Document 10XbXQXmKRam3LrKd1yrO8g9Z

12) OECD 416-OPPTS 870.3800, Reproduction and fertility effects (Two generation reproduction toxicity), 4 18-021 part 2 of 2 ARGUS 4 18-021 RESEARCH PATHOLOGY SERVICES. INC. 438 East Butler Avenue, New Britain, PA 18901 Phone: 215-345-7070 0 Fax: 215-345-4326 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 . HISTOPATHOLOGY REPORT SUBMITTED TO: Raymond G. York, Ph.D., D.A.B.T. Argus R.esearch 905 Sheehy Drive Horsham, PA 19044 SUBMITTED BY: Lm-+I&-- yhdh7,2&2 W.IRay Brown, D.V.M., Ph.D. Veterinary PathoIogist March ;7, 2003 Page 731 ARGUS 3 18-021 APPENDIX K HIST0PATH:OLOGY REPORT Page 730 ARGUS 4 15-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT TABLE OF CONTENTS Paqe . . REPORT Method ....................................................................................................................... 1 Results ....................................................................................................................... 3 Summary..................................................................................................................... 7 Quality Assurance Unit Statement ............................................................................. 9 Good Laboratory Practice Compliance Statement ................................................... 10 . . TABLES 1. Incidence and Degree of Severity of Histomorphologic Observations P Generation ................................................................................................. 11 2. Incidence and Degree of Severity of Histomorphologic Observations P Generation Reduced Fertility Animals ........................................................ 17 3. Incidence and Degree of Severity of Histomorphologic Observations F1 Generation................................................................................................ 19 4. Incidence and Degree of Severity of Histomorphologic Observations . F1 Generation Reduced Fertility PInimals ...................................................... 27 APPENDICES I. Histomorphologic Observations .P G'eneration....................................... 11. to 1-31 Key to Histomorphologic Observations ............................................................... 1-1 Tables I.? . Histomorphologic Observations .Group I Male Rats ............................... 1-2 12. . Histomorphologic Observations .Group II Male Rats .............................. 1-5 13. . Histomorphologic Observations .Group Ill Male Rats ............................. 1-8 1-4. Histomorphologic Observations .Group IV Male Rats........................... 1-11 1.5 . Histomorphologic Observations .Group V Male Rats............................ 1-14 16. . Histomorphologic Observations .Group I Female Rats......................... 1-17 17. . Histomorphologic Observations .Group I Female Rats......................... 1.20 18. . Histomorphologic Observations .Group Ill Female Rats....................... 1-23 19. . Histomorphologic Observations .Group IV Female Rats ...................... 1-26 1-10. Histomorphologic Observations .Group V Female Rats ....................... 1-29 Page 732 ARGUS 3 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT TABLE OF CONTENTS (Continued) Paqe II. Histomorphologic Observations-F1 Generation.. ...................... .............11-1 to 11-31 Key to Histomorphologic Observations ................................................... ........... 11-1 Tables 11-1. Histomorphologic Observations .- Group I Male Rats ..............................11-2 11-2. Histomorphologic Observations .- Group II Male Rats ............................. 11-5 11-3. Histomorphologic Observations .- Group Ill Male Rats ............................ 11-8 11-4. Histomorphologic Observations .- Group IV Male Rats.......................... 11-11 11-5. Histomorphologic Observations .- Group V Male Rats........................... 11-14 11-6. Histomorphologic Observations .- Group I Female Rats ........................ 11-17 11-7. Histomorphologic Observations .- Group II Female Rats.......................11-20 11-8. Histomorphologic Observations .. Group Ill Female Rats ...................... 11-23 11-9. Histomorphologic Observations .-Group IV Female Rats ..................... 11-26 11-10. Histomorphologic Observations .. Group V Female Rats ...................... 11-29 Ill. Individual Animal Gross and Histomorphology Data - P Generation .................................................................................. 111-1 to 111-300 IV. Individual Animal Gross and Histomorphology Data - F1 Generation................................................................................ IV-I to IV-300 Page 733 ARGUS 4 18-021 ORAL (GAVAGE) -NVO-GENERATlON (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTA.NE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY' NUMBER: T-7485.13 HISTOPATHOLOGY REPORT METHOD: Microscopic examination was made of the specified tissues from five groups of male and female Crl:CD@(SD)IGSBR \/AF/PIus@rats of the P and F1 generations used in a two-generation reproduction stiidy of potassium perfluorobutane sulfonate (PFBS). A brief outline of the study design is shown below. 30 0 0 10/15' I I I I II 30 30 3 10 I- Ill 30 100 10 10 1 30 10 1 :3 1 :I 130000 0 100/66.7' 10/15' 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 level (of the test substance 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 may 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. Research Pathology Services, Inc. -1 Page 734 ARGUS 4 18-021 ORAL (GAVAGE) TW0-GENERATI0N (ONE L I T E R PER GENERATICIN) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANESULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT The protocol-specified tissues were routinely processed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin for microscopic evaluation with the exception of the testes which were stained with the periodic acid-Schiff technique. The tissues specified for microscopic evaluation from the ten male and ten female randomly selected P and F1 generation adult rats of Groups I and V included adrenal glands, kidneys, liver, 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, when available, were examined from male and female rats of the P and F1 generations suspected of reduced fertility. Sections of the liver and kidneys, when available, and all tissues with gross lesions also were examined from the remaining adult male rats of the P and F1 generations. 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 735 ARGUS 418-021 0R A L (GAVAGE) -1TWO-GENERAT1ON (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT RESULTS: The type, incidence, and degree of severity of all histomorphologic observations in the P and F1 generation adult rats specified for microscopic examination are summarized in Tables 1 and 3, respecAiveIy. 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 I I , respectively. A key to the individual microscopic observations precedes Table 1-1 and Table 11-1. The gross necropsy observations, microscopic findings, and a correlation of the gross and microscopic changes, when applicable, are included in Appendices I l l and IV for the P and F1 generation parental adult rats, respectively. P Generation Adult Rats (Tables 1 arid 2, 1-1 to 1-10, Appendix 111): Treatment-related microscopic changes were observed in the liver of male rats of Groups IV and V and kidneys of male and female rats of Groups'IV and V. The treatment-related change in the liver consisted of increased size (hypertrophy) of hepatocytes of male rats of Groups IV and V. The liver cells were enlarged due to an increased amount of finely granular eosinophilic cytoplasm. This hypertrophy generally was present in all areas of the lobules, but did tend to be more prevalent and more prominent in the centrilobular region. The incidence and severity of rats with hepatocellular hypertrophy was dose-related (Table 1). A similar hepatic change was not observed in the male rats of Groups II and Ill or in any of the Group V female rats selected for examination. In the kidneys, the primary treatment-related microscopic change consisted of an increased incidence and severity of hyperplasia of the tubular and ductular epithelium of the inner medulla/papilla in male and female rats of Groups IV and V (Table 1). The affected tubules were more densely cellular with variable-sized nuclei. Also, there was an increased incidence of minimal or mild focal papillary edema in the Group IV and V female rats and Group V male rats. Focal necrosis of the papilla occurred in one Group V male rat and three Group IV female rats and Research Pathology Services, Inc. -3 Page 736 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT medullary tubular dilatation was seen in one Group IV and two Group V female rats. There were several other microscopic changes observed in the kidneys of male and female P generation rats, including the controls, but these were considered to have occurred spontaneously and were not considered to be associated with the treatment-related effects in the papilla. Hyperplasia of the papillary tubules also was seen in three Group Ill male rats and in none of the P generation control male rats. This incidence in the Group Ill male rats is not considered to be a treatmentrelated effect, as similar minimal or mild hyperplasia was observed in three P generation control female rats and three F:l generation control male rats. No treatment-related microscopic changes were observed in the reproductive organs of any of the male and female P generation rats selected for histopathologic evaluation that had been given 1000 mg/icg/day of the test substance. There were a few microscopic changes observed in these tissues of the male and female rats, but they generally occurred at single, low or similar frequencies between the control and compound-treatment groups (Table 1). These changes were typical of those that occur spontaneously in adult male and female rats used in reproduction studies. Growing and antral follicles and corpora lutea were present in the ovaries of all control and high dosage group P generation female rats selected for microscopic evaluation (Table I). Male 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. The male rats characterized as "reduced fertility" of the P generation are identified in the individual tables of microscopic findings in Appendix I as "SSRF". The type, incidence and degree of severity of these findings are summarized in Table 2. Similarly, the few changes observed in these "reduced fertility" male rats occurred sporadically and are of the type that occur spontaneously in male rats of this age and strain and were not compoundrelated. Focal or diffuse prostatic atrophy was observed only in treated "SSRF" male rats (one Group Ill and two Group V male rats) and in the none of the "SSRF" control rats (Table 2). However, focal1 prostatic atrophy was observed in three control male rats specified for the complete examination (Table I ) . -~~ ~ ~~ Research Pathology Services, Inc. -4 Page 737 ARGUS 4 18-021 ORAL (GAVAGE) -NO-GENERATION (ONE L I T E R PER GENERATICIN) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT F1 Generation Adult Rats (Tables 3 and 4, 11-1 to 11-10, Appendix IV): Microscopic examination of the liver of male rats and kidneys of male and female rats revealed treatment-related effects similar to those in the P generation male and female rats. In the liver, the treatment-related change consisted of minimal or mild increased size (hypertrophy) of hepatocytes in male rats of Groups IV and V of the F1 generation which was similar to that observed in the P generation male rats. The incidence and severity of this hepatic hypertrophy in the groups of F1 generation male rats also was dose-related (Table 3). This liver change was not observed in the F1 generation male rats of Groups II and I l l or in any of the F1 generation Group V female rats. Compound-related microscopic changes were observed in the kidneys of female rats of Group IV and male and female rats of Group V. The treatmentrelated changes consisted primarily of an increased incidence and severity of hyperplasia of the tubular and ductular epithelium in the inner medullary region and papilla. These tubules had increased amounts of small cells with prominent dark nuclei. Other changes considered to be treatment-related were an increased incidence of focal papillary edema in the Group V male rats and in the Group IV and V female rats. Papillary hemorrhage occurred at low incidences in the same groups of male and female rats. Sporadic incidences of focal papillary necrosis also were observed in two male rats of Group IV and one female rat each of Groups IV and V which also were considered to be compound-related. There were no treatment-related imicroscopic changes in the reproductive organs of the 10 male and 10 female F1 generation rats randomly selected for histopathologic examination that had been given 1000 mg/kg/day of the test substance. No compound-related microscopic changes were observed in any of the male or female rats identified as having "reduced fertility" (Table 4). There were a few changes in the reproductive tissues of these rats but they occurred sporadically or at Research Pathology Services, Inc. -5 Page 738 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOL.OGY REPORT similar incidences among the groups, including the controls, and none were treatment-related. Their type, incidence or severity was not affected by administration of the test substance. These rats are identified in the individual tables of microscopic findings as "SSRF" , "SDRF" or "SURF". No treatment-related microscopic changes were seen in any of the tissues specified for examination from the male and female rats of Groups II and I l l of the P and F1 generations: There were several other microscopic findings in the kidneys of male and female rats of the P and F1 generations. These changes were observed mostly in treated animals at a relatively low incidence and included pelvic hemorrhage, hyperplasia of the pelvic/papillary urothelium, pelvic mineralization and cortical tubular basophilia. Although these changes were seen at a low incidence mostly in rats of the compound-treatment groups, they were not considered to be directly compound-related as these changes do occur spontaneously in this strain of rat. The possibility, however, that their incidence or occurrence could have been exacerbated in association with the other treatment-related renal effects is a consideration. Similarly, focal papillary necrosis was observed in one F1 generation Group Ill male rat. This focus of necrosis was different from the treatment-related papillary necrosis in that it was a minimal focal area at the tip of the papilla in a rat with moderate pyelonephritis and this necrosis was considered to be part of the pyelonephritis and not the treatment-related change. 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 PFBS administration. These changes are listed and summarized in the attached histomorphology tables. ~ Research Pathology Services, Inc. -6 Page 739 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATlON (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT SUMMARY: Microscopic examination was made of the specified tissues from selected parental male and female rats of the P and F1 generations of an oral (gavage) two-generation (one litter per generation) reproduction study of potassium perfluorobutane sulfonate (PFBS). Four groups of 30 male and 30 female rats in each generation received 30, 100, 300, or 1000 mglkglday of the test substance. In each generation, an additional group of 30 male and 30 female rats received the vehicle only and served as control groups. 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. Also, there were no treatment-related changes in any of the organs specified for evaluation from .the P an F1 generation male and female rats that had been given 30 or 100 mglkgllday of PFBS. There were a few male and/or 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 available for examination that were designated as "reduced fertility" ariimals showed no consistent microscopic changes. The few changes that were seen in these "reduced fertility" rats were not considered to be treatment-related. Treatment-related microscopic changes were observed in the liver of male rats and and kidneys of male and female P and F1 generation rats that had been given 300 or 1000 mg/kg/day of PFBS. The treatment-related microscopic change in the liver of the P and F1 generation male rats of the 300 and 1000 mg/kg/day PFBS-treatment groups consisted of minimal or mild enlargement (hypertrophy) of hepatocytes. This effect was most prominent in centrilobular areas. The incidence and severity of this hypertrophy in these dosage groups in the two generations were dose-related. A similar effect in the liver was not observed in male rats of the lower dosage groups or in female rats of the 1000 mg/kg/day dosage group of either generation. Research Pathology Services, Inc. -7 Page 740 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT The treatment-related microscopic changes in the kidneys also occurred in male and female rats of the P and F1 generations. In the P generation, the treatment-related effects occurred in both sexes of the 300 and 1000 mg/kg/day dosage groups and in the F1 generation, the effects occurred in male rats of the 1000 mg/kg/day dosage group and in the female rats of the 300 and 1000 mg/kg/day dosage groups. The renal changes consisted primarily of hyperplasia of the tubular and ductular epithelium in the inner medulla and papillary region. The incidence and severity of this hyperplasia generally occurred at a dose-related incidence and severity. Other associated treatment-related changes that occurred at lower incidences and sporadic distributions in the P and/or F1 generation rats consisted of focal papillary edema, focal papillary necrosis, dilatation of medullary tubules and focal papillary hemorrhage. All microscopic changes observed in the other tissues specified for examination of the P and F1 generation adult male and female rats of this study were considered to have occurred spontaneously and to be incidental and unrelated to compound administration. Research Pathology Services, Inc. -a Pa.ge 741 ARGUS 4 18-021 ORAL (GAVAGE) 1WO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT QUALITY ASSURANCE UNIT STATEMENT All aspects of the tissue processing, microscopic slide preparation, histopathologic evaluation and report preparation for the study listed above have been performed according to the Standard Operating Procedures of Research Pathology Services, Inc. and were audited in accordance with the procedures established by the Quality Assurance Unit of Research Pathology Services, Inc. in compliance with the Good Laboratory Practice reglJlations specified in the protocol. Quality Assurance inspections were performed as shown below. There were no deviations from the protocol, Standard Operating Procedures andlor appropriate Good Laboratory Practice regulations noted during the conduct of the study that had any impact on study integrity. The summary report of QA