is equivalent to one milligram per kilogram (mg/kg), or one gram per million grams. For aqueous liquids, ppm is usually taken to De equivalent to milligrams per liter (mgll), because one liter of water has a weight very close to a kilogram, For gases or vapors, one ppm is equivalent to one microliter of gas per liter of gas. parts per billion Results pnnteq under this heading have been adjusted for moisture content. This increases the analyte weight concentration to approximate the value present in a similar sample without moisture. U.S. EPA data qualifiers: Organic Qualifiers A B C D E J N p U X,Y,Z TIC is a possible aldol-condensation product Analyte was also detected in the blank Pesticide result confirmed by GCIMS Compound quantitateq on a diluted sample Concantmtion exceeds the calibration range of the instrument Estimated value Presumptive evidence of a compound (TICs only) Concentration clffference between primary confirmation columns >25% Compound was not detected Defined in case narrative Inorganic Qualifiers B Value is <CRDL but >IDL E Estimated due to interference M Duplicate injection precision not mat N Spike sample not within control limits S Method of standarcl additions (MSA) used for calculation U Compound was not detected W Post digestion spike out of conti'ol limits " Duplicate analysis not within control limits + Correlation coefficient for MSA <0.995 Tests results relate only to the sample tested. Clients should be aware that a critical step in a chemical or microbiological analysis is the collection of the sample. Unless the sample analyzed is truly representative of the bulk of material involved, the test results will be meaningless. If you have questions regarding the proper techniques of collecting samples, please contact us. We cannot be held responsible for sample integrity, however, unless sampling has been performed by a member of our staff. This report shall not be reproduced except in full, without the written approval of the laboratory. WARRANTYAND MMITS OF LIABILITY - In acceptinganalyticalwork, we warrantthe accuracyof test resultsfor the sample as submitted.THE FOREGOING EXPRESS WARRANTY IS EXCLUSIVE AND IS GIVEN IN LIEU OF ALLOTHER WARRANTIES, EXPRESSED OR IMPLIED. WE DISCLAIM ANY OTHER WARRANTIES. EXPRESSED OR IMPLIED, INCLUDING A WARRANTY OF FITNESS FOR PARTICULAR PURPOSE AND WARRANTY OF MERCHANTABILITY. IN NO EVENT SHALLLANCASTER LABORATORIESBE LIABLEFOR INDIRECT, SPECIAL CONSEQUENTIAL. OR INCIDENTAL DAMAGES INCLUDING, BUT NOT '""TED TO, DAMAGESFOR LOSS OF PROFIT OR GOODWILL REGARDLESS OF (A) THE NEGLIGENCE (EITHER SOLE OR CURRENT) OF LANCASTERLABORATORIESAND (B) WHETHER LANCASTERLABORATORIES HAS BEEN INFORMED OF THE POSSIBILITYOF SUCH DAMAGES. We accept no legalresponsibilityforthe purposesfor whichthe clientusesthe test results. No purchaseorderor other_ for workshill be acceptedby LancasterLaboratorieswhich inc_ucleasny condibonlthat varyfrom the StandardTerms and Conditionsof LancasterLaboratoriesandwe hereby objecttOany conflicbngterms containedin any acceptanceor ordersubmittedbycJlent. Page 923 .'/," ARGUS 418-020 APPENDIX K HISTOPATHOLOGY REPORT Page 924 ARGUS 418-020 RESEARCH PATHOLOGY SERVICES, INC. 438 EastButlerAvenue,NewBritain,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. Ray Brown, D.V.M., Ph.D. Veterinary Pathologist March 25, 2002 Page 925 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LI'I-I-ER PER GENERATION) REPRODUCTIOIq OF AMMONIUM PERFLUOROOCTANOATE PROTOCOL 418-020 (AFPO) SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS TABLE OF CONTENTS REPORT Paqe Method ....................................................................................................................... 1 Results ....................................................................................................................... 3 Summary .................................................................................................................... 6 Quality Assurance Unit Statement ............................................................................. 8 TABLES 1. Incidence and Degree of Severity of Histomorphologic Observations P Generation ................................................................................................... 9 2. Incidence and Degree of Severity of Histomorphologic Observations - P Generation Reduced Fertility Animals ........................................................ 13 3. Incidence and Degree of Severity of Histomorphologic Observations F1 Generation ................................................................................................ 16 4. Incidence and Degree of Severity of Histomorphologic Observations F1 Generation Reduced Fertility Animals ...................................................... 22 APPENDICES I. Histomorphologic Observations - P Generation ....................................... I-1 to 1-18 Key to Histomorphologic Observations ............................................................... I-1 Tables I-1. I-2. I-3. I-4. I-5. I-6. I-7. I-8. I-9. 1-10. Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Observations Observations Observations Observations Observations Observations Observations Observations Observations Observations - Group I Male Rats ............................... I-2 - Group II Male Rats .............................. I-4 - Group III Male Rats ............................. I-6 - Group IV Male Rats ............................. I-8 - Group V Male Rats ............................ 1-10 - Group I Female Rats ......................... 1-12 - Group II Female Rats ........................ 1-14 - Group III Female Rats ....................... 1-15 - Group IV Female Rats ...................... 1-16 - Group V Female Rats ................... :...I-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: "1"-6889.6 HISTOPATHOLOGY REPORT TABLE OF CONTENTS (Continued) Page I1. Histomorphologic Observations-F1 Generation ..................................... I1-1to 11-20 Key to Histomorphologic Observations .................................................... -.........I1-1 Tables I1-1. 11-2. 11-3. 11-4. 11-5. 11-6. 11-7. 11-8. 11-9. 11-10. Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic Histomorphologic ObservationsObservationsObservations Observations Observations Observations ObservationsObservationsObservations Observations - Group I Male Rats .............................. 11-2 Group II Male Rats ............................. 11-4 Group III Male Rats ............................ 11-6 Grou_ IV Male Rats............................ 11-8 Grou _ V Male Rats ........................... I1-11 Grou_ I Female Rats ........................ 11-14 Grou_ II Female Rats ....................... 11-16 Grou_ III Female Rats ...................... 11-17 Grou _ IV Female Rats ..................... 11-18 Grou _V Female Rats ...................... 11-19 III. Individual Animal Gross and Histomorphology Data P Generation .................................................................................. II1-1to 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 - Fland F2 Pups ................................................................... V-1 .o Page 927 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE (AFPO) PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS METHOD: Microscopic examination was made of the specified tissues from .male and female CrI: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. Numberof Rats Group perSexper Generation Dosage (mg/kg/day) Concentration (mg/mL) DVoolsuamgee (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 substancewas considered100% pure for the purposeof 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 PathologyServices,Inc. -1 Page 928 o 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, epididymis, prostate, seminal vesicles and coagulating gland (male rats) or ovaries, oviducts, uterus, cervix and vagina (female rats). In addition, the reproductive tissues were examined from male and female rats of the P generation and male rats of the F1 generation suspected of reduced fertility. 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 Research for archiving. Research Pathology Services, Inc. -2 . Page 929 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITI'ER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE PROTOCOL 418-020 (AFPO) SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS RESULTS: The type, incidence, and degree of severity of all histomorphologic observations in the P and F1 generation adult rats are summarized in Tables 1 and 3, respectively. Tables 2 and 4 summarize the histomorphologic observations in the rats suspected of reduced fertility in the P and F1 generations, respectively. Individual microscopic findings from the P and F1 generation adult rats are presented in tabular form in Appendices I and II, respectively. A key to the individual microscopic observations precedes Table I-1 and Table I1-1. The gross necropsy observations, microscopic findings, and a correlation of the gross and microscopic changes, when applicable, are included in Appendices III and IV for the P and F1 generation parental adult rats, respectively. Macroscopic observations and corresponding microscopic findings in the tissues with grossly observed changes for the F1 and F2 pups are listed in Appendix V. P Generation Adult Rats (Tables 1 and 2, I-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 examination (Table 1). The change in the adrenal glands consisted of increased thickness and prominence of the zona glomerulosa due to cytoplasmic hypertrophy and vacuolation of the cells of this zone of the adrenal cortex. A similar adrenal effect 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 ResearchPathology Services,Inc. -3 . Page 930 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITI'ER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE (AFPO) PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS Appendix I as "SSRF". The type, incidence and degree of severity of these findings are summarized in Table 2. There were a few changes observed in these "reduced fertility" rats, but these changes occurred sporadically and are of the type that occur spontaneously in male and female rats of this age and strain (Table 2) and were not compound-related. All other microscopic changes observed in the male and female rats designated for microscopic evaluation were considered to have occurred spontaneously and to be unrelated to treatment. The type, incidence, or severity of these spontaneously occurring changes was not influenced by administration of the test substance. In general, these changes occurred at single, low, or similar frequencies among the control and compound-treatment groups. These changes are listed and summarized in the attached histomorphology tables. F1 Generation Adult Rats (Tables 3 and 4, I1-1to I1-10, 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 substance. examination that had been given 30 mglkglday of the test Microscopic examination of the adrenal glands revealed a treatment-related effect similar to that seen in the P generation male rats, consisting of an increased thickness and prominence of the zona glomerulosa due to cytoplasmic hypertrophy and vacuolation of cells of this zone of the adrenal cortex in 7/10 high dose male rats of the F1 generation (Table 3). This adrenal gland change 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 Iobules were enlarged due to an increased dense, Research Pathology Services, Inc. -4 .o Page 93 l ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LI3-FER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE PROTOCOL 418-020 (AFPO) SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS 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 male reproductive tissues were typical of those that occur spontaneously and their type, incidence or severity was not affected by administration of the test substance. None of the changes that were observed in these male rats were of sufficient degree to have resulted in reproductive insufficiency. These rats are identified in the individual tables of microscopic findings 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. -5 .. Page 932 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE (AFPO) PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS 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 generation pups of an oral (gavage) two-generation (one litter per generation) reproduction study of ammonium perfluorooctanoate (APFO). The concentrations used in the study were 0 (vehicle control), 1, 3, 10, or 30 mg/kg/day of the test substance. No treatment-related microscopic changes were observed in the reproductive organs of any of the male or female rats of the P and F1 generations designated for microscopic examination that were given any of the 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 F1 generation male rats exposed to 30 mg/kg/day of APFO. This change was characterized by hypertrophy and vacuolation of cells of the zona glomerulosa of the adrenal cortex. A similar effect in the adrenal glands was not observed in male rats of the lower dosage groups or in female rats of the 30 mg/kg/day dosage group of either generation. Microscopic examination of liver sections of F1 generation male rats which were observed grossly to be enlarged or have tan areas in the liver lobes showed up to marked diffuse hepatocellular hypertrophy. Single or lower incidences of hepatocellular necrosis also were observed in the male rats rats of these groups. There were a few male and female rats in each of the P and F1 generations that were classified 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 PathologyServices, Inc. -6 Page 933 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE PROTOCOL 418-020 (AFPO) SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS 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. -7 Page 934 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE (AFPO) PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS QUALITY ASSURANCE UNIT STATEMENT All aspectsof the tissue processing,microscopicslide preparation,histopathologicevaluationand report preparationfor the study listed above have been performed according to the Standard OperatingProceduresof ResearchPathologyServices,Inc. and were auditedin accordancewith the proceduresestablished by the Quality Assurance Unit of ResearchPathology Services, Inc. in compliancewith the GoodLaboratoryPracticeregulationsspecifiedin the protocol. QualityAssuranceinspectionswere performedas shownbelow. Therewereno deviationsfromthe protocol,Standard OperatingProceduresand/or appropriateGood LaboratoryPractice regulations notedduringthe conductof the studythat had any impacton studyintegrity. A summaryreportof QA inspectionswas submittedto theStudyDirectoron March25,2002. Datesof Inspection Study Phase 10125101,01115102 1110710011,/18/02 1111710112,/27/010,1/22/02 Trimming Embedding Microtomy 11/19/011,2/28/01,01/23/02 Staining 01/02/02 01/03/02 01/24/02 01/24/02 01128102 01/31/02 02/01102 03125102 Histopathology DataEntry DataVerification DataProcessing ReporPt reparation Pre-SubmissioAnudit DraftReport FinalReport DateReported to Management 10131101,01131102 11130101,01/31/02 11/30/011,2/31/01, 01/31/02 11/30/011,2/31/01, 01/31/02 01/31/02 01/31/02 01/31/02 01/31102 01131102 01131102 02/01102 03125102 DateReported toStudyDirector 09114101,02/01102 02/01/02 02/01102 02/01102 02/01/02 02/01102 02/01/02 11/01/010,2/01/02 11/02/01,02/01102 02/01102 02/01102 03125102 Research Pathology Services, Inc. K_ren W. Harkins, BS Quality Assurance Unit Page 935 Date =8 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 TABLE1 Incidence and Degree of Severity of Histomorphologic Observations P Generation Dose Group: Sex: Numberof Animals/6roup: ADRENAL6LANDS: NO. EXAMINED NO. NORMAL I II III IV V H 14 14 M M _3 15 _3 13 15 10 10 10 10 10 7 8 6 7 2 I II llI IV V F F F F F 13 4 3 4 13 10 0 0 0 10 8 0 0 0 9 -degeneration, cystic, cortex minimal [O1 [O] [0] [0] [O1 0 O O 0 0 [1] [O] [0] [0] [1] I 0 0 0 I -hypertrophy/vacuoaltion, zona glomorulosa minimal mild moderate [0] [0] [O] [2] [7] O0 0 2 1 O0 0 0 2 0 0 0 0 4 [Z] [0] [0] [0] [0] 1 0 0 0 0 O0 O O0 0 0 0 0 0 -vacuol ation, minimal mild moderate cortex PITUITARY: NO. EXAMINED NO. NORMAL -cyst(s). pars intermedia TESTIS: NO. EXAMINED NO. NORMAL [3] [2] [4] [1] [3] 1 2 2 1 3 2 O I 0 0 0 0 1 0 0 10 O O O 10 10 0 0 0 10 0 O0 0 O 13 4 2 2 15 12 3 2 1 13 [0] [0] [0] [0] [0] 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10 0 0 0 i0 9 0 0 0 10 1 0 0 0 0 -atrophy/degeneration, moderate marked multi focal -dilatation. rete testis -hypopl asi a, di ffuse marked EPIDIDYMIS: NO. EXAMINED NO. NORMAL [1] [O] [O] [O] [2] 1 O0 0 1 0 0 0 0 1 O1 0 1 1 [0] [1] [0] [1] [0] 0 1 0 1 0 13 4 2 2 14 I0 O 1 I 10 -atrophy minimal mild moderate [O] [1] [0] [1] [1] 0 I O 0 O 0 0 0 I 0 0 O 0 0 I -exfol i ated spermatogenic cell s minimal mild moderate [0] [1] [1] [0] [2] 0 OOO i 0 I 0 O O 0 O1 0 i = Total incidenceof specifiedlesion, all grades. -9 Page 936 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1 (Continued) Incidence and Degree of Severity of Histomorphologic Observations P Generation Dose Group: Sex: Numberof Animals/Group: EPIDIDYMIS (Continued) : I II III IV V M M M M M 13 ]5 1_ 13 15 I II F F 13 4 III IV V F F F 3 4 13 -hypospermia mild marked [0] [1] [1] [1] [2] 0 0 1 0 0 O1 0 1 2 -infiltration, minimal mild mononuclear-ce] 1, focal [3] [3] [O] [1] [2] 3 2 0 1 2 O1 0 0 O PROSTATE: NO. EXAMINED NO. NORMAL 13 3 2 1 14 4 1 Z 0 6 -atrophy,focal minimal mild [3] [0] [O] [0] [2] 2 O0 0 1 1 0 O 0 1 -dilatation, minimal mild moderate glandular, focal [2] [0] [O] [0] [2] 0 0 O O I I 0 0 0 I I O 0 0 0 -inflammation,chronic minimal mild [S] [2] [O] [i] [4] 3 I 0 0 2 Z I 0 i 2 -inflammation,suppurative,focal minimal mild SEMINAL VESICLES: NO. EXAMINED NO. NORMAL COAGULATINGGLAND: NO. EXAMINED NO. NORMAL OVARI ES: NO. EXAMINED NO. NORMAL [2] [0] [0] [0] [I] I 0 0 0 I I 0 0 0 0 13 3 2 1 14 13 3 2 1 14 13 3 2 1 14 13 3 2 1 14 11 2 I 0 ii 8 2 I 0 10 -cyst(s), intraovarian -cystic bursa(e) 2 0 0 O I I 0 0 0 0 OVIDUCT(S): NO. EXAMINED NO. NORMAL 10 2 1 0 11 10 2 I O 11 UTERUS: NO. EXAMINED NO. NORMAL 11 2 I 0 11 I 1 1 0 0 [ 1 = Total incidenceof specifiedlesion, all grades. -10 . Page 937 ARGUS 418-020 ORAL(GAVAfE) TWO-6ENERATIO(NONELITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 " SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1 (Continued) Incidence and Degree of Severity of Histomorphologic Observations P Generation Dose 6roup: Sex: Numberof Animals/Group: UTERUS(Continued): -distention, minimal mild moderate marked lumen -gland(s), endometrial, cystic -macrophages, pigmented minimal mild moderate marked CERVIX: NO. EXAMINED NO. NORMAL I II III IV V MMMMM ]3 ]) 13 13 15 I II F F 13 4 III IV V F F F 3 4 13 [1] [1] [O] [O] [3] 0 O OO1 1 0 OO1 0 0 0 O1 O1 0 0 O O 0 0 0 1 [10] [0] tO] [O] [10] 2 O0 0 1 I OO O 2 7 O0 0 6 0 0 0 0 I ii 2 I 0 I0 11 2 i O 9 -dilatation moderate VAGI NA: NO. EXAMINED NO. NORMAL tO] tO] [0] [O] [I] O O O O 1 I0 2 1 O I0 8 2 1 0 IO -mucification mild moderate [2] [0] [O] [O] [O] I 0 0 O 0 I 0 0 0 0 OVARIAN FOLLICLES/CORPORALUTEA: -absenceof corpora lutea -presenceof corpora lutea -presenceof growing/antralfollicles 0 0 0 0 I II 2 i 0 I0 II 2 I 0 ii EAR(S): NO. EXAMINED NO. NORMAL 0 2 O I 0 OO0 O O 2 1 1 3 2 O O O O O -chondropathy,auricular mild moderate marked EXTREMITIES: NO. EXAMINED NO. NORMAL -fracture [0] [2] tO] [1] tO] 0 OO0 O 0 2 0 i 0 0 0 0 O 0 0 0 0 O0 0 0 0 0 0 0 0 0 0 0 [2] [1] [I] [3] [2] O O O I O I 0 0 I i i I I I I 0 1 0 0 0 0 0 O 0 0 0 I 0 0 0 [ ] = Total incidence of specified lesion, all grades. -11 Page 938 ARGUS 418-020 ORAL(6AVA6E) TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1 (Continued) Incidence and Degree of Severity of Htstomorphologic Observations P Generation Dose Oroup: Sex: Numberof Animals/Group: EYES: NO. EXAMINED NO. NORMAL -cataract I II Ill IV V MM M M M 13 IS :[3 13 1S OO 0 0 0 0 O 0 0 O O0 0 0 0 I II Ill IV V F F F F F 13 4 3 4 13 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 -keratitis, chronic moderate KIDNEYS: NO. EXAMINED NO. NORMAL [O] [O] [0] [0] [0] O0 0 O0 0 1 2 1 2 0 0 O0 1 [0] [0] [1] .[0] [0] 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 -di l atati on, minimal mild moderate pel vi s [O] [1] [2] [11 1"1] 0 1 1 I 0 O0 0 0 1 0 0 i OO [O] 1"0] [O] [0] 1"0] 0 0 0 0 0 0 0 0 0 O 0 0 0 0 0 -hyperplasia, pelvic/papi11ary epi thel i urn, focal mild [O] 1"0] 1"0] [1] [0] 0 0 0 I 0 [0] [0] 1"0] 1"0] [0] 0 0 0 0 0 LUNG: NO. EXAMINED NO. NORMAL 1 0 0 0 0 0 O0 0 0 0 0 0 0 0 0 0 0 0 0 -hemorrhage,multi focal moderate [1] 1"0] 1"0] [0] [0] I 0 0 O 0 1"0] 1"0] [0] [0] [0] 0 0 0 0 0 -inflammation.interstitial,multifocal [1] 1"0] [0] 1"0] 1"0] moderate 1 O D 0 0 [0] [0] [0] 1"0] 1"0] 0 0 D D 0 PALATE: NO. EXAMINED NO. NORMAL -fracture 0 0 O O 0 0 O0 0 0 0 0 O0 0 1 0 0 0 0 0 0 O0 0 1 0 0 0 0 -hemorrhage marked 1"0] 1"0] 1"0] 1"0] [0] 0 O O 0 0 [1] [0] [0] [0] [0] 1 0 0 0 0 [ ] = Total incidence of specified lesion, all grades. -12 Page 939 ARGUS 418-020 ORAL(6AVAGE)TWO-6ENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLLIOROOCTANO(APTFEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE2 Incidence and Degree of Severity of Histomorphologic Observations - Reduced Fertility P 6enerati on Animals Dose Group: Sex: Numberof Animals/Group: ADRENALGLAND:S NO. EXAMINED NO. NORMAL I II III IV V M MM M M 3 3 _ _ 4 O O 1 O O OO1 0 O I II III IV V F F F F F 1 2 1 1 1 0 OO0 O 0 0 0 OO TESTIS: NO. EXAMINED NO. NORMAL 3 3 2 1 4 2 3 2 1 3 -atrophy/degenerati on, multlfocal moderate [1] [O] [O] [O] [1] 1 O0 O1 -dilatation. rete testis EPIDIDYMIS: NO. EXAMINED NO. NORMAL OOO0 1 3 3 2 1 4 3 Oi i 2 -atrophy moderate [O] [O] [O] [O] [I] O 0 0 0 I -exfol iated minimal mild moderate spermatogeni c cel 1s [O] [1] [1] [O] [2] O O O O I O i O 0 O O O 1 O I -hypospermi a mild marked [O] [O] [1] O 0 ! O O O [O] [Z] OO 0 2 -infiltration, minimal miId mononuclear-cell, focal [O] [2] [0] [O] [O] O 1 0 O O O I O 0 O PROSTATE: NO. EXAMINED NO. NORMAL 3 3 2 1 4 O 1 2 O3 -atrophy, focal minimal mild [3] [0] [O] [0] [I] 2 0 0 0 I I 0 0 0 0 -inflammation, minimal mild chronic SEMINALVESICLES: NO. EXAMINED NO. NORMAL COAGULATINGGLAND: NO. EXAMINED NO. NORMAL [1] [2] [O] Ell FO] 1 1 0 O0 O I O I O 3 3 2 1 4 3 3 2 1 4 3 3 2 1 4 3 3 2 1 4 [ ] = Total incidence of specified lesion, all grades. -13 Page 940 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE2 (Continued) Incidenceand Degree of Severityof HistomorphologicObservations- Reduced FertilityAnimals P 6enerati on Dose Group: Sex: Number of Animals/Group: DVARIES: NO. EXAMINED NO. NORMAL I II III IV V M M M M M 3 _ _ I 4 I II 11I IV V F F F F F I 2 I I I 1 2 1 'O 1 O 2 I O O -cyst(s), intraovarian I O O 0 I OVIDUCT(S): NO. EXAMINED NO. NORMAL UT[RU_: NO. EXAMINED NO. NORMAL I 2 I "O I 1 2 I O I 1 Z I O I I I I O O -di stentl on, 1umen moderate marked CERVIX: NO. EXAMINED NO. NORMAL VAGINA: NO. EXAMINED NO. NORMAL [0] [1] [O] [0] [1] 0 O O O I O I O O O 1 2 1 O I I 2 I O i I 2 1 O I O 2 1 O I -muclfication m%1d [1] [O] [O] [0] [0] 1 0 O O O OVARIAN FOLLICLES/CORPORALUTEA: -absenceof corpora lutea -presenceof corpora lutea O O O O 1 1 2 1 0 0 -presence of growing/antralfollicles I 2 1 O 1 EAR(S): NO. EXAMINED NO. NORMAL O I O O O O O O O O O O I O O O O O O O -chondropathy,auricular moderate marked [O] [I] [O] [O] [0] O I O O O 0 O O O O [O] [O] [I] [0] [0] O O O O O O O I O O KIDNEYS: NO. EXAMINED NO. NORMAL O 1 O0 2 0 0 0 0 1 OO 0 0 0 0 0 0 0 0 "_ = Total incidenceof specifiedlesion,all grades. -14 . Page 941 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE2 (Continued) Incidence and Degree of Severity of Hi stomorphologic Observations - Reduced Fertil ity Animals P Generation Dose 6roup: Sex: Nmnb_r of Animals/Group: KIDNEYS (Continued) : -dt 1atati on, pel vi s minimal mild I II III IV V MMMMM 3 3 _ 1 4 [0] [1] [O] [0] [1] O I O 0 O 0 0 0 0 I I II III IV V F F F F F I 2 1 1 1 [0] [0] [O] [O] [0] 0 0 0 0 0 0 0 0 0 0 [ ] = Total incidence of specified lesion, all grades. -15 .. Page 942 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE3 Incidence and Degree of Severity of Htstomorphologic Observations F1 Beneratton Dose Group: Sex: Numberof Animals/Group: ADRENALGLAND:S NO. EXAMINED NO. NORMAL I II III IV V MMMMM ;7 _ _ _6 _5 10 lO 10 10 9 6 6 9 8 2 I II F F 12 5 III IV V F F F 1 1 11 10 O 0 0 I0 10 0 O O9 -hyperplasia,cortical, focal minimal [O] [O] [O] [O] [0] 0 0 0 0 0 [O] [O] [O] [0] [i] 0 0 0 0 I -hypertrophy/vacuoaltion, zone glomerulosa minimal mild [O] [O] [0] [O] [7] 0 0 0 0 3 0 0 0 0 4 [O] [O] [O] [0] [O] 0 0 0 0 0 0 0 0 0 0 -vacuolation,cortex minimal LIVER: NO. EXAMINED NO. NORMAL [4] [4] [I] [2] [2] 4 4 I 2 2 0 O 6 9 10 0 O 0 0 O [0] [0] [0] [0] [0] 0 0 0 0 0 0 1 O 0 O O 0 0 O 0 -hematopoiesi s, extramedul 1ary, multlfocal minimal [0] [0] [i] [I] [I] O O I 1 1 [0] [0] [0] [0] [0] 0 O O O 0 -hypertrophy,hepatocellular, diffuse [0] [O] [6] [9] [101 mild 0 0 2 3 3 moderate marked O O 4 6 6 O O 0 0 1 [O] [0] [O] [0] [0] 0 0 O 0 O 0 O O 0 0 O 0 0 0 O -infarct,liver lobe O 0 O O O 0 1 O 0 O -inflammation,chronic, focal/multifocal[Ol [O] [2] [2] [i] minimal O O 1 I 1 mild 0 0 I 1 0 [01 [0] [O] [0] [O] 0 0 0 0 0 0 0 0 0 0 -necrosi s, focal/mul t i focal minimal mild [01 [O] [1] O O O 0 O 1 [31 [2] 1 O 2 2 [01 [0] [0] [01 [01 O 0 O 0 O 0 0 0 0 0 -necrosi s, si ngl e-cel 1 minimal [0] [0] [O] [1] [O] 0 O 0 I 0 [01 [O] [O] [(2)] [0] 0 0 0 0 0 TESTIS: NO. EXAMINED NO. NORMAL 12 3 2 2 I0 ii 3 ) 2 iO -atrophy/degeneratoin, multifocal minimal [I] [0] [0] [0] [0] I O 0 0 0 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 12 3 2 2 I0 I0 3 2 2 7 [ ] = Total incidenceof specifiedlesion, all grades. -16 Page 943 ARGUS 418-020 ORAL(GAVAfiE)TWO-GENERATIO(ONNE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE3 (Continued) Incidence and Degree of Severity of Hlstomorphologic Observations F1 6enerett on Dose Group: Sex: Numberof Animals/Group: I II III IV V MMMMM |7 |_ |9 _6 _5 EPIDXDYMIS(Continued) : -infiltration, minimal mononuclear-cell, focal [2] [0] [O] [0] [3] 2 O0 0 3 I II F F 1_ S III IV V F F F _ 1 11 PROSTAET: NO. EXAMINED NO. NORMAL 12 3 2 2 10 10 2 1 1 7 -atrophy. focal minimal mild [0] [0] [O] [I] [I] 0 0 O 1 0 0 0 0 0 i -dilatation,glandular,focal mild [I] [0] [0] [O] [0] I 0 0 0 0 -inflammation.chronic minimal mild [2] [I] [I] [0] [I] I i 0 0 I I 0 I 0 0 -inflamnation,suppurative minimal SEMINALVESICLES: NO. EXAMINED NO. NORMAL COAGULATINGGLAND: NO. EXAMINED NO. NORMAL OVARI ES: NO. EXAMINED NO. NORMAL [0] [0] [0] [0] [I] 0 0 0 0 I 12 3 2 2 i0 12 3 2 2 10 12 3 2 2 I0 12 3 2 2 10 10 0 0 0 10 10 0 0 0 9 -cyst(s), intraovarian UTERUS: NO. EXAMINED NO. NORMAL 0 O 0 O i 10 0 0 0 10 2 0 0 0 0 -distention, minimal mild moderate lumen [2] [0] [0] [0] [2] 1 0 O O 0 1 0 O O 0 0 O 0 0 2 [_ - Total incidence of specified lesion, all grades. -17 . Page 944 ARGUS 418-020 ORAL (GAVAGE)TWO-BENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLLIOROOCTANDAT(EAFPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -688g.6 TABLE3 (Continued) Incidenceand Degree of Severityof HistomorphologicObservations F1 Generation Dose Group: Sex: Number of Animals/Group: I II IIl IV V M M M M M _7 |3 _9 26 _5 I II Ill IV V F F F F F 12 5 I I 11 UTERUS (Continued:) -macrophages,pigmented minimal mild moderate marked [7] [O] [O] [O] [IO] O O D O 1 I 0 O O i 4 O 0 0 7 2 0 0 0 I CERVIX: NO. EXAMINED NO. NORMAL I0 0 0 0 I0 I0 0 0 0 I0 VAGINA: NO. EXAMINED NO. NORMAL i0 O 0 0 IO 6 OO O7 -inflammation,chronic, focal minimal [1] [O] [0] [0] [0] I 0 0 O 0 -mucification minimal mild moderate [4] [O] [0] [0] [3] 2 O 0 O O I 0 O O i I O O O 2 OVARIAN FOLLICLES/'CORPORLAUTEA: -presenceof corpora lutea 10 0 0 0 10 -presence of growing/antra]follicles PITUITARY: NO. EXAMINED NO. NORMAL 10 0 0 0 8 10 O O 0 6 10 O 0 0 10 10 O O 0 10 10 0 0 O9 -cyst(s), pars distalis 0 0 0 O 1 0 0 O0 1 -cyst(s), pars intermedia CECUM: NO. EXAMINED NO. NORMAL 0 0 0 0 1 0 0 0 I O 0 0 0 0 0 0 O 0 0 O 0 0 O 0 0 O 0 O O 0 -distention marked [0] [O] [0] [I] [0] O 0 0 1 O [O] [O] [0] [0] [O] 0 0 O O O -edema/i nfl ammation, submucosa mild COLON: NO. EXAMINED NO. NORMAL [0] [0] [0] [1] [0] 0 O 0 I 0 0 0 O I 0 0 OO0 O [0] [0] [0] [O] [0] 0 0 0 0 0 0 0 O 0 0 0 0 O0 0 [ ] = Total incidenceof specifiedlesion,all grades. -18 . Page 945 .... ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERfiENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE3 (Continued) Incidence and Degree of Severity of Histomorphologic Observations F1 Generation Dose Group: Sex: Numberof Animals/Group: I II III IV V M M M M M 17 1_ ]9 _ 25 I II F F 12 5 III IV V F F F 1 l 11 COLON(Continued): -di stent i on marked [0] [O] [O] [1] [0] O 0 0 I O [0] [O] [0] [O] [0] 0 O 0 O 0 EAR(S): NO. EXAMINED NO. NORMAL 0 O0 1 0 0 OO0 0 3 O0 0 1 0 0 0 O O -chondropathy, auricular moderate marked EYeS: NO. EXAMINED NO. NORMAL -abscess, periocular [0] [0] [0] [1] [0] 0 O0 0 O 0 0 0 i 0 4 0 0 0 2 I 0 0 O 2 O0 O0 0 [3] [0] [0] [0] [1] 1 0 OOO Z 0 0 0 1 0 O 0 1 0 0 O 0 0 0 OOO 1 0 -atrophy, i ri s/ci 1i ary body marked [1] [O] [O] [O] [0] i 0 0 0 0 [0] [0] [O] [O] [0] 0 0 O0 O -atrophy, retinal, mlld focal [1] [0] [0] [0] [O] I O O O O [O] [O] [0] [0] [O] O 0 O O O -inflammation, chronic, iris moderate [2] [O] [0] [0] [0] Z 0 OOO [0] [O] [0] [0] [0] O 0 0 0 0 -neuropathy, optic nerve(s) moderate [2] [O] [0] [0] [O] Z 0 0 O0 ILEUM: NO. EXAMINED NO. NORMAL 0 0 0 I O 0 0 0 0 0 -Advanced autolysis precludes evaluation 0 O0 1 0 [0] [O] [0] [O] [O] 0 0 0 OO 0 I 0 0 0 0 0 0 0 0 0 0 0 O0 -distention marked KIDNEYS: NO. EXAMINED NO. NORMAL [O] [0] [O] [0] [O] 0 0 0 O 0 0 0 0 3 0 0 O0 O0 [0] [I] [0] [0] [0] O 1 O 0 0 O 0 1 0 1 O0 0 0 O -dilatation, mild moderate pelvis [0] [0] [0] [3] [O] O O O Z 0 O O O I O [0] [0] [i] [0] [i] 0 0 1 0 0 O 0 0 0 i -hyperplasia, pelvic/papilIary urothelium minimal [0] [0] [0] [I] [O] O0 0 1 0 [O] [0] [O] [O] [0] 0 0 0 0 0 [ ] = Total incidence of specified lesion, all grades. -19 Page 946 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE3 (Continued) Incidence and Degree of Severity of Histomorphologic Observations F1 6enerati on Dose Group: Sex: Numbre of Animals/Grouo: KIDNEYS (Continued) : I II Ill IV V MMMMM ]7 |3 )9 76 _S I II F F 12 5 Ill IV V F F F 1 1 11 -mineralization, pelvis minimal [0] [0] [0] [I] [0] 0 0 0 I 0 [0] [0] [0] [0] [0] 0 0 0 0 0 -pyelonephrltis moderate [0] [0] [0] [0] [0] 0 0 0 0 0 [0] [0] [0] [0] [I] 0 0 O .0 I SKIN (GROSS LESION): NO. EXAMINED NO. NORMAL 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 O 0 0 0 0 -demati tls, chronic moderate [0] [0] [i] [0] [0] 0 0 I 0 0 [0] [0] [0] [0] [O] 0 0 0 0 0 -dermatitis, ulcerative moderate SPLEEN: NO. EXAMINED NO. NORMAL [I] [0] [I] EO] [0] I 0 i 0 0 0 0 0 1 1 0 0 O 0 0 [0] 60] [0] [0] [0] 0 0 0 0 0 1 0 0 O0 0 0 O0 0 -atrophy marked [0] [0] [0] [0] [1] 0 0 0 O 1 [1] [0] [0] [0] [0] 1 0 0 0 0 -necrosi s marked STOMACH: NO. EXAMINED NO. NORHAL [0] [0] [0] [1] [0] 0 0 0 t 0 0 O0 I 0 0 0 0 0 0 [0] [0] [0] J'O] [0] 0 0 0 0 O 0 i 0 0 0 0 0 0 0 0 -erosion{s), minimal mild glandularmucosa [0] [0] [0] [1] [0] 0 0 0 1 0 0 0 0 0 0 [0] [1] [0] [0] [0] 0 0 0 0 0 0 1 0 0 0 -peritonitis, focal minimal [0] [0] [0] [i] [0] 0 0 0 I O [0] [0] [0] [0] [0] 0 0 0 0 0 -ulcer{s),glandular area moderate [0] [0] [O] [I] [0] 0 0 0 I 0 [0] [0] [0] [0] [0] 0 0 0 0 0 TAIL: NO. EXAMINED NO. NORMAL 0 0 0 I 3 0 0 O 0 ? 0 3 0 0 I 0 I 0 0 0 -abscess 0 0 0 I 0 0 0 0 0 0 -constriction,focal 0 0 0 0 I 0 0 0 0 0 [ ] = Total incidence of specified lesion, all grades. -ZO .o Page 947 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLLIOROOCTANO(AFTPEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE3 (Continued) Incidence and Degree of Severity of Histomorphologic Observations F1 6eneration Dose 6roup: Sex: Numberof Animals/Group: TAIL (Continued): -hyperpl asi a/hyperkeratosi s moderate I lI III MMM lL7 13 lg IV V MM _6 25 [0] [O] [O] [1] [0] O0 0 1 0 I II F F 12 5 III IV V F F F 1 1 11 [O] [0] [0] [0] [O] 0 0 0 0 0 -inflammation,chronic minimal mild [0] [O] [0] [O] [O] O 0 0 O 0 0 0 0 0 O [O] [I] [O] [O] [I] O I O O O 0 0 0 "0 I -necrosi s, focal mild THYMU:S NO. EXAMINED NO. NORMAL 60] [O] [O] [0] [O] OOOOO O0 O1 O 0 0 0 0 0 [O] [1] [O] [0] [1] O 1 O O 1 0 0 0 0 0 0 OO0 0 -atrophy marked [0] [O] [O] [i] [O] 0 0 0 I O [O] [0] [O] [O] [O] 0 O 0 0 0 URETER: NO. EXAMINED NO. NORMAL OO0 OO OOO0 O 0 O O O 1 O O O O O -di stent i on marked [Ol [0] [0] [0] [0] 0 0 0 OO [0] [0] [0] [0] [1] 0 O 0 0 1 -hyperpl asia, mucosa moderate [O] [O] [O] [O] [O] OOOO0 [O] [O] [0] O0 O [O] [1] O 1 -inflammation, chronic mild URINARY BLADDER: NO. EXAMINED NO. NORMAL [O] [0] [O] [O] [O] 0 O 0 0 0 0 0 0 0 0 0 0 O0 O [O] [0] [O] [0] [I] 0 0 0 0 I 0 0 0 0 I 0 0 O0 O -cystltls, hyperplastic marked [0] [O] [O] [O] [O] 0 O O O 0 [O] [0] [O] [0] [I] 0 O O O 1 ] = Total incidenceof specifiedlesion,all grades. -21 Page 948 .... .. ,. ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER 6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE4 Incidenceand Degree of Severityof Histomorphoolgic Observations- Reduced FertiIity Animals F1 6eneratlon Dose Group: Sex: Number of Animals/Group: ADRENAL BLANDS: NO. EXAMINED NO. NORMAL TESTIS: NO. EXAMINED NO. NORMAL EPIDIDYMIS: NO. EXAMINED NO. NORMAL I II Ill IV V M M M M M 2 3 2 2 i D O 0 I 0 O D O 1 0 2 3 2 2 1 2 3 2 2 i 2 3 2 2 I 2 3 2 2 O -infiltration,mononuclear-ce11,focal minimal PROSTATE: NO. EXAMINED NO. NORMAL [0] [0] [0] [O] [i] O 0 O O 1 2 3 2 2 I 2 2 1 1 1 -atrophy, focal minimal [O] [0] [O] [I] [0] O 0 0 I O -inflammation,chronic minimal mild S_MINA_ VESICLES: NO. EXAMINED NO. NORMAL COAGULATINGGLAND: NO. EXAMINED NO. NORMAL [0] [1] [1] [0] [O] 0 I 0 O O O O I 0 0 2 3 2 2 1 2 3 2 2 1 2 3 2 2 1 2 3 2 2 1 [ ] = Total incidenceof specifiedlesion, all grades. -ZZ Page 949 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTIOI9 STUDY OF AMMONIUM PERFLUOROOCTANOATE IN RATS (AFPO) 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 = SD = SM = SSRF = Sacrifice-Scheduled Spontaneous Death Sacrifice-Moribund Scheduled (Reduced Fertility) I-1 Page 951 ARGUS 418-020 ORAL(6AVA6E) I'_IO-6ENERATION(ONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHMONIUHPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-1 Histamorphologic Observations P Generation Dose Group: Animal Number: Sex: Death Type: ADRENAL GLANDS: -vacuolation,cortex PITUITARY: 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 .... - - 2 TESTIS: -atrophy/degenerationm,ultifocal EPIDIDYMIS: -infiltration,mononuclear-ce11,focal PROSTATE: -atrophy, focal -dilatation,glandular, focal -inflammation,chronic -inflammation,suppurative,focal SEMINALVESICLES: COAGULATINGGLAND: - 3 - - - : 1 - - - - 2 I 1 - - 1 i - 3 2 - 1 - - ...... LUNG: -hemorrhage,multifocal <3> -inflammation,interstitial,multifocal <3> I-Z Page 952 ARGUS 418-020 ORAL(_kVAGE) TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-1 (Continued) Histomorphologic Observations P 6eneration Dose 6roup: Animal N_er: Sex: Death Tvoe: ADRENAL GLANDS: -vacuolation,cortex PITUITARY: I 13616 M SS I 13621 M SS I 13622 M SS I 13624 M SS I 13625 M $S I 13626 M SS - - I 2 TESTIS: EPIDIDYMIS: -infiltration, mononuclear-cell, focal PROSTATE: -dilatation, glandular, focal -inflammation, chronic -inflammation. suppurative, focal SEMINALVESICLES: COAGULATINGLAND: 1 1 - 2 - - 2 1 - - 2 - ...... ...... EAR(S): <*> I-3 .. Page 953 ARGUS 418-020 ORAL(GAVA6E)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-2 Htstomorphologt Observations P Generation Dose 6roup: Animal Number: Sex: Oeath Type: ADRENAL6LANDS: -vacuolation, cortex TESTIS: -dilatation, -hypoplasia, rate testis diffuse EPIDIDYMIS: -atrophy -exfollated spermatogenic cells -hypospermia -infiltration,mononucleer-cell,focal PROSTATE: -inflammation,chronic SEMINALVESICLES: II 13632 M $S II 13636 M $S II 13638 M SSRF 11 13639 M SSRF II 13642 M SS II 13644 M SS II 13645 M SS II 13646 M SS - - 1 <P> - - <4> - <1> - 2 <4> - <1> 1 Z COAGULATINGBLAND: EAR(S): -chondropathy, auricular KIDNEYS: -dilatation,pelvis <3> <1> I-4 Page 954 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 TABLE1-2 (Continued) Htstomorphologtc Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: II 13650 M SSRF 11 13651 M SS II 13652 M SS II 13653 M SS II 13654 M SS 1I 13655 M SS II 13656 M SS ADRENALGLANDS: -vacuolation, cortex TESTIS: 1 - EPIDIDYMIS: -infiltration,mononuclear-cell, focal 2 PROSTATE: -inflmtlon. chronic i SEMINALVESICLES: COAGULATINGLAND: EAR(S): -chondropathy, auricular <3> I-5 Page 955 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-3 Histomorphologic Observations P Generation Dose Group: Animal N_ber: Sex: Death Tvoe: III 13661 M SS Ill 13662 M SSRF III 13668 M SS Ill 13670 M SS Ill 13671 M SS Ill 13672 M SS III 13673 M SS ADRENAL GLANDS: -vacuolation,cortex I - TESTIS: EPIDIDYMIS: PROSTATE: SEMINAL VESICLES: COAGULATINGGLAND: KIDNEYS: -dilatation, pelvis <3> <1> I-6 .. Page 956 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOFN4HONIUHPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1-3 (Continued) Hi stomorphologiC Observat ions P GeneratI on Dose Group: Animal Number: Sex: Death Type: ADRENAL6LANDS: -vacuolation, cortex III 13674 M SSRF III 13675 M SS Ill 13676 M SS III 13682 N SS III 13683 M SS III 13684 M SS 2 - 1 3 - T_STt_: EPIDIOYMIS: -exfoliated spe_atogenic cells 3 -hypospermia 2 PROSTATe; SEMINAL VESICLES: COAGULATINGGLAND: I-7 .. Page 957 ARGUS 418-020 ORAL(GAVAGE)TI_-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOFANNONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-4 Hlstumorphologlc Observations P 6eneratton Dose Group: Animal Number: Sex: peath Type: 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 13705 M SS ADRENAL GLANDS: -vacuolation,cortex .... I TESTIS: -dilatation,rete testis -hypoplasia,diffuse - <P> - <4> EPIDIDYMIS: -atrophy -hypospermia -infiltration,mononuclear-cell,focal - <2> - <4> - <1> pROSTATE: -inflammation,chronic 2 SEMINAL VESICLES: COAGULATINGGLAND: I-8 Page 958 .. ARGUS 418-020 ORAL(C_VAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL 418-020 SPONSOR'SSTUDY NUMBER: T-B88g.6 TABLE I-4 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Nm_ber: Sex: Death T)(pe: ADRENAL GLANDS: -hypertrophy/vacuolationz,ona glomerulosa _AR(S): -chondropathy,auricular KIDNEYS: -dilatation,pelvis -hyperplasla, pelvlc/papillaryepithelium,focal IV 13708 M $S IV 13710 M SS IV 13711 M SS IV 13716 M SS IV 13717 M SS IV 13719 M SS - 1 I - <3> <1> <2> I-9 .. Page 959 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-5 Histomorphologtc Observations P Generation Dose Group: Animal Number: Sex: Death Type: ADRENAL GLANDS: -hypertrophy/vacuolationz,ona glomerulosa -vacuolation,cortex 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 i 3 3 2 - - I - i PITUITARY: - - - TESTIS: -atrophy/degenerationm,ultifocal .... <4> EPIDIDYMIS: -atrophy -exfoliated spermatogenic cells -hypospermia -infiltration. mononuclear-cell, focal PROSTATE: -dilatation,glandular,focal -inflammation,chronic -inflammation,suppurative,focal SEMINAL VESICLES: - - - - - - 1 1 - 2 2 - I - 2 .... ..... <3> <1> 4 - - - - - - - I COAGULATINGGLAND: ...... KIDNEYS: -dilatation,pelvis <-> <2> 1-10 Page 960 ARGUS 418-020 ORAL (RAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1-5 (Continued) Histomorphologic Observations P Generation Dose Group: Animal N_meber: Sex: Death Type: ADRENAL GLANDS: -hypertrophy/vacuolation, -vacuolation, cortex zona glomerulosa V 13735 M SS V 13736 M ss V 13741 M _SRF V 13742 M SS V 13743 M SS V 13744 M SS V 13750 M SSRF - 3 - 2 3 - 1 - - P_TUITARY: TESTIS: -atrophy/degenerationm,ultifocal -dilatation,rete testis - - - - <3> - - <-> - <P> - - - <-> EPIDIDYMIS: -exfoliated spermatogentc cells -hypospermia PROSTATE: -atrophy, focal -inflammation,chronic (3> .... <4> .... 2 ..... 1 I - - 1 - - _MINAL VESICLES: ...... COAGULATINGGLAND: ...... Page 961 .. I-II ARGUS 418-020 ORAL(6AVA6E) TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI-6 Histomorpho]ogtc Observations P 6eneratton Dose Group: Animal Number: Sex: Death Type: ADRENALGLANDS: PITUITARY: -cyst(s), pars intermedia 1 1380Z 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 P - - - OVARIES: -cyst(s), intraovarian OVIDUCT(S): UTERUS: -distention,lumen -macrophages, pigmented CERVIX: - - P - - - - - * - Z .... 3 3 - 3 3 .... VAGINA: -mucification 3 Z OVARIAN FOLLICLES/CORPORALUTEA: -presenceof corpora lutea -presence of growing/antralfollicles P P P P P P P P P P EAR(S): -chondropathy, PALATE: -fracture -hemorrhage auricular <3> <P> <4> . Page 962 1-12 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHHON[UHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 TABLEI-6 (Continued) Histomorpho|ogtc Observations P 6eneretlon Dose 6roup: Animal NBaber: Sex: De_th Type: ADRENAL6LANDS: -degeneration, cystic, cortex -hypertrophy/vacuolation. zone glomerulosa PITUITARY: I 13816 F SS I 13821 F SS I 13822 F SM I 13824 F SS I 13825 F SS I 13826 F SS 1 - - - 1 - - , intraovarien -cysticbursa(e) OVIDUCT(S): UTERUS: -macrophages, pigmented CERVIX: VAGINA: OVARIANFOLLICLES/CORPORLAUTEA: -presence of corpora ]utea -presence of growing/antral follicles _AR(S): -chondropathy, auricular P - - - P - - 1 2 3 3 3 1 ...... ...... P P P P P P P P P P P P <4> 1-13 .. Page 963 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUDROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1-7 Dose Group: Animal N_ber: Sex: Death Typ@: DVARIES: Hi stomorl_hool gtc Observattons P 6eneration II 13836 F SM II 13840 F SSRF II 13851 F SSRF II 13856 F SS OVIDUCT(S): UTERUS: -distention, lumen CERVIX: VAGINA: OVARIANFOLLICLES/CORPORLAUTEA: -presenceof corpora lutea -presenceof growing/antralfollicles EAR(S): -chondropathy,auricular EXTREMITIES: -fracture 4 P P <P> - P P <4> 1-14 Page 964 ARGUS 418-020 Dose Group: Animal Number: Sex: Death T_roe: OVARIES: ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOFAHHONILINPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 TABLE1-8 Hi stamorphologtc Observattons P Generation III 1386Z F SSRF III 13869 F SS Ill 13885 F SS OVIDUCT(S): UTERUS: CERVIX: VAGINA: OVARIAN FOLLICLES/CORPORALUTEA: -presence of corpora ]utea -presence of growing/antralfollicles EAR(S): -chondropathy.auricular EYES: -cataract -keratitis, chronic KIDNEYS: P P <4> <P> <3> ,*> 1-15 ._ Page 965 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 TABLEI-9 HistamorphologJc Observations P Generation Dose Group: Animal Number: Sex: Death Twe: IV 13898 F SS IV 13900 F SSRF IV 13901 F SS IV 13908 F SS OVARIES: * OVIDUCT(S): UTERUS: * CERVIX: * VAGINA: * OVARIAN FOLLICLES/CORPORALUTEA: * EAR(S): -chondropathy,auricular <4> <3> <2> .. Page 966 1-16 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 TABLE1-10 Histomrphologic Observations P Generation Dose Group: Animal N_nber: Sex: Death Twe: ADRENAL GLANDS: -degeneration,cystic, cortex PITUITARY: V 13921 F S$ V 13922 F _$ V 13927 F ss V 13928 F SS V 13929 F SSRF V 13933 F SS V 13934 F SS I - - OVARIES: -cyst(s), intraovarian P - - OVIDUCT(S): ..... UTERUS: -distention,lumen -gland(s),endometrial,cystic -macrophages,pigmented CERVIX: - - 3 3 - 2 3 - - - - P - 2 - 2 3 * - - - VAGINA: - - * - - - OVARIAN FOLLICLES/CORPORALUTEA: -absenceof corpora lutea -presenceof corpora lutea -presenceof growing/antralfollicles - - P P P P - P - P - P P P P P P EAR(S): -chondropathy,auricular <4> 1-17 Page 967 ARGUS 418-020 Dose Group: Animal N_nber: Sex: Death Type: ADRENLA GLANDS: PITUITARY: OVARIES: ORAL(GAVAGE)Tld3-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-0Z0 SPONSORSTUDYNUMBERT: -6889.6 TABLE1-10 (Continued) Histomorphologic Observations P Generation V 13935 F SS V 13936 F SS V 13942 F SS V 13943 F SS V 13944 F SS V 13946 F SS ..... ..... ..... OVIDUCT(S): UTERUS: -distention, lumen -macrophages, pigmented CERVIX: -dilatation VAGINA: ..... .... 1 1 4 3 3 3 - 3 - - - - - OVARIAN FOLLICLES/CORPORALUTEA: -presenceof corpora lutea -presence of growing/antralfollicles EAR(S): -chondropathy,auricular P P P P P P P P P P <3> 1-18 .. Page 968 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE IN RATS (AFPO) PROTOCOL 418-020 HISTOPATHOLOGY REPORT APPENDIX II HISTOMORPHOLOGIC OBSERVATIONS F1 GENERATION Page 969 ARGUS 418-020 ORAL (GAVAGE) TWO-GENERATION (ONE LI'FFER 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 = SD = SM = SSRF = Sacrifice-Scheduled Spontaneous Death Sacrifice-Moribund Scheduled (Reduced Fertility) I1-1 Page 970 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 TABLEII-1 Histomorphologic Observations F1 Generation Dose Group: Animal Number: Sex: Death TYPe: ADRENALGLANDS: -vacuolation, cortex TESTIS: I 1003 M _ I 1012 M _SRF I 1017 M SS I 1018 M SM - 1 - - EPIOIDYMIS: -infiltration,mononuclear-cell,focal 1 - PROSTAT{: - - SEMINAL VESICLES: - - COAGULATINGGLAND: - PITUITARY: - I 1019 M SM I 1020 M _M I 1022 M SS I 1024 M Sp I 1026 M SS 1 - - - EYES: -atrophy, iris/ciliarybody -atrophy, retinal, focal -inflammation, chronic, iris -neuropathy. optic nerve(s) SKIN (GROSS LESION): -dermatitis,ulcerative - - <-> <4> - - <-> <2> <3> <3> <-> - <3> <3> <-> - <3> II-2 Page 971 ARGUS 418-020 ORAL(CuWAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 TABLEII-1 (Continued) Histomorphologic Observations F1 Generation Dose Group: Animal Nmnber: Sex: Death TYPe: ADRENAL GLANDS: -vacuolation,cortex I 1034 N _ I 1035 M _ I 1040 M SSRF I 1047 M SS I 1048 M SS I 1051 M SS I 1052 M SS I 1054 M SS - - i 1 TESTIS: -atrophy/degenerationm,ultifocal - - - I - - _P_DIDYMIS: -infiltration,mononuclear-cell, PROSTATE: -dilatation,glandular,focal -Inflam_tlon, chronic focal - I .... - - Z - - - - - Z - - - i SEMINAL VESICLES: ...... GOAGULATINGGLAND: - - - PITUITARY: - - - II-3 Page 972 ARGUS 418-020 ORAL(6AVAGE)TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-2 Htstomorphologtc Observations F1 6eneretion Dose Group: Animal Number: Sex: Death Type: TESTIS: EPIDIDYMIS: II 1063 M SS II 1066 M SSRF II 1077 N SSRF II 1078 M SS II 1082 M SSRF <-> <-> II 1096 M SS II 1098 N SS PROSTATE: -inflammation,chronic 1 SEMINAL VESICLES: COAGULATINGGLAND: - - _DRENAL GLANDS: -vacuolation,cortex 1 - - . Page 973 II-4 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AVMONILIHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUNBERT: -6889.6 TABLEII-Z (Continued) Histomorphologtc Observations F1 6eneratton Dose Group: Animal Number: Sex: Death Type: II 1100 M SS II 1106 M SS II 1107 N SS II 1116 N SS II 1118 N SS ADRENAL GLANDS: -vacuolation,cortex 1 - I - - II 1120 M SS 1 Page 974 .. II-5 ARGUS 418-020 ORAL(RAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLLIOROOCTANO(AFTPEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE1I-3 Histomorphologtc Observations F1 6eneration Dose Group: Animal Number: Sex: Death Type: TESTIS: EPIOIDYMIS: III 1123 M SS III 1124 H SS III 1125 M SS III 1126 H SS III 1128 M SS III 1129 H SS III 1134 M SS III 1136 M SS III 1142 H SSRF III 1149 H SS PROSTATE: -inflammation,chronic 2 SEMINALVESICLES: COAGULATINGGLANp: ADRENALGLANDS: LIVER: -hematopoiesls, extramedullary, multifocal -hypertrophy, diffuse hepatocellular, -inflammation,chronic, focal/n_Itifocal -necrosis,focal/n_Itlfocal .... <1> - - - <3> <3> <2> <3> <2> <i> - <2> - - - SKIN (GROSS LESION): -dermatitis,chronic <3> -dermatitis, ulcerative <3> II-6 Page 975 .. ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUNPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLE11-3 (Continued) Htstomorphologtc Observations F1 6eneration Dose Group: Animal Number: Sex: Death Type: TESTIS: IIl 1154 M SS III 1156 M SS III 1159 M SS III 1154 M SS III 1165 M SS III 1167 M SSRF III 1175 M SS IIl 1177 M SS EPIDIDYHIS: PROSTATE: SEHINALVESICLES: COAGULATINGGLAND: ADRENALGLANDS: -vacuolation. cortex LIVER: -hypertrophy, diffuse hepatoce11ular, <Z> <3_ - 1 III 1180 M SS - II-7 .. Page 976 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-4 Histomorphologtc Observations FI _neration Dose Group: Animal Number: Sex: Death Type: TESTIS: EPIDIDYMIS: IV 1182 M SS IV 1189 M SS IV 1190 M $S IV 1191 M SS IV 1191 M SSRF IV 1193 M SS IV 1194 M SS IV 1197 M SS IV 1198 M SS PROSTATE: -atrophy, focal 1 SEMINAL VESICLES: COAGULATINGG_AND: ADRENAL GLANDS: LIVER: -hypertrophy, hepatocellular, diffuse -inflammation,chronic, focal/multifocal -necrosis, single-cell TAIL: -abscess -hyperplasia/hyperkeratosis - - - <3> <3> <3> <I> - - <1> - - <P> <3> Page 977 .. 11-8 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO{AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.G TABLEII-4 {Continued) HtstomoPphologtc Observations FI 6eneratton Dose Group: Animal Number: Sex: O_ath Type: TESTIS: IV IV IV IV IV 1ZOO 1ZO5 1206 1207 1Zll M M M M M _M SS, _$ S_RF SS IV 1212 M SS IV 1217 M SS IV 1218 M SS IV 1223 M SS EPIDIDYMIS: PROSTATE: SEMINAL VESICLES: COA6U_ATINGGLAND: ADRENAL 6LANDS: -vacuo]ation.cortex CECUM: -distention -edema/inflammation, submucosa COLON: -distention ILEUM: _IVER: -hematopoiesis, extramedullary, multifocal -hypertrophy, hepetocellular, -necrosis. focal/multi focal diffuse STOMACH: -erosion(s), -peritonitis, glandular mucosa focal -ulcer(s), glandular area THYMUS: -atrophy <4> <2> <4> <A> - - <3> <2> <2> - <1> <1> <3> <4> I <1> <2> <2> <1> - Page 978 II-9 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-4 (Continued) Htstomorphologtc Observations FI 6eneration Dose Group: Animal Number: Sex: Death Type: IV 1224 M SS ADRENA6LLANDS: -vacuolation, cortex EAR(S): -chondropathy, auricular KIDNEYS: -dilatation, pelvis -hyperplasta, pelvic/papillary -mineralization, pelvis <3> urothelium LIVER: -hypertrophy. hepatocellular, diffuse -inflammation. chronic, focal/multifocal -necrosis, focal/multtfocal SPLEEN: -necrosis IV 1225 M $_ IV 1229 N $_ IV 1232 M SS IV 1234 M SS IV 1235 M SS 1 <4> <2> - <3> <3> <2> <2> <4> IV 1236 M S$ IV 1240 M SS - <Z> <1> <1> II-1O Page 979 ARGUS 418-020 ORAL(6AVAGE)TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTARO(AATFEPO) IN RATS" PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -688g.6 TABLEII-S Htstomorphologic Observations FI 6eneration Dose 6roup: Animal Nmnber: Sex: Death Type: TESTIS: V 1241 M SS - V 1Z43 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 EPIDIDYMIS: - PROSTATE: -inflammation,chronic - SEMINALVESICLES: COA6ULATIN6LAND: ADRENAL6LANDS: -hypertrophy/vacuolation, zona glomerulosa Z -vacuolation, cortex - PITUITARY: -cyst(s), pars distalis - EYES: LIVER: -hypertrophy, TAIL: -constriction, hepatocellular, focal diffuse - - 1 1 Z 1 P - <-> <3> <-> <Z> <3> <P> Page 980 11-11 ARGUS 418-020 ORAL(GAVAGE)T1VO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AN#(ONIUNPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-6 (Continued) Htstomorphologtc Observations F1 Generation Dose Group: Animal Number: Sex: Death Type: TESTIS: V 1264 M SD V 1266 M S_ V 1268 M SS V 1269 M SS V 1270 M SS V 1271 M SS V 1273 M SS V 1275 M SN V 1276 M SS EPIDIDYMIS: -infiltration,mononuclear-cell, focal - PROSTATE: -atrophy,focal - -inflammation.suppurative I 1 2 - - SEMINALVESICLES: - - - COAGULATINGGLAND: ADRENALGLANDS: -hypertrophy/vecuolation, glomerulosa -vacuolation. cortex zone PITUITARY: -cyst(s). pars intermedia - 2 - - P - - - - 1 - 1 - * EYES: <-> LIVER: -hypertrophy, hepatocellu]ar, diffuse <4> -inflammation, chronic, focel/multifocal - -necrosis. focal/multifoca] <2> SPLEEN: -atrophy <2> <3> - <1> <2> <4> TAIL: <-> II-12 .. Page 981 . ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEI1-5 (Continued) Histomorphologtc Observations F1 Generation Dose Group: Animal Number: Sex: neath Tvoe: V 1278 M SSRF V 1279 M _ V 1283 M _S V 1287 M S_ V 1288 M SS V 1293 M SS V 1295 M SS T(ST_S: EPIDIDYMIS: -infiltration,mononuclear-cell,focal I 1 PROSTATE: - _ SEMINAL VESICLES: - - COAGULATING_AND: - ADRENALGLANDS: -hypertrophy/vacuolation, 91omerulosa zone PITUITARY: - i 2 - - LIVER: -hematopoiesis, extramedullary, multi focal -hypertrophy. hepatocellular, diffuse <1> <3> <2> - - <3> <3> 11-13 Page 982 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-6 Dose Group: Animal Number: Sex: Death Type: OVARIES: UTERUS: -distention, lumen -macrophages, pigmented C_RVIX: VAGINA: -mucification Histomorphologic Observations F1 6enerati on I 1312 F SS ..... I 1321 F SS I 1328 F SS I 1335 F SS I 1340 F SS I 1341 g SS .... 1 - 3 3 3 3 ..... - 2 3 OVARIANFOLLICLES/CORPORLAUTF.A: -presence of corpora lutea -presence of growing/antral follicles ADRENALGLANDS: PITUITARY: P P P P P P P P P P - - .... EAR(St: -chondropathy, auricular <4> <3> Page 983 II-14 ARGUS 418-020 ORAL(GAVAGE)T140-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUDROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.8 Dose Group: Animal Number: Sex: Death Tvoe: OVARIES: UTERUS: -distention, lumen -macrophages, pigmented CERVIX: VAgiNA: -inflammation, -mucification chronic, focal OVARIANFOLLICLES/CORPOR_AUT_A: -presence of corpora lutes -presence of growing/antral follicles ADRENALGLANDS: PITUITARY: TABLEII-6 (Continued) Hi stomorphologt c Observations FI 6eneration I 1342 F S_ - I 1345 F SS - I 1353 F SS - I 1355 F SS I 1359 F SS I 19780 F SS 2 4 4 2 1 - - 1 - 1 P P P P P P P P P P ..... ..... EAR(S): -chondropathy, auricular SPLEEN: -atrophy <4> <4> . Page 984 II-15 ARGUS 418-020 ORAL(GAVA6E)TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-7 Hi stomorphologtc Observations F1 6enereti on Dose 6roup: Animal Number: Sex: Death Type: ILEUM: -distention II 1365 F SD II 1373 F SD II 1374 F SS II 1407 F SS II 1415 F SS <4> _IVER: -infarct,liver lobe STOMACH: -erosion(s), glandularmucosa TAIL: -inflammation, chronic -necrosis, focal <P> <2> - <-> <1> <2> <-> - Page 985 . 