inspections was submitted to the Study Director on March 7, 2003. Dales of Inspection 12/06/01, 03/01/02 12107101,03/04102 02/01/02,03113/02 02/04/02, 03/14/02 03114102 04118/02 04/18/02 04/25,26,29,30/02 05/02/02 05/03/02 05107102 05/08/02, 06/14/02 03/07/03 Study Phase Trimming Embedding Microtomy Staining Organization & Review Histopathology Data Entry Data Verification Data Processing Report Preparation Pre-Submission Audit Draft Report Final Report Dale Reported to Management 12/31/01,03/31/02 12/31/01,03131102 02/28/02,03131102 02/28102,03131102 05/08/02 04130102 04130102 04130102 05/08/02 05/08/02 05/08/02 05/08/02,06/14102 03/07/03 Date Reported to Study Director 05/08/02 05/08/02 05/08/02 05108102 05/08/02 05108102 05108102 05108102 05/08/02 05108102 05/08/02 05108/02,06114102 03107103 Research Pathology Services, Inc. Karen W. Harkins, BS Quality Assurance Unit Page 742 Date -9 ARGUS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT All aspects of the above-referenced study performed by Research Pathology Services, Inc. were conducted according to: US. EnvironmentalProtection Agency (1998). Healtt. Effects Test Guidelines; Reproduction and Fertility Effects Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3800, August, 1998. U S .EnvironmentalProtection Agency (1997). Toxic Substances Control Act (TSCA) Test Guidelines; Final Rule. Reproduction& Fertility Effects, 799.9380 (cross-referencedto OPPTS 870.3800). Federal Register, August 15, 1997. U S . EnvironmentalProtection Agency. Federal Insecticide, Fungicide and RodenticideAcUToxic Substances Control Act ( F I F W S C A ) ; Good Laboratory Practice Standards; Final Rule. 40 CFR Part 16OIPart 792. Organisationfor Economic Cooperation and Development (1998). The Revised OECD Principles of Good Laboratory Practices [C(97)186/Final]. No deviations were noted that had any significant impact on the validity of the study. -1J R 9 f3 w hc- W. Ray Brohn, DVM, PhD, DACVP Veterinary Pathologist 7 , ou3 Date Research Pathology Services. Inc. -1 0 Page 743 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NJMBER: T-7485.13 TABLE 1 Incidence and Degree o f S e v e r i t y 3 f Histomorphologic Observations P Generation Dose Group: Sex : Number o f Animal s/Group: I I 1 I11 I V v MMMMM 30 30 30 30 30 I I 1 I11 I V v F F F F F 30 30 30 30 30 TESTIS: NO. EXAMINED NO. NORMAL -atrophy. diffuse marked 13 1 2 2 16 12 1 1 1 15 E11 EO1 COl E11 E11 10 0 1 1 - a t r o p h y . mu1t i f o c a l mild .edema, d i f f u s e marked E11 COl 101 COl EO1 10000 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 13 1 1 2 15 901111 -atrophy mild marked 10010 - hypospermi a mild marked E11 EO1 COl c11 c11 00001 10010 - i n f i l t r a t i o n , m o n o n u c l e a r - c e l l , focal E31 E11 LO1 [OI C41 m i n i mal 21004 mild 10000 PROSTATE : NO. EXAMINED NO. NORMAL 13 1 1 1 15 6 0 0 1 6 -atrophy. diffuse modera t e E01 EO1 [Ol [ O l E11 00001 -atrophy. focal minimal mild moderate 10002 00001 -inflammation. chronic m i n i mal mild [31 C11 E11 E01 C41 10102 21002 -prostatitis. suppurative minimal SEMINAL VESICLES: NO. EXAMINED NO. NORMAL 13 1 1 1 15 13 1 1 1 14 [ 3 = Total incidence o f specified lesion. a l l grades. - 11 Page 744 -~- ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (.ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUEI PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1 (Continued) Incidence and Degree o f Severity o f Histomorphologic Observations P Generstion Dose Group: Sex : Number o f Animal s/Group: I I1 I11 I V v MMYMM 30 30 30 30 30 I I1 I11 I V v FFFFF 30 30 30 30 30 SEMINAL VESICLES (Continued) : .a t r o p h y mild [Ol c01 COl COl c11 0 0 0 0 1 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 13 1 1 1 15 13 1 1 1 15 OVARIES : NO. EXAMINED NO. NORMAL -cyst(s), intraovarian 10 0 10 10 0 9 0 0 1 NO. NORMAL 10 0 10 10 0 10 NO. NORMAL - d i s t e n t i o n , lumen mild moderate marked -macrophages, minimal mild moderate pigmented 10 0 10 2 0 0 c11 LO1 [Ol c01 131 0 0 0 0 1 10 0 0 1 0 0 0 0 1 [SI c01 [Ol [OI 191 00003 3 000 2 5 0 0 0 4 NO. NORMAL 10 0 0 0 10 10 0 0 0 10 NO. NORMAL OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growing/antral f o l l i c l e s 10 0 0 0 10 10 0 0 0 10 10 0 0 0 10 10 0 0 0 10 NO. NORMAL 10 0 0 0 10 6 0 0 0 7 10 0 0 0 10 10 0 0 0 9 [ 1 = Total incidence o f specified lesion, a l l grades. - 12 Page 745 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NIJMBER: T- 7485.13 TABLE 1 (Continued) Incidence and Degree of Severity o f H i stomorphol ogic Observations P Generation Dose Group: Sex: Number o f Animal s/Group: I I1 I11 I V v M M M M M 30 30 30 30 30 I I 1 I11 I V v F F F F F 30 30 30 30 30 ADRENAL GLANDS (Continued) : -degeneration. cystic, cortex minimal [OI [OI E01 COl [OI 00000 [OI COl [OI [Ol 111 00001 . i n f i l t r a t i o n . mononuclear-cell , mu1t i f o c a l mild c11 [Ol [OI COI [OI 10000 [OI E01 [OI [OI LO1 00000 -vacuolation. cortex minimal 131 101 COI EOI [31 30003 C0l COI COl COl 101 00000 KIDNEYS : NO. EXAMINED NO. NORMAL - hyperpl asi a, epithelium. minimal mild moderate tubul ar/ductul ar papilla 30 30 30 30 30 15 20 19 14 6 C01 101 C31 C91 CW 00379 00029 00001 27 29 29 26 24 16 20 15 9 2 [31 C21 [51 [I61 [211 12479 201812 ~ 00010 -edema. p a p i l l a r y , f o c a l m i n i mal mild - necrosi s, papi 11a, focal m i n imal moderate -dilatation. minimal moderate - basophi 1ia , minimal mild moderate medullary tubules cortical tubules , focal E11 E11 P I C21 [61 11225 00001 COl COI [OI [Ol C11 00000 00001 E01 COI 101 COI COI 0 0 0 0 0 00000 E51 C4l C31 C11 E51 44314 10001 00000 [11 C11 [31 C81 C71 11377 00010 [OI COI 101 E31 COl 00010 00020 [OI LO1 101 c11 C21 0 0 0 0 1 00011 00001 00010 -cyst(5). medulla 10101 01001 -cyst(s). papilla 10000 01000 -cyst(s), perirenal - d i 1a t a t i o n . minimal mild moderate cortical tubules, focal 00001 EO1 C01 COI COl c11 00001 00000 00000 00000 101 EO1 lo1 c11 c11 0 0 0 0 0 00001 00010 [ 1 = Total incidence o f specified lesion, a l l grades. - 13 Pa.ge 746 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIJM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1 (Continued) Incidence and Degree o f Severity of H i stomorphol ogi c Observations P Generation Dose Group: Sex: Number o f Animals/Group: I I 1 I11 I V v MMMMM 30 30 30 30 30 I I 1 I11 I V v FFFFF 30 30 30 30 30 KIDNEYS (Continued) : - d i1atation. minimal mild moderate pel v i s .hemorrhage, pel v i s . m i n i mal mild 00011 [OI 101 E21 E11 0 0 10 0 0 11 C11 LO1 c11 COl c11 10000 0 0 1 0 1 00000 COl LO1 E01 COl [OI 00000 00000 - h y p e r p l a s i a , pel v i c l p a p i 11a r y u r o t h e l ium minimal mild E01 [Ol 111 C21 C41 00120 00004 - i n f i l t r a t i o n . m o n o n u c l e a r - c e l l . focal [ l o ] [51 [31 C11 [21 minimal 105 3 1 2 [OI COl COl COl [OI 00000 00000 COI [OI [I1 [I1 COl 00110 - m i n e r a l i z a t i o n . mu1t i f o c a l m i n i mal -mineral iz a t i on, minimal mild moderate pel v i s -nephritis. chronic, focal m i n imal - pyel it i s , c h r o n i c mild moderate -pyelonephritis mild [OI COl [Ol 101 t-01 00000 [Ol C O l C11 131 C11 00100 00011 '00020 101 101 101 101 [OI 00000 101 101 111 $1 c11 001 0 00001 101 101 [OI 101 COI 00000 C6l C71 C8l C5l C61 67856 101 KO1 111 101 COl 00100 00000 00000 101 c11 [Ol COl c11 01001 EO1 COI [Ol [OI 101 0 0 0 0 0 00000 E11 [OI 101 [Ol EO1 10000 LIVER: NO. EXAMINED NO. NORMAL 30 30 30 30 30 22 25 26 20 3 - c e l l u l a r a l t e r a t i o n , b a s o p h i l i c . f o c a l [Ol 101 101 C21 [Ol minimal 00020 - c e l l u l a r a l t e r a t i o n , c l e a r - c e l l , f o c a l [O] [l] [O] minimal 010 [OI [OI 00 .hematopoiesis. extramedullary minimal 111 COI 101 101 E11 10001 10 0 0 0 10 900010 COl [Ol COI LO1 COI 00000 COl E01 COl [OI COI 00000 [Ol LO1 101 101 COI 00000 [ ] = Total incidence o f specified lesion, a l l grades. - 14 Page 747 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIIJM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1 (Continued) Incidence and Degree o f S e v e r i t y 3f H i stomorphol o g i c Observations P Generation Dose Group: Sex: Number o f Animal s/Group: I I 1 I11 I V v MMMMM 30 30 30 30 30 I I 1 I11 I V v F F F F F 30 30 30 30 30 LIVER (Continued) : -hyperplasia. b i l e duct. focal COI minimal 0 .hypertrophy. hepatocellula r 101 minimal 0 mild 0 -inflammation, chronic, focal/multifocal[5] m inimal 5 r01 C O l c11 lo1 0010 [ O l COI C31 1261 00325 0001 [3] [2] [4] [5] 3 2 4 5 r01 c01 r01 [OI 101 0 0 0 0 0 C O l E01 101 C O l 101 00000 00000 C11 COI 101 C O I 101 10000 -vacuolation. hepatocellular. centrilobular mild LO1 t-01 LO1 [I1 101 00010 -vacuolation. hepatocellular. multifocal[ZI m inimal 1 mild 1 111 C21 02 1 0 [11 111 10 0 1 PITUITARY: NO. EXAMINED NO. NORMAL - c y s t (5) - hyperpl asi a, minimal p a r s d i s t a l is , f o c a l 11 0 0 0 10 800010 2 0 0 0 0 [I1 [ O l 101 C O l [ O l 10000 EAR(S) : NO. EXAMINED NO. NORMAL 0 1 0 1 0 0 0 0 0 0 -chondropathy, auricular mild marked COl c11 COl 111 101 0 0 0 1 0 01000 EXTREMITIES : NO. EXAMINED NO. NORMAL 00000 00000 -ankylosis 00000 -osteochondritis moderate C O l C O I C O l C O l 101 00000 SPLEEN : NO. EXAMINED NO. NORMAL 00000 00000 -abscess 00000 [ O I [ O I 101 C O I COl 00000 101 C O l 101 C O l C O I 00000 00000 10 0 0 0 10 800010 20000 [OI C O l COl COI C O l 00000 00000 0 0 0 0 0 COI COl L-01 COI LO1 00000 0 0 0 0 0 00010 00000 00010 [ O I [ O l COI 111 C O l 00010 10020 00000 00010 [ ] = Total incidence o f specified lesion, a l l grades. - 15 Page 748 ARGUS 3 18-021 ORAL (GAVAGE) TWO-GENERATIOh (ONE L I l l E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418~ 0 2 1 SPONSOR'S STUDY LUMBER: T-7485.13 TABLE 1 (Continued) Incidence and Degree o f Severity o f Histomorphologic Observations P Generation Dose Group: Sex: Number o f Animal s/Group: I I 1 I11 I V v MMMMM 30 30 30 30 30 I 11 I 1 1 I V v FFFFF 30 30 30 30 30 SPLEEN (Continued) : .a t r o p h y moderate -congestion. red pulp moderate -cyst(s), capsular -pigment mild [Ol E01 [OI 101 COl 00000 [OI 101 [OI [OI 101 00000 00000 COl COl [Ol [OI [Ol 00000 [OI COI [Ol c11 [OI 00010 C11 LO1 101 [Ol LO1 10000 10000 [OI [OI [OI [I1 101 00010 THY MUS : NO. EXAMINED NO. NORMAL congesti on minimal mild -hemorrhage. focal minimal TAIL: NO. EXAMINED NO. NORMAL -inflammation. chronic, focal moderate ~ necrosis moderate 21142 00001 [21 [11 [I1 P I E01 20130 01000 [Ol E01 [OI E11 [I1 00011 00000 00000 [OI [Ol [OI COI 101 00000 COl E01 [Ol COl COl 00000 00000 00000 00000 00100 00000 [OI LO1 111 [Ol COl 00100 COl [Ol c11 COl t-01 00100 [ ] = Total incidence of specified lesion. a l l grades. - 16 Page 749 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIIJM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NIJMBER: T-7485.13 TABLE 2 Incidence and Degree o f Severity o f Histomorphologic Observations . Reduced F e r t i l i t y Animals P Generation Dose Group: Sex : Number o f Animal s/Group: I I 1 I11 I V v MMMMM 31115 I I 1 I11 I V v FFFFF 31115 TESTIS: NO. EXAMINED NO. NORMAL -atrophy. diffuse marked -edema. d i f f u s e marked 31115 21114 c11 COl COl c01 c11 10 0 0 1 E11 c01 c01 LO1 COl 10000 NO. NORMAL 31115 10113 -atrophy mild marked loo00 .hypospermi a mild marked c11 [OI LO1 co1 c11 00001 10000 - i n f i l t r a t i o n . m o n o n u c l e a r - c e l l , f o c a l C11 C11 [OI COl E21 minimal 01002 mild 10000 PROSTATE : NO. EXAMINED NO. NORMAL 31115 20012 -atrophy, diffuse moderate -atrophy. focal minimal mild moderate - in f l ammation. c h r o n i c minimal mild SEMINAL VESICLES: NO. EXAMINED NO. NORMAL -atrophy mild COI [Ol c11 c01 c21 00100 00001 00001 c11 c11 c11 COl c11 00100 11001 31115 31114 COl c01 c01 co1 c11 00001 [ ] = Total incidence o f s p e c i f i e d l e s i o n , a l l grac:es. - 17 Page 750 ARGUS 4 18-02I ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418.021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 2 ( L o n t i n u e d ) Incidence and Degree o f S e v e r i t y o f Histomorphologic Observations ~ Reduced F e r t i l i t y Animals P Generation Dose Group: Sex : Number o f Animal s/Group: I I1 I11 I V v MMMMM 31115 I I 1 I11 I V v FFFFF 31115 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 31115 31115 KIDNEYS : NO. EXAMINED NO. NORMAL 31115 11111 00000 00000 ~ h y p e r p l a s i a , t u b u l a r / d u c t u l ar epithelium. papilla m i nimal mild 101 COI [OI coi 141 00002 00002 COl LO1 COl COl COl 00000 00000 - i n f i l t r a t i o n . m o n o n u c l e a r - c e l l , f o c a l [21 [O] [O] EO] 101 minimal 20000 COI [OI COI E01 [Ol 00000 LIVER: NO. EXAMINED NO. NORMAL ~ h e m a t o p o i e s i s ,e x t r a m e d u l l a r y minimal -hypertrophy, hepatocellula r minimal 31115 31111 COl COl 101 COI c11 00001 coi [OI [OI COI c41 00004 00000 00000 [OI 101 101 COI [OI 00000 COI [Ol COI 101 COI 00000 NO. NORMAL -congestion. red pulp moderate -cystts), capsular 00000 00000 E01 COl COI 101 101 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 00000 C11 COl COl COI COl 1 0 0 0 0 1 0 0 0 0 NO. NORMAL -congestion minimal 00010 00000 [Ol COI E01 c11 [OI 00010 00000 00000 [OI COl 101 [OI COl 00000 [ ] = Total incidence of specified lesion, a l l grades. - 18 Fage 751 ARGUS 418-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR ' S STUDY NUMBER: T - 7485.13 TABLE 3 Incidence and Degree o f S e v e r i t y of Histomorphologic Observations F1 Generation Dose Group: Sex : Number o f Animal s/Group: I I1 I11 IV v MMMMM 30 30 30 30 30 I I1 I11 IV v F F F F F 30 30 30 30 30 TESTIS : NO. EXAMINED NO. NORMAL -atrophy. diffuse marked -atrophy. focal mini mal 19 7 5 7 16 19 5 4 7 15 COl C11 [Ol 101 101 0 10 0 0 COI COl [11 COl COl 00100 degeneration , mu1ti f o c a l mild COl C11 E01 COl C11 01001 - r e t a i n e d Step 19 spermatids, Stage I X / X tubules 01001 EPIDIDYMIS: NO. EXAMINED NO. NORMAL 19 7 5 7 16 16 1 4 4 11 -atrophy moderate 101 c11 1:01 LO1 [;I 0100 -exfoliated spermatogenic c e l l s minimal moderate 101 C11 1:01 COl C11 01000 00001 .hypospermi a mild marked COl C11 I:ol 101 C11 00001 oiooo -infiltration. mononuclear-cell, focal C21 C41 1111 C31 E41 m i ni mal 24134 - m i crogranul oma(s) 10000 NO. NORMAL -atrophy. focal minimal mild moderate -inflammation. minimal mild moderate chronic 19 7 5 7 16 532111 [ai 121 [11 [61 c41 31032 41022 10110 C91 C21 P I C11 C21 71102 20010 01100 [ ] = Total incidence o f specified lesion, a l l grades. - 19 Page 752 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I n E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 3 (Continued) Incidence and Degree o f Severity o f H istomorphol ogi c Observations F1 Generation Dose Group: Sex: Number o f Animal s/Group: I I 1 I11 I V v MMMMM 30 30 30 30 30 I I1 F F 30 30 PROSTATE (Continued) : ~ prostatitis, suppurative m i n i mal SEMINAL VESICLES: NO. EXAMINED NO. NORMAL COAGULATING GLAND: NO. EXAMINED NO. NORMAL OVARIES : NO. EXAMINED NO. NORMAL -cyst(s), intraovarian - c y s t i c bursa(e1 OVIDUCT(S) : NO. EXAMINED NO. NORMAL r11 101 LO1 113 LO1 10010 19 7 5 7 16 19 7 5 7 16 11 1 10 0 11 10 111 111 UTERUS : NO. EXAMINED NO. NORMAL - d i s t e n t i o n , 1umen minimal marked -macrophages, minimal mild moderate pigmented CERVIX : NO. EXAMINED NO. NORMAL - d i s t e n t i on moderate VAGINA : NO. EXAMINED NO. NORMAL OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f c o r p o r a 1utea -presence o f growi n g / a n t r a l f a 1 1ic l es 11 1 10 [ll [ll 01 10 [SI COl 20 30 40 111 101 10 0 10 0 11 1 11 1 [ ]= T o t a l i n c i d e n c e o f s p e c i f i e d l e s i o n , a l l gra.3es. I11 I V F F 30 30 0 1 0 1 00 00 0 1 0 1 0 1 00 [OI c11 01 00 [Ol [;I 0 00 00 0 1 0 1 0 1 0 1 0 1 0 1 v F 30 10 10 0 0 9 9 10 2 101 0 0 C81 0 1 7 8 8 10 10 10 10 - 20 Page 753 ARGUS 41S-021 ORAL (G4VAGE) TWO-GENERATION (ONE L I l l E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 3 (Continued) Incidence and Degree o f Severity o f H istomorphol ogi c Observations F1 Generation Dose Group: Sex : Number o f Animal s/Group: I I1 I11 I V v MMMMM 30 30 30 30 30 I I 1 I11 I V v F F F F F 30 30 30 30 30 ADRENAL GLANDS : NO. EXAMINED NO. NORMAL 10 0 0 0 11 5 0 0 0 7 10 0 0 1 10 900010 -adenoma. c o r t i c a l 00001 00000 -degeneration, cystic, cortex mild E01 C O I C O I 101 C O I 00000 c11 E01 r01 COI C O I 10000 -hypertrophy, cortex, diffuse moderate COI COI COI COI COI 0 0 0 0 0 [OI [ O I [OI r11 C O I 0 0 0 1 0 -vacuolation, cortex minimal mild moderate [51 C O I E01 E01 PI 2 0 0 0 1 2 0 0 0 0 1 0 0 0 2 r01 [ O I C O l C11 COI 00010 00000 00000 NO. NORMAL - hyperpl asi a, e p i the1 ium. minimal mild moderate tubul arlductul ar papi 11a 29 28 29 28 28 21 17 14 11 4 C31 LO1 C11 C51 C211 3 0 0 4 8 001113 00000 -edema. p a p i l l a r y , f o c a l m inimal mild -necrosis, papill a. focal minimal mild - hemorrhage, papi 11a minimal mild C11 101 C11 101 C91 1 0 1 0 9 00000 COI c01 c11 c21 c01 00120 00000 0 0 0 0 2 -basophilia, cortical tubules, focal minimal mild C11 C21 [31 PI [ S I 1 2 3 2 3 0 0 0 0 2 -cyst(s), cortex 0 2 0 0 0 -cyst(SI, medull a 1 1 0 1 1 -cyst(s). papilla 0 0 1 1 0 - d i1a t a t i o n . c o r t i c a l tubules, focal mild moderate EO1 COI COl COI c11 0 0 0 0 1 00000 [ ] = Total incidence o f specified lesion, a l l grades. P,age 754 23 26 28 25 26 16 19 21 8 9 C21 C11 PI E131 C151 2 1 2 7 7 0 0 0 5 7 0 0 0 1 1 roi IOC IOC 0 0 0 [71 141 6 3 0 0 0 1 1 c01 COI C O l c11 c13 00000 0 0 0 1 1 [ O l 101 C O l C11 PI 00011 0 0 0 0 1 C O l 101 121 C11 C31 0 0 2'0 1 0 0 0 1 2 0 0 0 0 1 01001 00000 c11 C O I [ O I 000 1 0 0 111 [ O I 10 0 0 - 21 ARGUS 3 18-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 3 (Continued) Incidence and Degree of Severity of Hi stomorphologic Observations F1 Generation Dose Group: Sex: Number o f Animals/Group: I I1 I11 IV v MMMMM 30 30 30 30 30 I I1 I11 IV v FFFFF 30 30 30 30 30 KIDNEYS (Continued): -di1atation. pel vis mi ni mal mild marked c11 141 [:71 c71 c11 01340 12431 Oiooo -hemorrhage. pelvis mild moderate - hyperpl asi a , pel vi c/papi1 1 ary urothel i um minimal mild COI COI I:OI c21 131 00012 00011 COl C11 L11 C41 C21 00132 01010 - infi 1tration, fat-cell minimal [OI 101 [11 [OI [OI 0 0 1 0 0 -infiltration. mononuclear-cell, focal [31 [31 [41 C31 [I1 mi ni mal 33331 mild 00100 -minerali zation, mu1 ti focal minimal -mineralization. pel v)s mi ni mal mild moderate -nephritis. chronic, focal mi ni mal [Ol c21 E01 C11 COI 02010 C O l C11 C21 C41 C21 01010 00221 00011 COl COl COI c21 COI 00020 - pyel iti s , chronic minimal moderate 00000 -pyelonephritis mini mal moderate COl LO1 c11 [;I 111 000 1 00100 c11 113 121 co1 COl 10100 01100 00000 COI COl COI COl LO1 00000 00000 COI COI COl l-01 C11 00001 00000 [OI COI [Ol COI 101 00000 COI c11 E11 COI [I1 01101 00000 C31 C31 [$I C11 C21 33 12 101 c11 101 COI LO1 01000 00000 00000 COl COl COI COl ro1 00000 10000 COI [OI 101 COl co1 00000 00000 LIVER: NO. EXAMINED NO. NORMAL 29 28 29 28 28 20 20 24 17 12 10 0 0 1 10 90009 -cellul ar a1 teration. eosinophilic. focal mild [OI COI COl c11 [OI 00010 COI [ O l 101 COl 101 00000 [ ] = Total incidence of specified lesion, all grades. - 22 Page 755 ARGUS 41S-02 1 ORAL (GAVAGE) lW0-GENERATION (ONE L I l l E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL. 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 3 (Continued) Incidence and Degree o f S e v e r i t y o f Histomorphologic Observations F1 Generation Dose Group: Sex : Number o f Animals/Group: v I I 1 I11 IV MMMMM 30 30 30 30 30 v I I 1 I11 IV FFFFF 30 30 30 30 30 LIVER (Continued) : -congestion, acute moderate - c y t o p lasmic vacuo1a t i o n . d i f f u s e moderate E01 COI COI COI C11 00001 101 101 101 COl c01 00000 [OI 101 COI [OI [OI 00000 C11 101 E01 COI COI 10000 -hematopoiesis. extramedullary, mu1ti f o c a l [11 minimal 1 -hemorrhage. acute, focal [OI moderate 0 -hyperplasia, b i l e duct, focal COI minimal 0 -hypertrophy. hepatocellul ar 101 m i n i mal 0 mild 0 -inflammation. chronic, focal/multifocal[71 minimal 7 -lipidosis. tension. focal 0 - n e c r o s i s , f o c a l /mu1 t i f o c a l c11 m i n i mal 0 mild 0 moderate 1 PITUITARY: NO. EXAMINED 10 NO. NORMAL 8 -cyst(s1 1 - hyperpl asia, pars distal i s , focal C11 mild 1 101 101 COl C01 0000 [Ol LO1 COl EO1 0000 111 101 COI COI 1000 COI COI C ~ I 1141 00313 0001 [7] [5] C6l [SI 7563 1000 COl COl c21 121 0021 0001 0000 0 0 0 11 00011 0000 [OI COI COl [OI 0000 C O l C O l COl COI C O l 00000 COl COl COl C11 COl 00010 COI 101 COl COl 101 00000 COl 101 COI COI COI 00000 00000 COl COl COl COl c11 00001 00000 COl c01 COl [OI 101 00000 00000 00000 10 0 0 0 10 10 0 0 0 ' 1 0 00000 COI COI [Ol 101 101 00000 EAR(S) : NO. EXAMINED NO. NORMAL -chondropathy, mild moderate marked auricular 00030 00000 COl COI 101 C11 COI 00010 00000 00000 12042 00000 C11 C21 101 C41 E21 00001 00011 12030 [ 1 = Total incidence o f specified lesion, a l l grades. - 23 Page 756 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 3 (Continued) Incidence and Degree o f Severity o f Histomorphologic Observations F1 Generation Dose Group: Sex : Number o f Animal s/Group: I I1 I11 I V v MMMMM 30 30 30 30 30 I I1 I11 I V v FFFFF 30 30 30 30 30 EAR(S) (Continued) : -dermatitis, chronic, focal minimal 101 [OI 101 [Ol [Ol 00000 NO. NORMAL -dermatitis. chronic, focal mild moderate -inflammation. suppurative, joint capsule moderate - 0 s t e o a r t h r i t i s. chronic moderate -tendonitis. chronic mild 00100 00000 [OI [OI [OI [Ol [Ol 00000 00000 00011 00000 [OI [Ol [OI c11 [I1 00001 00010 -atrophy, retinal mild -cataract, bilateral -keratitis, chronic, focal minimal MAMMARY GLAND : NO. EXAMINED NO. NORMAL .adenocarcinoma PALATE : NO. EXAMINED NO. NORMAL -fracture - hemor rhage moderate 00000 00000 00000 10100 00000 10000 10000 00000 10000 [11 E01 [OI [OI [Ol 10000 10000 00000 10000 00000 00000 00000 [ ] = Total incidence o f specified lesion, a l l grades. - 24 Page 757 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY EIUMBER: T - 7 4 8 5 . 1 3 TABLE 3 (Continued) Incidence and Degree o f Severity o f H i stomorphol ogic Observations F1 Generation D o s e Group: Sex: Number o f Animal s/Group: I I 1 I11 I V v M M M M M 30 3 0 3 0 3 0 30 I I 1 I11 I V v F F F F F 30 30 30 30 30 THYMUS : NO. EXAMINED NO. NORMAL -atrophy mild - T A I L : NO. EXAMINED NO. NORMAL 00000 0 0 0 0 0 101 COI 101 COl COl 00000 00002 00001 0 1 0 0 0 00000 101 c11 E01 COI 101 01000 00010 00000 -abscess -dermatitis. chronic mild ~ hyperpl asi a/hyperkeratosi s moderate -inflammation, chronic moderate - necrosi s mild 00000 COl E01 COI COl C11 00001 [Ol COI COI COl 111 00001 COl COI C O l COl 101 00000 COI C O l COl COI COI 00000 00010 EO1 101 COI COl COl 00000 C O l COI COI 111 COI 00010 C O l COl COI C11 COl 00010 COl COI COI C11 101 00010 S K I N (GROSS L E S I O N ) : NO. EXAMINED NO. NORMAL -abscess -dermatitis. chronic, focal moderate 00020 00000 00010 E O 1 COl COI c11 L-01 00010 00000 00000 00000 ESOPHAGUS : NO. EXAMINED NO. NORMAL - b a c t e r i a1 c o l o n i es -distention moderate .hemorrhage moderate - necrosis marked -perforation 01021 00000 01000 COI c11 COl COI COI 01000 COI COI [Ol COl C11 00001 COl COI 101 111 COl 00010 00021 00000 00000 00000 COI 101 COI 101 C O l 00000 COI C O l EO1 LO1 C01 00000 C O l 101 COI COI COI 00000 00000 [ 3 = Total incidence o f specified lesion, a l l grades. - 25 Page 758 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS:!UM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR 'S STUDY NUMBER: T - 7485.13 TABLE 3 (Continued) Incidence and Degree o f Severity o f H i stomorphol ogic Observations F1 Generation Dose Group: Sex: Number o f Animal s/Group: I I 1 I11 I V v MMMMM 30 30 30 30 30 I I1 I11 I V v FFFFF 30 30 30 30 30 HEART: NO. EXAMINED NO. NORMAL -abscess -pericarditis. fibrinopurulent marked LUNG: NO. EXAMINED NO. NORMAL -pleuritis, fibrinopurulent marked 01010 00000 01000 COl C11 COI E11 [OI 01010 01000 00000 [OI C11 COI COl COl 01000 00000 00000 00000 COI COl COI COI 101 00000 00000 00000 COI to1 COI COI to1 00000 INTESTINES: NO. EXAMINED NO. NORMAL -distention moderate 01000 00000 COl 111 COl [OI LO1 01000 00000 00000 COl COI [Ol LO1 COI 00000 STOMACH : NO. EXAMINED NO. NORMAL 01000 01000 00000 00000 THORACIC CAVITY: NO. EXAMINED NO. NORMAL -abscess 00010 00000 0 0 0 1 0 00000 00000 0 0 0 0 0 TRACHEA: NO. EXAMINED 00010 NO. NORMAL 00000 -Advanced autolysis precludes evaluation 0 0 0 1 0 00000 00000 00000 [ 3 = Total incidence o f specified lesion, a l l gradcs. - 26 Page 759 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY KUMBER: T-7485.13 TABLE 4 - I n c i d e n c e and Degree o f S e v e r i t y o f H i s t o m o r p h c l o g i c Observations F1 Generation Reduced F e r t i l i t y Animals Dose Group: Sex : Number o f Animal s/Group: I I 1 I11 IV v MMMMM 107 5 7 6 I I1 I11 I V v F F F F F 64252 NO. NORMAL 107 5 7 6 105 4 7 5 -atrophy. diffuse marked 101 C11 COI COl COI 01000 -atrophy. focal minimal COl COI C11 EO1 COI 00100 - d e g e n e r a t i o n , mu1t i f o c a l mild E01 E11 COl E01 E11 01001 - r e t a i n e d Step 19 spermatids, Stage I X / X tubules 01001 NO. NORMAL 107 5 7 6 71443 -atrophy moderate COI C11 COl COl COl 01000 ~ e x f o l ia t e d spermatogenic c e l l s minimal moderate - hypospermi a mild marked COI t-11 COI COl C11 01000 00001 [Ol C11 COI 101 C11 00001 01000 - i n f i l t r a t i o n . m o n o n u c l e a r - c e l l . f o c a l C21 C41 [ll C31 121 minimal 2 4 1 3 2 -microgranuloma(s) 10000 -atrophy. focal minimal mild moderate .in f l ammati on, minimal mild moderate chronic 107 5 7 6 33214 C51 P I Dl 161 121 11031 31021 10110 C41 E21 C21 C11 C11 21101 20010 01100 C 1 = Total incidence of specified lesion, a l l grades. - 27 Page 760 ARGUS 3 15-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUP PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 4 ( C o r t i nued) - I n c i d e n c e and Degree of S e v e r i t y of H i s t o m o r p h o l o g i c Observations F1 Generdtion Reduced F e r t i l i t y Animals Dose Group: Sex : Number o f Animal s/Group. I I1 [I1 I V v MMIIMM 10 7 '5 7 6 I I 1 111 I V v FFFFF 6 4 2 5 2 PROSTATE (Continued) : -prostatitis. suppurative minimal SEMINAL VESICLES: NO. EXAMINED NO. NORMAL 107 5 7 6 107 5 7 6 COAGULATING GLAND: NO. EXAMINED NO. NORMAL 107 5 7 6 107 5 7 6 OVARIES : NO. EXAMINED NO. NORMAL -cyst(s), intraovarian .c y s t i c bur sa (e) 11 0 1 0 0 0010 11 0 0 0 10 0 0 0 OVIDUCT(S) : NO. EXAMINED NO. NORMAL 11 0 1 0 11 0 1 0 UTERUS : NO. EXAMINED NO. NORMAL - d i s t e n t i o n . lumen minimal marked CERVIX: NO. EXAMINED NO. NORMAL -distention modera t e 11 0 1 0 0 0000 c11 c11 c01 I21 COI 0 1010 10 0 0 0 11 0 1 0 01010 [ll to1 [Ol co1 101 10 0 0 0 VAGINA: NO. EXAMINED NO. NORMAL 00010 00010 OVARIAN FOLLICLESKORPORA LUTEA: -presence o f corpora lutea -presence of growing/antral f o l l i c l e s 11 0 1 0 11 0 1 0 [ ] = Total incidence o f s p e c i f i e d l e s i o n , a l l grades. - 28 Page 761 ARGUS 418-02I ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 4 (Continued) - I n c i d e n c e and Degree o f S e v e r i t y o f H i s t o m o r p h o l o g i c Observations F1 Generation Reduced F e r t i l i t y Animals Dose Group: Sex : Number of Animal s/Group: I 11 I11 I V v MMMMM 107 5 7 6 I I 1 I11 I V v FFFFF 64252 ADRENAL GLANDS : NO. EXAMINED NO. NORMAL -vacuolation. cortex mild 10000 00000 [11 COI EO1 [OI 101 10000 0 0 0 0 0 00000 COI COl COI COI [OI 00000 KIDNEYS : NO. EXAMINED NO. NORMAL -basophilia. cortical tubules, focal m in imal mild -cyst(s), cortex 97576 63430 COl COI COl COI C2l 00001 00001 01000 00000 00000 COl C01 COl COl COl 0 0 0 0 0 00000 00000 -cyst(s). medulla 10000 00000 -cyst(s). papilla 00110 - d i1a t a t i on, pel v i s minimal mild E01 C11 101 C21 LO1 01010 00010 -edema. p a p i l l a r y , f o c a l m i nimal C11 COl [OI COl C21 1 0 0 0.2 -hemorrhage, p a p i l l a mild r.01 COl LO1 [;I E11 000 1 -hemorrhage, pel v i s mild COl E01 [Ol COl C11 0 0 0 0 1 - hyperpl asi a, e p i the1 ium, m in imal mild tubul ar/ductul ar papi 11a 00004 - i n f i l t r a t i o n , mononuclear.cel1. f o c a l [OI [23 [13 C11 C11 minimal 02111 - m i n e r a l i z a t i o n , mu1ti f o c a l m inimal COl c11 COl COI COI 01000 -nephritis, chronic , focal minimal E01 [Ol COl c11 COI 00010 00000 COl COI COI 101 101 00000 00000 [OI COl COl COl 101 00000 101 COl COl COl COl 00000 EO1 LO1 COl [OI 101 0 0 0 0 0 00000 [Ol COl 101 EO1 LO1 00000 C O l COl 101 LO1 COl 00000 C O l [Ol 101 101 COl 00000 LIVER: NO. EXAMINED NO. NORMAL 97576 45453 00000 00000 [ 3 = Total incidence o f specified lesion, a l l grades. - 29 Page 762 ARGUS 4 18-011 ORAL (GAVAGE) TWO-GENERATION ;ONE LIllER PER GENERATION) REPRODUCTION STUDY OF POTASSIiJM PERFLUOROBUTANE SULFONATE (PFBS) It1 RATS PROTOCOL 418.021 SPONSOR'S STUDY NIJMBER: T-7485.13 TABLE 4 (Continued) Incidence and Degree of Severity of Histomorphologic Observations . Reduced Fertility Animals F1 Gene-ation Dose Group: Sex: Number o f Animal s/Group: I I1 I11 IV v MMMMM 107 5 7 6 I I1 I11 IV v FFFFF 64252 LIVER (Continued) : -cellul ar a1teration. eosinophil ic. focal mild COI COl LO1 C11 COI 00010 COI [OI [Ol r01 COI 0 0 0 0 0 -hematopoiesis,extramedullary. mu1 ti focal r11 minimal 1 .hyperpl asi a , bile duct, focal COI minimal 0 .hypertrophy, hepatocell ul ar COJ mi ni mal 0 -inflammation,chronic. focal/multifocal[4] mi ni mal 4 -lipidosis. tension, focal 0 COl C O l COl r01 0000 E11 COI COl COI 1000 roi COI ~ 1 1 r31 0013 131 [l] [O] 111 1101 1000 r01 COl [OI COl LO1 00000 COI COI COl [OI COl 00000 E01 COl r.01 COI 101 00000 COl COl COI COI [Ol 00000 00000 PITUITARY : NO. EXAMINED NO. NORMAL 10001 10001 00000 00000 EAR(S) : NO. EXAMINED NO. NORMAL -chondropathy, auricular mild moderate 00010 00000 [Ol COI COI C11 101 00010 00000 00010 00000 COI COl COl c11 COl 00000 00010 -inflammation. suppurative, joint capsule moderate -osteoarthritis,chronic moderate TAIL: NO. EXAMINED NO. NORMAL -abscess 00100 00000 COI COI [11 COl [Ol 00100 101 COI C11 COI COI 00100 00002 00001 0-0000 00000 00000 COI COI [OI 101 101 00000 0 0 0'1 0 00000 00010 [ 1 = Total incidence of specified lesion. all grades. - 30 ]?age 763 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY IIUMBER: T-7485.13 TABLE 4 K o n t i n u e d ) - I n c i d e n c e and Degree o f S e v e r i t y o f H i s t o m o r p h ~ i l o g i cObservations F1 Generation Reduced F e r t i l i t y Animals Dose Group: Sex : Number o f Animals/Group: I I1 I11 I V v MMMMM 107 5 7 6 I I1 I11 I V v FFFFF 6 4 2 5 2 TAIL (Continued) : -dermatitis, chronic mild - hyperpl asi alhyperkeratosi s moderate -inflammation. chronic . moderat e -necrosis mild SKIN (GROSS LESION) : NO. EXAMINED NO. NORMAL -dermatitis. chronic, focal moderate 00010 00000 E01 [OI [OI [I1 [OI 00010 00000 00000 [Ol COI [OI LO1 [OI 00000 [ ] = Total incidence o f specified lesion, all grades. -31 Page 764 ARGUS 4 18-02I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANESULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHC>LOGY REP0RT APPENDIX I HISTOM0RPH0LO1GI C 0BSERVATl0NS P GENERATION Page 765 ARGUS 4 18-021 ORAL (GAVAGE) 7WO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT KEY TO HISTOM0RPHC)LOGIC OBSERVATIONS - * <> <-> 0 A P 1 2 3 4 ss SD SSR SSRF SSGL SDGL = SMGL = 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. Indicated change or lesion present. Minimal degree or amount of indicated change or lesion. Mild degree or amount of indicated change or lesion. Moderate degree or amount of indicated change or lesion. Marked degree or amount of indicated change or lesion. Sacrifice-Scheduled S p o n t a n e o u s Death Scheduled Sacrifice (randoimly selected for histopathology) Scheduled (Reduced Fertility) Scheduled Sacrifice (examined due to presence of a gross lesion) Spontaneous Death (examined due to presence of a gross lesion) Sacrifice-Moribund (examinled due to presence of a gross lesion) 1-1 Page 766 ARGUS 418-011 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STU[)Y NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-1 Histomorphologic Observations P Generati on Dose Group: Animal Number: Sex : Death Tvoe: 1 15401. M SS 1 15402 M SS 1 15403 M SS 1 15404 M SS 1 15405 M SSR I 15406 M SS I 15407 M SSR I 15408 M SSRF I 15409 M SSR I 15410 M SS TESTIS : -atrophy, diffuse -edema, d i f f u s e EPIDIDYMIS: -atrophy -hypospermi a PROSTATE: -atrophy, focal 1 -in f l a m n a t i o n , c h r o n i c 2 SEMINAL V E S I C L E S : COAGULATING GLAND: ADRENAL GLANDS: KIDNEYS : -basophilia, cortical tubules, focal - i n f i l t r a t i o n , mononuclear-cell , focal -- 1 - - 1 - - LIVER: -hematopoiesis, extramedullary -in f l amnati on, c h r o n i c , f o c a l /mu1 t i f o c a l -vacuolation, hepatocellular, multifocal PITUITARY: -hyperpl a s i a, p a r s d i s t a l is , f o c a l 1-2 Page 767 ARGUS 4 18-02I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFEIS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STLIDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1 - 1 (Continued) Histomorphologic Observations P knerat i on Dose Group: Animal Number: Sex : Death T y p e : - T E S T I S : EPIDIDYMIS: -infiltration, mononuclear-cell , focal I 15411 M SSR I 15412 M SS I 15413 M SSR I 15414 M SSGL I 15415 M SS I 15416 M SSRF - I 15417 M SS I 15418 M SSR I 15419 M SS I 15420 M SS 1 PROSTATE: -prostatitis, suppurative SEMINAL VESICLES: COAGULATING GLAND: - - - - 1 - - - ADRENAL GLANDS: -vacuo1 ati on, cortex - 1 KIDNEYS : -basophilia, cortical tubules, focal -dilatation, pelvis -i nfi 1 trati on, mononuclear-cell , focal 11- - - - - - - - --- - - - - - -2 1 1 - 1 - - - 1 - - - L I V E R : -inflatmation, chronic, focal/multifocal - 1 ---1- - PITUITARY: -cyst ( s ) - - <p> THYMUS : -congest ion 1-3 Page 768 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1-1 (Continued) Histomorphologic Observations P Gerieration Dose Group: Animal Number: Sex : Death Type: TESTIS: EPIDIDYMIS: - i n f i l t r a t i o n , mononuclear-cell , focal PROSTATE : -atrophy, focal -inflamnation. chronic . -prostatitis, suppurative SEMINAL VESICLES: COAGULATING GLAND: 1 1 1 1 1 1 1 1 1 1 15421 15422 15423 15424 15425 15426 15427 15428 15429 15430 M M M M M M M M M M SSR SSR SS SS SSGL SSR SSRF S S SSR SS - - - - - - 2 I -- 1- 1 1 - - - - - - ADRENAL GLANOS: - i n f i l t r a t i o n , mononuclear-cell, multifocal 2 - - -vacuo1 a t i on I c o r t e x - 1 1 KIDNEYS : -basophilia. cortical tubules, -cyst (s) , medulla -cyst (s ) , papi 11a -edema, papi 11a r y , f o c a l - i n f i l t r a t i o n , mononuclear-cell focal , focal ---P- ----- - P - 1- - - - - - - - - - - 1 - - - 1 - 1 - - - LIVER: - i n f l a m n a t i o n , c h r o n i c , f o c a l /mu1 t i f o c a l - -1- - - -1- - PITUITARY: -cyst (s) THYMUS: -congestion - P - 1-4 Page 769 ARGUS 4 18-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POT.I\SSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUIIY NUMBER: T-7485.13 TABLE 1-2 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex : Death Type: I1 I1 I 1 I1 I1 I1 I1 I 1 11 I1 1543:. 15432 15433 15434 15435 15436 15437 15438 15439 15440 M M M M M M M M M M SS SS SS SS SS SS SS SS SSGL SS KIDNEYS : -basophilia. cortical tubules, focal -di 1atation. p e l v i s - i n f i l t r a t i o n , mononuclear-cell , focal - - 2 -- - 1 - - - 1 - - 1 - - -1- LIVER: -inflammation. chronic, focal/multifocal 1 - - -vacuolation, hepatocellular, multifocal - 2 - - - - 1 - EAR(S): -chondropathy, auricular 1-5 Page 770 ARGUS 418-02 1 Dose Group: Animal Number: Sex : Death Type: ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-2 (Continued) Hi stomorphologic Observations P Generation I1 I 1 I1 I 1 I 1 I 1 I 1 11 I 1 11 15441 15442 1 5 4 4 3 1 5 4 4 4 15445 15446 1 5 4 4 7 15448 1 5 4 4 9 1 5 4 5 0 M M M M M M M M M M SS SS SS SS SS SSGL SS SS SS SS KIDNEYS : -dilatation. pelvis -edema, papillary, focal -i nfi 1 tration, mononucl ear-cell , focal - - - - 1 - -1- - - 1 - LIVER: -cell ul ar a1 terati on, cl ear-cel 1 , focal - - - 1 - - -inflamnati on, chronic, focal/mul ti focal - -1- - - - THYMUS : -congestion 1-6 Page 771 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 TABLE 1-2 (Continued) Histomorphologic Observations P Gtanerati on Dose Group: Animal Number: Sex : Death Type: I 1 11 I 1 I1 I 1 I 1 I 1 I 1 I1 I 1 15451 15452 15453 15454 15455 15456 15457 15458 15459 15460 M M M M M M M M M M SS SS SSRF SS SS S S SS SS SS SS TESTIS: EPIDIDYMIS: - i n f i l t r a t i o n , mononuclear-cell , focal 1 PROSTATE: -inflamnati on, chronic 2 SEMINAL VESICLES: COAGULATING GLAND: 1-7 Page 772 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERAT::ON (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUCIY NUMBER: T-7485.13 TABLE 1-3 Hi stomorphologic Observations P Generati on Dose Group: Animal Number: Sex : Death Type: 111 111 111 111 111 111 111 111 111 111 15461 1 5 4 6 2 15463 15464 15465 1 5 4 6 6 15467 15468 1 5 4 6 9 1 5 4 7 0 M M M M M M M M M M SS SS SS SS SS SS SS SS SS SSGL TESTIS: -atrophy, multifocal <2> KIDNEYS : -basophilia, cortical tubules, focal - 1 - - - -hyperplasia, tubular/ductular epi the1 ium, papilla - i n f i l t r a t i o n , mononuclear-cell, focal - 1 - 1 1 - - - - - - - - LIVER: -inflamnation, chronic, focal/mul tifocal -vacuo1 a t i on, h e p a t o c e l lu l a r , mu1t if o c a l - 1 - - 1 - - 1 - - 1-8 Page 773 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATIdN (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOC3L 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-3 (Continued) Hi stomorphol3gic Observations P Generation Dose Group: Animal Number: Sex : Death Type: 111 15471 M SS 111 15472 M SS 111 15473 M SS I11 15474 M SSRF 111 15475 M SS 111 15476 M SSGL 111 15477 M SS 111 15478 M SS 111 15479 M SS 111 15480 M SS TESTIS : EPIDIDYMIS: PROSTATE: -atrophy, focal 1 - inf 1amnat ion, ch r o nic 1 1 SEMINAL VESICLES: COAGULATING GLAND: KIDNEYS : -dilatation, pelvis -edema, p a p i l l a r y , f o c a l - h y p e r p l a s i a , p e l v i c / p a p i 11a r y u r o t h e l ium - i n f i l t r a t i o n , mononuclear-cell , focal -mineral iz a t ion, p e l v i s LIVER: THY MUS : -congestion 1-9 Page 774 ~- ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1-3 (Continued) Hi stomorphologi c Observat i ons P Generation Dose Group: Animal Number: Sex : Death Type: I 1 1 I 1 1 1 1 1 111 I 1 1 I 1 1 I 1 1 1 1 1 111 111 15481 15482 15483 15484 15485 15486 15487 15488 15489 15490 HMMMMMMMMM ss ss ss ss ss ss ss ss ss ss KIDNEYS : -basophilia, cortical tubules, focal -cyst( s ) , medull a -dilatation, pelvis -edema, papi 1 1 ary, focal --1--1- - - - -P- - - -1- ---1- - - -hyperplasia, tubular/ductular epithel iurn, papilla - - - -infiltration, mononuclear-cell, focal - - - -pyelitis, chronic - 2 - -1- - 1 -- - - LIVER: - i nf1 amnati on, chroni c , focal/mu1 ti focal - - 1 - - - - 1-10 Page 775 ~- ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-4 Histornorphologic Observations P Generation Dose Group: Animal Number: Sex : Death T y p e : IV IV I V IV IV IV IV I V I V IV 15491 1 5 4 9 2 1 5 4 9 3 15494 15495 1 5 4 9 6 1 5 4 9 7 1 5 4 9 8 15499 15500 M M M M M M M M M M SS SS SS SS SS SS SS S S SSGL SSGL TESTIS: -atrophy, diffuse EPIDIDYMIS: -atrophy -hypospermia KIDNEYS : - -dilatation, pelvis - - 1 - <3> <2> - -hemorrhage. pel vi s - 1 - - - - <2> -hyperplasi a , pel vi c/papi 1 1 ary urothel i urn - - - - - - - <I> -hyperplasia, tubular/ductular epithelium, papilla -mineral i zation, pel vi s - 1 - 2 1 - -- 1 - - 1- -- <3> LIVER: -hyperplasia, bile duct, focal --1- --- --- -hypertrophy, hepatocellul ar - - 1 - - 1 - - -i nflamnation, chronic, focal/mul ti focal - -vacuolation, hepatocellular, centrilobular - - - - - - 1 '- -2 - 1 - -vacuolation, hepatocellular, multifocal 1 - - - - - - - - - 1-11 Page 776 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUIIY NUMBER: T-7485.13 TABLE I--4 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex : Death T y p e : IV IV IV IV IV IV IV I V I V IV 15501 15502 15503 15504 15505 15506 15507 15508 15509 15510 M M M M M M M M M M SS SS SS SSGL SS SS SSRF SS SS SS TESTIS: EPIDIDYMIS: PROSTATE: SEMINAL VESICLES: COAGULATING GLAND: KIDNEYS : -basophilia, cortical tubules, focal -edema, papi 1 1 dry. focal - - - 1 - - - 1 - - - -hyperplasia, tubular/ductul a r epi the1 i urn. papilla - 1 - - 2 1 - 2 - - -infiltration, mononuclear-cell , focal ---1- - - - - LIVER: -cell ul ar a1 terati on, basophi 1 i c , focal -1- --1- --- -inflamnation, chronic, focal/multifocal - 1 - - - - - - EAR(S): -chondropathy, auricular <2> THYMUS : -congest i on 1-12 Page 777 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFE,S) I N RATS PROTCCOL 418-021 SPONSOR'S STLDY NUMBER: T-7485.13 TABLE 1-4 (Cont inued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex : Death Type: IV IV IV IV IV IV IV IV IV IV 15511 15512 15513 15514 15515 15516 15517 15518 15519 15520 MMMMMMMMMM SS SS SS SS SS SS SS SSGL SSGL SSGL KIDNEYS : -di 1a t a t i on, pel v i s -edema, p a p i l l a r y , f o c a l - - -hyperplasia. p e l v i c / p a p i l l a r y urothel ium - - - - <2> - -1- - - - - <I> - - h y p e r p l a s i a . t u b u l a r / d u c t u l ar e p i the1 ium, papi 11a - - 1 - - - - -mineral iz a t i on, p e l v i s - - - - <3> - - LIVER: -hypertrophy, hepatocellu lar -in f l a m n a t i o n . c h r o n i c , f o c a l / m u l t i f o c a l - - - - - - - - - - - 1 - 1 - - THYMUS : -congestion -hemorrhage, focal 1-13 Page 778 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDf NUMBER: T - 7 4 6 5 . 