11-16 ARGUS 418-020 Dose Group: Animl Number: Sex: Death Type: ORAL(6AVAGE)lifO-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-8 Histomorphologic Observations F1 6eneretion KIDNEYS: -dilatation,pelvis III 1428 F SS _2> . Page 986 II-17 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PER6ENERATION} REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 TABLEII-9 Histomorphologic Observations F1 Generation Dose Group: Animal Number: Sex: Death Type: EYES: -abscess, periocular IV 1495 F SS <P> Page 987 .. II-18 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO{NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO{ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNIJHBERT: -6889.6 TABLEII-lO Histomorphol_ic Observations FI _neration Dose Group: Animal Number: Sex: Death Type: OVARIES: UTERUS: -distention,lumen -macrophages. pigmented CERVIX: V 1544 F SS ..... V 1546 F SS V 1548 F SS V 1551 F SS V 1552 F SS V 1557 F SS - - 3 3 4 3 - - - 3 - 3 2 "- VAGINA: -mucification - - - 3 OVARIAN FOLLICLES/CORPORALUTe: -presence of corpora lutea -presence of growing/antra] follicles ADRENALGLANDS: -hyperplasia, cortical, focal PITUITARY: -cyst(s). pars distalis P P P P P P 1 P P P P P EAR(S): -chondropathy, auricular TAIL: -inflammation.chronic -necrosis. focal <4> <2> <2> .. Page 988 11-19 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 TABLEII-lO (Continued) Histomorpho]ogic Observations F1 6eneratton Dose Group: Animal Number: Sex: Death Type: OVARIES: -cyst(s), intraovarian UTERUS: -macrophages, pigmented CERVIX: V 1573 F SS V 1579 F SS V 1589 F SS V 1593 F SS V 1598 F SS P 3 1 3 3 3 ..... VAGINA; -muctficetton - 3 2 - - OVARIANFOLLICLES/CORPOR_AUT_A; -presence of corpora lutes -presence of growing/antra] follicles ADRENALGLANDS: P P P P P P P P P P PITUITARY: KIDNEYS: -dilatation, pelvis -pyelonephritis URETER: -distention -hyperplasia, mucosa .... -inflammation,chronic <3> <3> <4> -"_ <3> <Z> URINARY BLADDER: -cystitis, hyperplastic <4> .. Page 989 II-20 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 III INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA P Generation KEY TO CORRELATION OF HISTOMORPHOLOGIC OBSERVATIONS Not applicable = Microscopic evaluationlcorrelation not appropriate or not required by protocol. Page 990 ARGUS 418-020 ORAL (6AVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL418-020 SPONSOR'SSTUDY NUMBER: T-6889.6 ANIMAL NUMBER: 13602 SEX: M Appendix III IndividualAnimal Gross and HistomorphologyData P Generation DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S}: GENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: infiltration,mononuclear-cell,focal (minimal) PROSTATE: inflammation,chronic (minimal) ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS COAGULATINGGLAND PITUITARY TESTIS ....................................................................................................... End of Record- 13602 SEMINAL VESICLES Page 991 III-I ARGUS 418-020 ORAL(6AVA6E) TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal 6mss and Mist_rphology Data P Generation ANIMALNUMBER1: 3609 SEX: M === == wmmmmmm = == = === = ==m = mm= = _ ==== == m = == === m =_==_ms_z GROSSOBSERVATIONIS): GENERALN: o gross changes. DOSEGROUP: I DEATHTYPE: Scheduled (Reduced Fertility) = ===== = = =_ = === m == = === =_ ========= ================= HISTO,<ORPHOLOGOIBCSERVATIONIS): Not applicable HISTOMORPHOLOGOICBSERVATIONS: PROSTATE: TESTIS: atrophy,focal (mild) atrophy/degenerationm,ultifocal (moderate) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL,LIMITS: COAGULATINGGLAND EPIDIDYMIS SEMINALVESICLES ....................................................................................................... End of Record- 13609 .. Page 992 ,III-2 ARGUS 418-020 ORAL(GAVAGE)I_/O-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal Gross and HlstomorphologyData P _neration ANIMAL NUMBER:13610 SEX: H mmmmmmmmmm_mm_m_mmmmm_m_z_smmmtmmmsmmm_mmmmmmmsmm_smmmm_m_mmmzm_zmmmmlmmm_s_szmm_1_m DOSEGROUP: DEATHTYPE: I Scheduled (Reduced Fertility) _m_ _m _mz GROSSOBSERVATION(S): G_NERAL:No gross changes. ................................................ HISTOHORPHOLOGOICBSERVATIONS: PROSTATE: ........................................................ HISTOMORPHOLOGOICBSERVATION(S): _----_. Not applicable .................................................. atrophy, focal (minimal) . .............................................. TH_ FOLLOWINGTISSUE(S) WEREWITHIN NORHALIHITS: COAGULATINGGLAND EPIDIDYHIS ....................................................................................................... End of Record- 13610 SEMINALVESICLES TESTIS Page 993 III-3 ARGUS 418-020 ORAL(GAVAGE}TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13611 SEX: M m_ssssl_i_mmi_sm_s_ssm_ssmss_zssm_m__z_mmssm_smsssm_sssms_ism_s1ssmssm_sssstz_mssa_s_H_szs GROSS OBSERVATION(S:) GENERAL:No gross changes. DOSE GROUP: DEATH TYPE: I Scheduled (ReducedFertility) Jzmstslzz_ssm_msmz HISTOMORPHO_OGICOBSERVATION{S}: Not applicable HISTOMORPHOLOGICOBSERVATIONS: PROSTATE: inflammation,chronic (minimal) atrophy, focal (minimal) THE FQLLOWINTGISSUE(S) WEREWITHIN NORMALIMITS: COAGULATINGGLAND EPIDIDYMIS End of Record- 13611 SEMINALVESICLES TESTIS Page 994 _ . _ o... III-4 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Histon_r_hology Data P Generation ANIMALNUMBER:13612 SEX: M = ----_--= = _ = = = = = _= = ===== == = = == == === = = I == = =_ _w_ll-lI-==== DOSE6ROUP: DEATHTYPE: _====_==----_ ===== I Sacrifice-Scheduled = = _=== = ====== = ===== = ============== GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL: No gross changes. Not applicable ....................................................................................................... THE FOLLOWINGTISSU{(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATINGGLAND SEMINALVESICLES --e .......................................... End of Record- 13612 EPIDIDYMIS PITUITARY TESTIS _ ......................................................... III-5 Page 995 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL 418-020 SPONSOR'SSTUDY NUMBER: T-6889.6 ANIMAL NUMBER: 13614 SEX: M Appendix ili IndividualAnimal Gross and HistomorphologyData P _neration DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): LUNG: All lobes- dark red areas too numerousto count ranging in size from pinpointto O.2cm in diameter. HISTOMORPHOLOGICOBSERVATION(S): hemorrhage,multifocal inflammation,interstitial,multifocal HISTOMORPHOLOGICOBSERVATIONS: LUNG: PROSTATE: hemorrhage,multifocal (moderate) inflammation,interstitial,multifocal (mederate) inflammation,chronic (mild) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINALVESICLES COAGULATINGGLAND TESTIS EPIDIDYMIS End of Record- 13614 PITUITARY Page 996 . III-6 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPROOUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMAL NUMBER: 13615 SEX: M A4opendixIII IndividualAniml Gross and Hist_rphology Data P Generation DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolation,cortex (mild) inflammation,suppurative,focal (minimal) dilatation,glandular,focal (moderate) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13615 SEMINAL VESICLES Page 997 .. ..... -o III-7 ARGUS 418-020 ORAL(RAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AI4MONIUIP4ERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L1B-020 SPONSOR'SSTUDYNUMBERT: -r)889.6 Individual Appendix III Animal Gross and Htatomorphology Data P 6eneration ANIMALNUMBER:13616 SEX: N DOSEGROUP: DEATHTYPE: I Sacrifice-Scheduled GROSSOBSERVATION(S): _AR(S): Swollen, both. ....................................................................................................... HISTONORPHOLOGOICBSERVATION(S): Tissue not available THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS PROSTATE COAGULATINGLAND SEMINALVESICLES EPIDIDYNIS TESTIS PITUITARY TISSUE(S) NOTAVAILABLEFOREVALUATION: EAR(S) ....................................................................................................... End of Record- 13616 Page 998 .. III-8 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -688g.6 Appendix III IndividualAnimal 6rosa and HistomorphologyData P _._neration ANIMAL NUMBER: 13621 SEX: M mm_ra_mmmmmumms_mmsRmmmmmiR_i_mmmlwm_mmmm_m_B_mma_mmmm_mmmm1i_BsB_iBBmm_s_s__ms_1_ DOSE 6ROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOHORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENALGLANDS PROSTATE COAGULATINGBLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 13621 PITUITARY Page 999 III-9 ARGUS 418-020 ORAL(GAVAGE)TVO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: 6889.6 Appendix III IndividualAnimal Gross and Histoeorphol_y Data P _neration ANIMAL NUMBER: 13622 SEX: M mmmmm_nmmsmIsm_umml_mm_sIwmar_mmst_lms_m_1_mmm1_I_R_a_s_sBss_m_m_s_z DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled swz_s_ GROSS OBSERVATION(S): GENERAL:No gross changes. ........................................... HISTUMORPHOLOGICOBSERVATIONS: PROSTATE: ------................................................. ffISTOMORPHOLOGIOCBSERVATION(S): Not applicable . ........................................................... inflammation,chronic (mild) _ .................................................. TME FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINALVESICLES COAGULATINGGLAND TESTIS EPIDIDYMIS ........................................................................................................ End of Record- 13622 PITUITARY _zzz_ Page 1000 .III-10 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL 418-020 SPONSOR'SSTUDY NUMBER: T-6889.6 ANIMAL NUMBER: 13624 SEX: M Appendix III IndividualAnimal Oross and Histomorphology Data P 6eneration DOSE6ROUP: DEATH TYPE: I Sacrifice-Scheduled GROSS OBSERVATION(S}: 6ENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: PROSTATE: HISTOMORPHOLOGICOBSERVATION(S}: Not applicable infiltration,mononuclear-cell,focal (minimal) inflammation,chronic (minimal) dilatation,glandular,focal (mild) THE FOLLOWIN6TISSUE(S)RERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COA6ULATINGGLAND PITUITARY ....................................................................................................... End of Record- 13624 SEMINAL VESICLES Page 1001 III-ll ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIOIS,TUDY OF AMMONIUMPERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL418-020 SPONSOR'SSTUDY NUMBER: T-6889.6 Appendix III Ind'vidua]Animal Gross and HistCnJrphologyData P Beneratton ANIMAL NUMBER: 13625 SEX: M DOSE ;ROUP: I DEATH TYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): HIST'J_ORPHOLOGIOCBSERVATION(S}; GENERAL:No gross changes. Not applicable ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: ADRENALGLANDS: PROSTATE: vacuolation, cortex (minimal) inflammation, suppurative, focal (mild) THE FOLLOWINGTISSUE(S)WERE _:THIN NORMAL LIMITS: COAGULATINGGLAND TESTIS EPID'DYMIS PITUITARY End of Record- 13625 SEMINAL VESICLES .. Page 1002 111-12 ARGUS 418-020 ORAL(6AVAGE)ll40-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIHAL NUMBER:13626 SEX: H Appendix Ill IndividualAnimal Gross and HistomorphologyData P Generation DOSEGROUP: DEATHTYPE: I Sacrifice-Scheduled GROSSOBSeRVATION(S): GENERAL:No gross changes. ........................................ HISTOHORPHOLOGOICBSERVATIONS: ADRENALGLANDS: EPIDIDYMIS: HISTOMORPHOLOGOICBSERVATION(S): Not applicable _ .............................................................. vacuolation, cortex (mild) infiltration,mononuclear-cell,focal (minimal) THE FOLLOVINGTISSUe(S)VERE WITHIN NORMAL LIM{TS: COAGULATINGGLAND TESTIS PITUITARY PROSTATE End of Record- 13626 SEMINAL VESICLES III-13 Page 1003 ARGUS 418-020 ORAL(6AVAGE) TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUNPERFLUOROOCTANO(ATPEFO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 ANIHAL NUHBER:13632 SEX: H Individual Animl Appendix III Gross and Htstomorphology Data P Generation DOSEGROUP: DEATHTYPE: II Sacrifice-Scheduled GROSSOBSERVATION(SI: GENERALN: o gross changes. THE FOLLOWINGTISSUE(S) WEREWITHIN NORHALINITS: ADRENALGLANDS End of Record- 1363Z HISTOHORPHOLOGOICBSERVATION(SI: Not mpplicable Page 1004 III-14 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLIJOROOCTANO(AATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal _ross and Htstomorphology Data P Generation ANIMAL NUMBER: 13636 SEX: M DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSSOBS{RVATION{SI: EPIDIDYMIDES:Right- small and flaccid, TESTES: Right- small and flaccid, HISTOMORPHOLOGICOBSERVATION(S): atrophy, EPIDIDYMIS hypospermia,EPIDIDYMIS infiltration,mononuclear-cell,focal, EPIDIDYMIS hypoplasia,diffuse, TESTIS dilatation,rete testis, TESTIS HISTOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: TESTIS: End of Record- 1363B atrophy (minimal) hypospermia(marked) infiltration,mononuclear-cell,focal (minimal) hypoplasia,diffuse (marked) dilatation,fete testis .o Page 1005 111-15 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHNONILIHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix IZI Animal Gross and Histomorphology Data P Generation ANIMALNUHBER:13636 SEX: M mmlmms_mwsmsi_gsms_m_ss_sis_mmssmm_._m_s_m_ms_m_smmm_sm_g_mss_mm_n_zs_B_=_s_s===_ GROSSOBSERVATION(S): EAR(S): Swollen, right, DOSEGROUP: OEATHTYPE: II Scheduled (Reduced Fertility) HISTONORPHOLOGOICBSERVATION(S): chondropathy,auricular HISTOMORPHOLOGICOBSERVATIONS: EAR(S): EPIDIDYMIS: chondropathy,auricular (moderate) exfollatedspermatogeniccells (mild) THE FOLLOWINGTISSU[(S)WERE WITHIN NORMAL LIMITS: COAGULATIN6GLAND PROSTATE SEMINAL VESICLES End of Record- 13638 TESTIS Page 1006 III-16 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix Ill Animal 6ross end Histomorphology Data P Generation ANIMALNUMBER1: 3639 DOSEGROUP: SEX: M DEATHTYPE: _lismsImm_simss1mmmimm_s_mmsmmmmmm_mmsmmsmmmmmmmmm_mmsmmmmIms_m_mmwmm_mms_m_mm_mms_s_=_s= II Scheduled (Reduced Fertility) GROSSOBSERVATION(S); KIDNEYS:Right- pelvis, slight dilation, HISTOHORPHOLOGOICBSERVATION(S): dilatation, pelvis HISTOMORPHOLOGOICBSERVATIONS: EPIOIOYHIS: KIDNEYS: PROSTATE: infiltration,mononucleer-cell,focal dilatation, pelvis (minimal) inflammation,chronic (mild) (minimal) TH_ FOLLOWINGTISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND SEMINAL VESICLES TESTIS End of Record- 13639 Page 1007 III-17 ARGUS 418-020 ORAL (6AVAGE)TWO-GENERATION(ONE LITTER PER 6ENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL 418-020 SPONSOR'SSTUDY NUMBER: T-6889.6 ANIMAL NUMBER: 13642 SEX: M Appendix Ill IndividualAnimal 6ross and MistomorphologyData P Beneration DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13642 Page 1008 .... . - Ill-18 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal Gross and Hiaton_rphologyData P _neration ANIHAL NUMBER1: 3644 SEX: M DOSEGROUP: II DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): 6ENERAL:No gross changes, ....................................................................................................... THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS ....................................................................................................... End of Record- 13644 HISTOMORPHOLOGOICBSERVATION(S): Not applicable Page 1009 III-19 ARGUS 418-020 ORAL(EAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:13645 SEX: M Appendix Ill IndividualAnimal Gross and Hist_o_hology Data P _neration DOSEGROUP: II DEATHTYPE: Sacrifice-Scheduled _ROSSOBSeRVATION(S): GENERAL:No gross changes. ....................................................................................................... THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS ....................................................................................................... End of Record- 13645 HISTQMORPHOLOGOICBSERVATION(S): Not applicable Page 1010 ,lll-ZO ARGUS 418-020 ORAL{GAVAGE)TWO-GENERATIO(NONELITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3646 SEX: M Individual Appendlx Ill Animal 6ross and Htstomorphology Data P Generation DOSEGROUP: DEATHTYPE: II Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: End of Record- 13646 vacuolation,cortex (minimal) Page 1O11 .. III-21 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gr_ss and Hfstomorphology Data P Generation ANIMAL NUMBER: 13650 SEX: M msmmmmm_mmmsmmmmmsmmg_mmmmm_mm_wim_mm_sm_mt_mim1_j_mm_mm_smimmmmmm_mmtmiammzsmmiz_m_ DOSE GROUP: DEATH TYPE: II Scheduled (Reduced Fertility) GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration,mononuclear-cell, focal (mild) inflammation,chronic (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND .................................................... End of Record- 13650 SEMINALVESICLES TESTIS _ .................................................. Page 1012 ' II1-22 ARGUS 418-020 ORAL (BAVABE)TWO-GENERATION(ONE LITTER PER 6ENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLUORDOCTANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Appendix III IndividualAnimal Gross and flistomorphologDyata P 6eneration ANIMAL NUMBER: 13651 SEX: M mmsmR_mmmwt mmsmst mIlssmmssmtmsnmilmmmst GROSS,O,BS{RVATION()S: 6ENERAL,:No gross changes. ......................................... HISTOMORPHOLOBOIBCSERVATIONS: ADRENAL6LANDS: End of Record- 13651 DOSE GROUP: DEATH TYPE: II Sacrifice-Scheduled mmHmmgSmm_._mm_s_mlmti_tzms_zsS_ss_SR _m_S_SZ_ _S_ HISTOMORPHOLOBICOBSERVATION(S:) Not applicable _--.. .......................................................... vacuolation, cortex (minimal) .- Page 1013 III-23 ARGUS 418-020 ORAL(_VAGE) _O-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFL_RO_TANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 ANIMAL NUMBER:13652 SEX: M Indivldual Appendix III Animal Gross and Histomorphology Data P 6eneratton DOSEGROUP: II DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL: No gross changes. Not applicable ....................................................................................................... THE FOLLOWINGTISSUE(S)WER{ W_THIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13652 Page 1014 Ill-Z4 ARGUS 418-020 ORAL (6AVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLUOROOCTANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal Gross and HistomorphologyData P 6eneration ANIMAL NUMBER: 13653 SEX: M DOSE 6ROUP: DEATH TYPE: II Sacrifice-Schedu]ed GROSS OBSERVATION(S): EAR(S): Swollen,right, ............................................. HITTOMORPHOLOGICOBSERVATIONS: EAR(S): End of Record- 13653 HISTOMORPHOLOGICOBSERVATION(S): chondropathy,auricular e ......................................................... chondropathy,auricu]ar (moderate) Page 1015 III-Z5 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3654 SEX: M Individual Appendix III Antmal 6ross and Hlstomorphology Data P Generation DOSEGROUP: DEATHTYPE: II Sacrifice-Scheduled 6ROSS OBSERVATION(S): GENERAL:No gross changes. ...................................................... HISTOMORPHOLOGICOBSERVATION(S): Not applicable . ................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL6LANDS End of Record- 13654 Page 1016 .... . .. III-26 ARGUS 418-020 ORAL(GAVAGE)TVO-GENERATIO(NONE LITTER PERGENERATION} REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18o020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix IIl Animal Gross and Histomorphology Data P Generation ANIHAL NUI4BER:13655 SEX: H DOSEGROUP: II DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... THE FOLLOWINGTISSUE(S} WEREWITHIN NORMALIHITS: ADRENALGLANDS End of Record- 13655 HISTOHORPHOLOGOICBSERVATION(S): Not app]icab]e III-27 Page 1017 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 ANIMALNUMBER:13656 SEX: M Individual Appendix III Animal Gross and Htstomorphology Data P Generation DOSEGROUP: DEATHTYPE: II Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ............................................. HISTOMORPHOLOGOICBSERVATION(S):. Not applicable . ......................................................... THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS End of Record- 13656 Page 1018 III-28 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 ANIMAL NUMBER:13661 SEX: N Kol_ndix III IndividualAnimal G_s: end Htstomorphology Oata P _neratlon OOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled 6ROSSOBSERVATION(S): GENERAL:No gross .............................................. changes. HISTOHORPHO_OGOICBSERVATIONS: ADRENALGLANDS: End of Record- 13661 HISTOMORPHOLOGICOBSERVATION(S): Not applicable _ ........................................................ vacuoletton, cortex (minimal) Page 1019 111-29 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal Gross and MistomorphologyData P Generation ANINAL NUMBER:13662 SEX: M mmmmmmm_m_mmsmmmmmmmzmsm_imm_ GROSS OBSERVAT)ON(S): G_N(RA_:No gross changes. mm_mmmmmmm_mmmmmmmmmmm_mmm=Imm_m_zmmmm_mmm DOSEGROUP: DEATHTYPE: III Scheduled (Reduced Fertility) == =_= =z= _ == == H_STOMORPHOLOGICOBSERVATION(S): Not applicable TH_ FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATINGGLAND TESTIS EPIDIDYMIS End of Record- 13662 PROSTATE Page 1020 .... .. _ "o III-30 ARGUS 418-020 ORAL(GAVAGE}TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -_889.6 ANIMALNUMBER:13668 SEX: H Individual Appendix III Animal Gross and Hist_rphology Data P Generation DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS End of Record- 13668 HISTOMORPHOLOGOICBSERVATION(S): Not applicable Page 1021 III-31 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AI4MONIUMPERFLUORDOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix 111 IndividualAnimal Gross and Hist_rphol_y P Generation Data ANIMALNUMBER1: 3670 SEX: M Imm_IIzI_II_IsII_ItII_IIm_II_IIIIs_sIII_II_I_II_I_II1III-aI_III_1I_IIII_IIIIII_II_IIII_III_ GROSSOBSERVATION(S): KIDNEYS:Right- pelvis, moderate dilation, ....................................................................................................... HISTONORPHOLOGO_BCSERVATIONS: KIDNEYS: End of Record- 13870 dilatation, DOSEGROUP: DEATHTYPE: III Sacrifice-Scheduled H_STOHORPHOLOGOIBCSERVATION(S): dilatation, pelvis pelvis (moderate) III-32 Page 1022 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal 6ross and HistomorphologyData P 6mneration ANIMALNUMBER:13671 SEX: M smmmslm_msm_smms _ mmmsm_sm_zmm_msm_sm_mm_msmnlltmm_Bsmmm_ GROSS OBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... THE FOLLOWINGTISSUE(S)W_RE WITHIN NORMAL LIMITS; ADRENAL GLANDS End of Record- 13671 DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled m B_ _ _B_ s _ _ m i _ _ I_ _ i_z _z_ zm m _s z _ _zz HISTOMORPHOLOGICOBSERVATION(S): Not applicable Page 1023 .III-33 ARGUS 418-020 ORAL(GAVAfiE)TWO-GENERATIO(NONELITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix lIl Animal Gross and Htstomorphology Data P Generation ANIMALNUMBER:13672 SEX: M DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled =_= GROSS OBSERVATION[S}: HISTOMORPHOLOGICOBSERVATION(S): KIDNEYS:Right- pelvis, slight dilation, dilatation,pelvis ................................. . ........................................... . ......................... HISTOMORPHOLOGICOBSERVATIONS: KIDNEYS: End of Record- 13672 dilatation,pelvis (minimal) = = Page 1024 III-34 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(AATPEFO} IN RATS PROTOCO4L16-020 SPONSOR'SSTUDYNUHBER:T-6889.6 ANIHAL NUHBER:13673 SEX: H Individual Appendix lll Animal Gross and Htstomorphology Data P Generation DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled GROSSOpSERVAT[ON(SI: GENERALN: o gross changes. ....................................................................................................... THE FOLLOWINGTISSUE{S) WERE WITHIN NORHALIHITS: ADRENALGLANDS ....................................................................................................... End of Record- 13673 HISTOHORPHOLOGOICBSERVATION(S): Not applicable Page 1025 1II-35 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTR PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNI.IHBERT: -6889.6 ANIMAL NUMBER: 13674 SEX: M Individual AniN1 Appendix III Gross and Htstamorphology Data P Generation DOSE GROUP: DEATH TYPE: III Scheduled (ReducedFertility) GROSS OBSERVATION(S): GENERAL:No gross changes. ............................................ HISTOMORPHOLOGOICBSERVATIONS: EPIDIDYMIS: . ........................... HISTOMORPHOLOGICOBSERVATION(S): Not applicable . .............................. hypospermia (mild) exfoliated spematogenic cells (moderate) TH_ FOLLOWINGTISSUE(S)WERE WITHIN NORMAL _IMITS: COAGULATINGGLAND PROSTATE SEMINAL VESICLES ....................................................................................................... End of Record- 13674 TESTIS Page 1026 ,III-36 ARGUS 418-020 ORAL(GAVAGE)TVO-GENERATION(ONELITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUNPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix III Animal 6ross and Htstomorphology Data P Generation ANIHAL NUNBER:13675 SEX: N _u_m_ms_i_nn_mmmmmi_mmmmiiims_m_mmmmsIi_smmmmm1i_mmmmmm_8t_mim_m_=mmzs_l-_zm_m_Z_s_= DOSEGROUP: DEATHTYPE: III Sacri fice-Schedul ed GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): Not applicab]e HISTONORPHOLOGOICBSERVATIONS: ADRENALGLAND:S End of Record- 13675 vacuol ati on, cortex (mi 1d) Page 1027 .- III-37 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 ANIHAL NUHBER:13676 SEX: H Individual Appendix III Antmal Gross and Htstomorphology Data P 6eneration DOSEGROUP: DEATHTYPE: III Sacrifice-Scheduled GROSSOBSERVATION{S): GENERALN: o gross changes. ....................................................................................................... THE FOLLOWINGTISSUE(S) W_REWITHIN NORHALIHITS: ADRENALGLANDS ................................................................................. End of Record- 13676 HISTOHORPHOLOGOICBSERVATION(S}: Not app]icable _ ..................... .- Page 1028 _ o ... III-38 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONILIHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAniNl Gross and Hist_rplnology Data P _mneration ANIHAL NUMBER:13682 SEX: M DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled 6ROSSOBSERVATION(S): GENERALN: o gross changes. ......................... . ......................... HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: End of Record- 13682 HISTOMORPHOLOGOICBSERVATION(S): Not applicable . ................................................... vacuolation, cortex (minima]) Page 1029 .III-39 ARGUS 418-020 ORAL(GAVAGE}TVO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNLINBERT: -6889.6 ANIMALNUMBER:13683 SEX: M Individual Appendix III Animal Gross and Histomorphology Data P 6eneration DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: vacuolation,cortex (moderate) ....................................................................................................... End of Record- 13683 Page 1030 III-40 ARGUS 418-020 ORAL(GAVA6E)11/O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUOYOF AMMONIUMPERFLIJOROOCTANO(APTEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNLINBERT: -6889.6 ANIMALNUMBER:13684 SEX: H Individual Appendix III Animal 6ross and Htatomorphology Data P 6eneratton DOSE6ROUP: DEATHTYPE: III Sacrifice-Scheduled 6ROSS OBSERVATION(S): 6ENERAL:No gross changes. ....................................... HISTOMORPHOLOGICOBSERVATION(S): Not applicable . ............................................................... THE FOLLOWIN6TISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL 6LANDS ....................................................................................................... End of Record- 13684 Page 1031 III-41 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Individual Appendtx III Animal 6ross and Hlstomorphology Data P 6eneretion ANIMALNUMBER:13693 SEX: M _ae_snmsmntml_tlimi_gi_iaelaln_al_iRmaem ms_niai_s_m_m_snsltt DOSEGROUP: IV DEATHTYPE: Sacri fi ce-Schedu] ed _il_s_s_st_ss_8_uts _w=_ GROSSOBSERVATION(S): GENERALN: o gross changes. .................