1 3 TA3LE 1-5 Dose Group: Animal Number: Sex : Death T y p e : Histomorphologic Observations P Geieration vvvvvvvvvv 15521 15522 15523 15524 15525 15526 15527 15528 15529 15530 M M M M M M M M M M SSR SS SSR SSR S S SSRF SSR S S SSRF SSGL TESTIS: -atrophy, diffuse <4> EPIDIDYMIS: -atrophy - -hypospermia - -infiltration, mononuclear-cell , focal - - - 1 - P R O S T A T E : -atrophy. diffuse -atrophy, focal - - 2 3 - -prostatitis, suppurative - 1 SEMINAL VESICLES: -atrophy 2 COAGULATING GLAND: ADRENAL GLANDS: -vacuolation, cortex KIDNEYS : -basophilia, cortical tubules, -cyst( s ) , medull a -dilatation, cortical tubules, -di latation. pel vis -edema. papillary, focal -hyperplasia, pel vi c/papi 1 lary -hyperplasia, tubular/ductular papilla -mineralization, pelvis LIVER: -hypertrophy, hepatocellular -infl amnation. chronic, focal/mul ti focal PITUITARY: - 1 - 1 - 1 - 1 - 1 - 1 1 1 - - 1 1 - - - 1-14 Page 779 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1-5 (Continued) D o s e Group: Animal Number: Sex : Death T y p e : TESTIS: Histomorphologic Observations P Generation vvvvvvvvvv 15531 15532 15533 15534 15535 15536 15537 15538 15539 15540 M M M M M M M M M M SSR SS SSRF SS SS SSR SS SSGL SSRF SS - - EPIDIDYMIS: -i nfi 1 trati on, mononucl ear-cell , focal - 1 PROSTATE: -atroDhv. focal -i nfl a&ati on, chronic. 1 2 - 3 2 SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: KIDNEYS: -basophilia, cortical tubules, focal -edema, papi 1 1ary, focal -hemorrhage, pelvis -hyperplasia, pelvic/papillary urothel ium -hyperplasia, tubul ar/ductular epi the1 i um, papi 1 1 a -necrosi s, papi 1 1 a, focal LIVER: -hematopoiesis. extramedullary -hypertrophy, hepatocellular -inflairmation, chroni c , focal/mu1ti focal -vacuolation, hepatocellular, multifocal PITUITARY: THYMUS : <-> 1-15 Page 780 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBE) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-5 (Continued) D o s e Group: Animal Number: Sex : Death T y p e : TESTIS: Hi stomorphologi c Observations P Generation vvvvvvvvvv 15541. 15542 15543 15544 15545 15546 1 5 5 4 7 15548 1 5 5 4 9 15550 M M M M M M M M M M SS SSGL SSRF SSR SSR SSR SDGL SSR SS SS <-> - - - EPIDIDYMIS: -infiltration, mononuclear-cell , focal - 1 PROSTATE: -atrophy, focal -inflammation, chronic. -prostatitis, suppurative SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: -vacuolation, cortex KIDNEYS: -basophi 1 ia, cortical tubules, focal -cyst( s ) , perirenal -- 1- - - - - - - - - - - - P -edema, papi 1 1 ary, focal 2 -hyperplasia, pelviclpapillary urothelium - 2 - - 1 - - - 1 - - - - - -hyperplasia, tubul ar/ductular epi the1 i urn, papilla -infiltration, mononuclear-cell , focal -pyelitis, chronic 2- 2 - 2 - - 1 1 - - 1 1 - - 1- - - - 3 - - - - - - - LIVER: -hypertrophy, hepatocellular -i nflamnation, chronic, focal/mul ti focal PITUITARY : 1 - - 1 - 1 1 - 1 1 1 - 1 - 1 1 1 - - - - THYMUS : -hemorrhage, focal 1-16 Page 781 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 TABLE 1-6 D o s e Group: Animal Number: Sex : D e a t h Type: Histomorphologic Observations P Generation I1III II Ill 15551 1 5 5 5 2 15553 15554 15555 15556 1 5 5 5 7 15558 15559 15560 F F F F F F F F F F SS SSR SS SS SS SS SS SSRF SSR SS OVARIES: OVIOUCT(S): UTERUS : -macrophages, pigmented 2 3 CERVIX: VAGINA: OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea P P -presence of growi ng/antral fol 1 i cl es P P ADRENAL GLANDS: KIONEYS : -di 1 atation, pelvis - -edema, papillary, focal 1- -hyperplasia, tubul ar/ductul ar epi the1 i urn, papilla -mineralization, multifocal -pyel onephri ti s ---12* 11- - * - --2* LIVER: PITUITARY: -cyst(s) P 1-17 P,age 782 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTXOL 418-021 SPONSOR'S STJDY NUMBER: T-7485.13 TABLE 1-6 (Continued) Histomorphologic Observations P Generat ion Dose Group: Animal Number: Sex: Death Type: OVARIES : OVIDUCT(S1: UTERUS : - d i s t e n t ion, 1umen -macrophages. pigmented CERVIX: VAG INA : O V A R I A N FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growi n g / a n t r a l f o l 1 ic l es ADRENAL GLANDS: KIDNEYS : -hyperplasia, tubular/ductular papi 11a -mineralization, multifocal - LIVER: PITUITARY: epi the1 ium, 1 15561 F SS 1 15562 F SSR 1 15563 F SS 1 15564 F SSR - 1 15565 F SSR 1 15566 F SSRF * 1 15567 F SS 1 15568 F SS 1 15569 F SS 1 15570 F SO - - * - -3* 3 33* - - * - * P P P * P P P * - - - - 1 - - - - - - - * * - - I 2 - - - - - - - - 1-18 Page 783 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-6 (Continued) Dose Group: Animal Number: Sex : Death T y p e : H i stomorphologi c Observations P Generati on 1 15571 F SSR 1 15572 F SSR 1 15573 F SS 1 15574 F SSR 1 15575 F SSR I 15576 F SSR I 15577 F SSRF 1 15578 F SS I 15579 F SS I 15580 F SS OVARIES : OVIDUCT(S): UTERUS : -macrophages, pigmented CERVIX: VAGINA: 3 - * - * * OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence of growi n g / a n t r a l fol 1ic l es P P P * P P P * ADRENAL GLANDS: KIDNEYS: -basophilia, cortical tubules, focal -mineralization, multifocal LIVER: -inflanation, chronic, focal/mul tifocal PITUITARY : -cyst (s) SPLEEN: -congestion, red pulp -cyst(s). capsular 1-19 P.age 784 ARGUS 4 18-02I ORAL (GAVAGET)WO-GENERATI~N (ONELITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOC3L 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1-7 Oose Group: Animal Number: Sex : Death Tvpe: Histomorphologic Observations P Generati on I1 I1 I 1 I1 I1 I1 I1 I1 I1 I 1 15581 15582 15583 15584 15585 15586 15587 15588 15589 15590 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss KIDNEYS : -cyst(s), papilla -edema, papi 1 1a r y , focal - h-y.p e r p l a s i a . t u b u l a r / d u c t u l a r ep papi i1a -mineralization. multifocal 1-20 Page 785 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1-7 (Continued) Histornorphologic Observations P Generation Dose Group: Animal Number: Sex : Death Type: I1 I1 I1 I 1 I 1 I1 I1 I 1 I 1 11 15591 15592 15593 15594 15595 15596 15597 15598 15599 15600 F F F F F F F F F F ss ss ss ss ss ss ss ss ss ss KIDNEYS: -mineralization, multifocal 1- - 1 - 1 - 1-21 Page 786 ARGUS 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFB';) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 TABLE 1-7 (Continued) Histomorphologic Observations P Gisnerat ion Dose Group: Animal Number: Sex : Oeath Type: OVARIES : OVIDUCT(S): UTERUS: CERVIX: VAG I NA : O V A R I A N FOLLICLES/CORPORA LUTEA: I 1 I 1 I 1 11 I 1 I 1 I 1 I 1 I 1 11 15601 15602 15603 15604 15605 15606 15607 15608 15609 15610 F F F F F F F F F F SS SS SSRF S S SS S S SS S S S S SS * * * * * * KIDNEYS : -cyst (s) , medulla -hyperplasia, tubular/ductular papi 1l a -mi n e r a l iz a t i on, mu1t if o c a l -nephritis, chronic, focal epi the1ium, 1-22 Page 787 ~~ ~ ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUClY NUMBER: 1 - 7 4 8 5 . 1 3 TABLE 1-8 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex : Death T w e : 111 15611. F SS I11 15612 F SS 111 15613 F SS 111 15614 F SS 111 15615 F SS 111 15616 F SSGL 111 15617 F SS 111 15618 F SS 111 15619 F SS 111 15620 F SS KIDNEYS : -di 1 atati on, pel vi s -edema, papillary, focal - - - - - - 2 ----1- -1- - -hyperplasia, tubular/ductular epithelium, papilla - - - 1 - -mineralization, multifocal - 1 - - 1 - - - EAR(S): <*> 1-23 Page 788 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFEISI I N RATS PROTIICOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 1-8 (Continued) Hi stomorphcslogic Observations P Elenerati on Dose Group: Animal Number: Sex : Death Type: 111 111 111 111 111 I11 111 111 111 111 15621 15622 15623 15624 15625 15626 15627 15628 15629 15630 FFFFFFFFFF ss ss ss ss ss ss ss ss ss ss KIDNEYS : -hyperplasia, tubular/ductular epi the1ium. papilla -1- - - 1 -mineralization, multifocal -mi n e r a l iz a t ion, p e l v i s - - - 1- - - -- 1 - 1 1 - 1-24 Page 783 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-8 (Continued) Histomorphologic Observations P Generat i on Dose Group: Animal Number: Sex : Death Type: OVAR I ES : OVIDUCT(S): UTERUS : CERVIX: VAGINA: O V A R I A N FOLLICLES/CORPORA LUTEA: 111 I11 111 111 111 I 1 1 111 111 111 111 15631 15632 15633 15634 15635 15636 15637 15638 15639 15640 F F F F F F F F F F SS SS SS SS SS SS SS SS SSGL SSRF .* * * * * * KIDNEYS : -edema. p a p i l l a r y , f o c a l -hyperplasia, tubular/ductular epi the1 ium, papilla - i n f i l t r a t i o n , mononuclear-cell , focal -mineralization, multifocal - T A I L : -in f l a m n a t i o n . c h r o n i c , f o c a l -necrosis 1-25 Page 790 ARGUS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-9 Histomorphologic Observations P Generation Dose Group: Animal Number: Sex : Death Type: IV IV IV IV IV IV IV IV IV IV 15641 15642 15643 15644 15645 15646 15647 15648 15649 15650 F F F F F F F F F F SS SS SS SS SS SS SS SS SS SSGL KIDNEYS : -edema, p a p i l l a r y , f o c a l - 1 2 - - 1 - - - - - h y p e r p l a s i a , t u b u l a r / d u c t u l a r epi the1 ium. papilla 1 2 3 - 1 1 - - - 2 -mi n e r a l iz a t ion, mu1t i f o c a l - - 1 - 1 - - - n e c r o s i s , papi 11a , f o c a l - - - - - - 3 EXTREMITIES: -ankylosis -osteochondritis 1-26 Page 791 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S S'I'UDY NUMBER: T-7485.13 TABLE 1-9 (Continued) Histomorphologic Observations P Generation Dose Group: Animal Number: Sex : Death Type: OVAR IES : OVIDUCT(S): UTERUS : IV IV IV IV IV IV IV IV IV IV 15651 15652 15653 15654 15655 15656 15657 15658 15659 15660 F F F F F F F F F F SS SS SS SS SS SS SSRF SS S S SS * * * CERVIX: VAGINA: * O V A R I A N FOLLICLES/CORPORA LUTEA: * KIDNEYS : -edema, papi 11d r y , f o c a l *- * * - I * 1- -hyperplasia, tubular/ductular epi the1 ium, papilla *2**-1*21- -mineralization, multifocal *I* * - * 1- - 1-27 Page 792 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFB:) I N RATS PROTOC.OL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 1-9 (Continued) Hi stomorphologi c Observations P Generation Dose Group: Animal Number: Sex: Death Tvoe: IV IV I V IV IV IV IV IV IV IV 1 5 6 6 1 15662 15663 15664 15665 15666 1 5 6 6 7 15668 15669 1 5 6 7 0 F F F F F F F F F F SMGL SS S S SS S S S S SSGL S S S S S S KIDNEYS : -basophilia, cortical tubules, focal -dilatation. cortical tubules, focal -dilatation, medullary tubules -edema, papi 1 1 ary, focal -hyperplasia, tubular/ductular epithelium. papi 1 1 a -i nfi 1 trati on, mononucq ear-cel 1 , focal -mineralization, multifocal -necrosi s , papi 1 1 a, focal SPLEEN : -abscess -atrophy -pi gmen t 1-28 Page 793 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE ( P F K ) I N RATS PROTOC.OL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TAESLE 1 - 1 0 Hi stomorphologi c Observati ons P Generation Dose Group: Animal Number: Sex : Death T y p e : OVARIES: OVIDUCT(S): V 15671 F SS V 15672 F SSR - V 15673 F SSR - V 15674 F SS V 15675 F SS V 15676 F SSRF * * V 15677 F SS V 15678 F SSR - V 15679 F SSRF * * V 15680 F SSR - UTERUS : -di stenti on. 1 umen -macrophages, pigmented CERVIX : VAGINA: - 2 32 - - * 3* 3*3 * - * OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea -presence o f growi ng/antral fol1 i cl es P P P P * P * P * P * P ADRENAL GLANDS: -degeneration, cystic, cortex 1- KIDNEYS: -basophi1 i a, cortical tubul es, focal -cyst(s), medulla -dilatation, cortical tubules, focal -dilatation, medullary tubules -edema, papi 11ary, focal -- P - - - - * * - - 2 * * - - - * -3' - - 1 - - *1- 'f - -hyperplasia, tubular/ductular epi the1 ium. papilla -minerali zation, mu1 ti focal 2- 1 - 1 2 1- 1 * 2 1* 1 * 2 - *1 LIVER: PITUITARY: 1-29 Page 794 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOR'S STLDY NUMBER: T-7485.13 TABLE 1-10 (Continued) Dose Group: Animal Number: Sex : Death Type: H istomorphologi c Observations P Elenerati on vvvvvvvvvv 15681 15682 15683 15684 15685 15686 15687 15688 15689 15690 F F F F F F F F F F SSR SS SSRF S S SSR SSR S S SSR SSRF S S OVARIES: -cyst(s), intraovarian P * * OVIDUCT(S): - * * UTERUS : - d i s t e n t i o n , lumen -macrophages, pigmented CERVIX: VAGINA: 4 - * * - 1 3 - * - * - O V A R I A N FOLLICLES/CORPORA LUTEA: -oresence o f coroora lutea P * P P -presence o f g r o i i n g / a & r a l f o l 1 ic l es P * P P ADRENAL GLANDS: - - KIDNEYS : -edema, papi 11a r y . f o c a l - - - 1 - -hyperplasia, tubular/ductular epithelium. papi 11a -mineralization, multifocal - 1 - 2 * * - 2 1 - 2 1 - LIVER: PITUITARY: - - - * 1 * - * - P* P * - *1 * 1 *1 - 1-30 Page 795 ARGUS 3 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUCY NUMBER: T-7485.13 TABLE 1-10 (Continued) Dose Group: Animal Number: Sex: Death Tme: Histornorphologic Observations P Generation vvvvvvvvvv 15691 15692 15693 15694 15695 15696 15697 15698 15699 15700 F F F F F F F F F F SS SSR SSRF SSR SS SS S S SS S S s s OVARIES: OVIDUCT(S1: UTERUS : -macrophages, p i grnented CERVIX: VAGINA: 1 * 2 * - * - O V A R I A N FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growi n g / a n t r a l f o l 1ic l es ADRENAL GLANDS: P * P P * P - KIDNEYS : -basophilia, cortical tubules, -dilatation, medullary tubules -dilatation, pelvis -edema. papi 11a r y , f o c a l focal - 1 ** - - - - - - * * 1- -* -2- --* 1- * - - - 1 1 - * -hyperplasia. tubular/ductular epithelium, p a p i 11a -mineralization, multifocal -nephritis, chronic, focal 2 - 2 * * - 2 - 1 - 2 - 1 1 2 - * * -1* - - - - - * LIVER: PITUITARY: 1-31 Page 796 ARGUS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT APPE.NDIX I1 HIS T 0M0RPH0LO(3IC 0BSERVATI0NS F1 GENERATION Paage797 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT - * <> <-> 0 A P 1 2 3 4 XB SM ss SD SM su SSR SDR SSGL SDGL SMGL SSRF SURF SDRF KEY TO HISTOMORPHOLOGIC OBSERVATIONS 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. Indicated change or lesion present. Minimal degree or amount of indicated change or lesion. Mild degree or amount of indicated change or lesion. Moderate degree or amount of indicated change or lesion. Marked degree or amount of indicated change or lesion. Primary benign neoplasm present Primary malignant neoplasm present Sacrifice-Scheduled Spontaneous Death Sacrifice-Moribund Sacrifice-Unscheduled Scheduled Sacrifice (randomly selected for histopathology) Spontaneous Death (randomly selected for histopathology) Scheduled Sacrifice (examined due to presence of a gross lesion) Spontaneous Death (examined due to presence of a gross lesion) Sacrifice-Moribund (examined due to presence of a gross lesion) Scheduled (Reduced Fertility) Unscheduled (Reduced Fertility) Spontaneous Death (Reduced Fertility) 11-1 Page 798 ARGUS 418-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 11-1 Hi stomorphologic Observations F1 Generation Dose Group: Animal Number: Sex : Death Type: TESTIS: 1 1 1 1 1 1 I I I 1 3 0 0 1 3 0 0 2 3003 3 0 0 4 3 0 0 5 3006 3 0 0 7 3 0 0 8 3 0 0 9 3 0 1 0 MMMMMMMMMM SSRF SSR SSRF SSGL SSRF SSRF SSRF SSR SS SS EPIDIDYMIS: - i n f i 1t r a t i o n , mononucl ear-cel 1 , focal -mi crogranul oma( s ) - - 1 1 - P - PROSTATE: -atrophy, focal -i nfl amnati on, chronic SEMINAL VESICLES: 3 1 2 2 1 1 - - 2 1 - 2 - COAGULATING GLAND: ADRENAL GLANDS: -vacuolation, cortex - KIDNEYS : -di latation, pelvis -edema, papi 11ary, focal -hyperplasia, tubular/ductular epi the1 i u m , papilla 1 - - - 1 - - L I V E R : -hematopoi es i s , ext ramedull a r y , mu1 t i focal -i nfl amnati on, chronic, focal /mu1 ti focal -necrosi s, focal /mu1 ti focal 2 - - -1- PITUITARY: PALATE: -fracture -hemorrhage 11-2 Page 799 ARGUS 41S-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 11-1 (Continued) Dose Group: Animal Number: Sex : Death Type: Histomorphologic Observations F1 Generat i on 111111 I II1 3011 3012 3013 3014 3015 3016 3017 3018 3019 3020 MMMMMMMMMM SSR SS SSR SSRF SSRF SSRF SS SSRF SS SSR TESTIS: EPIDIDYMIS: PROSTATE : -atrophy, focal -inflamnation, chronic -prostatitis, suppurative SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANOS: -vacuo1 ati on, cortex KIDNEYS : -cyst ( s ) , medull a LIVER: -infl amnati on, chronic, focal/mu1ti focal 11- PITUITARY: -cyst( s ) P EAR(S) : <*> 11-3 Page 800 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 11-1 (Continued) Dose Group: Animal Number: Sex : Death Type: Histomorphologic Observations F1 Generation I I I I 3021 3022 3023 3024 MMMM SDRF SS SSR SSR I 3025 M SS I 3026 M SSR I 3027 M SS I 3028 M SSR I 3029 M SS 1 3030 M SS TESTIS: EPIDIDYMIS: PROSTATE: -inflamnation, chronic - 11 - 1 SEMINAL VESICLES: COAGULATING GLAND: ADRENAL GLANDS: -vacuolation, cortex 3- - 2 KIDNEYS : -basophi 1ia, c o r t i c a l t u b u l e s , f o c a l - i n f i l t r a t i o n , mononuclear-cell, focal *-- - - - -1- * 1 - - - 1 - - 1 - LIVER: -inflamation, chronic, focal/multifocal * - - - - 1 - - - - PITUITARY: -hyperplasia, pars distalis, focal 11-4 Page 801 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PF8S:I I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 11-2 Dose Group: Animal Number: Sex : Death Tme: Histomorphologic Observations F1 Generation I1 I1 I1 I1 3181 3182 3183 3184 F F F F SSRF S S SS SS I1 3185 F SS I1 3186 F SS I1 3187 F SSRF I1 3188 F SS I1 3189 F SS I1 3190 F SS OVARIES : -cyst ( s ) i n t r a o v a r ian * P I OVIOUCT(S): * UTERUS : -distention, lumen CERVIX: VAG I NA : * OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea * P -presence o f growi n g / a n t r a l f o l 1ic l es * P 11-5 ,Page 802 ARGCS 41S-02 I ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUGROGUTANE SLLFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485 I? TABLE 11-2 (Continued) Dose Group Animal humoe- Sex : D e z t b Tvoe OVAR! ES OVIDVCT(S). UTERUS. CERVIX: VAGINA: Histomorohoiogic Observations F: Generation I 1 1; I ; I i 3 1 9 1 3192 3 1 9 3 3!94 FFFF S S SSGL S S S S ii ii 1: ,. I. I; 1; 3195 3197 3196 ji9C 2 2 3 : 52s: FFFF F F SS?' S S S S S S S S G - S S * * * * * OVARIAN FOLLICLES/CORPORA LUTEA: * KIDNEYS : -di 1atation, pel v i s - .:2> - * - -hyperplasia, tubular/ductular epithelium, papilla * - 1 - - -mineralization, multifocal - - 1 * 1 - - EAR(S1: -chondropathy. auricular 11-6 Page 803 .ARGUS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (OhE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUCY NUMBER 1-7365 !3 TABLE 11-2 (Continued) Histomorohologic Observations F1 Generati on Ocse Grouc. Animal humber. Sex Death Tvpe. OVARIES i: 1; Ii 11 !: 11 1: !: 1: 1. 3 2 0 2 3203 3204 3205 3206 3207 52% 3295 32:: 655: F F F F F F F F F F SS SS SS SS SSGi SSGL SSRr S S SS 5 s * OVIDUCT(S ) : UTERUS : CERVIX: VAGINA: * O V A R I A N FOLLICLES/CORPORA LUTEA: * K IONEYS : - c y s t (s), medulla -in f i 1t r a t i o n , mononuclear-cell , f o c a l -mineral i z a t i o n . mu1 ti f o c a l -mi n e r a l iz a t i on, p e l v i s - -1- - 1- * - T * - - P - 1- EAR(S): -chondropathy, auricular THYMUS : -atrophy Page 804 XRGCS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION I ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSILJM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1-7485.1: TABLE [I-3 OOSe Group Animal Number. Sex Death Type - T E S T I S : -atrophy, focal Histomorphologic Observations F1 Gene-ation I i I 111 I 1 1 111 l!: 1;; 1:: i:: i i : ::: 3 0 6 1 3362 3063 3064 3065 3066 3067 3068 3069 307C M M P M M M M P P P SSRF SD 55 SSRF SS S S S S S S R C S S S 5 1 EP!DIDYMIS: -infiltration. mononuclear-cell, focal 1 - PROSTATE: - 1 nf1 amnati on, chroni c 1 3 SEM!N4L VESICLES: COAGULATING GLAND: KIDNEYS : -cyst(s), papilla -edema, papillary. focal -infi 1 tration, fat-cel 1 -infiltration. mononuclear-cell , -mineralization, pelvis focal - * -P- - * - -- 1- - - - i**f - - - 2- -- 1-- 1-- --- - - LIVER: 1nf1 amnation, chroni c , focal/mu1ti focal - t - -1 - 11-8 .4RGCS 4 I S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER 1 - 7 4 8 5 13 TABLE 11-3 (Continued) Dose G r o m Animal Number Sex Deatb TyDe H i stomorohologic Observations F 1 Gerierati on !I! 111 11: 11: I! !I! !I; 1:: 1:: 1:: 3 0 7 1 3 0 7 2 3 0 7 3 3 0 7 4 3 0 7 5 307.5 3 0 7 7 3278 3 0 7 3 j@f.c M M M M M V M P M P ss ss ss 5s ss ss ss sc ss sc KIDNEYS -basophil la, cortical tubules, focal - - 1 ! -di 1 atat ion, pel vi s 2 - 2 1 2 - 1 - -hyperplasia. oelvic/paoillary urothelium - - 1 - -hyperpi as1 a , tubul ariductul a r epi tnel iurn. papi 1 la 2 - -infiltrarion, mononuclear-cell, focal - 1 - -mineralization. pelvis. 2 - - - LIVER: -1nflamnation. chronic. focal/rnultifocal - 1 1 - - 11-9 Page 806 ARGUS 1 1S-07 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS I U H PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: 1-7485.13 TABLE 11-3 (Continued) Dose Group A n i mal humoer . Sex Dezth Tvoe. - TESTIS : EPIDIDYMIS: Histomorohologic Observations F l Generation 111 I!i 111 1:: I I i I l ! I T ! ::: I : : 1:: 3081 3082 3083 3084 3085 3086 3087 3C88 3089 H M M M H H I M I P S S SSQE SC S S S S S r SS SS S S S S S S PROSTATE: -atrophy, focal SEMINAL VESICLES: COAGULATING GLAND: KIDNEYS: -basophi 1 i a, cortical tubules, focal -dilatation, pelvis -infiltration. mononuclear-cell. focal -necrosis. papilla, focal -pyelonephritis. multifocal 1 - 1- - - L I V E R : -inflamnati on, chronic, focal /mu1 ti focal 1 - - 1 - - EXTREMITIES : -1nf1amnation. suppurative, joint capsule -osteoarthritis, chronic 11-10 Page 807 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.1: TABLE: 11-4 H i stomorpnol ogi c Observations F l Generation PROSTATE: -atropny, focal -1 nfl amnati o n , cnroni c -prostatitis. suppurative - 2 2 -1 1 2 1 - SEMINAL VESICLES: COAGULATING GLAND: - KIDNEYS: -dilatation. pelvis <2> - - -hemorrhage, pelvis -hyperplasia, pel vi c/papi 1 1 dry urothel i um - - - * * * * * * - 2 - 2 - -hyperplasia. tubular/ductular epithelium, papi 1 1 a - - 1 - t * - 2 -mineralization, mu1 ti focal - - - * * - 1 - -mineral i zati on, pel vi s - - *--2 -necrosi s , papi 1 1 a. focal - - * * - 1 -LhI VyEpeRr: trophy. hepatocell u l a r -inflamnati on, chronic, focal/mu1 ti focal - 1 1 - - - * * - - **1-1 EAR(S): -cnondropathy, auricular SKIN (GROSS LESION): -abscess -dermatitis. chronic, focal ESOPHAGUS: -necrosis -perforation - <4> <p> <p> HEART: -pericarditis. fibrinopurulent THORACIC CAVITY: -abscess TRACHEA: 11-11 Page 808 ORAL (G4VAGE) TWO-GENERATION (ONE LITER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL. 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 11.4 Dose Group, Animal Numoer : Sex : Death T o e ' Histomorphologic Observations F1 Generation IV IV IV IV IV I1 I\ Ii' ii I1 3091 3092 3093 3094 3095 3096 3097 3098 3000 3100 M M M M M M M M M M SSRF SS SSRF SSRF SSRF SDGL SMGL S D G i SS SS TESTIS: EPIDIDYMIS: PROSTATE : -atrophy. focal .inf1 ammation. chroni c -prostatitis. suppurative 2 112 2 1- SEMINAL VESICLES: COAGULATING GLAND: KIDNEYS : -dilatation. pelvis .hemorrhage, pel vi s c2> . * * * * - 2 - hyperpl as1a. pel vi c/papi1 1 ary urothel ium . * -2 - hyperplasi a, tubul ar/ductular epithelium, papi 1 1 a - 1 -* * - 2 -mineralization. multifocal **-1- -mineralization. pelvis * * -2 -necrosis. papilla. focal * * -1 LIVER: -hypertrophy, hepatocellular -inflammation. chronic, focal/multifocal 1- 1 - EAR(S) : -chondropathy. auricular * * * * 1 - 1 SKIN (GROSS LESION): .abscess -dermatitis. chronic, focal E- SneOcPrHoAsGiUSs : -perforation - <4> cp> cp> HEART : -pericarditis. fibrinopurulent THORACIC CAVITY: .abscess TRACHEA: 11-12 Page 809 ORAL ( M V A G E ) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF P O T A S S I JM PERFLUOROBUTANE SULFONATE ( P F B S ) I N RATS PROTOCOL 418.021 SPONSOR ' S STUDY NUMBER: T - 7485.13 TABLE 11-4 (Continued) Hi stomorphologic Observations F1 Generation Dose Group: Animal Number. Sex. Death T y p e . I V IV IV IV I V I V I i I i I i I \ 3101 3102 3103 3104 3105 3106 3107 3105 3109 2110 M PI M M M M M M P I" SSRF SS SSGL SS SSRF SS SS SS SS SS TESTIS: EPIDIDYMIS: .infi 1 tration. mononucl ear-cell , focal 1 1 PROSTATE : -atrophy. focal 1 3 SEMINAL VESICLES: COAGULATING GLAND: KIDNEYS : -cyst(s), medulla - P - .hemorrhage, pel vi s -hyperplasia. pelvic/papillary urothelium . -3-1- -hyperplasia. tubular/ductular epithelium, papilla -1- -infiltration. mononuclear-cell , focal -1.1-- 1 - - m i neral izati on, pel vi s -1- -3. -necrosis. papilla, focal -1. LIVER: .inflammation. chronic. focal/multifocal - -necrosis. focal/multifocal -11 -1 EAR(S) : -dermatitis, chronic, focal C 1' 11-13 Page 810 XRGCS 1I S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 18- 021 SPONSOR'S STUDY NUI4BER: T - 7 4 8 5 . 1 3 TABLE 11-4 (Continued) Dose Grouo Animal Numoer . Sex Death T y o e . H i stomorphologic Observations F1 Generation IV IV IV I\ IV IL I'v i i IV 11 3111 3112 3113 3114 3 1 1 5 3116 3117 3116 3119 3 1 2 0 M M M M M M M M M M SS SSRF SS SSGL 55 SS SS CS SS SS TESTIS: EPIDIDYMIS: -infiltration. mononuclear-cell, focal 1 PROSTATE. SEMINAL VESICLES : COAGULATING GLAND: KIDNEYS: .basophi 11a, cortical tubules. focal -1-1 --cyst(s). papilla - P - di 1 atation, pel vi s 1 1 - 2 -- 1 1 2 - -hyperplasia. pelvic/papillary urothelium . -1- -1. -hyperplasia. tubul arlductular epithelium. oaoi 11 a - 1 --1. -mineralization. pelvis -2- -nephritis. chronic. focal -1- -1. LIVER: -cellular alteration, eosinophilic, focal . 2 hypertrophy, hepatocell ul ar -1- - 1nfl arnmation, chronic . focal /mu1ti focal - -1-1- -necrosis. focal/multifocal -1- EAR(S) : -dermatitis. chronic. focal Page 8 11 ORAL (GAVAGE) TUO-GENERATION (ONE LITTER PER GEYERATIOY! REDRGDUCiION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER. T-7435 13 TABLE 11-5 (Continued) Histomorphologic Observations F l Genwati on Dose Grouo Animai ElumDer Sex. Death Tvoe - T E S T I S : EDIDIDYMIS: -infiltration. moncnuclear-cell, focal V V V V V V L i 3131 3132 3133 3134 3135 3136 3137 ?:36 M )I M M M M M M SSRF SSRF S S SS SS SDGL 5 3 - S S PROSTATE : -atropny. focal 2 SEM!NAL VES!CLES: COAGULATING GLAND: ADRENAL GLANDS: -aaenoma, cortical KIDNEYS : -basophilia, cortical tubules, focal -edema. papillary, focal -hemorrhage, papilla -hemorrhage, pelvis -hyperplasia, pelvidpapi 1 lary urothel i urn -hyperplasia, tubular/ductul ar epi the1 ium, papi 1 1 a * -infiltration, mononuclear-cell , focal * -mineralization, pelvis * -pyel onephri ti s * LIVER: -hypertrophy. hepatocellular 1 * * 1 - TAIL: C-> ESOPHAGUS : -hemorrhage -perforation i.v 312: 3:;: P F' SC S S 3 - 11-15 Page 812 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NIJMBER. T - 7 4 8 5 . 1 3 T A B L E 11-5 (Continued) Dose Group. Animal N u m b e r Sex. Death T v o e . Hi stomorpnol ogi c Observations F 1 Generation V V V V V L \i i v i 3 1 4 1 3 1 4 2 3 1 4 3 3 1 4 4 3 1 4 5 3146 3 1 3 7 313& 2;49 3!52 M M M H M W M P H H SSR SSR SSRF S S SSRF SDR S S S S i S S SSr; TESTIS. EPIDIDYMIS. -infiltration. mononuclear-cell, focal 1 - 1 i PROSTATE: -atropny. focal -i nflamnati on, chronic . 2 1 SEMINAL VESICLES: COAGULATING GLAND: - ADRENAL GLANDS: -vacuolation, cortex 1 KIDNEYS : - -basophilia, cortical tubules, focal -cyst ( s ) , medull a - 2 - - - - P - -dilatation. pelvis - - 2 - - -edema, papillary, focal 1- - - 1 - - 1 -hemorrhage, pel vi s -3- - -hyperplasia, tubular/ductular epi the1 ium, papi 1 1 a -mineral i zation, pel vi s 2 - 1 1 2 -3- - 1 1 - 1 - - L I V E R : - -congestion, acute - -3- -hypertrophy, hepatocell ular - 2 - 1 1 1 - 1 - - - -inflamnation, chronic, focal/multifocal 1 - -1- -1- - PITUITARY: - - T A I L : -dermatitis, chronic -hyperplasia/hyperkeratosi s 11-16 Page 813 ~~ ARGCS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS IUH PERFLUOROBUTANE SULFONATE (PFBS) [N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 6 5 . 1 3 TABLE 11-6 D o s e GroilD: Animal NumDer: Sex : Death Type: OV4RIES : OVIOUCT(S): Histomorpho1og.c Observations F i Gentnrati on I : 1 3 1 5 1 3152 3153 3154 F F F F SSR SSR SSRF S S * * 3155 F SS2' * t 3!56 3 ! 5 7 F F 88'2- 55 UTERUS: -macrophages. pigmented CERVIX : 2 I. * * - * * VAGINA: OVARIAN FOLLICLES!CORPORA LUTEA: -presence of corpora lutea P P * * -presence of growing/antral follicles P I' * * ADRENAL GLANDS: KIDNEYS: -dilatation. cortical tubules. focal ' -mineralization, multifocal - -pyelitis, chronic - * ' 3 - *I* *-*3- LIVER: -cytoplasmic vacuolation. diffuse 3- PITUITARY: EYES: -cataract, bilateral MAHHARY GLAND: -adenocarcinoma zi5E 3155 ::6: C _- SS SL :: - * * 11-17 Page 814 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER T-7485.13 TABLE 11-6 (Cont1 nued) Histomorpqologic Observatlons F 1 Generat 1on Dose Group Animal Number. Sex. Deatb Tvoe I i I i I 3161 3162 3163 3164 3165 3155 ?:ST F ' F F F i S S R SSRc SSRF 8 8 9 : S S R S S SS OVAR I E8 : -cys:(s]. intraovarian -cystic bursa( e) OVIOUCT(S): * * * * * * * * * UTERUS: -di stent ion, 1 urnen -macrophages, pigmented 7 * * 3 * n * CERVIX: -distention VAGINA . T n * - * n * OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growing/antral fol 1 i cl es P * * * P P * n * P ADRENAL GLANDS: -degeneration, cystic, cortex 2 KIDNEYS : -dilatation, pelvis -mineralization, multifocal * * - 1 * * * - 1 - LIVER: PITUITARY: 21% :i!? F SS: SS? SS?' ? F - <4> 1 3 - - 3 T P P P P P P - * T - - 11-16 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NIJMBER: 1-7485.!3 TABLE 11-6 (Continued) Dose Group: Animal Number: Sex: Death T v o e : Hi stomorphologi 3 Observatlons F1 Generatran i r 1 I I 3 1 7 1 3 1 7 2 3 1 7 3 3 1 7 4 3!75 F F F F F SSR SSR ss SS SS 5170 317? F ; -2:7E r ss SSL SSR OVAR! ES : OV!DVCT(S): UTERUS : -macrophages, pigmented 2 2 CERVIX: VAGINA: OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea I' P -presence of growi ng/antral f o l l i c l e s I' P ADRENAL GLANDS: KIDNEYS : -hyperplasia, tubular/ductular epithelium, papilla -mineral i z a t i o n , mu1t i focal 1- LIVER: P!TUITARY: EAR(S) : -chondropathy, auricular 3179 3162 F F ssK SS 3 P P - - 1 11-19 Page 8 16 .\RGCS 1I S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFGS) I N RATS PROTOCOL 41s-021 SPONSOR'S STUOY NUMBER: T-7485.1; TABLE 11-7 Oose iiroug. Aqimal Numoer: Sex: De.tb T v o e , Histornorohciogic Observations F i Generation li 11 I 1 I1 i: i: .,.. .... .. I; .. iA 3181 3i82 3183 3164 3185 3 1 S i 5!87 31EE a199 2191" F F F F F F F F F C SSRF ss ss ss ss ss ssa- ss ss ss ova?:Es: - c y s ~ ( s ) i, n t r a o v a r i a n * P OV!DUCT(S): * UTERUS : - d i s t e n t i o n , lumen * Cl> CERV!X: VAGINA: * OVARIAN FOLLICLES/CORPORA LUTEA: * -presence of corpora lutea -presence o f growi ng/antral fol 1icl es * KIDNEYS : t P P - - 11-20 Page.817 XRGL'S 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P0TASS:UH PERFLUOROBUTANE SULFOHATE ( P F B S ) :N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 11-7 ( C o n t i n u e d ) Dose Group: A n i m a l Nurntxr: Sex : Death Tvoe: Hi stomorphol og. c Observati ons F l Generati on i i : I 11 I : !i 1: I I ;: ,. ., I, -I 3 1 9 1 0 1 9 2 3 1 9 3 3154 j i g 5 2 1 5 7 3196 i 1 9 C 3200 2231 F F F F F F F F F F SS SSGL SS SS SSRc S S S S S S SSZL S5 OVARIES: OVIOUCT(S): UTERUS: CERVIX : VAGINA OVARIAN FOLLICLES/CORPORA LUTEA. KIDNEYS -dilaration. pelvis -hyperplasia, tubular/ductular epi the1 ium, papilla -mineral izati on, mu1 ti focal - - * 1 - 1 * 1 - - EAR(S): -chondropathy. auricular <A> 11-21 Pagz 8 18 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) It1 RATS PROTOCOL 418-021 SPONSOR'S STUDY NIJMBER: 1-7485.13 TABLE I 1-7 (Cont inued) Close Group: Animal humber: Sex: Death TvDe: OVAR! ES : OVIDUCT(S): UTERUS: CERVIX : VAGINA: O V A R I A N FOLLICLES/CORPORA LUTEA: Histornorphologic Observations F l Genei-at ion I! 1 : !I i I !! .. .. ._ .. i. 3 2 0 2 3 7 0 3 3 2 0 4 3 2 0 5 3 2 0 6 3 2 C 7 3 2 2 E 220s 32:: F F F F C F F C r ss s s Ss S S SSGL SSG? SSi;; S S SS * * * * * * KIDNEYS: -cyst(s), medulla - i n f i l t r a t i o n , mononuclear-cell, -mineralization. multifocal -mineralization, pelvis focal - 1- -1- - - ** - - * - EAR(S): -chondropathy, auricular <4> THYMUS: -atrophy -,... 6551 r SS P 1 I 1-22 Page 819 XRGCS 4 1S-02 I ORAL (GAVAGE) TUO-GENERATION :ONE L I T T E R PE2 GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 8118-02! SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . !3 TABLE 11-8 Dose G r o u p : Animal NumDer: Sex : Death Tvue. Histornorohoiogic Observations F1 Generation 111 1 1 1 1 1 1 11: 1 1 : 1:: 1:: 1:: . . . . I . .I..- . 3211 3212 3213 3214 32!5 3215 32;7 32iE 32;s 52:i FFFFFFF F C 55 SS SS SSGL SS SS SS SS SS SS KIDNEYS: -aiiaration, pel vis - - EYES : -arrophy, retinal -keratitis. chronic, focal 11-23 Page 823 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFOhATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY VUMBER: T-7485.!3 TABLE 11-8 (Continued) Histomcrpholcgic Observations F1 Generati on Dose G r 3 U D : Animal &umber: Sex: Death Tvoe: 11: 11: 1:; 1:; I!: 1:: ::1 322: 3222 3 2 2 3 3 2 2 4 3 2 2 5 3 2 2 6 322: F F F F F F C 5s s s ss ss SSR' s s s s OVARI ES : OVIDUCT(S): UTERUS: - C E R V I X : * VAGINA: * OVARIAN FOLLI C?ES/CORPORA LUTEA : * KIDNEYS: - hpyappeir1pllaa s i a , t u b u l a r / d u c t u l a r epithelium. 1 1 - * -mineral ization. mu1 t i focal 1- - ::: ::: ::: 2226 3225 322: F F sc ss SI -1 11-24 Page 821 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY bIUMBER: T - 7 4 6 5 . 1 5 T A B L E 11-8 ( C o n 1 inued) Hi stomorohologi c Observations Fl Generat 1 on Death Tvoe: OVAR I ES : OVIOUCT(S): UTERUS: CERVIX : VAGINA: OVARIAN FOLLICLES/CGRPORA LUTEA: KIDNEYS : -basophi 1i a , cortical tubules, focal -di 1 atati on. oelvi s -infiltration, mononuclear-cell, focal ss ss ss 5s ss SS SS?' 5 s SSGL ss * * * * * -- 1 - 1 - - 1 - * * - c2> - * 11-25 Page 822 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUY PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 TABLE 11-9 Histomorphologic Observations F1 Generation Dose GWUC: Animal Number: Sex : D e ~ t l lTvoe: 1 V I V I V iV 1 V !V !\ !V Ik :I 3241 3242 3243 3246 3245 3 2 4 6 3 2 4 7 3248 3240 325: FFFFFFFFFF SS SSRC SSrJ? S S SS S S SS SS S S SSG? OVARIES : 1 OVIDUCT(S): UTERUS : CERVIX: VAGINA: * OVARIAN FOLLICLES/CORPORA LUTEA: * KIDNEYS: -edema, papillary, focal -hemorrhage, papi 1 1 a 1* - - 2 - "1- -hyperplasia. tubul ar/ductular epi the1 ium. papi 1 1 a 1 * 2 2 2 EAR(S): -chondropathy, auricular c4> -1-- 11-26 Page 523 ORA? (GAVAGE) TWO-GENERATIOh (ONE L I T T E R PER GENERATION) REPROOUCTION STUOY OF POTASSIUM PERFLUOROGUTANE SULFOEtATE (PFGS) I N RATS PROTOCOL 4 18-021 SPONSOR'S STUDY NUMBER: T-7485.13 TABLE 11-9 (Continued) Dose Grcuo: Animal NurnDer: Sex : Death Tvpe: Histomcrphologic Observations F1 Generation I V IV I V I \ !v IV I\ 1\. !i Ik 3251 3252 3253 3256 3255 3256 3257 3258 3259 326: F F F F F F F F F F SS SSRF SS SSGL SS SS SSGL S S SS S S OVARIES : OV!DUCT(S): * UTERUS: CERVIX : * VAGINA: * OVARIAN FOLLICLES/CORPORA LUTEA: * ADRENAL GLANDS. -hypertropny, cortex, di ffuse -vacuolation. cortical, focal KIDNEYS : -basophil la. cortical tubules, focal * -dilatation. cortical tubules, focal * -hyperplasia, tubular/ductular eplthel ium, papilla -necrosi s , papi 1 1 a. focal 1 - * -pyelitis. chronic 1 LIVER: -hemorrhage, acute. focal EAR(S): -chondropathy, auricular 11-27 Page 824 ORAL (GAVAGE) TWO-GENERATION (ONE L i T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE ( P F B S ) :N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 TABLE 11-9 ((Continued) Oose Grous: Animal Number: Sex : Death T v o e : OVAR I ES : OVIDUCT(S): H i stomorphol og:c Observations F 1 Generati on I V I v i v il IV I \ !