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable b .................................................. THE FOLLOWINGTISSUE{S) WER_ WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13693 _s_sm== Page 1032 .. III-42 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAniml Gross and Hist_rphol_y P Generation Data ANIMALNUMBER:13695 SEX: M l_mamisql_liniZmlwmslHRmRsls_ms_mmRm_tm_m_m_mmmmzsi1mmsm_mmmmmw_mzmmm_m_z_z_s_- GROSSOBS_RVATIONI}S: GENERAL:No gross changes. DOSEGROUP: DEATHTYPE: IV Sacrt fi ce-Scheduled ==_ z SZl=mZzmm= HISTOMORPHOLOGOICBSERVATION(S: I Not applicable THE FOLLOWINGTISSUE(S) W{REWITHIN NORMALIMITS: ADRENALGLANDS End of Record- 13595 Page 1033 1II-43 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION} REPRODUCTIOSNTUDYOF AHMONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 Individual Appendix III Animal 6ross and Histomorphology Data P 6eneration ANIHALNUMBER1: 3699 SEX: H mm_Iismsm_mmm_zsIsszizm_mms_R1s_m_s_sm_m_Rmm_m_z_s._mz_m_1_m_mm_istm_m_ GROSSOBSERVATION{S): GENERALN: o gross changes. DOSEGROUP: DEATHTYPE: IV Sacrifice-Scheduled HISTOHORPHOLOGOICBSERVATION{S): Not applicable THE FOLLOWINGT_SSUE{S)WEREWITHIN NORMALIMITS: ADRENALGLANDS End of Record- 13699 III-44 Page 1034 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal Gross and Histmrphology Data P _neration ANIMAL NUMBER: 13700 SEX: M DOSE GROUP: DEATH TYPE: IV Scheduled (ReducedFertility) GROSS OBSERVATION(S}: HISTOMORPHOLOGICOBSERVATION(S): GENeRAl: No gross changes. Not applicable ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: PROSTATE: inflammation,chronic (mild) THE FOLLOWINGTISSU{($}WER{ WITHIN NORMAL LIMITS: COAGULATINGGLAND EPIDIDYMIS SEMINALVESICLES ....................................................................................................... End of Record- 13700 TESTIS Page 1035 III-45 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:13703 SEX: H Appendix III IndividualAnimal Gross end llist_rphology Data P 6e_ration DOSEGROUP: DEATHTYPE: IV Sacri fi ce-Schadul ed GROSS OBSERVATION(S:) GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATION(S:) Not applicable THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13703 Page 1036 III-46 ARGUS 418-020 ORAL(GAVAGE)T1VO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3704 SEX: M Individual Appendix III Animal 6ross and Htstomorphology Data P _eneratlon DOSEGROUP: DEATHTYPE: IV Sacrifice-Scheduled GROSSOBSERVATION[S): GENERALN: o gross changes. ..................................... HISTOHORPHO_OGOICBSeRVATION(S): . ................................................................. Not applicable THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 13704 Page 1037 III-47 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:13706 SEX: M Individual Appendix III Animal Gross and Htstomorphology Data P Generation DOSEGROUP: DEATHTYPE: IV Sacrifice-Scheduled GROSSOBSERVATION(S): EPIDIDYMIDES:Right- small and flaccid, TESTES: Right- small and flaccid, HISTOMORPHOLOGICOBSERVATION(S): atrophy, EPIDIDYMIS hypospermia,EPIDIDYMIS infiltration,mononuclear-cell,focal, EPIDIDYMIS hypoplasia,diffuse, TESTIS dilatation,rete testis, TESTIS HISTOMORPHOLOGICOBSERVATIONS: 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 III-48 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AHNONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-0Z0 S_NSOR'S STUDYN_BER: T-6889.6 Individual Appendix III Animal 6ross and Hlstomorphology Data P 6eneration ANIMALNUHBER:13708 DOSEGROUP: IV S_: H D_TH TYPE: Sacrifice-Scheduled IIllImimiIlIII_ImIIl_IillIImll ISImIIImIJmmlmla.mm_msI_llmmll_lm_mIlIIIIII_mI_IllI=II=lIII_Sl Ill GROSSOBSERVATION(S: ) GENERAl:No gross changes. HISTOHORPHOLOGOICBSERVATIONS)[ : Not applicable THE FOLLOWINGTISSUE(S) WEREWITHIN NORHAL[N[TS: ADRENALG_NDS End of Record- 13708 Page 1039 .- 111-49 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Ikol_ndlx III IndividualAnimal 6ross and Histomorphology Data P Generation ANIHALNUMBER:13710 SEX: M lll_II=l=IIl =_=_ II _ II = Ill = Ill === = : _lllllI_llll_IIlllI_Illllll= DOSEGROUP: DEATHTYPE: == IIl = ==_ IV Sacrifice-Scheduled III = ====_= I === = = I == I === I=I ===== GROSSOBSERVATION(S): JAM(S): Swollen, ....................................................... right, HISTUMORPHOLOGOICBSERVATION(S): chondropathy, . ............................................... auricular HISTOMORPHOLOGOICBSERVATIONS: EAR(S): End of Record- 13710 chondropathy, auricular (moderate) Page 1040 III-50 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Appendix Ill IndividualAniml Gross and HistomorphologyData P _neration ANIMALNUMBER1: 3711 SEX: N lmm_lmmm_lsmZssm_l_m_mlm_l_mlm_la_mlll_l1_l_mm_llmm_m_lmI_mm_mlm_m_tll_lls_ll_s_1ml_l_zz_s_ GROSSOBSERVATIONIS): GENERAL:No gross changes. DOSEGROUP: DEATHTYPE: IV Sacrifice-Scheduled HISTOHORPHOLOGOICBSERVATION{S): Not applicable H]STOHORPHOL06IOCBSERVATIONS: ADRENALGLANDS: End of Record- 13711 hypertrophy/vacuolation, zona glomerulosa {minimal) Page 1041 m 111-51 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:13716 SEX: M Appendix III IndividualAnimal Gross and Hist_rphology Data P _mneration DOSEGROUP: DEATHTYPE: IV Sacrifice-Scheduled GROSS OBSeRVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: End of Record- 13716 HISTOMORPHOLOGICOBSERVATION(S}: Not applicable hypertrophy/vacuolation, zona glomerulosa (minimal) Page 1042 III-52 ARGUS 418-020 ORAL (BAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OFAMMONIUM PERFLUORDOCTANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 ANIMAL NUMBER: 13717 SEX: M Individual Appendix Ill Animal Gross and Htstomorphology Data P Generation DOSE GROUP: DEATH TYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): KIDNEYS:Right- pelvis, slight dilation, dilatation,pelvis hyperplasia,pelvic/papillaryepithelium,focal ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: KIDNEYS: dilatation,pelvis (minimal) hyperplasia,pelvic/papillaryepithelium,focal (mild) ....................................................................................................... End of Record- 13717 Page 1043 .. III-S3 ARGUS 418-020 ORAL(GAVAGE)TIJO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF ANHONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Individual Appendix III Animal 6rou and Htstomorphology Data P 6eneratton ANIMALNUMBER1: 3719 SEX: H _IImIImIIIII_mzIIIIsIIIIIIIIIIII_IIIIIsIf_mIIII_m_I_IsIIIII_IIwIIIImIIIIIIIIIIII_I_III1_IIIIzIz_II_ GROSSOpS_RVATION(S): GENERALN: o gross changes. ................................................................ THE FOqLOWIN8TISSUE(S) WEREWITHIN NORHALLIHITS: ADRENALGLANDS End of Record- 13719 DOSEGROUP: IV DEATHTYPE: Sacrifice-Scheduled HISTOHORPHOL06IOCBSERVATION(S): Not app]icable _ ...................................... Page 1044 .o III-54 ARGUS 418-020 ORAL(GAVAGE)"I'WO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix III Animal Gross and Htstomorphology Data P Generation ANIMALNUMBER1: 3721 SEX: H DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAl: No gross changes. HI_TOMORPHO_DG_COBSERVATION(S): Not applicable HISTOMORPHO_OGOICBSERVATIONS: ADRENALGLANDS: EPIDIDYMIS: PROSTATE: ....................................................................................................... hypertrophy/vacuolation, zona glomerulosa (minimal) infiltration, mononJclear-cell, focal {minimal) inflammation, chronic (mild) THE FOLLOWINGTISSUe(S)WERE WITHIN NORMAL _IMITS: COAGULATINGGLAND PITUITARY SEMINALVESICLES End of Record- 13721 TESTIS .. Page 1045 III-55 ARGUS 418-020 ORAL(GAVAGE)T1VO-6ENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix Ill Gross and Histomorphology Data P Generation ANIHAL NUHBER:13722 SEX: H smimmwm8msm_R_1BzBmm`_imm_zmmz_s8ms_mm_mmm_m_mm_m_8_ms_m_ssm_m_ms_z_IzmmZs_z_8_m_E--m-- DOSEGROUP: V DEATHTYPE: Sacri lice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATIONS: ADRENALGLANDS: EPIDIDYHIS: PROSTATE: ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): Not applicable hypertrophy/vacuolation, zona gl omerulosa (moderate) infiltration, mononuclear-cell, focal (minimal) dilatation, glandular, focal (mild) THE FOLLOWINGTISSUE(S) WER_WITHIN NORHAL_IMTTS: COAGULATINGGLAND PITUITARY SEHINALVESICLES End of Record- 13722 TESTIS III-56 Page 1046 ARGUS 418-020 ORAL(GAVAGE)Tt_O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix llI IndividualAniml 6r_ss and Hist_rphology Data P _neration ANIHAL NUMBER:13728 SEX: N = = = = DOSEGROUP: DEATHTYPE: === V Sacrifice-Scheduled == == = = === === == GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTONORPHO_OGOICBSERVATION(S): Not applicable HISTOHORPHOLOGOICBSERVATIONS: ADRENALGLANDS: ....................................................................................................... hypertrophy/vacuolation, zona glomerulosa (moderate) vacuolation, cortex (minimal) THE FOLLOWINGTISSUE(S) WEREWITHIN NORNALLIHITS: COAGULATINGGLAND EPIDIDYHIS SEHINALVESICLES TESTIS ....................................................................................................... End of Record- 13728 PITUITARY PROSTATE Page 1047 .III-57 ARGUS 418-020 ORAL(GAVAGE}TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3729 SEX: M Individual Appendix III Animal 6ross and Histomorphology Data P 6eneration DOSE6ROUP: DEATHTYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): KIDNEYS:Right- pelvis, slight dilation. No microscopicchange to correlate ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: KIDNEYS: No microscopicchange to correlate ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND EPIDIDYMIS SEMINAL VESICLES TESTIS .................................................. End of Record- 13729 KIDNEYS PROSTATE . .................................................... Page 1048 .III-SB ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Histamorphology Data P Generation ANIMALNUMBER1: 3731 SEX: M DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION[S): GENERAL:No gross changes. ............................................... HISTOHORPHOLOGOICBSERVATIONS: ADRENAL GLANDS: PROSTATE: HISTOHORPHOLOGICOBSERVATION(S): Not applicable . ....................................................... hypertrophy/vacuolationz,ona glomerulosa (mild) inflammation,chronic (mild) dilatation,glandular,focal (minimal) THE FOLLOWINGTISSUE(S}WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13731 SEMINAL VESICLES Page 1049 III-59 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUNPERFLUOROOCTANO{AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 Individual Appendix Ill Animal Gross and Histomorpho]ogy Data P 6eneratton ANIHALNUHBER:13732 SEX: H = z= _= _ = z = GROSSOBSERVATION(S): L[VER: All lobes pale, tan in color, TESTES:Bt]ateral- red. DOSEGROUP: V DEATHTYPE: Sacrifice-Horibund = == z_==========_ =_ == == _z= HISTOHORPHOLOGOICBSERVATION(S): necrosis, centrilobu]ar atrophy/degeneration, multifocal. TESTIS HISTOHORPHOLOGO]CBSERVATIONS: LIVER: TESTIS: End of Record- 13732 necrosis, centrilobular (moderate) atrophy/degeneration, multifocal (marked) . Page 1050 ,III-60 ARGUS 418-020 OPAL (GAVAGE)TWO-GENEPATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO} IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAniml Gross and Hlstomorphol_y Data P Generation ANIMALNUMBER1: 3733 SEX: M DOSEGROUP: DEATHTYPE: V Scheduled (Reduced Fertility) GROSSOBSERVATION(S): EPIDIDYMIDES:Left- small and flaccid, KIDNEYS:Right- pelvis, slight dilation, HISTOMORPHOLOGICOBSERVATION(S): exfoliatedspermatogeniccells, EPIDIDYMIS atrophy, EPIDIDYMIS dilatation,pelvis HISTOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: KIDNEYS: _ exfoliated spermatogenic cells atrophy (moderate) hypospermia (marked) dilatation,pelvis (mild) (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND PROSTATE SEMINAL VESICLES End of Record- 13733 TESTIS o- Page 1051 III-61 ARGUS 418-020 OPAL(6AVA6E) TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMHONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:13734 SEX: M Individual Appendix Ill Animal Gross and Histomorphology Data P Generation DOSE6ROUP: DEATHTYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHO_OGICOBSERVATIONS: ADRENAL GLANDS: PROSTATE: vacuolationocortex (mni_l) inflammation,suppurative,focal (mlniml) THE FOLLOWINGTISSUE(_)WERE WITHIN NORMA_ LIMIT_: COAGULATINGGLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 13734 SEMINAL VESICLES Page 1052 III-62 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPROOUCTIOSNTUDYOFAHHONIUHPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 ANIHAL NUMBER:13735 SEX: M Individual Appendix Ill Antmal Gross and Htstomorphology Data P 6eneration DOSEGROUP: DEATHTYPE: V Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOHORPHDLOGOICBSERVATION(S): Not applicable HISTOHORPHOLOGOICBSERVATIONS: PROSTATE: ....................................................................................................... atrophy, focal (mild) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS SEMINALVESICLES COAGULATINGGLAND TESTIS ....................................................................................................... End of Record- 13735 EPIDIDYMIS PITUITARY Page 1053 1II-63 ARGUS 418-020 ORAL(GAVAGE)llVO-GENERATION(ONE LITTER PERGENERATION} REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3736 SEX: N Individual Appendix III Animal Gross and Histomorphology Data P Generation DOSEGROUP: DEATHTYPE: V Sacrifice-Scheduled GROSSOBSERVATION(S): G_NERA_:No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: ADRENALGLANDS: PROSTATE: hypertrophy/vacuolationz,ona glomerulosa (moderate) inflammation,chronic (minimal} THE FOLLOWINGTISSUE(S}WERE WITHIN NORMA_ LIMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PITUITARY ....................................................................................................... End of Record- 13736 SEMINAL VESICLES Page 1054 .. III-64 ARGUS 418-020 OPAL (GAVAGE)TWO-GENERATIO(ONNE LITTER PER6ENEAATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAniml Gross and Hist_rphol_y P _neration Data ANIMAL NUMBER1: 3741 SEX: M DOSEGROUP: DEATHTYPE: V Scheduled (Reduced Fertility) GROSSOBSERVATION(S): EPIDIDYMIDES: Bilateral- soft and flaccid, TESTES: Bilateral-soft and flaccid, HISTOMORPHOLOGOICBSERVATION(S): hypospermia, EPIDIDYMIS exfoliated spermatogenic cells, EPID1DYMIS atrophy/degenerationm,ultifocal,TESTIS dilatation,rete testis, TESTIS HI)TOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: TESTIS: hypospermia(marked) exfoliatedspermatogeniccells (moderate) dilatation,rete testis atrophy/degenerationm,ultifocal (moderate) THE FOLLOWINGTISSUE(S1 WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND PROSTATE SEMINALVESICLES End of Record- 13741 Page 1055 III-65 ARGUS 418-020 ORAL(GAVA6E)TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 Individual Appendix III Antmal Gross and Htstamorphology Data P Generation ANIHAL NUHBER:13742 SEX: H tm_t tsmm_mmmm mm_mm_smsls_smmtm_ts=_mtssm_m_lmt DOSEGROUP: V DEATHTYPE: Sacri fice-Schedul ed _l_m=l_lft = = =m = al_11===a=mz ----_,a==z==malmm = GROSSOBSERVATION(S: ) GENERAL:No gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S: ) Not app]icabl HISTOHORPHOLOGOICBSERVATIONS: ADRENALGLAND:S ....................................................................................................... hypertrophy/vacuol at i on, zona gl omerulosa (mild) vacuo]ation, cortex (minima]) THE FOLLOWINGTISSUE(S) ;/EREWITHIN NORHALI,IHITS: COAGULATINGGLAND SEHINALVESICLES EPIDIDYHIS TESTIS ....................................................................................................... End of Record- 13742 PITUITARY PROSTATE Page 1056 .o III-66 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUORDOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Individual Appendix III Animal Gross and Htstamorphology Data P 6eneratton ANIMALNUMBER:13743 DOSEGROUP: SEX: M DEATHTYPE: mmmimmmmmmm_mmmmmmms8l_mmmmmzmmm_zsRmgrmm_mm_mmmmmmmwswmmsmmmmms_mE_zzmzfmmi1=m=m_mmmzm_mmmmtm===_ V Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable HI_TOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: PROSTATE: ....................................................................................................... hypertrophy/vacuolation, zona glomerulosa (moderate) inflammation, chronic (minimal) THE FOLLOWINGTISSU[(S) WEREWITHIN NORMALIMITS: COAGULATIN6GLAND EPIDIOYMIS PITUITARY TESTIS ....................................................................................................... End of Record- 13743 SEMINAL VESICLES Page 1057 .. -III-67 ARGUS 418-020 ORAL(6AVAGE)TMO-6ENERATION(ONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHHONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Appendix III IndividualAniml 6_se and Hlstm_rphology Data P _neration ANIMALNUMBER1: 3744 SEX: M DOSEGROUP: DEATHTYPE: V Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLO6O1BCSERVATION(S): Not applicable THE FOLLOWINGTISSUEfS) WEREWITHIN NORMALIMITS: ADRENALGLANDS PROSTATE COAGULATINGLAND SEMINALVESICLES EPIDIDYNIS TESTIS End of Record- 13744 PITUITARY Ili-68 Page 1058 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3750 SEX: M Individual Appendix Ill Animal Gross end Htstomorphology Data P 6eneratlon DOSEGROUP: DEATHTYPE: V Scheduled (Reduced Fertility) GROSS OBSERVATION(S): TESTES: Left- large. HISTOMORPHOLOGICOBSERVATION(S): No microscopic change to correlate, TESTIS HI_TOMORPHOLOGICOBSERVATIONS: PROSTATE: TESTIS: ...................................................... atrophy, focal (minimal) No microscopic change to correlate _ ................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND EPIDIOYMI5 SEMINALVESICLES End of Record- 13750 TESTIS .. Page 1059 1II-69 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-QZO SPONSOR'SSTUDYNUNBERT: -6889.6 Individual Appendix Ill Animal Gross and Histomorphology Data P Generation ANINAL NUHBER:13802 SEX: F _II I --If= =_I II GROSSOBSERVATION(S): GENERAL:No gross changes. _II I HISTOHORPHO_OGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: PITUITARY: UTERUS: VAGINA: DOSEGROUP: DEATHTYPE: -- I --_I= I Sacrifice-Scheduled _I=II =II====sI== ==========_=== HISTOHORPHOLOGOICBSERVATION{S): Not applicable presence of corpora lutea presence of growing/antral fo]licles cyst(s), pars tntermedia macrophages, pigmented (moderate) distention, lumen (mi]d) muciftcation (moderate) THE FOLLOWINGTISSUE(S) WEREWITHIN NORHALUHITS: ADRENALGLANDS CERVIX End of Record- 13802 OVARIES OVIDUCT(S) Page 1060 III-7O ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUNPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix III Gross and Htstoeorphology P Generation Data ANINALNUNBER:13804 SEX: F mmr_miiisi_sImmIz_tRm_ltzsm_mss_ml_sm_mm_m_mmIm_uzi_smm_z_m_Rzmmm_I_mmm_ms_ DOSEGROUP: DEATHTYPE: I Sacrifice-Noribund GROSSOBSERVATION(S): HEAD:Broken palate, ....................................................................................................... HISTOHORPHOLOGOICBSERVATIONS: PALATE: ....................................................................................................... End of Record- 13804 HISTONORPHOLOGOICBSERVATION(S): fracture, PALATE hemorrhage, PALATE fracture hemorrhage (marked) Page 1061 III-71 ARGUS 418-020 ORAL(GAVAGE)T1VO-GENERATIO(ONNE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AHHONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix Ill Animal 6Poss and Histomorphology Data P 6eneration ANIMALNUMBER:13809 SEX: F Im_mImIIIImIIsIImmmImI_sIIIIIsiiIII_IIimIIm_smIImIsImm1m_IIIII_mIII_ImIIsII_sI_IImII_IIIIsI_= DOSEGROUP: DEATHTYPE: I Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... H_STOHORPHOLOGOIBCSERVATION(S): Not applicable HISTOHORPHOLO_OICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: ....................................................................................................... presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALLIHITS: ADRENALGLANDS PITUITARY ............................................................ End of Record- 13809 CERVIX VAGINA OVARIES . .......................................... OVIDUCT(S) =m_=._ =z Page 1062 .. .1II-72 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLUOROOCTANOATE(APFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13811 SEX: F DOSE GROUP: DEATH TYPE: ] Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAl: No gross changes. ................................................ HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: OVARIES: VAGINA: HISTOMORPHO_OGICOBSERVATION(S): Not applicable _ ...................................................... presence of corpora lutea presence of growing/antral cyst(s), intraovarian muctfication (mild) follicles THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: CERVIX OVIDUCT(S) ....................................................................................................... End of Record- 13811 UTERUS .III-/3 Page 1063 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Htstomorphology Data P Generation ANIMALNUMBER:13812 SEX: F 8mmmmmmmmRss_tssmnmmmssm_smmmsgrmsmm_mm_m_smmm_lm_Bma_li_mm_mm_I_zs_1_=_z_ DOSEGROUP: I DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: ....................................................................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWINGTISSUe{S) WER_ WITHIN NORMA_]NITS: ADRENAL GLANDS VAGINA CERVIX OVARIES ....................................................................................................... PITUITARY TISSUE(S)NOT AVAILABLEFOR EVALUATION: OVIDUCT(S) ....................................................................................................... End of Record- 13812 Page 1064 111-74 ARGUS 418-020 ORAL(6AVAGE)TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix III Animal Gross and Histomorphology Data P Generation ANIHAL NUNBER:13814 SEX: F IIIIIIIII_II_I_sI_IIII_BIII_II_IIIIIIIII_III_RIIII_III_IIIIIIIIIII_I_II_III_II_IIsIII_IsII_IIII_I_ GROSSOBSERVATION(S): EAR(S): Swollen. right, DOSEGROUP: DEATHTYPE: I Sacrifice-Scheduled HISTOHORPHOLOGOICBSERVATION(S): chondropathy, auricular HISTOHORPHO_O6OICBSERVATIONS: EAR(S): End of Record- 13814 chondropathy, auricular (moderate) Page 1065 -III-75 ARGUS 418-020 ORAL(GAVAGE)llIO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLLIOROOCTANO(APTFEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal 6ross and Hist_rphology Data P Generation ANIMALNUMBER:13815 SEX: F DOSEGROUP: I DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. HISTOHORPHOLOGOICBSERVATION(SI: Not applicable HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: presence of corpora lutea presenceof grc_ving/antraflollicles UTERUS: macrophages,pigmented {moderate) ....................................................................................................... THE FOLLOWINGTISSUe(S)VERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES --_ ..................................................................................................... End of Record- 13815 OVIDUCT(S) Page 1066 III-76 ARGUS 418-020 ORAL(6AVAGE)TliO-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 ANIMALNUflBER:13816 SEX: F Individual Append|x III Animal Gross end Histomorphology Data P Generation DOSE6ROUP: DEATHTYPE: I Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATIONS: ADRENALGLANDS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: HISTOHORPHOLOGOICBSERVATION(S): Not app]icab]e degeneration, cystic, cortex (minima]) presence of corpora ]utea presence of growing/antra] fo]]icles macrophages, pigmented (minimal) THE FOLLOWINGTISSUE(S) WEREWITHIN NORHALIHITS: CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13816 PITUITARY III-77 Page 1067 ARGUS 418-020 ORAL(RAVAGE)T_Q-GENERATION(ONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHNONIUNPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix III Animal Gross and Htstomovphology Data P 6eneration ANIHALNUHBER:13821 SEX: F IIIIIa"iIII_IImI_IIIIIIIIIIIII_IIIIIIII_III_Ig"sIIII_I_II_IIIIII_I_IIsIIIIIIIII_I GROSSOBSERVATION(S): GENERALN: o gross changes. ........................................... HISTOHORPHOLOGOICBSERVATIONS: ADRENALGLANDS: OVARIANFOLLICLES/CORPORLAUTEA: OVARIES: UTERUS: DOSEGROUP: DEATHTYPE: I Sacrifice-Scheduled IIII I ImIl_ =I _ I _II HISTONORPHOLOGOICBSERVATION(S): Not applicable _ ........................................................... hypertrophy/vacuolation, zone glomerulosa presence of corpora ]utea presence of growtng/antral follicles cyst(s), intraovarian macrophages, pigmented (mild) (minima]) THE FOLLOWINGTISSUE(S) WEREWITHIN NORHALLIHITS: CERVIX OVIDUCT(S) End of Record- 13821 PITUITARY VAGINA Page 1068 ,III-78 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -3889.6 Individual Appendix III Animal 6ross and Htstomorphology Data P 6eneration ANIMAL NUHBER:138ZZ SEX: F mmImmmmmmmImmmmIIImmImmmImmIIIIImmmmImm_mIImmmmImmmmmImmIImImmIIIIImmIIIIIImII_III_III_II===_===_Is DOSEGROUP: DEATHTYPE: I Sacrifice-Moribund GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGOICBSERVATIONS: OVARIANPOLLICLES/CORPORLAUTEA: UTERUS: ....................................................................................................... presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWINGTISSUE(S) WEREWITHIN NORHALIMITS: ADRENALGLANDS PITUITARY CERVIX VAGINA ....................................................................................................... End of Record- 13822 OVARIES OVIDUCT(S) Page 1069 III-79 ARGUS 418-020 ORAL(GAVAGE}TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNLIHBERT: -6889.6 Individual Appendix III Animal Gross and Histomorphology Data P Generation ANIHALNIJHBER:13824 SEX: F DOSEGROUP: DEATHTYPE: mimiImmns_mmmmmmm_mmimsRsmmmmlRmmmzmms_m_m_MBimm_mm_imm_81wmsz1_smm_sEsm_mm_m_m_zm_=_=_1=s_= I Sacrifice-Scheduled GROSSOBSERVATION{S): GENERAL:No gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION{S): Not app]icable HISTOHORPHO_OGOICpSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: presence of corpora lutea presence of growing/antra1 follic]es macrophages, pigmented (moderate) THE FOLLOWINGTISSUE(S) WEREWITHIN NORNALLIHITS: ADRENALGLANDS PITUITARY CERVIX VAGINA End of Record- Z3824 OVARIES OVIDUCT(S) Page 1070 III-80 ARGUS 418-020 ORAL (RAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL418-020 SPONSOR'SSTUDYNUMBERT: -6889.B Appendix III IndividualAnimal Gross and HistomorphologyData P _neration ANIMAL NUMBER: 13825 SEX: F mm_msmmmmmmmmm_mm_smmm1mm_smimEm_smm_mmmmmmtmmm1nmm_s_m_mm_1_mmt_s_i_m_m_1_z_m_ GROSS OBSERVATION(S): EAR(S):Swollen, both. DOSE GROUP: DEATH TYPE: I Sacrifice-Scheduled HISTOMORPHOLOGICOBSERVATION(S): chondropathy,auricular HISTOMORPHOLOGICOBSERVATIONS: EAR(S): OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: chondropathy, auricular (marked) presence of corpora lutea presenceof growing/antralfollicles macrophages,pigmented (moderate) / THE FOLLOWINGTISSUE(S)W[RE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13825 . Page 1071 III-81 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATWEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:13826 SEX: F Individual Appendix III Animal Gross and Hlstomorphology Data P 6eneretlon DOSEGROUP: DEATHTYPE: I Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: OVARIES: UTERUS: H_STOMORPHOLOGOIBCSERVATION[S): Not applicable presence of corpora lutea presence of growing/antra] follicles cystic bursa(e) macrophages, pigmented (minimal) THE FOLLOWINGTISSUE(S)WER_ WITHIN NORMAL _IMITS: ADRENAL GLANDS CERVIX OVIDUCT(S) ....................................................................................................... TISSUE(S)NOT AVAILABLE FOR EVALUATION: VAGINA End of Record- 13826 PITUITARY Page 1072 .- lll-8Z ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUOYNUHBERT: -688g.6 ANIMALNUMBER1: 3836 SEX: F Appendix III IndividualAniml Gross and Hist_rphology Data P Generation DOSEGROUP: DEATHTYPE: II Sacrifice-Moribund GROSSOBSERVATION{S): HISTONORPHOLOGOICBSERVATION(S}: EXTREMITIES:Swollen limbs, left front leg, left fracture front paw. ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: EXTREMITIES: End of Record- 13836 fracture Page 1073 -III-83 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Htstomorphology Data P Generation ANIMAL NUMBER: 13840 SEX: F DOSE 6ROUP: DEATH TYPE: II Scheduled (ReducedFertility) GROSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: presenceof corpora lutea presenceof growing/antralfollicles THE FOLLOWINGTISSUE(S)W{RE WITHIN NORMA_ LIMIT_: CERVIX VAGINA OVARIES OVIDUCT(S) ....................................................................................................... End of Record- 13840 UTERUS Page 1074 o ,III-84 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IIl Animal 6ross end Htstomorphology Data P Generation ANIMALNUMBER1: 3851 DOSEGROUP: SEX: F DEATHTYPE: 1mmmm_mmnmmmlmu_mmmmm_lsmmmIm_lmm_m_m_l_mmmmmmmmmnm_mmI_lmlwmmmm_zsmmtsfmm_mmmmz_m=R=_ll_mm_ II Scheduled (Reduced Fertility) GROSSOBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLDOOICBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: UTERUS: ....................................................................................................... presenceof corpora lutea presenceof growing/antralfollicles distention, lumen (marked) THE FOLLOWINGTISSUE{S)WERE WITHIN NORMAL LIMITS: CERVIX OVARIES OVIDUCT(S) ....................................................................................................... End of Record- 13851 VAGINA Page 1075 .. III-85 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -5889.6 Individual Appendix III Animal Gross and Histamorphology Data P Generation ANIMALNUMBER1: 3856 SEX: F slmlmmS_mm=msmz_l_mmmzm2_22== GROSS OBSERVATION{S): EAR(S): Swollen,right, 2 _mmz_msln_m_m_mms_m_= DOSEGROUP: DEATHTYPE: _ smm_zmmm_m_m_m_m_ II Sacrifice-Scheduled = 2zt _=222 2 2 2 2 = 22222 HISTOMORPHOLOGICOBSERVATION(S): chondropathy,auricular HISTOMORPHOLOGICOBSERVATIONS: EAR(S): End of Record- 13856 chondropathy,auricular (marked) Page 1076 .. III-86 ARGUS 418-020 ORAL(GAVAGE)"r_O-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AHMONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAnimal 6r_ss and Histm_rphology Data P _neration ANIMALNUMBER1: 3862 DOSEGROUP: SEX: F DEATHTYPE: _mmmmzm_ssm_ws_lmS_z_z_I_mzmmsmmmmmmm_m_m_mmm_Ia_wmmm_mmm_mm_m_mm_m_mm_m_mm_zm_m_mm__z_ III Scheduled (Reduced Fertility) GROSSOBSeRVATION(S): EAR(S): Swollen, both. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGOICBSERVATIONS: EAR(S): OVARIANFOLLICLES/CORPORLAUTEA: ....................................................................................................... chondropathy, auricular (marked) presence of corpora lutea presence of growtng/antral follicles TH_ FOLLOWINGTISSUe(S) WEREWITHIN NORMALIMITS: CERVIX VAGINA OVARIES ....................................................................................................... End of Record- 13862 OVIDUCT(S) UTERUS Page 1077 111-87 ARGUS 418-020 ORAL(GAVAGE)llJO-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAniml 6ross and Hist_r1_hology Data P Generation ANIMALNUMBER:13869 SEX: F ssmm_mms_smS_mz_zIi_l_mzmzm_m_m__mzEss8_w_1iz_8m_mZmzmm_z_sm_lzz_m_z_z_ DOSEGROUP: DEATHTYPE: IIl Sacrifice-Scheduled GROSSOBSERVATION(SI: EYES: Traumatized cornea, ....................................................................................................... HISTOMORPHOLOGOICBSERVATION(S): keratitis, cataract chronic HISTOMORPHOLOGICOBSERVATIONS: EYES: End of Record- 13869 keratitis,chronic (moderate) cataract Page 1078 .. III-88 ARGUS 418-020 ORAL(BAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3885 SEX: F Appendix III IndividualAnimal Gross and Hist_rphol_y P _neration Data DOSEGROUP: III DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): HISTOMORPHOLOGOICBSERVATION(S): KIDNEYS:Left- pelvis,marked dilation. Tissue not available ....................................................................................................... TISSUE(S)NOT AVAILABLEFOR EVALUATION: KIDNEYS ....................................................................................................... End of Record- 13885 Page 1079 III-89 ARGUS 418-020 ORAL(GAVABE)TldO-fiENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.B ANIMALNUMBER:13898 SEX: F Appendix III IndividualAniml Brass and Hlst_rphology Data P Generation DOSE6ROUP: DEATHTYPE: IV Sacrifice-Scheduled 6ROSSOBSERVATION(S): EAR(S): Swollen. right, ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: EAR(S): ....................................................................................................... End of Record- 13898 HISTOMORPHOL06OICBSERVATION(S): chondropathy, auricular chondropethy, auricular (marked) Page 1080 .o III-90 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 3900 SEX: F Individual Appendix III Animal 6ross and Htstomorphology Data P Generation DOSEGROUP: DEATHTYPE: IV Scheduled (Reduced Fertility) GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... TISSUE(S] NOT AVAILABLEFOREVALUATION: CERVIX OVARIANFOLLICLES/CORPORLAUTEA OVARIES OVIDUCT(S) UTERUS VAGINA ....................................................................................................... End of Record- 13900 HISTOMORPHOLOGOIBCSERVATION(S}: Not applicable Page 1081 .III-91 ARGUS 418-020 ORAL(GAVAGE}TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOTSTUDY OF AMMONIUM PERFLUOROOCTANOATE(APFO) IN RATS PROTOCOL 418-020 SPONSOR'SSTUDY NUMBER:T-6889.6 Appendix III IndividualAnimal Gross and HistomorphologyData P Generation ANIMAL NUMBER: 13901 SEX: F mm_si=_mms_=zmmz_=i_ms_s_i_==1_Is=8_sisI_tam_ss_tim_i8mw=muiazz_=mwz=siZ_zsml==_=_zZ==z_=_====== DOSE GROUP: DEAT:ITYPE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen, right, HISTq'ORPHOLOGICOBSERVATION(S): chond opathy, auricular HISTOMORPHOLOGICOBSERVATIONS: EAR(S): End of Record- 13901 chondropathy,auriG.lar (moderate) Page 1082 . III-92 ARGUS 418-020 ORAL(C_VAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Individual Appendix Ill Animal Gross and Histomorphology Data P 6eneratton ANIMAL NUMBER:13908 SEX: F DOSEGROUP: IV DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen, right, HISTOMORPHO_OGICOBSERVATIONS: EAR(S): End of Record- 13908 HISTOMORPHOLOGICOBSERVATION(S): chondropathy,auricular chondropathy, auricular (mild) Page 1083 III-93 ARGUS 418-020 ORAL(6AVAGE)I_O-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 ANIHAL NUMBER1: 3921 SEX: F Individual Appendix Ill Animal Gross and Histomorphology Data P 6eneration DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAl:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: HISTOMORPHO_OGOICBSERVATION(S): Not applicable presence of corpora l utea presence of growing/antra1 follicles macPophages, pigmented (moderate) THE FOLLOWZNTGISSUE(S) WEREWITHIN NORHAL_IMITS: ADRENALGLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13921 OVIDUCT(S) Page 1084 .... o ,III-94 ARGUS 418-020 ORAL(RAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix III Gross and Histomorphology Data P Generation ANIMAL NUMBER: 13922 SEX: F DOSE GROUP: OEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S}: GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: UTERUS: presenceof corpora lutea presenceof growing/antra]follicles _crophages, pigmented(moderate) THE FOLLOWINGTISSU{(S)WER{ WITHIN NORMAL LIMITS: ADRENALGLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13922 OVIDUCT(S) Page 1085 .. III-95 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Histomorphology Data P Generation ANIHALNUMBER1: 3927 DOSEGROUP: SEX: F DEATHTYPE: mmmmmmmmmmmsms_smmmmsmmmmmlmmm_sm_1mmmsm_mmmm_mmmmmmmImm_1Rmmsm_zimmm_zmmmm1_11B_si_m_m_mm_m_ V Sacrifice-Scheduled GROSSOBSERVATION(S): EAR(S): Swollen, right, ....................................................................................................... HISTOHORPHOLOGOICBSERVATIONS: EAR(S): ....................................................................................................... End of Record- 13927 HISTOHORPHOLOGOICBSERVATION(S): chondropathy, auricular chondropathy, auricular (marked) Page 1086 .III-96 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUMPERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 ANIMALNUMBER:13928 SEX: F Individual Appendix III Animal 6ross end Htstomorphology Data P 6eneration DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S}: GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATION(S}: Not applicable HISTOHORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: ....................................... presence of corpora 1utea presence of growing/antral follicles macrophages, pigmented (mi]d) distention, lumen (mild) _ ............................................................... THE FOLLOWINGTISSUE[S) WEREWITHIN NORMALIH|TS: ADRENALGLANDS ..................................................... OVARIES OVIDUCT(S) . ................................................. PITUITARY TISSUE(S} NOTAVAILABLEFOR EVALUATION: CERVIX VAGINA ..................................................... End of Record- 13928 . ................................................. Page 1087 .. -III-97 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal 6ross and Htstomorphology Data P 6eneration ANIMALNUMBER1: 3929 SEX: F DOSE6ROUP: DEATHTYPE: V Scheduled (Reduced Fertility) GROSSOBSERVATION(SI: GENERALN: o gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: OVARIES: UTERUS: HISTOMORPHOLOGOICBSERVATION(S): Not applicable absence of corpora lutea presenceof growing/antralfollicles cyst(s), intraovarian distention,lumen (moderate) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: CERVIX OVIDUCT(S) VAGINA End of Record- 13929 Page 1088 o. Ill-gB ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Animal Gross and Histomorphology Data P Generation ANIMALNUHBER:13933 SEX: F _mIIII_m_IIm_II_m_I_ImmIIII_IIm_IIm_l_IIII_llmm_II_IllIs1mI_I_IIIIIIsII_tIIIII_IIIIIIIImIIIIIII_m GROSSOBSERVATION(S): GENERALN: o gross changes. DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled HISTOHORPHOLDGOICBSERVATION(S): Not applicable HISTOHORPHOLOGOICBSeRVATiONS: ADRENALGLANDS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: degeneration, cystic, cortex (minimal) presence of corpora lutea presence of growing/antral follicles gland(s), endomatrial, cystic macrophages, pigmented (mild) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: CERVIX VAGINA OVARIES OVIDUCT(S) End of Record- 13933 PITUITARY .. Page 1089 .III-99 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHHONIIJMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix III Animal Gross end Histomorphology Data P Generation ANIHAL NIJMBER1: 3934 SEX: F DOSEGRq_: DEATHT?ME: V Sacrifice-Schedu]ed GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTONORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: ....................................................................................................... presence of corpora lutea presence of growing/antra1 follicles macrophages, pigmented (moderate) TH_ FOLLOWINGTISSUE(S) WEREWITHIN NORHALLIMITS: ADRENALGLANDS PITUITARY .............................................................................. End of Record- 13934 CERVIX VAGINA OVARIES OVIDUCT{S) . ........................ Page 1090 . III-I00 ARGUS 418-020 ORAL(RAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L1B-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix III IndividualAniml Gross and Hist_rphology Data P _neration ANIMALNUMBER:13935 SEX: F mtm_mmm_mlswmm_mm_sBm_lmlmmzsw=_m_mm_lmmm_mINmmmm_mmmm_m_w_m_m_ts_ DOSEGRO_P: DEATHTylm: V Sacrifice-Scheduled _w_m_ mm z_s _ Bi GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: presence of corpora l utea presence of growing/antral follicles macrophages, pigmented (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY ............................................ End of Record- 13935 CERVIX VAGINA OVARIES OVIDUCT(S) . .......................................................... Page 1091 III-101 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFD) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix Ill IndividualAnimal Gross and Histmrphol_y P Generation Data ANIMAL NUMBER:13936 SEX: F DOSEGRg_P: DEATHTlqlE: smmmmmmwsim==_za_zm_m_mmmmmzm===zsmmmm_s_mi_Rm1_m_mmm_s=_zmm_mmmmm_m_=_zm_mz_=_ms_==s8Z_sm=_m= V Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ................................................. H_STOMORPHOLOGOIBCSERVATION(S): Not applicable _ ..................................................... HISTOMORPHOLOGOTBCSERVATIONS: CERVIX: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: dilatation (moderate) presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (marked) THE FOLLO_;NGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANOS VAGINA OVARIES OVIDUCT(S) End of Record- 13936 PITUITARY -.--.._m.._ Page 1092 .o . 3 -- III-i02 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMAL NUMBER: 13942 SEX: F Individual Appendix Ill Animal 6ross and Histomorphology Data P Generation DOSE GROUP: DEATH TIDE: V Sacriflce-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: presenceof corpora lutea presenceof growing/antralfollicles UTERUS: macrophages,pigmented (moderate) ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES ....................................................................................................... End of Record- 13942 OVIDUCT(S) Page 1093 III-I03 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PRDTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix III Antmal 6ross and Histomorphology Data P emneratton ANIMALNUMBER1: 3943 SEX: F l_ll_l_lll_lll_lllll_lll_l_ll_lll_l_s_llll_lllllll_lz_l_llll_llllllzl_llEl_ill_l_l DOSEGROUP: V DEATHT_E: Sacrifice-Scheduled _lilll= GROSSOBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ....................................................................................................... H_STOMORPHOLOGICOBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: presence of corpora lutea presenceof growing/antralfollicles UTERUS: macrophages,pigmented (moderate) ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES ....................................................................................................... End of Record- 13943 OVIDUCT(S) Page 1094 HI-104 ARGUS 418-020 ORAL(BAVABE)TWO-BENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendlx III Animal Gross and Htstomorphology Data P 6eneration ANIMALNUMBER1: 3944 SEX: F _mm_s_s_m_sw_s_m_i8s_m_mm_ji_s_sm_z_m_sz=_=_====_=_=_s_=_=_ DOSE6ROUP: DEATHT$1E: V Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAl: No gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: ....................................................................................................... presence of corpora lutea presence of growing/antra1 follicles n_cropheges, pigmented (moderate) distention, lumen (minimal) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 13944 OVIDUCT(S) Page 1095 . 1.11-105 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATPEFO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix Ill Animal Gross and Htstomorphology Data P 6eneration ANIMAL NUMBER: 13946 SEX: F 1m_tRmmmnm_t_ismsmmlssRma_m_s_m_s_m_m_tm_miRsRB_1_mw_E_mBB_m_i_ms_I=_s_=_== GROSS OBSERVATION(S): EAR(S): Swollen. DOSE GROUP: V DEATH T_Iz_: Sacrifice-Scheduled HISTOMORPHOLOGICOBSERVATION(S): chondropathy, auricular HISTOMORPHOLOGOICBSERVATIONS: EAR(S): End of Record- 13946 chondropathy, auricular (moderate) Page 1096 Ill-t06 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 IV INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA F1 Generation KEY TO CORRELATION OF HISTOMORPHOLOGIC OBSERVATIONS Not applicable = Microscopic evaluationlcorrelation by protocol. not appropriate or not required . Page 1097 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUMBER1: 003 SEX: M smmm_Rmmm_mw_mmms_m_sm_m_mmmm_mmmismmmmmmmm_a_mi_mli_mmm GROSSOBSERVATION(S): GENERALN: o gross changes. HISTOMORPHOLOGOICBSERVATIONS: EPIDIDYMIS: infiltration, DOSE6R_J_P: I DEATHTI_WE: Sacrifice-Scheduled _zm_zzm _zzm_zzs_ s_ _ HISTOMORPHOLOGOICBSERVATIONIS): Not applicable mononuclear-ce11, focal (minimal) THE FOLLOWINGTISSUE(S) WERE WITHIN NORMALIMITS: ADRENALGLANDS SEMINAL VESICLES COAGULATINGLAND TESTIS End of Record- 1003 PITUITARY PROSTATE IV-1 Page 1098 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniml Gross and Hist_rphology Data FI Generation ANIMAL NUMBER: 1012 SEX: M DOSE GRp,_P: I DEATH T_PE: Scheduled (ReducedFertility) GROSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOIGC OBSERVATION(S}: Not applicable THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL [,IMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1012 SEMINAL VESICLES Page 1099 IV-2 ARGUS 418-020 ORAL(GAVAGE)T'a'O-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal 6ross and Hist_rphology Data FI Generation ANIMAL NUMBER: 1017 SEX: M DOSE GR{_I_P: I DEATH T_E: Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAl:No gross changes. Not applicable ........................................................................................................ HISTOMORPHOLOGICOBSERVATIONS: ADRENAL 6LANDS: .................................................... vacuolation,cortex (minimal) . ................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: CDAGULATINGGLAND EPIDIDYMIS PITUITARY SEMINAL VESICLES TESTIS ....................................................................................................... End of Record- 1017 PROSTATE IV-3 Page 1100 ARGUS 418-020 ORAL(GAVAGE)TWO*GENEP.ATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorphology Data Frl Generation ANIMALNUMBER:1018 SEX: M DOSEGR_,J_P: I DEATHTImPE: Sacrifice-Moribund GROSS OBSERVATION(S): EYES: Corneal opacity, both eyes. HISTDMORPHDLOGICOBSERVATIONS: EYES: .......................................................... End of Record- I018 HISTOMORPHOLOGICOBSERVATION(S): inflammation,chronic, iris neuropathy,optic nerve(s) inflammation,chronic, iris (moderate) neuropathy,optic nerve(s) (moderate) _ ............................................. IV-4 Page 1101 ARGUS 418-020 ORAL(6AVAGE}llVO-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Appendix IV IndividualAnimal 6ross end Miztomorphol_y Data FI _neration ANIMALNUMBER1: 019 SEX: M DOSEGRIP: I DEATHTlmlmE: Sacrifice-Moribund GROSSOBSERVATIONIS): EYES: Corneal opacity, both eyes. ........................................... HISTOMORPHOLOGICOBSERVATIONS: EYES: End of Record- 1019 HISTOMORPHOLOGOICBSERVATION(S): inflammation, chronic, iris neuropathy, optic nerve(s} . ............................................................ inflammation,chronic,iris (moderate) neuropathy,optic nerve(s) (moderate) .. Page 1102 IV-5 ARGUS 418-020 ORAL (GAVAGE)TWO-6ENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(AFPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data F'I 6eneration ANIMAL NUMBER: 1020 SEX: M DOSE GRpJ_P: I DEATH T_qWE: Sacrifice-Moribund GROSS OBSeRVATION(S): EYES: Corneal opacity, both eyes. HISTDMORPHOLOGICOBSERVATION(S): No microscopic change to correlate HISTOMORPHOLOGICOBSERVATIONS: EYES: ............................................ No microscopicchange to correlate . ........................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: EYES ........................................................................................................ End of Record- 1020 IV-B Page 1103 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(AFPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal Gross and Htstomorphology Data F1 6eneration ANIMAL NUMBER: 1022 SEX: M m_m_=_=_=_=_=_=_m_zm_m_.mrJ_l_=it=__=_= GROSSOBSERVATION(S): H_AO: Lesion, left side, l.Ocm in diameter, DOSE GROL_P: DEATH T_PE: I Sacrifice-Scheduled = ===mm= = = == == = == = = = == H_STOMORPHOLOOGBICSERVATION(S): dermatitis,ulcerative,SKIN (GROSS LESION) HISTOMORPHOLOGICOBSERVATIDNS: SKIN (GROSS LESION): End of Record- 1022 dematitis, ulcerative (moderate) IV-7 Page 1104 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(AFPO) IN RATS PRC)TOCOL418-020 SPONSOR'SSTUDY NUMBER:T-6889.6 Appendix IV IndividualAnimal 6ross and HlstomorphologyData FI Generation ANIMAL NUMBER: 1024 SEX: M GROSS OBSERVATION(S): LUNG: Mottled dark red, all lobes, HISTOMORPHOLOGICOBSERVATIONS: LUNG: End of Record- 1024 DOSE GR(_t_P: I DEATH TImVE: SpontaneousDeath HISTOMORPHOLOGICOBSERVATION(S): hemorrhage,multifocal hemorrhage,multifocal (mild) IV-8 Page 1105 ARGUS 418-020 ORAL(GuWAGET) WO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHNONIUNPERFLUOROOCTANO(ATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and H1stomorphology Data F'I Generett on ANIMALNUMBER:1026 SEX: M DOSEGRIP: I DEATHT'PPE: Sacrifice-Scheduled GROSSOBSERVATION(S): EYES: Right eye enlarged, HISTOMORPHOLOGOIBCSERVATION(S): atrophy,retinal, focal atrophy, iris/ciliarybody HISTOMORPHOKOGICOBSERVATIONS: ADRENAL GLANDS: EYES: vacuolation,cortex (minimal) atrophy,retinal,focal (mild) atrophy, iris/ciliarybody (marked) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY End of Record- 1026 PROSTATE Page 1106 IV-9 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PRO,TOCO41L8-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data F1 Generation ANIMAL NUMBER: 1034 SEX: M DOSE GROUP: DEATH T_mE ====================================================================================================== I Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL: No gross changes. Not applicable ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATINGGLAND SEMINALVESICLES EPIDIDYMIS TESTIS End of Record- 1034 PITUITARY Page 1107 . IV-lO ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Mistomorphology Data F1 Generation ANIMAL NUMBER: 1035 SEX: M = DOSE GROUP: I DEATH T_E: Sacrifice-Scheduled : == == = _ = =_======= ===== GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENAL GLANDS PROSTATE COAGULATINGGLAND SEMINAL VESICLES EPIDIDYMIS TESTIS End of Record- 1035 PITUITARY Page 1108 . IV-t1 ARGUS 418-020 ORAL(GAVAGE)TI40-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal (iross and Histomorphology Data F1 6eneration ANIMALNUMBER1: 040 SEX: M III_I_mIII_IIu_III_I_IIIm_II_I_III_II_III_mIIII_IIII_II_I_IIIIIIIIIII_=_I_II_II==I===_III_= GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE_RO_P: I DEATHTINmE: Scheduled (Reduced Fertility) HISTDMORPHO_OGICOBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1040 SEMINALVESICLES Page 1109 o. IV-12 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data F1 Generation ANIMALNUMBER1: 047 SEX: H DOSE6R(_: DEATHT_PE: I Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. .......................................... H_STOMORPHOLOGOIBCSERVATIONS: EPIDIDYMIS: PROSTATE: HISTOHORPHOLOGOICBSERVATION(S): Not applicable _ ............................................................ infiltration, mononuclear-cell, focal inflammation, chronic (mild) dilatation, glandular, focal (mild) (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATINGGLAND PITUITARY End of Record- 1047 SEMINAL VESICLES Page 1110 IV-13 ARGUS 418-020 ORAL(GAVAGE)TI,'O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Appendix IV IndividualAniml Gross and Hist_rphology Data FI _neration ANIMALNUMBER1: 048 SEX: M DOSEGR(_J_P: I DEATHTI_uE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTOHORPHDLOGOICBSERVATION(S): Not applicable TH[ FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS COAGULATINGLAND PROSTATE SEHINALVESICLES ........................................................................................................ End of Record- 1048 EPIDIDYNIS TESTIS PITUITARY Page 1111 o. IV-14 ARGUS 418-020 ORAL(GAVAGE)lldO-GENERATION(ONE LITTER PER 6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal Gross and HistomorphologyData FI _mneration ANIMAL NUMBER:1051 SEX: M DOSEGR_L_P: I DEATHTIlmE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAl: No gross changes. ....................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable _ ................................................ HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: vacuolation,cortex (minimal) TESTIS: atrophy/degenerationm,ultifocal (minimal) ........................................................................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND SEMINALVESICLES EPIDIDYMIS PITUITARY ....................................................................................................... End of Record- 1051 PROSTATE Page 1112 IV-15 ARGUS 418-020 ORAL(GAVAGE)"II_-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data FZ Generation ANIMAL NUMBER: 1052 SEX: M DOSE GRIP: I DEATH TT_wE: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. .......................................... HISTOMORPHOLOGICOBSERVATION(S}: Not applicable . ............................................................ HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: vacuolation,cortex (minimal) ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND SEMINALVESICLES EPIDIDYMIS TESTIS PITUITARY ........................................................................................................ End of Record- 1D52 PROSTATE Page l 113 .. IV-16 ARGUS 418-020 OPAL(fiAVAGE)TWO-GENEPATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO{AATFEPO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 Appendix IV IndividualAnimal Gross and Histomrl)_logy Data FI Generation ANIMALNUMBER1: 054 SEX: H DOSEGROUP: I DEATHT_IE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. HISTOMORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: PROSTATE: infl,_nmationc,hronic (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL _IMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATINGGLAND TESTIS EPIDIDYMIS End of Record- 1054 PITUITARY Page 1114 . . 3 ._ IV-17 ARGUS 418-020 ORAL(6AVAGE)TI40-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUNPERFLUORDOCTANO(AATFERO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Htstomorphology Data F1 6eneratton ANIMALNUMBER:1063 SEX: H DOSE6ROJ_P: 11 DEATHT' _mE: Sacri ft ce-Schedul ed 6ROSSOBSERVATION(S): 6ENERAL:No gross changes. ................................................. HISTOHORPHOLOGOICBSERVATION(S): Not applicable . ...................................................... THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIHITS: ADRENAL6LANDS End of Record- 1063 IV-18 Page 1115 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889,6 Individual Appendix IV Animal Gross and Histomorphology Data FI Generation ANIMALNUMBER1: 066 SEX: M _-_-mm_mss_Izsi=mi_zsmmm_mz_mzm=_=_ra_s_mmmmura_mm_mm_s_i_tis_ms_m_s_m_mIzw_m_zm==_z_s_==_n_=z_= DOSE6R[_P: DEATHTf_E: I! Scheduled (Reduced Fertility) GROSS OBS{RVATION(S): GENERAL:No gross changes. _--. .................................................... HISTOMORPHOLOGICOBSERVATION(S): Not applicable . ................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PROSTATE End of Record- 1066 SEMINAL VESICLES Page 1116 IV-19 ARGUS 418-020 ORAL(BAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMHONIUMPERFLUOROOCTANO(AATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorphalogy Data F1 6eneration ANIMAL NUMBER: 1077 SEX: M DOSE 6RQJ_P: II DEATH TTPE: Scheduled(ReducedFertility) 6ROSS OBSERVATION(S): H)STOHORPHOLOGICOBSERVATION(S): GENERAl:No gross changes. Not applicable ....................................................................................................... HISTOHORPHOLOGICOBSERVATIONS: PROSTATE: inflammation,chronic {minimal) THE FOLLOVIN6TISSUE(S)VERE WITHIN NORMAL LIMITS: COAGULATINGGLAND EPIDIDYMIS SEMINAL VESICLES ....................................................................................................... End of Record- 1077 TESTIS m I V - - 2 0 Page 1117 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERAT10(NONELITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUMBER:1078 SEX: M DOSEGRQJ_P: II DEATHTY_E: Sacrifice-Scheduled GROSS OBSERVATION{S): GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATION{S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: vacuolatlon,cortex (minimal) ........................................................................................................ End of Record- 1078 IV-Z1 Page 1118 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMAL NUMBER: 1082 SEX: M DOSE GRq_LP: II DEATH TY_hE: Scheduled(ReducedFertility) GROSS OBSeRVATION(S): HISTOMORPHOLOGICOBSERVATION(S): EPIDIDYMIDES:Left- small. No microscopicchange to correlate, EPIDIDYMIS TESTES: Left- small, flaccid. No microscopicchange to correlate,TESTIS ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: EPIDIDYMIS: TESTIS: ....................................................................................................... No microscopic change to correlate No microscopic change to correlate THE FOLLOWINGTISSUEIS) WEREWITHIN NORMAL_IMITS: COAGULATINGGLAND TESTIS EPIDIDYMIS PROSTATE ........................................................................................................ End of Record- 1082 SEMINALVESICLES Page 1119 .. _. - . _. IV-22 ARGUS 418-020 ORAL(GAVAGE)I't,K)-6ENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONILMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Appendix IV IndividualAnimal Gross and HlstomorphologyData FI _neration ANIMALNUMBER:1096 SEX: N DOSE6RO_P: DEATHTAPE: II Sacrifice-Scheduled 6ROSSOBSERVATION(S): 6ENERAL:No gross changes. ....................................................................................................... HISTONORPHOLOGOICBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S) WEREWITHIN NORNALLIMITS: ADRENAL6LANDS ................................... End of Record- 1096 . .................................................................... Page 1120 IV-23 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Indlvldual Appendix IV Anlmal Gross and H1stomorphology Data F1 6enerati on ANIMALNUMBER:1098 SEX: N DOSEGROUP: DEATHT_I_: II Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ----. ..................................................................................................... THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALLINITS: ADRENALGLANDS ................................................................ End of Record- 1098 HISTOHORPHOLOGOICBSERVATION(S): Not applicable _ ....................................... IV-24 Page 1121 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data F1 _neration ANIMAL NUMBERl:lO0 SEX: M 8mmm_m_i_wism_m_mmmmmm_s_m_mmmmmm_mm_mmmm_m_mmmss_m_s_lz_t GROSSOBSERVATION(S): 6ENERAL:No gross changes. ............................................... HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: ................................................ End of Record- 1100 DOSE6Rq_P:: II DEATHTY_E:: Sacrifice-Scheduled z_= ==_ HISTOMORPHOL06OICBSERVATION(S): Not applicable _ ........................................................ vacuolation, cortex (minimal) _ ....................................................... Page 1122 IV-25 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and H(stomorphotogy Data FI Generation ANIMALNUMBER1: 106 SEX: M III=I=rl_IIIImIIIII==_===IiIIII==_=II==_===II_IIIIIImw_1sII_-_sIIs_=m_III_iI====_==II_=_=_====_====== GROSS OBSERVATION(S): 6ENERAI_:No gross changes. THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALEl_ANDS End of Record- 1106 DOSEGRqW,P: II DEATHTYIm:_ Sacri fice-Schedu] ed HISTOMORPHOLOGICOBSERVATION(S): Not applicable Page 1123 'IV-26 ARGUS 418-020 ORAL(6AVAGE)TVO-6ENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUHPERFLUOROOCTANO(ATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data FI _neration ANIMALNUMBER1: 107 SEX: M ms_m_ szm_ _ _ mm_s mm_ _ m __m_mm_c-_mmm_sz_zlmmmmmmm GROSSOBSERVATION(S): GENERAL:flo gross changes. DOSEGRqI_P: II DEATHTYI_: Sacrifice-Scheduled _ z_ _ _ _ HISTOHORPHOL06IOCBSERVATION(S): Not applicable HISTOMDRPHOLOGOICBSERVATIONS: ADRENALGLANDS: End of Record- 1107 vacuolation, cortex (minimal) _ _mz Page 1124 1V-27 ARGUS 418-020 ORAL(GAVAGE)T1VO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.B Appendix IV IndividualAnimal 6ross and Hist_rphology Data FI Generation ANIMALNUMBER1: 116 SEX: M DOSEGR(_JJ_: II DEATHTYleE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. .................................................... HISTOMORPHOLOGOICBSERVATION(S): Not applicable . ................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1116 Page 1125 IV-28 ARGUS 4 ! 8-020 ORAL(6AVAGE)TldO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMNONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniml Gross and Hist_rphol_y FI Generation Data ANIMALNUMBER1: 118 SEX: M DOSEGROUP: II DEATHT_: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. THE FOLLOWINGTISSUE{S) WEREWITHIN NORMAL_NITS: ADRENALGLANDS End of Record- 1118 HISTOMORPHOLOGOICBSERVATION(S): Not applicable IV-29 Page 1126 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANHONIUNPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNIJNBER:T-6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 _ratic_ ANIMALNUMBER1: 120 SEX: M mlssl_ElmisImml_lsB_m_m_m_l_ll_s_i_smm_Nsllsmz_lsRmlsm_lmmmls_z_Bz_m_z_z_=====l=====z=== GROSSOBSERVATION(S): GENERALN: o gross changes. DOSEGROUP: DEATHTIOE: II Sacrifice-Scheduled HISTOMORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: End of Record- 1120 vacuolation,cortex (minimal) IV-30 Page 1127 ARGUS 418-020 ORAL{GAVAGE)TWOGENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and H4stomorphology Data F1 6eneration ANIMALNUMBER:1123 SEX: H = ==_= =::== ==== := =: :=----.==== _z ----:.I=:= = ==I = ===::= _==_ llH=W, an=_=LV, anl_:=llH=Sl=Hlr'al GROSSOBSERVATION(S): HEAD: Swollen snout, DOSEGRIP: DEATHTYPE: III Sacri fice-Schedul ed _ S = .=I = _== z Z:=: ===-----=S_ ZZ::====L'=:== = =::= --.--=----.=_ ::l=J==----"--"--='==----.=-----_= =_ H_STOMORPHOLOOGBICSERVATION(S); fracturewith callus formation deviation,nasal septum HISTOMORPHOLOGICOBSERVATIONS: HEAD: End of Record- 1123 fracturewith calIus fo_mation deviation,nasal septum IV-31 Page 1128 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMHONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal Gross and Hist_rphol_y FI _neration Data ANIHAL NUHBER:1124 SEX: H DOSEGROUP: DEATHT_E: IIl Sacrifice-Scheduled GROSSOBSERVATION(SI: _IVER: Left lateral lobe- tan areas too numerous to count, ranging from pinpoint to 0.3om. HISTOHDRPHOLOGOICBSERVATION(S): hypertrophy, hepatocellular, necrosis, focal/multifocal diffuse hematopoiesis, extramedullary, multi focal HISTOHORPHOLOGOICBSERVATIONS: LIVER: End of Record- 1124 hypertrophy, hepatocellular, diffuse (moderate) necrosi s, focal/mul ti foe:a] {mi l d) hematopoiesis, extramadullary, multi focal (minima]) IV-32 Page 1129 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Anima] Gross and Hlstomorphology Data FI Generation ANIMALNUMBER1: 125 SEX: M mismiii8mm_imIwII_i_mssi_sm_sBi_m_i_m_m_mmmm_ssm_miRmm_mjzmms_s8_Z_m_mi_s_mBm GROSSOBSERVATION(S): LIVER: Left lateral lobe- tan areas (4) ranged in size from pinpointto O.Icm. DOSEGROUP: III DEATHT_DE: Sacrifice-Scheduled HISTOHORPHOLOGOICBSERVATION(S): hypertrophy, hepatocellular, diffuse inflammation,chronic, focal/multifocal HISTOMORPHOLOGICOBSERVATIONS: LIVER: End of Record- 1125 inflammation,chronic, focal/multifocal(mild) hypertrophy,hepatocellular,diffuse (moderate) Page 1130 .. IV-33 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO{AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -68Bg.6 Individual Appendix IV Animal 6ross and HJstomorphology Data F1 Generation ANIMALNUMBER:1126 SEX: H DOSEGROUP: III DEATHTIW_E: Sacrifice-Scheduled GROSSOBSERVATION(S): HEAD:Lesion, neck, right side, 2.0 x 0.5cm; lesion, head, top, Oo2cmin diameter; leston, head, right side, O.2cm in diameter; lesion, head, left side, 0.2cm in diameter. LIVER: Left lateral lobe- tan areas ranging from a pinpoint to O.2cm in size, too numerousto count. H_STOHORPHO_OGOIBCSERVATION(S): dermatitis, chronic, SKIN (GROSSLESION) dermatitis, ulcerative, SKIN (GROSSLESION) hypertropF_, hepatocellular, diffuse inflammation, chronic, focal/multifocal HISTOMORPHOLOGOICBSERVATIONS: LIVER: SKIN (GROSS LESION): End of Record- 1126 inflammation,chronic, focal/multifocal(minimal) hypertrophy,hepatocellular,diffuse (mild) dermatitis,chronic (moderate) dermatitis,ulcerative(moderate) Page l 13l .. IV-34 ARGUS 418-020 ORAL(6AVAGE)Tt/O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUOYOF AMMONIUPMERFLUODOOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross end Histomorphology Data F1 6eneration ANIMALNUMBER:1128 SEX: N sImmtIimssmmi_ssmmlmzsmmIsms_is_maHmjs_s_s_gsm_m_m_m_ms_s8_sBmm_m_sl_sm_s_jmm_w_s_Bzsm1_sm_= GROSSOpSERVATION(S): _IV(R: Left lateral lobe- tan area, 0.4 x 0.2cm. DOSEGR_L_P: III DEATHTI_E: Sacrifice-Scheduled HISTUMORPHOLOGOICBSERVATION(S}: hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGOICBSERVATIONS: LIVER: End of Record- 1128 hypertrophy, hepatocellular, diffuse (moderate) Page 1132 IV-35 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLLIOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Mistomorphology Data FI 6ermration ANIMALNUMBER:1129 SEX: M = = = === I = = z GROSS OBSERVATION(S): GENERAL:No gross changes. ........................... . ............................................................................ TH_ FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS End of Record- 1129 DOSEGROJJ_: III DEATHTYI_: Sacrifice-Scheduled = = == HISTOMORPHOLOGICOBSERVATION(S): Not applicable ==_ == Page 1133 IV-36 ARGUS 418-020 ORAL(6AVAGE}"T_O-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AI_ONIUM PERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data F1 Generation ANIMAL NUMBER: 1134 SEX: M lllllllllll = llllllllllllllll=l=lllll=lllllll=lllllllllllllllllllllll=lllll=l= DOSE GR.CLVP: III DEATH Tl_mE: Sacrifice-Scheduled = _=llllllll=l= == II == = == =I=I$ = GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S}: GENERAL:No gross changes. Not applicab]e ........................................................................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS ......................................................................................................... End of Record- 1134 Page 1134 __ . . o- _ IV-37 ARGUS 418-020 ORAL(BAVABE)TIdO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN PATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorpho_ogy Data F1 Generation ANIMALNUMBER:1136 SEX: M IIIIIII_III_IsI_IIII_IIII_II_IIIImIIIIIIIIIII_IImIIIIII_IIIII_II_II_I_II=_I_=_I_=II======I_=_I=_ DOSEGROUP: III DEATHT_PE: Sacrifice-Scheduled GROSSOBSERVATION(S): HISTDqORPHOLOGOICBSERVATION(S): H_AD: Swollen snout, fracturewith callus formation necrosis, tooth rhinitis,suppurative ....................................................................................................... HISTOMORPHO_OGICOBSERVATIONS: HEAD: fracturewith callus formation necrosis, tooth rhin'itis,suppurative{mild) ........................................................................................................ THE FOLLOVINGTISSUE(S)VERE VITHIN NORMAL LIMITS: ADRENAL GLANDS ........................................................................................................ End of Record- 1136 IV-38 Page 1135 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLDORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 142 SEX: M Individual Append1x IV Animal 6ross and Htstomorphology Data F1 6enerati on DOSEGROUP: III DEATHT_IE.: Scheduled (Reduced Fertility) GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATIONS: PROSTATE: HISTOMORPHOLOBICOBSERVATION(S): Not applicable inflammation,chronic (mild) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGBLAND EPIDIDYMIS SEMINAL VESICLES End of Record- 1142 TESTIS IV-39 Page 1136 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV 6ross and Histomorphology Data F1 Generation ANIMALNUMBER1: 149 SEX: H m_smmmsimmlmm_mmm_m_ms_m_tss_j_i_mmmmn_mam_s_m_mmzss_m_mt_sa_mle_zs_Imf_i_ GROSSOBSERVATION(S): GENERAl: No gross changes. DOSEGROUP: III DEATHTY_E: Sacrifice-Scheduled HISTOMORPHOLOGICOBSERVATION{S): Not applicable THE FOLLOWINGTISSUE(S}WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1149 = =_s_= Page 1137 .. , IV-4O ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data FI Generation ANIMALNUMBER1: 154 SEX: H DOSE6R(_P: DEATHTYIPE: III Sacrifice-Scheduled GROSSOBSERVATION(S): G_NERA_:No gross changes. THE FOLLOIdINGTISSUe{S) WEREWITHIN NORMA_LIM[T_: AORENAL6LANDS End of Record- 1154 HISTOMORPHOLOGOICBSERVATION(S): Not applicable IV-41 Page 1138 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Individual Appendix IV Animal Gross and Histmorphology F1 Generation Data ANIMALNUMBER1: 156 SEX: H DOSE6RQ_P: DEATHTfPE: III Sacrifice-Scheduled GROSSOBSERVATION(S): LIVER: Left lateral lobe- 6 tan areas, pinpoint to O.3cm. HISTOHORPHOLOGOICBSERVATION(S}: hypertrophy,hepatocellular,diffuse HISTOMORPHOLOGIC.OBSERVATIONS: LIVER: End of Record- 1156 hypertrophy,hepatocellular,diffuse (mild) Page 1139 . IV-42 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHNONIUHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Appendix IV IndividualAnimal Gross and HistomorphologyData FI _neration ANIMALNUMBER:1159 SEX: M DOSEGP_O_P: III DEATHT_E: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. THE FOLLOWINGTISSUe(S) WEREWITHIN NORMALIHITS: ADRENALGLANDS End of Record- 1159 HISTOHORPHOLOGOICBSERVATION(S): Not applicable -. . .*- Page 1140 _ IV-43 ARGUS 418-020 ORAL(fiAVAGE) TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AI_ONILIMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 Individual AppendSxIV Antmal 6ross and Hlstomorphology Data F1 Generation ANIMALNUMBER:1164 SEX: M DOSE6R_P: DEATHTI_,: III Sacrifice-Scheduled m_ mw_zmsmz_z _ m_zm sz_z _ _m m _s---m_mms_mllmmslc_ s zszm_tz_m_ z_ _ _z _z _ t GROSSOBSERVATION(S}: GENERAL:No gross changes, ........................................................................................................ HISTOHORPHOLOGOICBSERVATION(S]: Not app]icab]e THE FOLLOWINGTISSUE(S} WEREWITHIN NORMA_LIHITS: ADRENALGLANDS End of Record- 1164 IV-44 Page 1141 ARGUS 418-020 ORAL(GAVAGE)TWOoGENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniml Gross and Hist_rphology Data F1 Generation ANIMALNUMBER1: 165 SEX: H DOSEGROUP: DEATHTilDE: 8_m_L1Rmmmsmm_s_zmmmm_mmmmmm_mmm_mmmmmsmg_mm_a_K_lmarmarmm_mm_mmm_m_s1mm_sz_8mm_msz_smm_sZz_sz III Sacrifice-Scheduled GROSSOBSERVATION(S): qIVER: Left lateral lobe- tan areas too to count, ranging in size from pinpoint O.2cm. ....................................................................................................... numerous to HISTOMORPHOLOGOIBCSERVATION(S}: hypertrophy, hepatocellular, diffuse HISTOMORPHOLOGICOBSERVATIONS: LIVER: ......................................... End of Record- 1165 hypertrophy,hepatocellular,diffuse .............................................................. (moderate) Page 1142 _+ - o - :._, "- IV-45 ARGUS 418-020 ORAL(fiAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889,6 Appendix IV IndividualAnlml Gross and Htstomorphology Data Fit 6enerati on ANIMAL NUMBER: 1167 DOSE GROUP: SEX: msmmRmmmtt M DEATH T_OE: mmm _mmmms_mmmss_mImmszs_is_Imm_tm_i_l_m_smmt_mmmmmRm_mssmmmzmmummmmmi_mm_mml_=_sssz_ III Scheduled (ReducedFertility) GROSS OBSERVATION(S): HTSTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ........................................................................................................ TH_ FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS." COAGULATINGGLAND TESTIS ..................................... End of Record- 1167 EPIDIDYMIS PROSTATE . ................................................................. SEMINAL VESICLES Page 1143 . IV-46 ARGUS 418-020 ORAL(6AVAGE)TI40-GENERATION(ONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLLIOROOCTANO(AFTPEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6Port and Htstomorphology Data F1 6eneratton ANIHAL NUHBER:1175 SEX: X alaliIslal=alalIllea=al_scslaSla=alalsal_alIal=lallal=_alalIalIalalllIalalalal 6.ROSSOBSERVATION{S): 6ENERAL: No gross changes. DOSE6R_P: DEATHT_PE: III Sacr_ lice-Scheduled l aDalalalalalalIalalalalallala=ISIl_II=maImae_IS=alasIalals=s alaes==s=s=====a= IS=a=a=al=lS= ==w. H[STOMORPHOL06IOCBSERVATION(S): Not applicable THE FOLLOWTNT6ISSUe(S) i/ERE WTTH]NNORHALI,]H]TS: ADRENALGLANDS End of Record- 1175 Page 1144 IV-47 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV 6ross and Histoeorphology F1 Generation Data ANINAL NUHBER:1177 SEX: N mmmmmm_sm_mm_smm_s_mi_mss_1_anHr_m_m_1_ul_tim_ai_s_m_s_mz_m_ GROSSOBSERVATION(S): GENERALN: o gross changes. ........................................................................................................ HISTOHORPHO_OGOICBSERVATIONS: ADRENALGLANDS: .................................................. End of Record- 1177 DOSEGROIJP: III DEATHTI_E: Sacrifice-Scheduled ss _s HISTOHORPHOLOGOICBSERVATION(S): Not applicable vacuolation, cortex (minimal) _ ..................................................... Page 1145 .. IV-48 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHHONILIHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Individual Appendix IV Anfmal Gross and Histomorphology Data Frl Generation ANINAL NUNBER:1180 SEX: H DOSEGR_]_P: Ill DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... THE FOL_OW[NGTISSUE(S) WEREWITHIN NORHALLIHITS: ADRENALGLANDS ....................................................................................................... End of Record- 1180 H]STOHORPHOLDGOICBSERVATION{S): Not applicable ]V-49 Page 1146 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV Gross and Histomorphology Data FI Generation ANIMALNUMBER:1182 SEX: M DOSEGRgJ_P: IV DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS End of Record- 1182 Page 1147 . ' IV-50 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBER:T-6889.6 ANIMALNUMBER1: 189 SEX: M Appendix IV IndividualAnimal Gross and Hist_rphol_y FI _neration Data DOSE6ROUP: DEATHT_DE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ........................................................................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMA_ LIMITS: ADRENAL GLANDS ........................................................................................................ End of Record- 1189 Page 1148 IV-51 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniml Gross and Hist_rphology Data FI Generation ANIMALNUMBER:1190 SEX: M DOSEGROUP: IV DEATHTidE: Sacrifice-Scheduled GROSS OBSERVATION[S): LIVER: Left lateral lobe, median lobe- tan areas ranging from a pinpointto O.2cm in size, too numerousto count, HISTOMORPHOLOGICOBSERVATION(S): hypertrophy,hepatocellular,diffuse inflammation,chronic, focal/multifocal necrosis, single-cell HISTOMORPHOLOGICOBSERVATIONS: 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)TIJO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal 6ross end HlstomorphologyData FI Generation ANIMALNUMBER:1191 SEX: M ulmmmimsimmssBszmmmmmimsi_imzmmmmmmm1s_immmmmm_mwmimm_mmmmsmmsu_Immmi_msmssmm_ls=m_z GROSSOBSERVATION(S): LIVER: Lateral lobe- tan areas too numerousto count ranging in size from pinpoint to O.lom DOSEGROJUP: IV DEATHT_PE: Sacrifice-Scheduled _ s_= H|STOHORPHO_OGO_BCSERVATION(S): hypertrophy,hepatocellular,diffuse qlSTOMORPHOLOGICOBSERVAT|ONS: LIVER: End of Record- 1191 hypertrophy,hepatocellular,diffuse {moderate) Page 1150 .o IV-53 ARGUS 418-020 ORAL(GAVAGE)TVO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data FI Generation ANIMALNUMBER:1192 SEX: M DOSEGROUP: IV DEATHTY_E: Scheduled (Reduced Fertility} GROSSOBSERVATION(S): GENERAL:No gross changes. ........................................................................................................ HISTOHORPHOLOGOICBSERVATION(S): Not applicable HISTOHORPHOLO6OICBSERVATIONS: PROSTATE: ........................................................................................................ atrophy, focal (minimal) THE FOLLOWINGTISSUE(S) WER_WITHIN NORMALIMITS: ADRENAL GLANDS TESTIS COAGULATINGGLAND EPIDIDYMIS ........................................................................................................ End of Record- I192 SEMINALVESICLES Page 1151 IV-54 ARGUS 418-020 ORAL(GAVAGE)I_O-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONILIHPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNLIHBERT: -6889.6 Appendix IV IndividualAnimal 6r_ss and Hist_rphology Data FI _neratlon ANINAL NUHBER:1193 SEX: H IIIIIIIIIIIlIIIIIIIIIIIIIIIIIlIIIIIIE_IIII_ GROSSOBSERVATION(S): LIVER: Left lateral lobe- four tan areas, pinpointto 0.2cm. DOSEGR(_P: DEATHTI_E: IIIIIIIIIIIZlIII IV Sacrifice-Scheduled II IIlIIIllIl _ II II _ I HISTONORPHOLOGOICBSERVATIONIS): hypertrophy, hepatocellular, diffuse HISTOHORPHOLOGOICBSERVATIONS: LIVER: End of Record- 1193 hypertrophy,hepat_ellular, diffuse (mderate) IV-55 Page 1152 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Hlstomorphology Data F1 6eneration ANINAL NUHBER:1194 SEX: N ========================================================================================= DOSE6R(_: OEATHT?PE: IV Sacrifice-Scheduled GROSSOBSERVATION(S): 6ENgRAL: No gross changes. .................................................. HISTOHORPHOLOGOICBSERVATION(S): Not applicable . .................................................... THE FOLLOWIN6TISSUE(S) WEREWITHIN NORHLA LIMIT_: ADRENALGLANDS ........................................... End of Record- 1194 _ ........................................................... Page 1153 IV-56 ARGUS 418-020 ORAL(GAVAGE)TWO-6ENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Hlstomorphology Data F1 6eneration ANIMALNUMBER1: 197 SEX: H DOSE6ROUP: DEATHT_tE: IV Sacrifice-Scheduled GROSS OBSERVATION(S): TAIL: Tip missing 5.Ocm from base. HISTOMORPHOLOGOICBSERVATIONS: TAIL: End of Record- 1197 HISTOMORPHOLOGICOBSERVATION(S): hyperplasia/hyperkeratosis abscess hyperplasia/hyperkeratosis abscess (moderate) IV-57 Page 1154 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNLIHBERT: -6889.6 ANIHAL NUHBER:1198 SEX: N Indtvidu81Antmal Appendtx IV 6ross 8rid Htstomorphology Oata FI 6eneretion DOSEGROUP: DEATHT_.: IV Sacrifice-Scheduled GROSSOBSERVATION(SI: GENERALN: o gross changes. ........................................................................................................ THE FOLLOWINGTISSUE(S) WEREWITHIN NORHlALIHITS: ADRENALGLANDS .............................................................. End of Record- 1198 HISTOMORPHOLOGOICBSERVATION(SI: Not applicable _ ......................................... IV-58 Page 1155 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross end Htstomorphology Data F1 Generation ANIMALNUMBER1: 200 SEX: M _mmI_mmm_mmm_mm_III_mm_m_I_mm_m_mm_mmm_mI_I1I_III_mIIImsI_I_I_II_mI_I_I_III_I_ DOSEGROU_P: IV DEATHT_: Sacrifice-Moribund GROSSOBSERVATION(S): GASTROINTESTINATLRACT: Intestines- distended with gas; stomach, cardiac region- ulcerations one region too numerous to count, range in size from pinpoint to 0.1cm in diameter, second region five ulcerations pinpoint size in diameter, THYMUS:Small. ........................................................................................................ HISTOHORPHOLOGOICBSERVATION(S): ulcer(s), glandular area, STOMACH erosion(s), glandular mucosa, STOMACH peritonitis, focal, STOMACH Advancedautolysis precludes evaluation. distention. distention, COLON CECUM edema/inflammation, submucosa, CECUM atrophy ILEUM HISTOMORPHOLOGICOBSERVATIONS: CECUM: COLON: ILEUM: STOMACH: THYMUS: distention (marked) edema/inflammation,submucosa (mild) distention (marked) Advanced autolysisprecludes evaluation ulcer(s),glandulararea (moderate) erosion(s),glandularmucosa (minimal) peritonitis,focal (minimal) atrophy (marked) AUTOLYSIS PRECLUDES EVALUATION: ILEUM End of Record- 1200 Page 1156 +. IV-S9 ARGUS 418-020 ORAL(C_VAGE)TI_O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANHONILRP4ERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Hlstomorphology Data F1 6eneratton ANIMALNUHBER:1205 SEX: H mmmi_m_smmmt_zssRmmmsii_s_misz_izwlm_s_8sm_im_B_g_I1_imisI_s_ms_s_sim_s8sR_m1i_ZsS_s_z_im_m_m_ GROSSO_SERVATION(S): LIVER: Left lateral size from pinpoint count. lobe- tan areas ranging in to O.5cm, too numerous to DOSEGRO_J_: IV DEATHTYlPE: Sacrifice-Scheduled HISTOHORPHOLOGOICBSERVATIONfS): hypertrophy, hepatocellular, necrosis, focal/multifocal diffuse HISTOHORPHOLOGOI__S[RVATIONS; LIVER: ----_ ........................................... End of Record- 1205 necrosis, focal/nJltifocal(mild) hypertrophy,hepatocellular,diffuse (moderate) . ........................................................ IV-60 Page 1157 ARGUS 418-020 ORAL(C_VAGE)TWO-GENERATIO(ONNE LITTER PERBENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L16-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Individual Anlml Appendix IV 6ross and Histomorphology Data F1 6eneration ANIMALNUMBER1: 206 SEX: M DOSEGR_I_P: IV DEATHTItPE: Sacrifice-Scheduled GROSSOBSERVATION(S): LIVER: Left lateral lobe- tan ares, too numerous to count, ranging in size from pinpoint to 0.5 x 0.1cm. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): hypertrophy,hepatocellular,diffuse HISTOMORPHOLOGOtBCSERVATIONS: LIVER: End of Record- 1206 hypertrophy, hepatocellular, diffuse (mild) Page 1158 IV-61 ARGUS 418-020 ORAL(RAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV Gross and Histomrphology FI Generation Data ANIMAL NUHBER:1207 SEX: N DOSEGROUP: DEATHT_wE: mmmmmmmmmmmmm_simsmm_mm_mmm_mi_mmsmmm_ii_ma_ma_m_m_1z_m_mmmmmmm_mm_arm_mm_s_mmmmR_s_1_mm_mm_ IV Scheduled (Reduced Fertility) GROSSOBSERVATION(S): GENERALN: o gross changes. ........................................................................................................ HISTOHORPHOLOGOICBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S) W_R_WITHIN NORHALLIHITS: COA6ULATIN6GLAND TESTIS EPIDIDYNIS ........................................................................................................ End of Record- 1207 PROSTATE SEHINALVESICLES Page 1159 1V-62 ARGUS 418-020 ORAL(RAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 ANIHAL NUHBER:1211 SEX: M Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation DOSEGROUP: DEATHTflt: IV Sacrifice-Scheduled GROSSOBSERVATION(S): G_NERAL:No gross changes. ........................ _ .............................................................................. HISTOMORPHOLOGOICBSERVATION(S): Not applicable THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS ................................................ End of Record- 1211 . ...................................................... IV-63 Page 1160 ARGUS 418-020 ORAL(GAVAGE)ll40-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLLIOROOCTANO(AFTPEO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 212 SEX: M Appendix IV IndividualAnimal Sross and Histo_rphology Data F1 Generation DOSEGROUP: IV DEATHT_.: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. ........................................................................................................ HISTOMORPHOLOGOICBSERVATION(S): Not applicable THE FOLLOWINGTISSUe(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS ........................................................................................................ End of Record- 1212 IV-64 Page 1161 ARGUS 418-020 ORAL(GAVAGE)Ti/O-GENERATION(ONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIHAL NUMBER:1217 SEX: H Individual Appendix IV Animal Gross and H|stomorphology Data F1 Generation DOSEGROUP: DEATHT_itE: IV Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. ........................................................................................................ HISTOHORPHO_OGOICBSERVATIONS: ADRENALGLANDS: ........................................................................................................ End of Record- 1217 HISTOHORPHOLOGOICBSERVATION(S): Not applicable vacuolation, cortex (minima]) Page 1162 IV-6S ARGUS 418-020 ORAL(GAVAGE)TIVO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AJ4HONIUPMERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T6889.6 Individual Appendix IV Animal 6ross and Histomorphology Data F1 Generation ANIMALNUMBER:1218 SEX: M s_lmlsmmsmj_E=smslmssmsfu_s=_mis_msmmsm_t_m_m_m_im_r_mB_m=ms_msmB_m_t_lm=ma_m===m_BB_ 6R055 OBSERVATION(S): _IVER: Left lateral lobe- one tan and black area, 0.2 x 0.2cTn;caudate lobe- one tan area, 0.4cm. OOSE6RI_P: DEATHTYY: IV Sacrifice-Scheduled HISTOHORPHOLOBOICBSERVATION(_): hypertrophy,hepatocellular,diffuse necrosis, focal/multlfocal hematopoiesis,extramedullary,multifocal HISTOMORPHOLOGICOBSERVATIONS: LIVER: .................................................. End of Record- 1218 necrosis,focal/multlfocal(minimal) hematopoiesis,extramedullary,multifocal (minimal) hypertrophy,hepatocellular,diffuse (mild) o ..................................................... IV-66 Page 1163 ARGUS 418-020 ORAL(6AVA6E) TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross end Histomorphology Data F1 Generation ANINAL NUMBER:1223 SEX: H DOSE6R_J_P: IV DEATHT_mE: Sacrifice-Scheduled 6ROSSOBSERVATION(S): LIVER: Left lateral lobe- tan area, too to count, ranging in size from pinpoint O.2cm in diameter. ....................................................................................................... numerous to HISTOHORPHOL06IOCBSERVATION(S}: hypertrophy, hepatocellular, diffuse HISTOHORPHOLOGOICBSERVATIONS: LIVER: ........................................................................................................ End of Record- 1223 hypertrophy, hepatocellular, diffuse (mild) IV-67 Page 1164 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHOHIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorphotogy Data FI Generation ANIMALNUMBER1: 224 SEX: M DOSEGROUP: IV DEATHTI_: Sacrifice-Scheduled GROSSOBSERVATION(S): KIpNEYS: Right- pelvic dilation, slight, HISTOMORPHOLOGOICBSERVATIONS: KIDNEYS: End of Record- 1224 dilatation, HISTUMORPHOLOGOICBSERVATION(S): dilatation, pelvis pelvis (moderate) IV-68 Page 1165 ARGUS 418-020 ORAL(6AVAGE)I"WO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross end Histomorphology Data F1 6eneration ANIMAL NUMBER: 1225 SEX: M 6ROSS OBSERVATION(S): GENERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: ADRENALGLANDS: End of Record- 1225 DOSE 6Ri_L_P: IV DEATH TIPPI_: Sacrifice-Scheduled HISTOMORPtlOLOGIOCBSERVATION(S): Not applicable vacuolation, cortex (minimal) Page 1166 IV-69 ARGUS 418-020 ORAL(GAVAGE)TI40-fENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBERT: -6889.6 Individual Appendix IV Animal 6eoss and Histomorphology Data F1 6eneration ANIMALNUMBER1: 229 SEX: M DOSEGRQPU:, DEATHTYPE:: IV Sacrifice-Scheduled GROSS OBSERVATION(S): EAR(S): Swollen,both. SPLEEN: Tan area, 2.0 x 1.5cm, extends into the parenchyma. HISTOMORPHOLOGICOBSERVATION(S): chondropathy,auricular necrosis HISTOMORPHOLOGICOBS{RVATIONS: EAR(S): SPLEEN: End of Record- 1229 chondropathy, auricular necrosis (marked) (marked) Page 1167 IV-70 ARGUS 418-020 ORAL(GAVAGE)T1/O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOFAHMONIUHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -5889.6 Individual Appendix IV Animal 6ross and Hlatoeorphology F1 6eneration Data ANIMALNUMBER:1232 SEX: N DOSE6ROMP: IV DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATION(S): KIDNEYS:Right- pelvic ................................................................ dilation, slight, HISTOMORPHOLOGOICBSERVATIONS: KIDNEYS: End of Record- 123Z HISTOHORPHOLOGOICBSERVATION{S): dilatation, pelvis . ....................................... dilatation,pelvis {mild) [V-71 Page 1168 ARGUS 418-020 ORAL(GA'IAGE)llVO-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIO3NTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -_889.6 Individual Appendix IV Animal Gross and Hista;_,rphology F1 Generation Data ANIMALNUMBER1: 234 SEX: N _ms_m_m_m_mm_mmm_m_m_mm_mm_m_mm-$um_m_mmmm_mmm_mmmmmm_mmmsmmmmmmm_mmm_m=== DOSE,IROUP: DEATHT_: IV Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): LIVER: Tan areas, median lobe ole tan area O,,2cm. left lateral lobe too numerous to count, ranging from pinpoint to O.7cm. ........................................................................................................ hypertrophy,hepatocellular,diffuse necrosis, focal/multifocal inflammation, chronic, focal/multifocal HISTOMORPHOLOGOICBSERVATIONS: 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)11dO-GENERATIO(ONNE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMHONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBER:T-6889.6 Individual Appendix IV Animal Gross and Htstomorphology Data F1 6eneratton ANIMALNUMBER:1235 SEX: M _m_smm_Iim_8mm8t_IizsIsz_smmtm_mm8s_mm8ma8_8i_88_mzs_ssmmsmszs_m_mIs_zBHzs_zz_mmtz_ GROSS OBSERVATION(S): LIVER: Tan areas, median lobe too numerousto count ranging in size from pinpointto O.3om, left lateral lobe 4-5 tam areas ranging from pinpoint to O.Icm. DOSE6RqIJP: DEATHTYPE: IV Sacrifice-Scheduled HISTOMORPHOLOGICOBSERVATION(S): hypertrophy,hepatocellular,diffuse HISTOMORPHOLDGOICBSERVATIONS: LIVER: .................................................. End of Record- 1235 hypertrophy, hepatoce]lular, _ ..................................................... diffuse (moderate) Page 1170 IV-/3 ARGUS 418-020 ORAL(6AVABE)T1VO-6ENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV Gross and Histomorphology Data F1 Generation ANIMALNUMBER1: 236 SEX: M DOSE6ROMP: IV DEATHTY_E: Sacrifice-Scheduled GROSSOBSERVATIONIS): G_NERAL:No gross changes. ......... _ ............................ HISTOMORPHOLOGOICBSERVATION(S): Not applicable o ................................................................. THE FOLLOWIN6T_SSU_IS) WEREWITHIN NORMALIHITS: ADRENALGLANDS End of Record- 1236 IV-74 Page 1171 ARGUS 418-020 ORAL(6AVA6E) TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF ANNONIUNPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data FI Generation ANIMAL NUMBER: 1240 SEX: M DOSE GROUP: IV DEATH TY_PE: Sacrifice-Scheduled 6ROSS OBSERVATION(S): HISTOMORPHOLOOICOBSERVATION(S): KIDNEYS:Right- pelvic dilation,slight, dilatation,pelvis mineralization,pelvis hyperplasia,pelvic/papillaryurothelium ........................................................................................................ HISTOMORPHOLOGICOBSERVATIONS: KIDNEYS: dilatation,pelvis (mild) mineralization,pelvis (minimal) hyperplasia,pelvic/papillaryurothelium (minimal) ........................................................................................................ End of Record- 1240 Page 1172 IV-75 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMON|UMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Appendix IV IndividualAniml 6r_ss and Hist_rphology Data F1 Generation ANIMAL NUMBER: 1241 SEX: M DOSE GROUP: V DEATH TY_zE: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: HISTOMORPHOLOGICOBSERVATION(S): Not applicable hypertrophy/vacuolation, zona glomerulosa (mild) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY ......................................................................................................... End of Record- 1241 PROSTATE Page 1173 IV-/B ARGUS 418-020 ORAL(6AVAGE)TI_O-6ENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMHONIUMPERFLUOROOCTANO(ATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Anieal Appendix IV 6ross and Histoeorphology F1 6eneration Data ANIHAL NUMBER:1243 SEX: H DOSEGROUP: V DEATHTY_E: Sacrifice-Scheduled GROSSOBSERVATION(S): HEAD: Lesion, ............................ 0.2cm in diameter, _ ........................................................................... HISTUMORPHOLO6OICBSERVATIONIS): dermatitis, chronic HI_TOHORPHQLO6O1CBSERVATIONS: HEAD: End of Record- 1243 dermatitis, chronic (moderate) IV-77 Page 1174 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Htstomorphology Data F1 6eneratton ANIMALNUMBER1: 244 SEX: M iII_I_II_II_IIIIIIII_Ii_IIII_IIII_iI_InIIIII_III_II_I_III_IIIIIIIIIIIIIIII_IIIIIIII_IIIIIIIIII GROSSOpSERVATION(S): GENERAL:No gross changes. ........................................................................................................ HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: PITUITARY: DOSEGROUP:: V DEATHTY_E:: Sacrifice-Scheduled H_STOMORPHOLOGOIBCSERVATION(S): Not applicable hypertrophy/vacuolatton, zona gIomerulosa (minimal) vacuolation, cortex (minimal) cyst(s), pars dtatalts THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND EPIDIDYMIS PROSTATE TESTIS ........................................................................................................ End of Record- 1244 SEMINAL VESICLES Page 1175 IV-78 ARGUS 418-020 ORAL(GAIAGE) TWO-GENERATIO(NONE LITTER PER GENERATION) REPROOUCTIOSNTUOYOF AHMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniml Gross and Hist_rphology Data FI _neration ANIMALNUMBER1: 250 SEX: M B_Rsmm_t_m1_smmimm8_m_t_zs_lesBi_slt_mm1mBmm_s_lmzlL-_m_=m_imm_R=_=szzssmmzzm=_zlz=1ls==== GROSSOBSERVATION(S): TAIL: Annular constriction. DOSEGROUP: V DEATHTYI_E: Sacrifice-Scheduled HISTOMORPHOLOGOICBSERVATION(S): No microscopic change to correlate HISTOMORPHQL061COBSERVATIONS: TAIL: No microscopic change to correlate THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: TAIL End of Record- 1250 Page 1176 _ .. - - - __ IV-79 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Htstomorphology Data F1 6eneration ANIMALNUMBER:1251 SEX: M DOSE6ROMP: V DEATHT/P[: Sacrifice-Scheduled GROSSOBSERVATION(S): HISTOHORPHOLOGOICBSERVATION(S): _|VER: Left lateral lobe and median lobe- tan areas, too numerous to count, ranging in size hypertrophy, from pinpoint to O.3c_ in diameter. ........................................................................................................ hepatocellular, diffuse HISTOMORPHOLOGICOBSERVATIONS: LIVER: hypertrophy,hepatocellular,diffuse (moderate) ........................................................................................................ End of Record- 1251 Page 1177 IV-8O ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorphology Data F1 Generation ANIMALNUMBER:1254 SEX: M _I_mI_I_II_l_u_ll_l_m_mmm_-_--_Ilm_m1E_mm_II_ImI_III_I_I_I_IIII_II GROSSOBSERVATION(S): GENERALN: o gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: ADRENAGL LANDS: PROSTATE: ......................................................................................................... DOSEGROJJP: V DEATHTYPE: Sacrifice-Scheduled HISTOMORPHOLOGOICBSERVATION(S): Not applicable hypertrophy/vacuolation, zona glomerulosa (mild) inflammation, chronic (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMA_ _IMITS. COAGULATINGGLAND TESTIS EPIDIDYMIS PITUITARY End of Record- 1254 SEMINAL VESICLES Page 1178 IV-81 ARGUS 418-020 ORAL(GAVAGE}TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV Gross and Histomrphology F1 6eneretion Data ANIMALNUMBER1: 256 SEX: N DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled GROSSOBSERVATIONIS): LIVER: Left lateral lobe- tan ........................................................................................................ area, 0.Bcm. HISTOMORPHOLOGOICBSERVATION(S): hypertrophy, hepatocellular, diffuse HISTOMORPHO_OGOICBSERVATIONS: LIVER: End of Record- 1256 hypertrophy, hepatocellular, diffuse (mild) Page 1179 . IV-82 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMAL NUMBER: 1262 SEX: M Individual Appendix IV Animel Gross and Hlstomorphology Data F1 Generation DOSE GROUP: DEATH T_PE: V Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Tan areas, median lobe five tan areas pinpoint to O.3cm; left lateral lobe tan six tan areas pinpointto O.lcm. TAIL Annular constrictionsof tail. .................................................. HISTOMORPHOLOGICOBSERVATION(S): hypertrophy,hepatocellular,diffuse constriction,focal _ .................................................... HISTOMORPHOLOGICOBSERVATIONS: LIVER: TAIL: ................................................... End of Record- 1262 hypertrophy,hepatocellular,diffuse (moderate) constriction, focal _ .................................................... IV-83 Page 1180 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION} REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUMBER1: 263 SEX: M DOSEGROUP: DEATHTYPE: V Spontaneous Death GROSS OBSERVATION(S): EYES: Corneal opacity, both eyes. HISTOMORPHOLOGICOBSERVATION(S): No microscopic change to correlate HISTOMORPHOLDGICOBSERVATIONS: EYES: No microscopic change to correlate THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: EYES End of Record- 1263 IV-84 Page l 181 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.B Appendix IV IndividualAniml Gross and Hlst_rphology Data F1 Generation ANIMALNUMBER1: 264 DOSEGROUP: SEX: M DEATHTYPE: _mEs_m_mi===_=mmim_=m_=====m_=mmmmmmiml_mssmm:ms_m_mm_iB=m_s_lm=m_==============_=======_============ V Spontaneous Death GROSSOBSERVATION(S): EYES: Corneal opacity, ........................................ both eyes. HISTOMORPHOLOGOICBSERVATION(S): No microscopic _ ............................................................... change to correlate HISTQMORPHOLOGOICBSERVATIONS: EYES: ........................................................................................................ No microscopic change to correlate THE FOLLOWINGTISSUE(S)WER_ WITHIN NORMAL _IMITS: EYES ........................................................................................................ End of Record- 1264 Page 1182 .. IV-85 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 266 SEX: M Appendix IV IndividualAnimal Gross and Hist_rphology Data FI Generation DOSEGROUP: V DEATHTYPE: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. ........................................................................................................ HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: PITUITARY: PROSTATE: HISTOMORPHOLOBICOBSERVATION(S): Not applicable hypertrophy/vacuolation, .zona glomerulosa (mild) cyst(s),pars intermedia inflammation, suppurative (minimal) THE FOLLOW;NGT_SSUE(S) WERE WITHIN NORMA_L;MITS&_. COAGULATINGLAND EPIDIDYMIS SEMINALVESICLES End of Record- 1266 TESTIS Page 1183 IV-86 ARGUS 418-020 ORAL (6AVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLLIORDOCTANOAT(EAFPO) IN RATS PROTOCOL 418-020 SPONSOR'SSTUDYNUMBER:T-6889.B ANIMAL NUMBER: 1268 SEX: M Individual Appendix IV Animal 6ross and Histomorphology Data F1 Generation DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): LIVER: Tan area, median lobe too numerousto count ranging in size from pinpointto 0.4 x O.Zcm. HISTOMORPHOLOGICOBSERVATION(S): hypertrophy,hepatocellular,diffuse necrosis, focal/multifocal HISTOMORPHOLOGICOBSERVATIONS: LIVER: necrosis,focallmultlfocal(mild) hypertrophy,hepatocellular,diffuse (marked) ........................................................................................................ End of Record- 1268 Page 1184 IV-87 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONELITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMAL NUMBER:1269 SEX: M Individual Appendix IV Animal 6ross and Htstomorphology Data F1 6eneratton DOSEGROUP: DEATHTYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL: No gross changes. Not applicable ....................................................................................................... THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PROSTATE ........................ End of Record- 1269 COAGULATINGGLAND EPIDIDYMIS SEMINAL VESICLES TESTIS . ............................................................................... PITUITARY Page 1185 IV-88 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER:1270 SEX: M Appendix IV IndividualAniml Gross and Hist_morphologyData FI Generation DOSEGROUP: DEATHTYPE: V Sacrifice-Scheduled GROSSOBSERVATION(S): TAI_: Annular constriction. ........................................................................................................ HISTOMORPHOLOGOICBSERVATIONS: TAIL: ......................................................................................................... HISTONORPHOLOGOICBSERVATION(S): No microscoDic change to correlate No microscopic change to correlate THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: TAIL ........................................................................................................ End of Record- 1270 Page 1186 .. IV-89 ARGUS 418-020 ORAL(GAVAGE)I_O-GENERATION(ONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal Gross and Hist_rphology Data F1 Generation ANIMALNUMBER:1271 SEX: M mmtii_smmmsimim_mjjssm_smmmmimmmm_1jgmmmmmmmmRmmmmmim_mmmm_m_ms_m_m_m_m_sis_m_mz8sm_s_m_m_ DOSEGROUP: DEATHTYPE: V Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAl: No gross changes. ........................................................................................................ HISTOMORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOL061COBSERVATIONS: EPIDIDYMIS: PROSTATE: infiltration,mononuclear-cell,focal (minimal) atrophy, focal (mild) THE FOLLOWING TISSUE(S)W_RE WITHIN NORMAL LIMITS: ADRENAL GLANDS TESTIS COAGULATINGGLAND PITUITARY End of Record- 1271 SEMINAL VESICLES Page 1187 IV-90 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUM PERFLUOROOCTANOATE(AFPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal 6ross and HistomorphologyData FI Generation ANIMAL NUMBER: 1273 SEX: M mjjsmmmmmi_mmzB_imsm_mz_ismszssmz_immis_mmma_mm_m_MmmmNsss_nsi_m_m_m_zm__mz_1_1_z_z_ DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL: No gross changes Not applicable ........................................................................................................ HISTOMORPHOLOGICOBSERVATIONS: ADRENAL GLANDS: hypertrophy/vacuolationz,one glomerulosa (minimal) vacuolation,cortex (minimal) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: COAGULATINGGLAND EPIDIDYMIS PROSTATE TESTIS ......................................................................................................... SEMINALVESICLES COMMENTS: PITUITARY The pituitarywas damaged at necropsyand the section that could be obtainedwas not adequatefor evaluation. ......................................................................................................... TISSUE(S)NOT AVAILABLEFOR EVALUATION: PITUITARY End of Record- 1273 Page 1188 IV-91 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889.6 ANIMALNUMBER1: 275 SEX: M Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation DOSEGROUP: DEATHTYPE: V Sacrifice-Moribund GROSSOBSERVATION(S): _VER: Median lobe- tan areas too numerous to count ranging in size from pinpoint to O.Icm. SPLEEN: Sma11. HISTOHORPHOLOGOICBSERVATION(S): hypertrophy, hepatocellular, necrosis, focal/multifocal atrophy diffuse HISTOMORPHO_OGICoBSERVATIONS: LIVER: SPLEEN: End of Record- 1275 necrosis,focal/multifocal(mild) hypertrophy,hepatacellulsr,diffuse (mild) atrophy (marked) Page 1189 o. IV-92 ARGUS 418-020 ORAL(6AVAGE)TtVO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross end Histomorphology Data F1 6eneratton ANIMALNUMBER:1276 SEX: X DOSE6ROMP: V DEATHTYImE: Sacrifice-Scheduled 6ROSSOBSERVATION(S): LIVER: Large. HISTOMORPHOLOGOICBSERVATION(S): hypertrophy,hepatocellular,diffuse inflammation,chronic, focal/multifocal HISTOHORPHOLOGICOBSERVAT(ONS: LIVER: End of Record- 1276 inflammation,chronic, focal/multifocal(minimal) hypertrophy,hepatocellular,diffuse (moderate) IV-93 Page 1190 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATION(ONE LITTER PER GENERATION) REPRODUCTIONSTUDY OF AMMONIUMPERFLUORDOCTANOATE(AFPO) IN RATS PROTOCOL418-020 SPONSOR'SSTUDY NUMBER: T-6889.6 Appendix IV IndividualAnimal Gross and HistomorphologyData F1 Generation ANIMAL NUMBER: 1278 SEX: M DOSE GRO_: V DEATH TYIw_: Scheduled (ReducedFertility) GROSS OBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ........................................................................................................ HISTOMORPMOLOGICOBSERVATIONS: EPIDIDYMIS: infiltration,mononuclear-cell,focal (minimal) ........................................................................................................ THE FOLLOWINGTISSUE(S)WER_ WITHIN NORMAL 41MITS: COAGULATINGGLAND PROSTATE SEMINAL VESICLES ........................................................................................................ End of Record- 1278 TESTIS Page 1191 . IV-94 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOFAHHONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.B Appendix IV IndividualAnimal Gross and HistanorphologyData FI Generation ANIMALNUMBER:1279 SEX: M DOSEGRIP: V DEATHTI_mE: Sacrifice-Scheduled GROSSOBSERVATION(S): LIVER: Left lateral lobe- tan areas too numerous to count. HISTOMORPHOLOGOICBSERVATION(S): hypertrophy,hepatocellular,diffuse HISTOMORPHOLOGICOBSERVATIONS: LIVER: End of Record- 1279 hypertrophy,hepatocellular,diffuse {moderate) Page 1192 IV-9S ARGUS 418-020 ORAL{GAVAGE)11/O-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AHMONILINPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Hiatomorphology Data F1 Generation ANIHAL NUHBER:1283 SEX: H _mi_tmmi_mmmmm_m_m_mmmm_i_m_mmnt_---_---_tmmm_m_m_tmt_m_mm_m_amms_m_m_s_t_imt= GROSSOBSERVATION(S): LIVER: Left lateral and median lobes- tan areas too numerousto count ranging in size from pinpoint to 0.3 x O.lom. DOSEGROUP: DEATHTOIL: V Sacrifice-Scheduled HISTOHORPHOLOGOICBSERVATION(S): hypertrophy, hepatocellular, diffuse hematopoiesis, extramedu]lary, multifocal HISTOHORPHOLOGOICBSERVATIONS: LIVER: End of Record- 1283 hematopoiesis, extramedullary, multifocal (minima]) hypertrophy, hepatocellular, diffuse (mild) IV-96 Page 1193 ARGUS 418-020 ORAL(GAVA6E)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AHHONILIHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6rosa and Hietomrphology F1 6eneratton Data ANIHAL NUHBER:1287 SEX: H DOSE6ROMP: DEATHTYIi[: mmmm_m_mmmtmmm_mmmmm_mmsm_H_mmmmiss_sssmmg_mm_m_Bm_m_m_mmmmmmm_mm_mm_jmmmmm_mm_i_mmm1Rs_m_mmmm_m_ V Sacrifice-Scheduled 6ROSSOBSERVATION(S): 6ENERAL:No gross changes. HISTOHORPHO[.06IOCBSERVATION(S): Not applicable HISTOHORPHO_OGOICBSERVATIONS: ADRENALGLANDS: EPIDIDYHIS: hypertrophy/vacuolation, zona glomerulosa (minima]) infiltration, mononuclear-cel], focal (minima]) THE FOLLOWINGTISSUE(S) WEREWITHIN NORHALLIHITS: COAGULATINGLAND TESTIS PITUITARY End of Record- 1287 PROSTATE SEHINALVESICLES Page 1194 - IV-97 ARGUS 418-020 ORAL (GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONILJP4ERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBER:T-6889.6 Individual Appendtx IV Animal Gross and H]stomorphology Data FI Generation ANIHAL NUMBER:1288 SEX: N DOSEGRO_: DEATHTYPE: V Sacrifice-Scheduled GROSSOBSERVATION(S}: G_NERAL:No gross changes. ....................................................................................................... HISTOMORPHOLOGOICBSERVATIONS: ADRENALGLANDS: ........................................................................................................ HISTOMORPHOLOGOICBSERVATION(S): Not applicable hypertrophy/vacuolation, zona glomerulosa (mild) THE FOLLOWINGTISSU_(_) W_R_WITHIN NORMALIMITS: COAGULATINGLAND SEMINALVESICLES EPIDIDYMIS TESTIS ....................................................................................................... End of Record- 1288 PITUITARY PROSTATE Page 1195 o IV-98 ARGUS 418-020 ORAL(6AVAGE)"I'WO-GENERATIO(ONNE LITTER PERGENERATION} REPRODUCTIOSNTUDYOF AHHONIUNPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6ross and Histomorpholooy Data F1 6eneration ANIMALNUHBER:1293 SEX: H B_m1mmmmmm_1m_mmmm_mmmmmmm_mmszmmmwm_aIzm1mmmm_msmmmms_m_'_jzmmm_m_'_mz_zs_I_m_m_ DOSE6RO,_J_: V DEATHTyImE: Sacrifice-Scheduled GROSSOBSERVATION(S): LIVER: Left lateral tan areas ranging O.5om. .................................................... lobe too numerous to in size from pinpoint count to HISTOMORPHOLOGOICBSERVATION(S): hypertrophy, hepatocellular, diffuse _ ................................................... H|STQHORPHOLOGOICBSeRVATiONS: LIVER: End of Record- 1293 hypertrophy, hepatocellular, diffuse (moderate) - . ._ .'- Page 1196 __ IV-99 ARGUS 418-020 ORAL(GAVAGE)T1VO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -fi889.6 Ko_ndix IV IndividualAnimal Gross and Histomorp_mlogyData FI _neration ANIHAL NUMBER1: 295 SEX: M DOSEGRO)_: DEATHTylm_: V Sacrifice-Scheduled GROSSOBSERVATION(S): HISTOMORPHOLOGOICBSERVATION(S): LIVER; Left laterallobe four tan and white areas h_ertrophy_ hepatocellular,diffuse ranging in size from pinpointto O.3om. ........................................................................................................ HISTOMORPHOLO61COBSERVATIONS: LIVER: ..................................................... End of Record- 1295 hypertrophy,hepatocellular,diffuse (moderate) . ................................................. Page 1197 IV-tOO ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.B Individual Animl Appendix IV Gross end Histomrphology F1 _neration Data ANIMALNUMBER1: 312 SEX: F _msmmm_mImmmitsmimmmusmmsmw_iimmmmmmmm_-__mmmzmarmmm1rmmmms_mmmmm_mmmm_mm_m_m_mm_m_ DOSE6RI_P: DEATH_E: I Sacrifice-Scheduled GROSSOBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S): GENERAL:No gross changes. Not applicable ........................................................................................................ HISTOMORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: presenceof corpora lutea presenceof 9rowing/antralfollicles THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENALGLANDS PITUITARY CERVIX UTERUS OVARIES VAGINA ........................................................................................................ End of Record- 1312 OVIDUCT(S) Page 1198 IV-lOl ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1Seneratton ANIMAL NUMBER:1321 SEX: F DOSEGP_UP: DEATH l_mE: I Sacri fice-Scheduled GROSS06_ERVATION(S): GENERALN: o gross changes. ........................................................................................................ HISTOMORPHO_O_OICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTE.A: UTERUS: HISTOHORPHOLOGOICBSERVATION(S): Not applicable presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWINGTISSUEIS) WERE WITHIN NORMALIMITS: ADRENALGLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1321 OVIDUCT(S) Page 1199 IV-lO2 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLDORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Anlmal Gross and Hietomorphology Data F1 Generation ANIMALNUMBER:1328 SEX: F DOSE6RJ_P: DEATHI_IIIE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAl: No gross changes. HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: VAGINA: HISTOMORPHOLOGOIBCSERVATION(S): Not applicable presence of corpora lutea presence of growing/antralfollicles macrophages, pigmented (moderate) muclfication (mild) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1328 OVIDUCT(S) Page 1200 .. 'IV-t03 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 6eneretion ANIMALNUMBER1: 335 SEX: F _I_I_m_I_I_mmmIIm_mm_gmmm_m1m_m_m_I_m_I_mimB_msmIImIIm_mm_m_mmI_iImmmI_Im GROSSOBSERVATION(S): EAR(S): Swollen, both. ....................................................................................................... DOSEGRJ_P: DEATHT_IIE: I Sacrifice-Scheduled HISTOMORPHOLOGOICBSERVATION(S): chondropathy, auricular HISTOMORPHO_OGICOBSERVATIONS: EAR(S): OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: chondropathy,auricular (marked) presence of corpora lutea presenceof growing/antralfollicles macrophages, pigmented (moderate) THE FOLLOWINGTISSUE(S) WERE WITHIN NORMALIMITS: ADRENALGLANDS PITUITARY CERVIX VAGINA ....................................................................................................... End of Record- 1335 OVARIES OVIDUCT(S) Page 1201 .IV-104 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AJ_ONILIHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-DZ0 SPONSOR'SSTUDYNUMBERT: -6889.6 Indiv|dual Appendix IV Animal Gross and Hlstomorphology Data F1 6eneration ANIMAL NUMBER: 1340 SEX: F OOSE 6P_P: DEATH T_PE: I Sacrlfice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. HISTOMORPHOLOGICOBSERVATION(S): Not applicable HISTOMORPHOLOGICOBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: VAGINA: ........................................................................................................ presence of corpora lutea presence of growing/antra1 follicles macrophages, pigmented (moderate) distention, lumen (minimal) mucification (moderate) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES ....................................................................................................... End of Record- 1340 OVIDUCT(S) Page 1202 o. IV-IO5 ARGUS 418-020 ORAL(GAVAGE)T_/O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCT]OSNTUDYOF AHHON[UHPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 Indivial Anizl Appendix IV 6ross and Hintomorphology Data F1 6eneration ANINAL NUNBER:1341 SEX: F _mmlmtmmmsssmm_mam_mwlr_msmmmlsmRIssmmm_mmlmmsmIHr_m_mmmmgm_us_ms_m_mt DOSEGP_P: DEATH_PPE: I Sacrifice-Scheduled J_m_ml_mm_s_R_s_szIBBm_ GROSSOBSERVATION(S): EARtS): Swollen, both. ........................................................................................................ H($TOHORPHOLOGOICBSERVATION(S): chondropathy, auricular H|STOMORPHOLOGOICBSERVATIONS: EAR(S): End of Record- 1341 chondropathy, auricular (moderate) Page 1203 IV-106 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUDROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUMBER1: 342 SEX: F DOSEGI_P: DEATHTT?E: I Sacrifice-Scheduled GROSSOBSERVATION(S): _AR(S): Swollen, both. HISTOMORPHOLOGOICBSERVATION(SI: chondropathy, auricular HISTONORPHOLOGOICBSERVATIONS: EAR(S): OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: ....................................................................................................... chondropathy, auricular (marked) presence of corpora lutea presence of growlng/antra] follicles distention, lumen (mild) THE FOLLOWINGTISSUE(S)W_RE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES ........................................................................................................ End of Record- 1342 OVIDUCT(S) Page 1204 IV-I07 ARGUS 418-020 ORAL(6AVAGE)TI_O-GENERATIO(NONE LITTER PER 6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniNl 6ross and HistomorphologyData FI 6eneratlon ANIMALNUMBER:1345 SEX: F DOSEGRIP: I DEATHllmlmE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: presence of corpora lutea presence of growing/antral follicles VAGINA: inflammation,chronic, focal (minimal) ................................ mucification(minimal) _ ....................................................................... THE FOLLOWINGTISSUE(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-GENERATIO(ONNE LITTER PERGENERATION} REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(A'FrEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAniml Grams and Hiatomrq_Inol_yData FI _neration ANIMALNUMBER1: 353 SEX: F DOSEGRJ_P: DEATHT_ImE: I Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL: No gross changes. ........................................................ HISTOMORPHO_OGICOBSERVATION(S): Not applicable _ ............................................... HISTOMORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: UTERUS: ........................................................................................................ presence of corpora lutea presence of growing/antral follicles macrophages, pig_wented (nmrked) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES ....................................................................................................... End of Record- 1353 OVIDUCT(S) Page 1206 .. IV-109 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-0Z0 SPONSOR'SSTUDYNUMBERT: -6889,6 Individual Appendix IV Anlml 6ross and Htstomorphology Data FI Generation ANIMALNUMBER1: 355 SEX: F I_II_I_I_I_I_II_I_III_III_IIIIIIIII_I_I_I_I_IIIIII_II_I_IIIIII_IIIII_IIII_I_IIIII_IIz DOSEGRp_P: I "DEATHT_IWE: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. ........................................................................................................ HISTOMORPHO_061COBSERVATION(S): Not applicable HISTOMORPHOLOGOICBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: presenceof corpora lutea UTERUS: presenceof growinglantralfollicles macrophages, pigmented(mrked) ........................................................................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES ....................................................................................................... End of Record- 1355 OVIDUCT(S) Page 1207 .. ' IV-110 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFERO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Antml Appendix IV Gross and Htstomorphology Data F1 6eneretion ANIMALNUMBER1: 359 SEX: F smIm_mmIImmmnmIIIIImIImmmI_ImmmImmImIIIm_Im__mmmm_mIssm_mImIII_ImImIm_mmI_mImII_I_IIImm_m_ DOSEGRI_P: DEATHT_ImE: I Sacrifice-Scheduled GROSSOBSERVATION(S): GENERALN: o gross changes. ........................................................................................................ HISTOMORPHOLOGOICBSERVAT[ON(S): Not applicable HISTOHORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: presence of corpora lutea presence of growlnglantral follicles UTERUS: macrophages, pigmented {mild) VAGINA: muclflcatlon (mni_l) ----. .................... . ......... o ..................................................................... THE FOLLOWINGTISSUE(S)WERE VITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX OVARIES End of Record- 1359 OVIDUCT(S) Page 1208 IVQ111 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AATFEPO} IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorphology Data F1 Generation ANIMALNUMBER1: 9780 SEX: F DOSEGROUP: I DEATHTYPE: Sacrifice-Scheduled 6ROSSOBSERVATION(S): SPLEEN:Small. HISTOHORPHOLOGOICBSERVATIONS: SPLEEN: End of Record- 19780 HISTOHORPHOLOGO[CBSERVATION(S): atrophy atrophy (marked) Page 1209 1V-112 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLIX)RDOCTANOA{ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Animl Appendix IV 6ross and Htstomorphology Data F1 _mneration ANIMALNUMBER1: 365 SEX: F GROSSOBSERVATION(S): TAIL: Tip missing, ............................................. HISTOHORPHOLOGICOBSERVATIONS: TAIL: End of Record- 1365 DOSEGR_P: DEATHTI_E: II Spontaneous Death HISTOHORPHOLOGOICBSERVATION(S): necrosis, focal _ .......................................................... necrosis,focal (mild) Page 1210 IV-113 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 . SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUMBER1: 373 SEX: F lm_mlmms_m_s_tziz_z_-_s_w-wlzL.sR_m_mRm_mm_mms_ms_m_1_m_zm_maeaRm_z_t_z=s_as_zm_s==_w= GROSSOBSERVATION(S): GASTROINTESTINATLRACT: Stomach and intestinesdistention, LUNG:Dorsal surface, right apical lobe, depressect white area, 0.3cIn in diameter, DOSEGRJ_P: II DEATHT_lWE: Spontaneous Death HISTOHORPHOLOGOICBSERVATION{S): erosion(s), glandu]ar distention, ILEUM necrosis, focal macrophages, alveoli, mucosa, STOHACH focal HISTOMORPHOLOGOICBSERVATIONS: ILEUM: LUNG: STOHACH: .............................................. End of Record- 1373 distention (marked) necrosis, focal (mild} macrophages, alveoli, erosion(s), glandular . ......................................................... focal (mild) mucosa (mild) Page 1211 IV-114 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Indlvidual Appendix IV Animal Gross and Histomorphology Data FI Generation ANIMALNUHBER:1374 SEX: F IIII_I_mI_mII_I_I_IIIIIIIII_mI_IIImIII_I_-_I_m_m_I_IIIII_I_IIIIIIII_IIII_IIIIIIIIIIIII_III= DOSEGROUP: II DEATHTY_E: Sacrifice-Scheduled GROSSOBSERVATION(S): TAIL: Annular constrictions of the tail. ........................................................................................................ HISTOHORPHOLOGOICBSERVATION(S): No microscopic change to correlate HISTOHORPHOLOGOICBSERVATIONS: TAIL: ........................................................................................................ No microscopic change to correlate THE FOLLOWINGTISSUE(S) WER_WITHIN NORMALLIHITS: TAIL ....................................................................................................... End of Record- 1374 Page 1212 IV-115 ARGUS 418-020 ORAL(GAVAGE)TMO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomrpho'logy Data F1 6eneration ANIMALNUMBER1: 407 SEX: F ImIImi_mImmmmmsmmmIImlmmlmlm_ImItmmmmm_'_ImmI GROSSOBSERVATION(S): TAIl: Tip missing, ............................................................... HISTOMORPHOLOGOICBSERVATIONS: TAIL: ........................................................................................................ End of Record- 1407 m .... DOSE6ROMP: II DEATHTI_:: Sacrifice-Scheduled _miIIIImImimmumImImmmmmlmmmimImSIIm_I_SiIImmmmImmW H|STOMORPHOLOGOICBSERVATION(S): inflammation, chronic D ........................................ inflammation, chronic (minimal) Page 1213 IV-116 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AHHONIIJHPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUHBER:1415 SEX: F DOSEGRIP: DEATHT1qrE: 11 Sacrifice-Scheduled GROSSOBSERVATION(S): LIVER: Left lateral lobe- mass adhered to left lateral lobe, 2.0 x 1.2 x 0.4cm, fine. HISTOHORPHOLOGOICBSERVATION(S): infarct, liver lobe HISTOHORPHOLOGOICBSERVATIONS: LIVER: End of Record- 1415 infarct,liver lobe Page 1214 IV-117 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(ONNE LITTER P[R GENERATION) REPRODUCTIOSNTUDYOF AHHONIUHPERFLDOROOCTATNEO(AA,FPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUHBER:T-6889.6 Individual Appendix IV Animal Gross and Histomorphology Data F1 6eneration ANIHALNUHBER:1428 SEX: F DOSEGP_P: DEATHTI"P[: III Sacrifice-Scheduled GROSSOBSERVATION(S): KIDNEYS:Pelvic dilation, slight, bilateral, HISTOHORPHOLOGOICBSERVATION(S): dilatation, pelvis HISTOHORPHOLOGOtCBSERVATIONS: KIDNEYS: End of Record- 1428 dilatation, pelvis (mild) Page 1215 . IV-118 ARGUS 418-020 ORAL(BAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Ap_ndlx IV Animal 6ross and Histomo_hology F1 Generation Data ANIMALNUMBER:1495 SEX: F =II== = z=_== ====z======== =I_II_ImIIIZI_II_IImIIIISIIII_I_III=I= DOSEGRIP: DEATHTWIE: IV Sacrifice-Scheduled = _i=zml= m ==I===== =================== == GROSS OBSERVATION(S): H_STOMORPHOLOGICOBSERVATION(S): EYES: Soft tissue surroundingeye swollen, abscess, periocular ........................................................................................................ HISTOMORPHOLOGICOBSERVATIONS: EYES: ........................................................................................................ End of Record- 1495 abscess, periocular Page 1216 IV-119 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMHONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 individual Appendix IV Animal 6ross and Histomorphology Data F1 8eneratt on ANINAL NUMBER1: 544 SEX: F mmmmmm_mmm_mmmmmmmm_mm_mmmmmmmm_mm_mm_mmm_mm_mmmmmmmmm_mmmmmmmmmm_mmmmmmmmm_mmmmmmmmmmmmmmmmmm GROSS OBSERVATION(S): GENERAL: No gross changes. DOSE6R_P: DEATHT?I_: V Sacrifice-Scheduled HISTOMORPHDLOGICOBSERVATION{S): Not applicable HISTOMORPHOLOGICOBSERVAT)ONS: ADRENAL GLANDS: OVARIAN FOLLICLES/CORPORALUTEA: PITUITARY: UTERUS: hyperplasla,cortical,focal (minimal) presenceof corpora lutea presenceof growing/antralfollicles cyst{s),pars distalis macrophagesopigmented {moderate) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: CERVIX End of Record- 1544 OVARIES OVIDUCT(S) VAGINA Page 1217 IV-12O ARGUS 418-020 ORAL(GAVAGE)TI_O-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOFAHHONIUHPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUNBERT: -6889.6 Individual Appendix IV Animal Gross end Hlstomorphology Data F1 6eneretion AN]HALNUMBER:1546 SEX: F DOSEGRIP: DEATHT1qWE: mi1mi_mmmmmiz=m_mBmmimismm_im_m_n1mmsmmmsimslaml_s_m_s_mimm_m_ummsmiimmmiRmmm_mmmm_msm_1_mm_m_m V Sacrifice-Scheduled GROSSOBSERVATION]S): GENERAL:No gross changes. ....................................................................................................... HISTOHORPHOLOGOICBSERVATION(S): Not applicable HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: presence of corpora ]urea presence of growing/antra1 follicles macropheges, pigmented (marked) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMAL_MITS: ADRENAL GLANDS PITUITARY CERVIX VA61NA OVARIES End of Record- 1546 OVIDUCT(S) Page 1218 . IV-121 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PER GENERATION) REPRODUCTIOSNTUDYOF AHMON[UMPERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Htstomorpt_)logy Data F1 Generation ANIMALNUMBER:1548 SEX: F DOSEGRp_P: DEATHTI_E: V Sacrifice-Scheduled GROSSOBSERVATION(S): EARlS}: Swollen, right, HISTOMORPHOLOGOICBSERVATIONS: EAR(S): OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: H_STOMORPHOLOGOIBCSERVATION(S): chondropathy, auricular chondropathy, auricular {marked) presence of corpora lutea presence of growing/antra] follicles macrophages, pigmented (moderate) distention, lumen (moderate) THE FOLLOWINGTISSUE[S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1548 OVIDUCT(S) Page 1219 .- IV-122 ARGUS 418-020 ORAL(fAVAGE) TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal Gross and Hlstomorphol_y Data FI _neration ANIMALNUMBER1: 551 SEX: F tmwmm _=_m==_=m====_=l_=m=_m=m_=m=mm=mm=mmlmm88_ DOSEGP_I_P: DEATHT_PE: _mmmmummmmmmmmmm_mmmmRmlmzms=_ V Sacrifice-Scheduled zzz=z=ml=m:z=_z=z=z= ==Iz=_=l=Z=m GROSSOBSERVATION(S): HISTOHORPHOLOGOICBSERVATION(S): TAIL: Tip missing 11 cm from the base. inflammation,chronic necrosis, focal ....................................................................................................... HISTOMORPHOLOGICOBSERVATIONS: TAIL: inilammation, chronic (miId) necrosis,focal (mild) ....................................................................................................... End of Record- 1551 Page 1220 .IV-123 ARGUS 418-020 ORAL(GAVAGE)TVO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal Gross and Histomorpho]ogy Data FI Generation ANIMAL NUMBER:1552 SEX: F DOSEGROUP:: V DEATHT_E: Sacrifice-Scheduled GROSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATION{S): Not applicable HISTOHORPHOLOGICOBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: UTERUS: presence of corpora lutea presenceof grc_ing/antralfollicles macrophages, pigmented (r_derate) distention,lumen (moderate) THE FOLLOWINGTISSUE(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(6AVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -B889.6 Individual Appendix IV Animal Gross and Htstomorphology Data FI _retlen ANIMALNUMBER:1557 SEX: F DOSE6R_J_P: V DEATHTlqmE: Sacrifice-Scheduled GROSSOBSERVATION(S): GENERAL:No gross changes. ........................................................................................................ HISTOMORPHOLOGOICBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: UTERUS: VAGINA: HISTOMORPHOLOGOICBSERVATION(S): Not applicable presence of corpora lutea presenceof growing/antralfollicles macrophages,pigmented (mild) mucification(moderate) THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS CERVIX OVARIES PITUITARY ........................................................................................................ End of Record- 1557 OVIDUCT(S) Page 1222 __ - . . _ _ . ,. 3 . .IV-IZ5 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLUOROOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Individual Appendix IV Animal 6rosa and Histomorpho'logy Data F1 6eneration ANIMALNUMBER1: 573 SEX: F DOSEGRIP: DEATHl_E: mmmm_mimmmimm_mmm_ari_smmmmm_mmmmmm_lui_-_tm_im_m_im_wammmmmmmmmmmmmsmsR_aBam_mmtmmms_mm V Sacrifice-Scheduled _OSS OBSERVATION(S): GENERAL:No gross changes. HISTOMORPHOLOGICOBSERVATION[S): Not applicable H[_TOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMALIMITS: ADRENALGLANDS PITUITARY CERVIX VAGINA OVARIES End of Record- 1573 OVIDUCT(S) Page 1223 IV-126 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUORDOCTANO(AATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -68896 Individual Appendix IV Animal Gross and Histomorphology Data F1 Generation ANIMALNUMBER1: 579 SEX: F _mmnmm_ns_m_mm_mmsm_simw_Rsmm_i_s_mRa_s_ss_m_a"BmlImm_sm_z_ss_mms_s_Z_sz_z_z==_========s GROSSOBSERVATION(S): GENeRAl:No gross changes. DOSEGR_)J_P: V DEATHT_PE: Sacrifice-Scheduled HISTOMORPHDLOGOICBSERVATION(S): Not applicable H_$TOMORPHO_OGOIBCSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: VAGINA: presence of corpora lutea presence of growing/antra] follicles macrophages, pigmented (minimal) muctftcatton (moderate) THE FOLLOWINGTISSUE(S) WEREWITHIN NORMA_IMITS: ADRENALGLANDS PITUITARY CERVIX ....................................................................................................... End of Record- 1579 OVARIES OVIDUCT(S) Page 1224 IV-127 ARGUS 418-020 ORAL(6AVAGE)TWO-GENERATIO(NONE LITTER PER6ENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(AAXFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal 6_ss and Hist_rphology Data FI _neration ANIMAL NUMBER:1589 SEX: F DOSEGR_P: DEATHT_PE: V Sacrifice-Scheduled 6ROSSOBSERVATION(S): 6ENERAL:No gross changes. ................................................ HISTOMORPHOL06OICBSERVATION(S): Not applicable _ ...................................................... HISTOMORPHOLOGOICBSERVATIONS: OVARIANFOLLICLES/CORPORLAUTEA: UTERUS: VA6INA: ...................................... presence of corpora lutea presence of growing/antral follicles macrophages, pigmented (moderate) muctfication (mild) . ................................................................. THE FOLLOWIN6TISSUE(S) WEREWITHIN NORMALIMITS: ADRENAL6LANDS PITUITARY CERVIX ....................................................................................................... End of Record- 1589 OVARIES OVIDUCT{S} Page 1225 IV-128 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUMPERFLUOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.6 Appendix IV IndividualAnimal Gross and Hist_rphology Data FI Generation ANIMALNUMBER:1593 SEX: F DOSEGRp_P: V DEATHT_ImE: Sacrifice-Scheduled GROSS OBSERVATION(S): KIDNEYS:Right- pelvis moderate dilation, URETER:Calculi, 1.0 x O.5xm, one located at the caudal end of each ureter, URINARYB_ADDER:Walls thickened, ........................................................................ HISTDMORPHOLOGICOBSERVATION(S): dilatation,pelvis pyelonephr_tis distention hyperplasia, mucosa inflammation, chronic cystitis, hyperplastic _ ............................... HISTOMORPHOLOGOICBSERVATIONS: KIDNEYS: OVARIANFOLLICLES/CORPORLAUTEA: OVARIES: URETER: URINARYBLADDER: 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 FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS VAGINA CERVIX .............................................. End of Record- 1593 OVIDUCT(S) PITUITARY . ......................................................... Page 1226 IV-129 ARGUS 418-020 ORAL(GAVAGE)TWO-GENERATIO(NONE LITTER PERGENERATION) REPRODUCTIOSNTUDYOF AMMONIUPMERFLLIOROOCTANO(ATFEPO) IN RATS PROTOCO4L18-020 SPONSOR'SSTUDYNUMBERT: -6889.8 ANIMALNUMBER:1598 SEX: F Individual Appendix IV Animal 6ross and Histomorphology Data F1 Generation DOSEGROUP: DEATHT_E: V Sacrifice-Scheduled GROSSOBSERVATION(S): HISTOMORPHOLOGICOBSERVATION(S1: GENERAL: No gross changes. Not applicable ........................................................................................................ H!,STOMORPHOLOGIOCBSERVATIONS: OVARIAN FOLLICLES/CORPORALUTEA: presenceof corpora lutea presenceof growing/antralfollicles UTERUS: macrophages,pigmented (moderate) ........................................................................................................ THE FOLLOWINGTISSUE(S)WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS PITUITARY CERVIX VAGINA OVARIES ........................................................................................................ End of Record- 1598 OVIDUCT(S) Page 1227 IV-130 ARGUS 418-020 STUDY ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION OF AMMONIUM PERFLUOROOCTANOATE (AFPO) PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 HISTOPATHOLOGY REPORT IN RATS APPENDIX V INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA GROSS LESIONS - F1 and F2 Pups Page 1228 ARGUS 418-020 OP,.AL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE IN RATS (APFO) PROTOCOL 418-020 SPONSOR'S STUDY NUMBER: T-6889.6 APPENDIX V Q Individual Animal Gross and Histomorphology Gross Lesions - F1 and F2 Pups Data Dam #, Group #, Pup # 13921, GroupV, Pup #1 13946, Group I, Pup #10 1304, GroupI, Pup #1 1383, GroupII, Pup #6 1459, GroupIII, Pup #14 1476, GroupIII, Pup #3 1523, GroupIV, Pup #11 1523, GroupIV, Pup #3 Gross Observation(s) Mouth-mass #3, 0.2 x 0.3 x 0.1cm Kidney-right, pelvis, dilated, moderate Kidney- pelvis,dilated, slight Kidney-right,dilation, pelvis,moderate Kidney-bilateral,dilation, pelvis,moderate Kidney-right, pe!vis, dilated, slight Tail- bent Domed head; braindilatedthirdand lateral ventricles,marked Eye- rightnot present Histomorpholo,qicObservations Tissue notavailable Tissue notavailable Dilatation,pelvis, moderate Dilatation,pelvis,moderate Dilatation,pelvis, mild Dilatation,pelvis, mild Tissue notavailable Dilatation,ventricular,marked Confirmedmicroscopically V-1 Page 1229 ARGUS 418-020 APPENDIX L HISTORICAL CONTROL DATA Page 1230 ARGUS 418-020 FEMALE FERTILITY HISTORICALCONTROL DATA Cd:CD_BR VAF/Plus[Cd:CI_(SD)IGS BR VAF/Plus] RATS SUMMARY 1995-2002 1891 TOTAL LITTERS AVERAGE MINIMUM MAXIMUM DELIVERED LITTERS N 4 IMPLANTATION SITES PER DELIVERED LITTER N 63 MEAN 15.3 13.4 33 S19 17.7 PUPS FOUND DEAD OR PRESUMED CANNIBALIZED # STUDIES INCL. IN ANALYSIS 93 93 93 DAY 1 N N % 0.4% 0.0% 2.71= 72 DAYS 1-.4 DAYS 15-21 N N % 2.2% 0.0% 9.0% 88 N N % 0.3% 0.0% 3.8% 68 VIABILITY INDEX (Day 4) % 97.8% 91.0% 100.0% 84 N N VIABILITY INDEX (Day 7) % 1.0 91.5% 100.0% 10 N N LACTATION INDEX % 98.8% 94.4% 100.0% 77 N N SURVIVING PUPS/LITTER Day 1 MEAN 14.2 12.0 16.1 92 Page 1231 ARGUS 418-020 FEMALE FERTILITY HISTORICALCONTROL DATA Cd:CD_BR VAF/Plus [CrI:CD(SD)IGSBR VAF/Plus] RATS SUMMARY 1995-2002 1891 TOTAL LITTERS AVERAGE DELIVERED LITTERS N Day 4 (Precull,ng) MEAN 13.9 Day 4 (Postculling) MEAN 8.7 Day 21 MEAN 11.8 PUP WEIGHT/LITTER (GRAMS) Day 7 MEAN 13.0 Day 14 MEAN 26.0 Day 21 MEAN 40.9 MINIMUM 4 11.4 7.6 6.0 10.6 21.2 31.1 MAXIMUM 33 15.6 10.0 15.5 17.6 34.8 60.4 # STUDIES INCL. IN ANALYSIS 93 89 27 67 62 46 67 Page 1232 ARGUS 418-020 DURATION OF GESTATION HISTORICALCONTROL DATA, CrI:CD_BR VAF/Plus [CrI:CD_{SD)IGS BR VAF/PlusJRATS 1997-2002 SUMMARY 1428 TOTAL LITTERS # STUDIES INCL. IN AVERAGE MINIMUM MAXIMUM ANALYSIS DELIVERED LITTERS N 8 33 59 DURATIOONFGESTATION INDAYS MEAN 22.6 21.7 23.2 59 Page 1233 ARGUS 418-020 SEXUAL MATURATION HISTORICALCONTROL DATA CH:CD_BR VAF/Plus_ (CrI:CD_(SD)IGS BRVAF/Plus) RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 1995 - 21)1)t) SUMMARY 42 STUDIES INCLUDED IN ANALYSIS SEXUAL MATURATION MALE RATS Preputial Separation (Avg. day postpartumobs.) N MEAN FEMALE RATS Vagina Patent (Avg.day postpartumobs.) N MEAN AVERAGE MINIMUM MAXIMUM 46.1 43.9 47.7 32.1 30.1 34.0 Page 1234 ARGUS 418-020 SEXUAL MATURATION HISTORICALCONTROL DATA CH:CD_BR VAF/Plus (CH:CD_(SD)IGS BR VAF/Plus)RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 142 03/21/95 Seg. III 148 06/13/95 151 07/20/95 Harmonized Hamnonized Seg. II/111 Seg. II/111 187 07/23/96 Seg. II/111 188 08/05/96 Repro.and Postnatal 192 08/30196 Seg. II/111 199 10109196 Seg. Will SEXUAL MATURATION MALE RATS N 25 25 25 25 25 25 25 PreputiaSl eparation (Avg. day postpartumobs.) 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. daypostpartumobs.) MEAN 32.4 32.1 31.9 32.2 31.6 31.8 31.4 Page 1235 ARGUS 418-020 SEXUALMATURATION HISTORICALCONTROL DATA CrI:CD_BR VAF/Plus (CrI:CD_(SD)IGS BR VAF/Plus)RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 208 10/25/96 EmbryoFetal Dev. 222 01114/97 Seg. IIIIII 228 01/23/97 Pre and Postnatal Dev. 234 03/05197 Seg. II/111 SEXUAL 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 CH:CD_BRVAF/Plus_ (CrI:CD_(SD)IGS BRVAF/Plus)RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 242 04109197 251 06/02/97 Seg. II/111 Pre and Post Natal 255 06/11/97 Seg. II/111 258 07118/97 Seg. IIIIII 266 09/30/97 Seg. IIIIII 282 02/03198 Pre and Post Natal 290 03/10/98 Dev. Neurotox. SEXUAL MATURATION MALERATS 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 CH:CI_)BR VAF/Plus (CH:CD_SD)IGS BR VAF/Plus) RATS CODE: DRAFT FINAL REPORT MAIL DATE: TYPE OF STUDY: 294 94/30/98 305 06/23/98 310 08/03/98 345 01/28/99 Neurobehav. Comb. Pil.+ Oral (Garage) De.v.Neurotox. Dev. Full Dev. + 6-wk, toxicity Peri/PostRepro. and toxicokin. 353 03/05199 Multi-Gen. 359 04/21/99 Dev. Neurotox. SEXUAL MATURATION MALE RATS N 60 25 PreputialSeparation (Avg. day postpartumobs.) MEAN 45.2 46,7 FEMALE RATS N 60 25 Vagina Patent (Avg. claypostpartumobs,) MEAN 31.6 32.1 14 60 30 57 45.1 45.4 46.1 47.2 15 60 30 51 32.2 31.6 32.5 32.0 Page 1238 ARGUS 418-020 FEMALE FERTILITY HISTORICALCONTROL DATA CrI:CDBR VAF/Plus[CrI:CI_(SD)IGS BR VAF/Plus] RATS 1992 - 2002 SUMMARY 3343 TOTAL RATS AVERAGE MINIMUM MAXIMUM # STUDIES INCLUDED ESTROUS CYCLING OBSERVATIONS RATS EVALUATED N 8 48 131 PREDOSAGE ESTROUS CYCLING ESTROUS STAGES/7 DAYS MEAN 2.0 2.0 2.0 2 ESTROUS STAGESI14 DAYS MEAN 3.4 2.4 3.9 79 ESTROUS STAGES/15 DAYS MEAN 3.6 3.6 3.6 1 ESTROUS STAGES/16 DAYS MEAN 3.9 3.9 3.9 1 MEAN NUMBER OF COMPLETE ESTROUS CYCLES/GROUP MEAN 3.7 3.5 3.8 3 RATS WITH 6 OR MORE CONSEC DAYS OF DIESTRUS N 0 2 85 RATS WITH 6 OR MORE CONSEC. DAYS OF ESTRUS N 0 0 85 MEAN ESTROUS CYCLE LENGTHGROUP MEAN 4.1 4.1 4.1 3 PRECOHABITATION CYCLING ESTROUS MEAN NUMBER OF COMPLETE ESTROUS CYCLES/GROUP MEAN 3.2 3.2 3.2 4 ESTROUS STAGESI14 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 CrI:CD_BR VAF/Plus [CrI:CD_(SD)IGS BR VAF/Plus] RATS 1992 - 2002 SUMMARY 3343 TOTAL RATS AVERAGE MINIMUM MAXIMUM # STUDIES INCLUDED RECOVERY PER. ESTROUS CYCLING ESTROUS STAGES/28 DAYS MEAN 5.0 5.0 S.0 1 RATS WITH 6 OR MORE CONSEC. DAYS OF DIESTRUS N 0 0 1 RATS VVITH6 OR MORE CONSEC. DAYS OF ESTRUS N 0 0 1 Page 1240 ARGUS FEMALE FERTILITY HISTORICAL CONTROL DATA Cd:CD_BR VAF/Plus_ [CrI:CD(I_(SD)IGS BR VAF/Plus_] RATS 418-020 1992 - 2002 SUMMARY 3343 TOTAL RATS AVERAGE MINIMUM MAXIMUM # STUDIES INCLUDED RATS IN COHABITATION DAYS IN COHABITATION RATS THAT MATED RATS WITH CONFIRMED MATING DATES RATS MATING DAYS 1,-4 DAYS 5-7 RATS MATED BY FIRST MALE DAYS 1-7 DAYS 8-14 DAYS 15-21 RATS MATED BY SECOND MALE DAYS 8-14 DAYS 15-21 FERTILITY INDEX COPULATION INDEX PREGNANCY RATE RATS PREGNANT/RATS IN COHABITATION N MEAN N % 2.8 99.3% 7 1.6 87.5% 40 5.2 100.0% N 7 39 N % 96.0% N % 4.0% 96.0"/, 4.0% 96.0% 4.0% N % 97.0% N % 2.1% N % 2.0% 84.0% 0.0% 0.0% 100.0% 18.0% 4.0% N % 2.6% N % 2.0% N N % 83.0% N N % 98.5% N N % 96.7% 0.0% 0.0% 64.0% 93.3% 92.0% 12.S% 8.0% 100.0% 100._& 100.0% N N % "g3.1% 64.0% 100.0% 117 11S 111 11S 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 9ossl,_ on_,_. A HocshornP,A 19044 Telephon_(.215) 443.8710 T_x: t2IS)443-8Sa7 ARGUS RESEARCH Charles FUver Laboratories Discoveryand DevelopmentServices 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 Insechcide, 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: Inspection Phase Inspection Date(s) Date(s) Findings Submitted to Study Director Protocol TS Preparation TS Administration Natural Delivery/ Litter Observations Blood Collection Male Sacrifice/ Sperm Evaluations Dam/Litter Sacrifice Vaginal Patency Preputial Separation F1 Natural Delivery/ Litter Observations F1 Blood Collection F1 Male Sacrifice/ Sperm Evaluations F1 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 21 JUN 01 03 JUL 01 12 MAR 01 12 MAR 01 13 MAR 01 30 MAR 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 Date(s) Findings Submitted to Management 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 JUL 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 Page 1244 ARGUS 418-020 Inspection Phase Report Tables Report Text Revised Report Inspection Date(s) Date(s) Findings Submitted to Study Director 30 JUL 01 and 03 AUG 01 30 JUL 01 to 05 AUG 01 17-21 DEC 01 06-09 AUG 01 13-14 AUG 01 17,20,21,26 DEC 01 26-27 DEC 01 27 DEC 01 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 Date(s) Findings Submitted to Management 03 AUG 01 06 AUG 01 21 DEC 01 09 AUG 01 14 AUG 01 26 DEC 01 27 DEC 01 27 DEC 01 25 MAR 02 Matthew J. Vaneman, B.S. Date Manager of Regulatory Compliance Cynthia M. Kelsch Date Quality Assurance Associate/Team Leader and Principal Auditor Page 1245