\ 3 2 6 1 3262 3263 3260 3265 3266 3?6' F F F F C F F SSGL S S SSRc S S S S S S S S ? : * i l I\' ;i 3266 3265 3;7? F F F S S S S SSFI' * * UTERUS : -distention, 1 umen CERVIX: t VAG I NA : * OVARIAN FOLLIC?ES/CORPORA LUTEA: -presence o f corpora lutea * -presence o f growing/antral follicles t P * P * KIDNEYS : - -edema. papillary, focal -hyperplasia, tubular/ductular epi the1 ium. papi 1 1 a -mi neral i zat1 on, mu1ti focal I * l - * 1 1 * * 1 - ' 1 - * - -1* EXTREMITIES: -dermatitis, chronic, focal -tendonitis, chronic - T A I L : -abscess -hyperplasialhyperkeratosis -i nfl amnati on, chronic -necrosis 11-26 Page 825 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!E-021 SPONSOR'S STLlOY NUMBER: 1 - 7 4 8 5 . i 3 TABLE 11-10 Dose Group: Animal h u m e r : Sex: Death Tyoe: CV4RIES: CVIOUCT(S): H i stornorpnologic Observations F1 Generation V V V V k \ v i 1 3271 3272 3273 3274 3275 3275 5277 j Z i E 327s ??E: F F F F F i r C F C' SSGL SSR SS9 SSRP SC S S S S SL' S S 5' * * UTERUS : -macrophages, pigmented CERVIX : VAGINA: - 3 * - * * OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growing/antral follicles ADRENAL GLANDS: P P * P P * - KIDNEYS : -cyst( s ) , cortex - - * -P - -cyst ( s ) , medull a -edema, papillary, focal - ** P - 1 - 2 - -hemorrhage. papilla - - *1- -hyperplasia, pelvic/papillary urothel ium - - *1- - -hyperplasia. tubul ar/ductular epi the1 i urn. papi 1 1 a. -mineralization. multifocal -necrosi s, papi 1 1 a, focal - 1 - - 2 ** 1 1 - 1 3 2 - -1 -2* - - L I V E R : PITUITARY: EAR(S): -chondropathy, auricular 11-29 'Page 826 .-IRGCS 4 18-02 I ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U H PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NLJHSER 7 - 7 4 6 5 . 1 3 TABLE 11-10 (Continued) Dose Group Anima7 Number, Sex. Death Type OVAR I ES . OVIDUCT(S). hi stomorphologio Observations F1 Gener-at1 on VVVL!'L ! 2281 3262 3283 3264 2265 3286 326: F F F F F F r SS SI! SS SSF SS SSR SSS 1 b i 3285 3?96 ?Z?? i C SSQ SS? S5 UTERUS: -macrophages, pigmented CERVIX: VAGINA: 2 3 3 3 3 - f OVARIAN FOLLICLES/CORPORA LUTEA: -presence of corpora lutea P -presence of growi ng/antral fol 1 icl es P ADRENAL GLANDS: - KIDNEYS : -basophi 1ia , cortical tubules, focal -hyperpi asi a , tubul ar/ductul a r epi the1 i um. papilla 1 * - - -mineralization, multifocal - *1- P P P P P P P P - - - ----2 - - LIVER: PITUITARY: EXTREMITIES: -oermatitis. chronic, focal ABDOMINAL CAVITY: <2> <*> Page 827 - , ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTAHE SULFOHATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 2 TABLE 11-10 (Continued) HistomorDhologic Observations F1 Generation Dose Groug: Animal Numoer: Sex : Oeath Type: OVARIES: OVIDUCT(S): 1'VVVb 1 v 1 3291 3292 3293 3294 5225 :2OE.. :2?? FFFFFFF c SSR S S SS SS SS?: SSR SS? SC * * * UTERUS : -macrophages, pigmented CERVIX: VAG INA : '33 * * OVARIAN FOLLICLES/CORPORA LUTEA: -presence o f corpora lutea -presence o f growing/antral foll icles * P P * P P ADRENAL GLANDS: KIDNEYS : -basophilia, cortical tubules, focal -edema. papillary. focal -hemorrhage, papilla -hyperplasia, tubular/ductular epi the1 ium. papilla -infiltration, mononuclear-cell , focal - f -11* 2 1 2 * * -- 1 LIVER: -in fl amnat i on, chroni c , focal /mu1 ti focal PITUITARY: i \1 32'3s ?3:1 c S S 5: 2 * * 11-31 Page 828 0FWL (GAVAGE) TWO-GENERATI0N (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT APPENDIX Ill 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 829 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE ( P F G S ) I N RATS PROTGCO- 418-021 SPONSOR'S STUDY NUMBE?: 1-7485. i 3 A N I M A L NUHEE?: 15401 SEX: M Appendix 111 I n d i v i o u a i Animal Gross and hi stomorpnoi ogy D a t a P Generation DOSE GROUP: DEATH TYPE: I Sacr:fice-Scheab;ec 111-1 Pdse 330 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IM RATS PROTOCOL 4.18-021 SPONSOR'S STUOY NLIMBER: 7 - 7 4 8 5 . 1 3 Apoendix I11 I n d i v i d u z l A n i m a l G r o s s arid H i s t o m o r p h o l o g y Dits P Generation GROSS OBSERVA?IOY(S!: HISTOMORDHOLOGIC CFSERVA?ICN(S:: HISTOk!ORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S ! WERE W I T H I N NORMAL L I M I T S : 111-2 Page 831 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUCY NUMBER: T-7485. i? Appencix I11 I n d i v i d u a l Animal Gross and Histomorphology Da?a P Generation GROSS CSSEQVAT!OY(S): G E N E R A ? : No gross changes. HISTOMORPHOLOGIC O S S E R V A T I O N S : HISTOMORPHOLOGIC 0 5 S E 4 V 4 T ! O N ( S ) . Not appl icab1e 111-3 Page 532 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 Indivioual A n i m a l Gross and H i stmorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: .K.ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.i.l.t.r.a.t.i.o.n... .m.o.n.o.n.u.c.l.e.a.r.-. c. .e.l.l.,. .fo. c.a.l. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .L.I V.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f R e c o r d - 1 5 4 0 4 111-4 ._ Page 833 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) ( w a s ) REPROCUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR`S STUDY NUMBER: T-7485.!? Apoendix I11 I n d i v i d u a l Animal Gross and Histomorpnology Car. P Generation HISTOHORPHO?OGIC OBSERVATIONS: LIVER: infl anmat ion, chronic, focal /mu1 t ifocal (minimal ) PROSTATE: inf 1 amnat ion, chron ic (mi 1 d) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.r.o.p.h.y.,. .f.o.c.a.l. .(.m. i. .n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMA? L I M I T S : ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .P.IT. U. .I.TA.R. .Y. . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S. .T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 1 5 4 0 5 111-5 Page 834 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) R E P R O O K T I O N STUCY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOk'S STUDY NUMBER: 1-7485.13 Aooendix 111 I n d i VI auai Animal Grass and HI stomorphol ogy Data P Generation AN MAL NUMBER: 154 SEX: M GROSS 09SEQVSTION(S): HISTOMORPHOLOGIC OESEQVA:!CN(S). HISTOMORPHOCOGIC OBSERVATIONS: LIVER: vacuolation, hepatocellular, multifocal (mild) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: 111-6 Page 835 : ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PRGTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p p e n d i x I11 I n d i v i a u a l A n i m a l Gross and H i s t o m o r p h o l o g y Data P Generation GROSS OSSERVATIOV(S): HISTOMORPHOLOGIC OBSERVATION(S): GENERAL: No gross changes. N o t appl ic a b 1 e ----------_-------______________________-------------.-------------------------------------------------- THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS LIVER TESTIS COAGULATING GLAND PITUI TARY EPIDIDYMIS PROSTATE KIDNEYS SEMINAL VESICLES 111-7 Page 836 -. XRGCS 418-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41s-021 SPONSOR'S STUDY NUMBER: T-7485.13 Append1x I I I I n d i v i d u a l Animal Gross and Histomorpnoiogy Cara P Generation GROSS OSSERVDT!ON(S): EPIDIOWIOES: Right- small. TESTES: Right- flaccid. atrophy, EPIDIDYMIS hypospemia, EPIOIOYMIS atrophy, diffuse, TESTIS edema, d i f f u s e , T E S T I S HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS : TESTIS: atrophy (marked) hypospermia (marked) i n f i l t r a t i o n , mononuclear-cell, focal (minimal) atrophy, d i f f u s e (marked) ---- edema, d i f f u s e (marked) .--------------__-__------------------------------- --- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND LIVER PROSTATE SEMINAL VESICLES --------_-_-----------------------------------------.--------------------------------------------------- End o f Record- 15408 111-8 Page 837 .ARGUS -!IS-(??I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIIIM PERFLUOROBUTANE SULFONATE (PFBS) I h RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and Histomorpnology Cata P Generation HISTOMORPHOLOGIC OSSERVATIONS: KIDNEYS : PITUITARY: PROSTATE: i n f i l t r a t i o n , mononuclear-cell , focal (minlmal ) hyperplasia. pars distalis. focal (minimal) atropny. focal (mild) 111-9 ?age 838 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: i-7485.!3 Appendix III Individua: A n i m a l G r o s s and H i s t m o r p n o i o g y Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S 1 WERE WITHTN NORMAL L I M I T S : Page 839 111-10 ORAL (GAVAGE) TWO-GENERATION ( O t i E LITTER PER GENERATION] REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFeS) I N RATS PROTOCOL 418-021 SPONSOR ' S STUDY NUMBER: T-7485. !3 ApDendlx 111 I n d i v l o u a l Animal Gross and histomorphology 3ata P Generation GQOSS OBSEQVPTION(S). HISTOMORDHOLOGIC OBSERV4'ION:S' HISTOMORPHCLOGIC OBSERVATIONS. EPIDIDYMIS: infiltration, m o n o n u c l e a r - c e l l , f o c a l ( m i n i m a l KIDNEYS : basophilia, cortical tubules, focal (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n. .f.i l.t.r.a. t.i.o. n. ... .m.o. .n.o.n.u.c.l.e.a.r.-.c.e.l.l,. .f.o.c.a. .l . .(m. .i.n.im. al THE FOLLOWING TISSUE(5) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS PROSTATE COAGULATING GLAND SEMINAL VESICLES LIVER TESTIS PITUITARY Page 840 111-11 ORAL (GAVACE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REP?O3UCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 419-021 S P O N S J R ' S STUDY NUMaER: T - 7 4 8 5 . :3 A p o e n d i x 111 I f i d i v i c s z : A n i m a l Gross and H i s t o m o r p h o l o g y D a c a P Generation HISTOMORPHO?OG!C OBSERVATIONS: 111-12 O2AL (GAVA3E) TWO-GENEPATION (ONE L I T T E R PER GENERATION) RiF2ODLICT;ON STUDY OF POTASSIUM PERFLUORCBUTANE SULFONATE (PFBS) I N RATS PiiOTCCOL 418-021 SPCNSOE'S STU3Y NUF6ER: i - 7 4 8 5 .!3 A p p e n d i x 111 I n d i v i a u a l A n i m a l G r o s s and Histomorpnology D a t a F Generation GROSS O E S E R V A T I O U I S ) . PISTOMOQPHOLOGIC OBSERVATIOR(S). HISTOYORDHOLOCIC OESERVATIONS: A.D.R. .E.N.A.L. G. .LA. N. .D.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . .v.a.c.u.o.l.a.t.io. .n.,. .c.o.r.t.e.x. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( 5 ) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLANO EPIDIDYMIS KIDNEYS LIVER .P.I T.U. .I T.A.R. .Y. . . . . . . . . . . . . . . . . .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M. .IN.A. L. .V.E. .S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . End of Record- 15413 Page 832 111-13 ORAL (GAVASE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBSI I N RATS PROTOCOL 413-021 SPONSOR'S STUDY NUMSEG: T-7465.!3 I n d i v i c u a l Anima: Append1x II I Gross and t l ~ s t o m o r o n o ! o g y Ca:a P GeneraTlon P!TU!TPBv: Brown area <O.lcm d i a m e t e r . THYMUS: P i n p o i n t red areas, t o o numerous t o count. cyst(s) congestion HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : PITUITARY: THYMUS: i n f i l t r a t i o n . mononuclear-cell, cyst(s) congestion (minimal) focal (minimal) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: LIVER End o f Record- 15414 Page 843 ~ 111-14 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PEG GENEZATION) REPRODUCT!ON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PfESJ I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.15 Aopendix II! i n a i v i o > a l Animal Gross and Histomorpnology Cat2 P Generation GROSS OBSERVAT!ON(S). HISTOHOQpI'OLOS!: O?SSERV4T!ON(S! G. .E.N.E.R.A.L.:. .N.o. .g.ro. .s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S! WERE WITFIN NORM4L LIM!TS: K--ID_N_EY_S_______---__.__L_IV_ER___________________-------------------------------------------------------------- End o f Record- 15415 Page 844 111-15 O R A ? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIJH PERFLUOROBUTANE SULFONATE (PFBS) IY RATS PROTOCOL 418-02: SPONSOR'S STUCY NUMEER: T-7485.13 Aopendix 111 i n a l v i aual Animal Gross and Hi stomorpnol cgy Data P Generation GROSS OBSERVATION(SI: HISTOMOR~YOLOGICOSSERVATION!S). THE FOLLOWING TISSUE(S) WERE WITH!N NORMAL LIMITS: Page 845 111-16 023.L (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) RE?2CDUCTION STUDY O F POTASSIUM PERFLUOROaUTANE SLlLFONATE (PFBS) I N RATS PROTOCOL 418-02: SPONSOR'S STUDY NUMBEk: T-7485.13 Apoencix 111 I n d i v i d u a l Animal Gross and h i stornorphoi ogy Cata P Generation HISTOHORPHCLOGIC CeSSERVATIONS: .L.IV.E. R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.la. .m.n.a. .ti.o.n.,. .c.h. .r o. .n.i c. ., .f.o.c.a. .l/.m.u. .l .t.i.f o. .c.a.l. .(.m.i.n.i.m.a.l.). . . . . . . . . . . 111-17 c Page 846 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 A p p e n d i x 111 Indi v i m a l A n i m a l G r o s s a n d H i stornorpnol ocy D a t a Q Generation GROSS OBSERVAT:ON(S!: H!STO~ORPHOLOGIC OSSERVAT!ON(S): HISTOMORPHOLOGIC OYSERVATIONS: KIDNEYS : infiltration, mononuclear-cell, focal (minimal) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p. .r.o.s.t.a.t.i.t.i s. ., . .s.u.p.p.u.r.a.t.i.v.e. .(.m.i.n.i.m.a. .l ). . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WEQE W I T H I N N O R M A L LIM!TS: ADRENAL GLANDS P ITUITARY COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS LIVER Page 847 111-18 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF PCTASSIUM PERFLUOROBUTANE SULFONATE (PFSS) I N RATS PROTOCS!. 418-021 SPONSOK'S STUDY NUMBER: 1 - 7 4 8 5 . 1 5 A p p e n d i x I11 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r o n o c;y P Generation Oar2 GROSS CSSERVATION(S): HISTOMORPHC?CG!C OSSERVATI04iS\ ' GENERA?: No gross changes. N o r appl icab1e ________________________________________----------------------------------------------------------- Page 848 111-19 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL C18-02! SPONSOR'S STUDY NUMGER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a i Gross and H i stomorpncl3cy 2212 P Generation GROSS 08SERVAT!ON(S): HISTOMORPHOLOG!C CSSERVAT!ON(S): G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H!STOMORPHOLOGIC OBSERVATIONS: K I ONEYS : d i 1a t a t i o n , pel v i s ( m i 1d ) Page 849 I 11-20 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PF9S) I N RATS PROTCCO!. 418-021 SPONSOR'S STGDY NUMBER: 7-7465.13 Appendix 111 I n d i V I oual Animal Gross and H i sIomorpno1 ogy 0a:a P Generation GROSS OESERVATION!SI. HISTOMORPHOLOGIC C B S E R V A T I O N S : ADRENAL GLANDS: i n f i l t r a t i o n , mononuclear-cell, multifocal (mild) KIDNEYS : in f i 1t r a t i o n . mononucl e a r - c e l l , f o c a l (mi nimal ) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) PROSTATE: p r o s t a t it i s , suppurat ive (mi n i mal ) ....................................................................................................... 111-21 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.13 Appendix I 1 1 I n d i v i d u a l Animal Gross and H i stomorpnology Darz P Gerleration GROSS OBSERVATION(S! : HISTOYO9PKILOG:C @SSERV4TION(S): G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a. p. .p.l .1.ca. b. .1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC O B S E R V A T I O N S : ADRENAL GLANDS: vacuolation, cortex (minimal) KIDNEYS : cyst(s), papilla PITUITARY: cyst(s1 .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.tr.o.p. h. .y., . .fo. .c.a.l. .(.m.i.n.i.m.a. .l). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS LIVER SEMINAL VESICLES Page851 - 111-22 ARGL'S 1I S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROSUTANE SiiLFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross ana Histornorpnolopj D a t a P Generation HISTOMORPHOLOGIC O B S E R V A T I O N S : .L.IV.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .in. .fl.a.m. .m.a. .ti.o.n... .c.h. .ro. .n.ic. ., . .f o. .c.a.l./ r.n.u. .l t.i.f.o.c.a.l. .(.m. .i.n.im. .a.l.). . . . . . . . . THE FOLLOWING TISSUEiS) WERE WITHIN NORMAL LIMITS: K. .ID.N. E. Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15423 Page 852 111-23 ORAL (GA'iAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PEQFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 416-02: SPONSOR'S STUDY AUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y DaI? P Generation GROSS OSSERVATION(S) : H ISTOMORPHOLOGIC OBSERVATION ( S ' HISTOMORPHOLOGIC OBSEQVATIONS: K.I.D.N.E.Y. .S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.y.s.t.(.s. .),. .m. .e.d.u.l .l a. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S, WERE W I T H I N NORMAL L I M I T S : Page 853 111-24 .\RGCS 4 1S-02 I ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: 1-7465.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology 0a;a P Generation .TH. .Y.M.U.S.:. .R.e.d.,. .p.i.n.p.o.i.n.t. .a.r.e.a.s. .n.u.m. .e.ro.u.s. .t.o. .c.o.u. n. .t.. . . . . . . . . . .c.o. .n.g.e.s.t.io.n. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: K IDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) basophi 1ia, c o r t i c a l t u b u l es, f o c a l (mi1d) .TH. .Y.M.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.o.n.g. .e.s.ti.o.n. . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 854 111-25 .4RGC7S4 IS-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Oara P Generation GROSS OESERVATIOV[S\. HISTOMOQPHOLOGIC 0SSEQVATICN:S). HISTOHORPHOLOGIC OBSEQVATIONS: THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 855 111-26 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I11 Individual Animal Gross and H i stomorphology D a t a P Generation HISTOMORPHOLOGIC OBSERVATIONS: Page 856 111-27 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I 1 1 I n d i v i d u a l Animal Gross d n d Histomorphology Da:a P Generation GROSS OBSERVATION(S) . HISTOMOQPHOLOGIC O B S E R V A T i O H ( S ! . HISTOMORPHOLOGIC 0 9 5 E R V 4 T I O N S : KIDNEYS : basophilia, cortical tubules, focal (minimal) .L.IV.E. R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n. .f .l a.m. .n.a.t.i o.n.,. .c.h. .ro. .n.ic. ., . .fo. c. .a.l ./m.u.1. .t.i.f .o.c.a.l. .(.m.i.n.i.m.a.l.). . . . . . . . . . . End o f Record- 15428 Page 857 111-28 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY YUMBER: T - 7 4 8 5 . 1 3 Aopendix I11 Individual A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a P Generation GROSS OBSERVATION(S!: HISTOMORDHOLOG!C C@SER'L4TION(S). THE FOLLOWING T I S S U E ( 5 ) WERE W I T H I N NORMAL L I M I T S : Page 858 111-29 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY O f POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!8-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix 111 Indiv i dual Anlrnal Gross and Hi stomorphol ogy Data P Generation GROSS OBSERVATION(S1: HISTOMORWOLOGIC OBSEQVAT!ON(S): GENERAL: No gross changes. Not appl icab1e ....................................................................................................... THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 859 111-30 ORAL (GAVAGE) TWO-GENERATIOh (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-321 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpnology Da:a P Generation GROSS OESFQV4:ION(S): HISTOMORPHOLOG!C OBSEQVAT!ON(S\ HISTOMORPHOLOG!C O B S E R V A T I O N S : KIDNEYS: d i l a t a t i o n , pelvi s (mi 1d) -LI-V-E-R-:---------------------------------i-n-fl-a-m-n-a-t-io-n-.--c-h.r.o-n-i-c-, -f-o-c-a-l -/m-u-1-t-i-f-o-c-a-l --(m--in-i-m-a-l -) ----------------------- End o f Record- 15431 Page 8c) 111-31 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROEUTANE SULFON.4TE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.12 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphology Data P Generation HISTOYOSPHOLOGIC OBSERVATIONS: .L.IV.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .v.a.c.u.o.l.a.t.i.o.n... .h.e.p. .a.t.o.c.e.l.l.u.l a. .r., .m. .u.l.t.i f.o.c. .a.l. .(.m. i.l.d.). . . . . . . . . . . . . Page 861 .._ I 11-32 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCCL 418-021 SPONSOR'S STUOY NUMEER: T-7485.13 Appencix I11 I n d i v i a u a l Animal Gross and Histomorpnology D a t z P Generation THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 862 111-33 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I11 Individual Animal Gross and Hi stomorphol ogy Data P Generation GROSS OESERVATION(5): G . E . N . E . R . A . L . : . . No .. . gross ...... changes. ......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Not .... .a.p.p.l.1.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 863 111-34 .ARGL.S 118-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) R i P R O D U C T I O N STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix 111 I n t i v i dual Animal Gross and H i stomorphol ogy D a m P Generation H!STOMORPHOLOGIC OBSERVATIONS: .K.ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .b.a. .s.o.p.h. i.l.i a. ., .c.o. .r.t i.c.a. .l .t.u.b. .u.le. .s., . .f o. .c.a.l. .(.m.i.n.i.m.a. .l). . . . . . . . . . . . . . . Page 864 111-35 ORAL (GAVAGE) TWO-GENERATICIN (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Oat.- P Generation GROSS O@SERVATION(S): HISTOMORWOLOGIC oBsERvaTroN(s!: THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I M I T S : Page 865 111-36 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS; I N RATS PROTOCOL 4 18-02 1 SPONSOR'S STUDY NUMBEG: 1 - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v1 dual A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a P Generation GROSS OBSEQVATION(S): HISTOMORPHOLOGIC OBSERV4T!ON(S!: Page 866 111-37 ARGUS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIIIM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485. i 3 Appendix 111 I n d i v i d u a l Animal Gross and H i stornorpnology Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVCTION(S): G-_EN-E-R_A_L:-N-o_-g-r-o-s_s _ch_a_ng_e_s._----------------------------N--o-t -a-p-p-l-i-c-a-b-1-e------------------------------------------ HISTOMORPHOLOGIC OBSERVATIONS: Page 867 111-38 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SiiLFOtiATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMSER: 1-7485.13 Appendix 111 I n d i v i d u a l Animai G r o s s and H i stomorphol ogy Oata P Generation HISTOMORPHOLOGIC OBSERVATIONS: EAR( S) : chondropathy. auri c u i a r (marked) .L.I V.E. .R.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.la.m. .n.a. t.i.o.n.,. .c.h. .r o. .n.i .c., . .f o. .c.a.l./m. .u1. .t.i.f.o.c.a.l. .(.m. .i n.i.r.n.a.l .). . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 868 111-39 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I11 I n d i v i d u a l Animai Gross and H i stomorpnology Data P Generation GROSS OBSESVATION(S): HISTOHORPHOLOG!C O F S E R V A T I O N ( S ) : HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS : dilatation. pelvis (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .b.a.s. .o.p.h.i.l.i a.,. .c. .o.r.t .i c.a. .l . .tu. .b.u.l.e.s.,. .f.o.c.a.l. .(.m. .in. .im. .a.l.). . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL LIMITS: .L .I V. E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15440 Page 869 111-40 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l Animal Gross and Histomorphology Dara P Generation GROSS O B S E R V A T I O N ( 8 ) : HISTOMORPHOLOGiC OSSERV&'ION(S). THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I M I T S : .K.ID.N.E.Y.S. . . . . . . . . . . . . . . . . . ... .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d of R e c o r d - 15441 Page 870 - 111-41 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFSS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMSER: T - 7 4 8 5 . 1 3 A p o e n d i x 111 I n a i v i d u a l A n i m a l G r o s s and H i s t o m c r p h o i o g y Da:a P Generation GROSS O@SERVATION(S): HISTOHORPHOLOGIC OBSERVATION(S): THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page S7i 111-42 XRGCS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: 1-7485.13 Appendix 111 Individual A n i m a l G r o s s and H i s t o m o r p h o l o g y Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC O@SERVAT!3V(S). HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K. .I D.N.E. Y. S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15443 Page 872 .:' 111-43 ARGL'S 118-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7485.13 Appendix 111 Individual A n i m a l G r o s s and H i stornorpho!ogy Data P Generation Page873 -- 111-44 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Czta P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OESERVATiON(S!: THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K. .I D.N. E. .Y.S. . . . . . . . . . . . . . . . . '. . . L. I.V.E. R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15445 Page 874 111-45 ORAL (GAVAGE) TWO-GENERATION (ONE L!TTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l ogy C a r ? P Generation GROSS OBSERVATION(S): HISTOMORPHOLOG!C 0ESERVA::ON ( S ! HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 875 111-46 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.13 ADpendix 111 I n d i v i d u a l Animal Gross and Histomorpnology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: K IONEYS : edema, p a p i l l a r y , f o c a l ( m i n i m a l ) .L.IV.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.e. .l l.u.l.a. r. .a.l.t.e.r.a.t.i.o.n.,. .c. .l e. .a.r.-.c.e.l.l ,. . .fo. .c.a.l. .(.m.i.n.i.m.a. .l). . . . . . . . . . . . End o f Record- 15447 Page 876 111-47 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSILiM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 18-02 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p D e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation GROSS OSSERVATIONfS): H!STOY09PHCLOG!C 02SERVATION(S). Page 877 111-48 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUGY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Hlstornorphology Da:a P Generation ANIMAL NUMB R : 154 SEX: M GROSS OBSERVATION(5): H!STOMORPHOLOGIC OSSERVAT!@N(S!. H!STOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS : di latation. pel v i s (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.i.l .t .r a. .t.i .o.n.,. .m. .o.n.o.n.u.c.l.e.a.r.-.c.e.l.l .,. .f.o.c.a.l. .(.m. .in.i.m. .a.l .) . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 878 111-49 .4RGLS 4 1I-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) RiPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I11 I n d i v i d u a l A n i m a l G r o s s and H i s t o r n o r p h o l o g y Da:j P Generation GROSS OBSERVATION(8): HISTOMORPHOLOG!C OSSERVAT!ON(S): Page 879 111-50 ARGLS J1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SLLFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and Hi stomorphology Data P Generation THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 880 111-51 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and H i stmorphology Data P Generation GROSS OSSERVATION(S): HISTOMORPHOLOGIC 09SEQV4TION( S ) : HISTOMORPHOLOGIC OBSERVATIONS: .K.ID.N..E.Y.S.:....................................i.n.f.i.l.t .r .a.t.i.o.n.,..m..o.n.o.n..u.c.le..a.r.-c.e..ll., ..f.o.c.a.l...(m..i.n.im..a.l.)........... THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: .L.IV.E. R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15452 Page 881 111-52 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I 1 1 I n d i v i d u a l Animal Gross and Histomorphology Cat; P Generation GROSS OESERVATION(S): HISTOMORPHOLOGIC OFSERVATIOY(S): HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f i l t r a t i o n , mononuclear-cell, focal (minimal) -P-R-O-S-T-A-T-E-: ----------------------------------i-n-f-la--m-m--a-t-io--n-.--c-h-r-o-n-i-c--(-m--i l-d-)-------------------------------- THE FOLLOWING TISSUEIS) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND TESTIS KIDNEYS LIVER S E M I N A L VESICLES Page 882 111-53 ARGUS 418-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and H i stornorphology Oata P Generation GROSS O@SERVATION(S): HISTOMORPHOLOGIC OSSERVATION(S): Page 883 111-54 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i stomorphol ogy G a t a P Generation T H E FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 884 111-55 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I 1 1 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation Page 885 111-56 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I 1 1 Individual Animal Gross and Hi stornorphology Data P Generation ANIMAL NUMBER: 5 SEX: GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S1: THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: Page 886 111-57 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROCUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histornorphoiogy Oat; P Generation HISTOMORPHOLOGIC OBSERVATIONS: -K-I_ON_EY_S_: ______________-_--------b-a-s-o-p-h-i-l-i a-,--c-o--r t-i-c-a-l--t u-b--u-l e-s-,--f-o-c-a-l--(-m--in-i-m-a-l-)------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: -L-IV-E-R______----_-__-_____________________------------------_------------------------------------------- End o f Record- 15458 Page 887 111-58 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix 111 Individual Animal Gross and H i stomotphology Gata P Generation GROSS OBSERVATION(S): HISTOMORPHOLOCIC OBSERVATION(SI : G_E_N_ER_AL_: _N_o _g_ro_ss__ch_a_ng_es_. ___________________N_ot_a_p_pl_ic-a-b_1-e-----_------------------------------------------- Page 888 111-59 ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUOY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and H i stomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : basophilia, cortical tubules, focal (minimal) --------------_-_________________i_n _f i _1t_r a_t_i o_n-,--m-o-n-o-n-u-c-l-e-a--r -- c--e-l l--,--fo-c--a-l --(-m-i-n-im--a-l-)--------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: -L-IV-E_R-__-_--_--___-------------------------------------------------------------------------------------- End o f Record- 15460 Page 889 111-60 ARGUS 418-02I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I11 Individual Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC OSSERVATION(S1 : G--E-N_ER_AL_: _N_o_g_ro_s_s _ch-a-n-g-e--s.-------------------------------N-o-t--a-p-p-l-i-c-a-b-l-e---------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : h y p e r p l a s i a . t u b u l a r / d u c t u l a r e p i the1 iurn, p a p i 11a ( m i n i m a l ) -L-IV-E-R--: -------------------------------------v-a-c-u-o-l-a-t-i-o-n-,--h-e-p-a--t o--c-e-l l-u-l-a-r-.--m-u--l t-i-f-o-c-a-l--(-m--in-i-m--a-l)------------ End o f Record- 15461 Page 890 111-61 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION] REFRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE StiLFGNATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: T-7485.13 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 891 111-62 ARGUS 418-021 ORAL (GAVAGE)TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histmorphology Oat2 P Generation GROSS OESERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: basophilia, cortical tubules, focal (minimal) --------------______-------------------i n--f i-l-t-r-a-t-i-o-n-.--m--o-n-o-n-u-c-l-e-a-r---c-e-ll-,--f-o-c-a-l--(-m--in-i-m--a-l)------------------- Page 892 111-63 ARGUS 418-021 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix I11 Individual Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: K-I--D-N-E-Y-S-:---------__-----------------------h-y-p-e-r-p-l-a-s-i-a-,--t-u-b-u-l-a-r-/-d-u-c-t-u-l-a-r--e-p-i-t--h-e-l-i-u-m-,--p-a-p-i-l-l-a--(-m--i n-i-m--a-l )-- THE FOLLOWING T I S S U E I S ) WERE WITHIN NORMAL LIMITS: Page 893 111-64 ~ ~~ ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n l m a l G r o s s and H i s t o m o r p h o l ogy D a t a P Generation GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATIONS: HISTOMORPHOLOGIC CSSERVATION(S): Page 894 111-65 ARGUS 418-021 ORAL (GAVAGE) TUO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 Individual Animal Gross and H i stomorphology Data P Generation Page 895 111-66 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: .L.IV.E..R.:......................................in..fl.a.m..n.a.t.i.o.n....c.h.r.o.n..ic.,...f o..c.a.l./ m..u.l.t.i.f.o.c.a.l..(.m..in.i.m..a.l.) ......... Page 896 111-67 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 Individual Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(8): HI STOMORPHOLOGIC OESERVAT104 ( S): G-E-N-E-R-A_L_: _N_o _gr_o_ss__ch_an_g_es-.____________________No_t_a-p-p-l-1-c-a-b-1-e----------------------------------------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 897 111-68 ARGUS 418-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418- 021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i stornorphol ogy Dara P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): Page 898 111-69 ARGUS 418-021 ORA? (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.15 A p p e n d i x I11 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D z t a P Generation HISTOMORPHOLOGIC OBSERVATIONS: Page 899 I 11-70 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix I 1 1 I n d i v i d u a l Animal Gross and Histomorphology Cata P Generation GROSS OBSERVATION(5): HISTOMORPHOLOG!C O S S E R V 4 T I O N (S! : Page 900 111-71 ARGUS 418-021 ORAL (GAVAGE) TUO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7465.13 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Data P Generation GROSS OBSERVATION!SJ: HISTOMORPHOLOGIC OSSEQVATION(S) ' Page 901 111-72 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): H ISTOMORPHOLOGIC OBSERVATIOY ( S !: HISTOMORPHOLOGIC OBSERVATIONS: .KI..O.N.E.Y.S.:...................................d..i l.a.t.a.t.i.o.n....p..e.l.v.i.s..(.m.i.n.i.m.a.l.)................................ THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: LIVER -----_______________--------*-------------------------------------------------------------------------- End o f Record- 15473 Page 902 111-73 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: T-7485.13 Appendix I11 Individual Animal Gross and Histomorpnology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: PROSTATE : inflamnation. chronic (minimal) __-------__-___-____---------------a-t-r-o-p-h-y-,--f-o-c-a-l---(-m-i-n-i-m-a-l-)-------------------------------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Pa.ge 903 111-74 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 1 1 1 Individual Animal Gross and Histomorphology Data P Generation ARGUS 418-021 Page 904 111-75 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCCL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o i o g y Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OSSERVPT!ON(S) : HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : - -_ Page 905 111-76 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 9 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . I ? Appendix I11 I n d i v i d u a l Animal Gross and H i s t o m o r p h o l o g y Cata P Generation GROSS OBSERVAT!ON(S): H ISTOMORPYOLOS I C 05s ERV4: I ON !S : Page 906 111-77 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY N'JHSER: T-7485.1: A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Data P Generation ANIMAL NUMBER: 5 SEX: M GROSS OBSERVATION(S): HISTOHORPHOLOGIC OBSERVATION(S): THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K--I D-N-E--Y -S--------__--_-----L-I-V-E-R-------------------------------------------------------------------------- E n d of R e c o r d - 15478 Page 907 111-78 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485 .!3 Appendix I11 Indivioual Animal Gross and Histomorphology Data P Generation THE FOLLOWING T!SSUE(S) WERE W I T H I N NOQMAL LIM!TS: Page 908 111-79 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data P Generation GROSS OBSERVATION(S): HISTOHORpFOLOG!C OeSERVAT:ON(S'. .G.E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H!STOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a.r.y.,. .f.o.c.a. .l . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NOQMAL LIMITS: Page 909 111-80 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUOY NUMBER: T - 7 4 8 5 . 1 3 Appendix I11 f n d i v i dual A n i m a l Gross and H i stomorpnoi ogy DaTa P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC OBSERV,4T!ON(S!. Page 910 111-81 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 Indlvidual Animal Gross and Histomorphology 3a:a P Generation GROSS OSSERVArION(S): HISTOMORPHOLOGIC 09SE9V4T:3N!S! GENERAL: No gross changes. Not applicable ________________________________________----------------------------------------------------------- HISTOMORPHOLOGIC O B S E R V A T I O N S : Page 91 1 I11-62 .ARGL'S 4 IS-02 1 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFaS) I N RATS PROTOCOL 418-021 SPONS04'S STUDY NUMBER: T-7485.1: Appendix 111 Individual Animal Gross and h i stomorpnol ogy Daxa P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIOQS: HISTOMORPHOLOGIC CESERVST!ON(SI. Page 9 12 111-83 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i sromorghol ogy Oats. P Generation GROSS OESERV4TION(S) : Page 9 13 111-84 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REP2OOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix 111 I n d i v i oual Animal Gross and h i stomoronol ogy D a t a P Generation GROSS OBSEQVAT!ON(S): HISTOHOAPHO?@G!C O!!SSERVAT:ON(S): Page 914 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIllM PERFLUOROSUTANE SULFONATE (PFBS) IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NLIMEER: T - 7 4 8 5 . 1 3 Appendix 111 Individual Animal Gross HistomorpholoEy Caia P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: H I STOMOR PHOLOGIC 03s E R V d T ION iS ) : THE FOLLOWING TISSUE(5) WERE WITHIN NORMAL LIMITS: Page 915 111-86 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRCOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Hi stomorpnolcgy Gata P Generation GSOSS OBSERVATIOY(S): HISTOYORL"OL0GIC C S S E R V A T ! O Y ( S ) : HISTOMORPHOLOGIC OBSERVATIONS: K1ON EYS : dilatation, pel vis (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y. p. .e.r.p.la. .s.ia. ., .t.u.b.u. .l a. r./.d.u.c. .t u. .l a.r. . .e.p.i .th. e. .1.iu. .m... .p.d.D.i.1.l.a. .(.m. .in.i.m.a. .l ). ?age 9 16 111-87 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODCCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 Appendix I11 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y L a t a P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OSSERV4TIOY ( S \ ' THE FOLLOWING TISSUE(S) WERE W I T H I N NORM4L L I M I T S : Page 9 I 7 111-88 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPOKSOR'S STUDY NUMaER: T-7485.13 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and Hi s t o m o r p n o l sgy Data P Generation GROSS OESERVATION(S1: HISTOMORDHOLOGIC 055EQVATI!IN(S). HISTOMORPHOLOGIC OBSERVATIONS: K. .ID.N. .E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.y.s. .t (.s.). .,.r.n.e.d.u.ll.a. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .L.I V.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 15489 Page 9i8 111-89 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROCUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 A o p e n d i x 111 Individual A n i m a l Gross ana H i s t m r p h o l ogy Data P Generation GROSS OESERVATION(S): HISTOMORPKILOGIC OBSEFVAT!OU(S!: Page 919 111-90 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Apoendix 111 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data P Generation H!STOYORPHOLOGIC O B S E R V A T I O N S : KIONEYS: h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 iurn. papi 1 l a (minimal ) .L.IV.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v. .a.c.u.o.l.a.t.io.n. .. . .h.e.p.a. .to.c. .e.ll.u.l.a.r.,. .m.u.1.t.i.f.o.c. .a.l . .(m. .i.n.im. .a.l.). . . . . . . . . . End o f Record- 15491 Page 920 111-91 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTAHE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y Data P Generation GROSS OBSERVATIOY(S): HISTOMORPYOLOGIC O?SEQV4i!OY(S?. THE FOLLOWING T:SSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 921 111-92 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR ' S STUDY NUMBER: T-7485.13 Aopendix 111 I n a i v i d u a l Animal Gross and Hi stomorpnol ogy Cara P Generation ANIMAL NUMBER: !5493 SEX: H DOSE GROUP: DEATH TYPE: IV Sacrifice-Scneouyec GROSS OBSERVATION(S): HISTOHOROHOLOGIC OBSEQV4T!OY(S!. H!STOHOPPHOLOGIC O B S E R V A T I O N S : KIDNEYS: m i n e r a l iz a t i on, p e l v i s (mi 1d ) hemorrhage, p e l v i s (minimal) LIVER: hypertrophy, hepatocellular (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h. .y.p.e.r.p.l.a.s.i.a.,. .b.i.l.e. .d.u.c.t.,. .f.o.c.a. l. .(.m. .in. .im. .a.l.) . . . . . . . . . . . . . . . . . . . . End of Record- 15493 Page 922 111-93 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I 1 1 Individual Animal Gross and Hi stomorpnol ogy Oata P Generation H!STOMORPHO?OGIC OBSERVATIONS: Page 923 111-94 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E U T : O N ) REPROCUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-02: SPONSOR'S STUDY NUMBER: 1-7485.13 ADoendix 111 I n d i v i d u a l Animal Gross and Histomorphoiogy 0a:a P Generation GROSS OSSERVATION(S\ : HISTOMORPHCLOGIC CSSE?VLT:OY(S~: GENERAL: No gross changes. Not appl 1cab1e ________________________________________------------------------------------------------------------ THE FOLLOWING TISSUEfSl WERE W I T H I N NORMAL LIMITS: K. .ID.N.E. Y. .S. . . . . . . . . . . . . . . . ... . .L.IV.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15495 Page 924 I 11-95 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: T-7485.13 Append1 x I I I I n o i vi, dual Animal Gross and Hi stomorpnol ogy Ea:? P Generation GROSS OGSERVAT!ON(S): HISTOMORPHOLOGIC OBSEQVATIONS: HIST@MORPH@?OGIC @BSERV,4':ON IS 1 : Page 925 111-96 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 Individual Animal Gross and Histomorphology Data P Generation GROSS OSSERVATION(5): HISTOMORPHOL06IC ' J E S E 9 V A T ! C V f S ) : HISTOMORPHOLOGIC OSSERVATIONS: KIDNEYS: d i 1a t a t i on, p e l v i s (minimal ) .L.IV.E. R. .:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n. .f l.a.m. .n.a.t.i.o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./.m.u.1.t.i.f.o.c. a. .l . .(.m.i.n.im. .a.l.). . . . . . . . . . End o f Record- 15497 ' Page926 111-97 .ARGCS 4 IS-02 1 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFRS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphol ogy OaCa P Generation GROSS OSSERVATION(S): HISTOHORPHOLCGIC OBSERVATIOV(j): HISTCHORPHOLOGIC OBSERVAT!ONS: KION EYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 iurn, paoi 11a (minimal ) .L.I V.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .v.a.c.u.o.l.a.t.i.o.n.,. .h.e.p.a. .t o. .c.e.l.l u. l.a.r.,. .c. e. .n.t.r.i l.o. b. .u.l.a.r. .(.m. i.l.d.). . . . . . . . . . End o f Record- 15498 Page 927 111-98 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 A p p e n d i x 111 Individual A n i m a l G r o s s a?d H i s t o m o r p n o i o g y D a t a P Generation GROSS CBSERVAiIONfS!. HISTOMORPHOLOGIC @3SE2VATICfl(S): HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : L. .I V.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f R e c o r d - 1 5 4 9 9 Page 928 111-99 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: i - 7 4 8 5 . 13 Appendix 111 Insividual Animal Gross and Histomorcnology Oara P Generation GROSS OSSERVA'IOY ( S ) EPIDIDYMIDES Left- small KIDNEYS Right- pelvis dilated, dark red suostance found in pelvis. TESTES: Left- flaccid, small, HISTOMORPHOLOGIC OSSERV&-IOY(S! hypospermia. EPIOIOYMiS atrophy, EPIOIDYM!S dilatation, pelvis mineral ization, pelvis hyperplasia. pelvic/papll lary hemorrhage. pelvis atrophy, diffuse, TESTIS u r o t h e i ium HISTONORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS : LIVER: TESTIS: hypospermia (marked) atrophy (marked) dilatation. pelvis (mild) mineralization. pelvis (moderate) hyperpl as1 a, pel vi c/papi 1 1 ary urothel i um (minimal ) hemorrhage, pelvis (mild) i nflamnati on, chronic, focal/mul ti focal ( m i nimal ) atrophy, diffuse (marked) Page 929 I I 1-100 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 415-02i SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 i n d i v i d u a l Animal Gross and Histomorpnology Ca:a P Generation GROSS OBSERVATION(S): I 11-101 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 ApDendix 111 Inaividua? Animal Gross and H i stornorpholagy Data P Generation GROSS O!SERVAT!ON(S): H!STOHORPHOLOGIC DSSiRVA'!ON:S). HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r epi the1 iurn, papi 11a (minimal ) LIVER: cellular alteration, basophilic, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.la. .m.n. a. .ti.o.n... .c.h. .r o. .n.i.c., . .f o. .c.a.l./m. u.1. .t.i.f.o.c.a.l. .(.m.i.n.i.m.a.l.). . . . . . . . . . . End o f Record- 15502 . Page 93 1 111-102 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpnology Data P Generation GROSS OSSERVATION(SI: H!STOMORPHOLOGIC OGSERVS'!ON(S \ : THE FOLLOU!NC TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 932 I I 1-103 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEUTION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUH6E2: T-7465.13 Appendix I11 Individual Animal Gross and H i stomorpnclogy Dara P Generation GROSS OBSERVATION(S) : H!STOMORDHOLOG!C 03SERV4T!31~(S'. H!STOMORWOLOGIC OBSERVATIONS: EAR(S): chondropathy, auricular (mild) K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n. .f.i .l t.r.a. .t i.o. .n... .m.o. n. .o.n.u.c.l.e.a.r.-.c.e.ll.,. .f.o.c. .a.l . .(.m.i.n.i.m.a. l.). . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W!TH!N NORMAL LIMITS: - Page933 111-104 .4RGCS4I E-02i ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.1: Appendix 111 I n d i v i a u a l Animal G r o s s and H i stomorphoiogy DaTa P Generation GROSS OSSERVATION(S): HISTOMORPHOLOGIC OBSfQVA?!OV(S). HISTOMORPHOLOGIC OBSERVATIONS: K. .ID.N.E. Y. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e. .rp.l.a.s.1.a.,. .t.u.b.u. .l a. r./.d.u. c. .t u. .l a.r. . .e.p.i .th.e. 1. .i.ur.n.. . .p.a.p.i.1.1.a. .(.m.i.1.d.). . . . THE FOLLOWING T I S S U E ( 5 ) WERE W I T H I N NORMAL L I M I T S : .L.I V.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d of Record- 15505 Pase 934 111-105 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 ApDendix 1 1 1 Inalvloual Animal Gross and Hlstomorphology Data P Generation GROSS O3SERVATIONfS): H!STOFIORPHOLOGIC OSSERVATICY(5). HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithelium. papilla (minimal) edema, papillary, focal (minimal) L. .I.V.E.R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.e.l.l.u.l.a.r. .a.l.t.e.r.a.t.i.o.n. ,. .b.a.s.o.p. h. .i.l.i.c.,. .f.o.ca.l. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . End of Record- 15506 Page 935 111-106 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.13 Apoendix 111 I n d i v i d u a l Animal Gross and Histomorpnoiogy Dara P Generation GROSS OBSERVATION(S). H!STOHORPHOLOGIC OES!RV4T!OV(S! - T. .H.Y.M.U.S.:. .R.e.d. .p.i n. .p.o.i.n.t. .a.r.e.a.s. .n.u.m.e.r.o.u.s. .t.o. .c.o.u.n.t... . . . . . . . . . . .c.o.n.g.e.s.t.1.o.n. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 93G I 11-107 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PER GENERATION) REPROOUCTiON STUDY OF POTASSIUM PERFLUOROSUTANE SULFONATE (PFSS) IN RATS PROTOCOL 4 16-02 1 SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix I 1 1 Inaividual Animal Gross and Histmorpnology Oata P Generation AN VAL UMBER: 15 SEX: M GROSS OBSERVATION(S): HISTOMORPHOLOGIC OESERVAT!OU( 5 ) : G.E. .N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : basophilia, cortical tubules, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s. i. .a.,.t.u.b.u.l.a.r./.d.u.c.t.u.l.a.r. . .ep.i. .t.h.e.1.i.u.m... .p.a.p.i.1.l.a. .(.m.i.I.d.). . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15508 Page 937 I I 1-108 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: T-7485.13 Apoendix 1 1 1 Individual Animal Gross and Histomorphoiogy Data P Generation GROSS 03SERVATION(S': HISTOMORPHOLOGIC CsSERVA-ION(S): THE FOLLOWING TISSUE(8) WERE WITHIN NORMAL LIMITS: Page 938 111-109 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFaS) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUDY NUMBER: T-7485. i3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation GROSS OSSERVLTION(S): HISTOFORPHCLCG!C CSSSERV?T!ON(S): THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .K.ID.N.E. .Y.S. . . . . . . . . . . . . . . . . . .'.L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15510 Page 939 111-110 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485.13 Aopendix 111 I n a i v i d u a l Animal Gross and Histomorphology Dara P Generation THE FOLLOWING TISSUE(S) WERE WITYIN NORMAL LIMITS: Page 940 111-111 ORAL (GAVAGE) TUO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOI- 418-021 SPONSOZ'S STUOY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l A n i m a l G r o s s and H i stornorphoi ogy 0a:z P Generation GROSS OBSERVAT!ON(S). H!STOYORPHOLOGIC OBSiRVATIOh!S) THE FOLLOWING T!SSUE(S) WERE W!THIN NORYAL LIMITS: Page 941 111-112 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NLIMBER: T-7485.i: Appendix II! I n d i v i d u a l A n l m a i G r o s s and H i s t m o r o n o l ogy D a t a P Generation GROSS OBSEQVATION(S): THE FO?LOW!NG T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 942 111-113 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I11 I n d i v i o u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation GROSS OESERVAT!ON(S): HISTOMORPHOLOGIC OSSEQVAT13N!S): THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : Page 943 111-114 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMaER: T - 7 4 8 5 . 1 3 Appendix I11 i n d i v i d i l a l Animal G r o s s and H i s t o m o r p n o i o g y Data P GeneraEion GROSS OBSERVATION!S): HISTOMORPHOLOGIC OBSERVATIONS: H!STOMORPHOLOGIC O@SERV4TION(S). Page 944 111-115 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Apoendix I 1 1 Individiial Animal Gross and Histomcrpnology Data P Generation GQOSS OZSERVFT!ONfS): H!STOYORPHOLOG!C CESSEQVA:!3K!S). G. .E.N.E.R.A.?.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOW?NG T!SSUE(S) WERE W I T H i N N0RM4i LIMITS: K. .ID.N. .E.Y.S. . . . . . . . . . . . . . . . . ... . L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15516 Page 945 111-116 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix 111 I n d l v l d u a l A n i m a l G r o s s and H i stomoronology OaZa P Generation GROSS OSSERVATION(S): HISTOYOQPHOLCGIC CSSERVAT!ON(S). Page 946 111-117 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I11 Individual Anlmal Gross and Hi stmorpnology Data P Generation GROSS OBSERVATION(S): KIDNEYS: Right- pelvis dilated, slight; pelvis filled with dark red substance HISTOMORPHOLOGI: 03SERV4T!ON(S) ' di latation. pel vis mineralization. pelvis hyperpi asla, pelvic/papi 1 lary urothel ium congest1 on HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : dilatation, pelvis (mild) mineralization. pelvis (moderate) hyperplasia, pel vic/papi 1 1 ary urothel i urn (minimal ) LIVER: hypertrophy, hepatocellular (minimal ) T. .H.Y.M.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.o.n.g.e.s.t.i.o.n. .(.m.i. n. i. m. a. l. ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15518 Page 947 111-118 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATiONj REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7485.13 Appendix 111 I n d i v idLal Animal Gross and Hi stomcrpnol ogy Data P Generation ANIMAL NUMBER: 15519 SEX: M DOSE GROUP: DEATH TYPE: IV Scnedul i (Gro Le GROSS OBSERVATION(S): HISTOWORPHOLOGIC OSSERVATION(S): THYMUS: Red, p i n p o i n t a r e a s , t o o numerous t o congestion _c_o u_n_t ._ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : edema, p a p i l l a r y , f o c a l ( m i n i m a l ) LIVER: in f l a m n a t i o n . c h r o n i c , f o c a l /mu1 t i f o c a l ( m i n i m a l ) T.H.Y.M.U.S. .:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.o.n.g.e.s.t.i.o.n. .(.m.i.n.i.m.a. .l). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15519 Page 948 111-119 ARGCS 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUCY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Aopendix 111 I n d i v i dual Animal Gross and H i stomorphol ogy Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OPSERVAT!ON(S): T_H-Y-M_US_: _R_e_d,_p_i_n p_o_i n_t_a_re_a_s,__nu_m_er_ou_s_t_o_c_o_un_t._______he_m_o_rrh-a--g-e-, -f-o-c-a--l ---------------------------------------------- HISTOMORPHOLOG!C O B S E R V A T I O N S : THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: K. .ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15520 Fage 949 111-120 ORAL (GAVAGE) TWO-GENERATIOh (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpnology Da:a P Generation GROSS OBSERVCTION(S): HISTOMOQPHOLOGIC OSSERV4TIOY( S : HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: KIDNEYS: LIVER: vacuolation, cortex (minimal) basophilia. cortical tubules, focal (minimal) hyperplasia, tubular/ductular eplthelium, papilla hypertrophy, hepatocellular (minimal ) (mild) THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL L I M I T S : COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS PITUITARY PROSTATE Page 950 111-121 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR ' S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpholopy Data P Generarion ANIMAL NUMBER: 15522 SEX: M DOSE GROUP: DEATH TYPE: V Sacrifice-Scneaulea HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: hyperplasia, edema, p a p i l - - - - _ _ _ -h-y-p-e-r-t r-o-p-h-y-,- - - Page 951 111-122 ARGL'S 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 2 Appendix III I n d i v i oual A n i m a l G r o s s and H i s t m c r p n o l cgy Ea-a P Generation GROSS OBSERV4TION(S): H!STOMORPHOLOGIC CSSERVST!ONiS!. HISTOMORWOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS COAGULATING GLANO EPIDIOYMIS KIDNEYS .P.I T.U. .I T.A.R. .Y. . . . . . . . . . . . . . . . . .P.R. .O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M. .IN.A. .L.V. .E.S.IC. .LE. .S. . . . . . . . . . .T.E.S. .T.I S. . . . . . . . . . . . . . . . . E n d of R e c o r d - 15523 Page 952 I 11-123 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology D a t a P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC OBSERVATION( S ) ' HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f i 1t r a t i on, mononuclear-cel 1 , f o c a l (minimal ) KIDNEYS: h y p e r p l a s i a , t u b u l a r / d u c t u l a r epi the1 1 urn, papi 11a (minimal ) LIVER: hypertrophy. hepatocellular (minimal ) PROSTATE : prostatitis, suppurative (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a. .tr.o.p.h. .y., . .fo. .c.a.l. .(.m. .il.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S1 WERE W!THIN NORMAL L I M I T S : ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY SEMINAL VESICLES Page 953 I 11-124 ARGUS 1 18-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l Animal Gross and H i stomorphology Data P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC O@SERVkTIONS( ) : THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: K. .I D.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15525 Page 954 111-125 .ARGLS 41 S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and F i s t o m o r p n o l o g y %:a P Generation GROSS OBSERVATION(S): HISTOMOR'JHOLOGIC 09SERV4TI3N(S!. .G.E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a. .p.p.l .i.c .a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND . EPIDIDYMIS KIDNEYS LIVER .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S. .T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 15526 Page 955 111-126 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02f SPONSOR'S STUDY NUMBER: T-7485 .!3 Apoendix 1 1 1 Individual Animal Gross and H i stomorpnology Data P Generation GROSS OBSERVATION(S): H!STOMORPHOLOGIC OBSERVAT!ON:S'. G.E. .N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOG!C OBSERVATIONS: ADRENAL GLANDS: vacuolation. cortex (minimal) KIONEYS: hyperplasia, tubular/ductular epithel ium, papilla (minimal) LIVER: infl amnation. chronic, focal/mu1 ti focal (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.t.r.o.p.h.y. .,.h.e.p.a.t.o.c.e.l.l. .u.l.a.r. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS PITUITARY PROSTATE .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15527 Page 956 111-127 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i oual Animal Gross and H i stomorpho; ogy Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOCIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : cyst(s.1, medulla dilatation, cortical tubules, focal (minimal) .L.IV.E.R. .:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.t.r.o.p.h.y.,. .h. .e.p.a.t.o.c.e. .l l.u.l.a.r. .(.m.i.n.i.m.a. .l). . . . . . . . . . . . . . . . . . . . . . End o f Record- 15528 Page 957 111-128 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS IUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485.13 AoDendix 111 I n d i v i d u a l Animal Gross and Histomorpnoiogy Data P Generation GROSS OBSERVAT!ON(S): EPIDIDYMIDES: Small, bilateral i n f i l t r a t i o n , mononuclear-cel!, fccai, EPIDIDYMIS HISTOMORPHOLOGIC O B S F R V A T I O N S : EPIDIDYMIS: KIDNEYS : LIVER: PROSTATE : SEMINAL VESICLES: TESTIS: atrophy (mild) hypospermia ( m i 1d) i n f i 1ti-at ion, mononuclear-cel 1 , f o c a l (minimal ) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 iurn, p a p i 11a (mi I d ) hypertrophy, hepatocellul ar (minimal ) atrophy. diffuse (moderate) atrophy (mild) . . . . .a.tr.o.p. .h.y.,. .d.i.f.f u. .s.e. .(.m. .a.rk.e. d. .) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S1 WERE W I T H I N NORM4L L I M I T S : Page 958 111-129 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) IN RATS PROTOCCL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 Individual Animal Gross and Histomrpnology Data P Generation ANIMAL NUMBER: 15530 DOSE GROUP: V SEX; M DEATH TYPE: Scneduled (Gross Lesion) ....................................................................................................... GROSS OBSERVATION(S). HISTOMORPHOLOCIC OBSERV3iiON( S ) : KIDNEYS: Right- pelvis, moderately dilated: dark di 1 atation, pel vis red sumtance found in kidney pelvis. mineralization, pelvis hyperplasia, pelvic/papillary urcthel ium hyperplasia, tubular/ductular eoitnel ium, papilla . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .b. a. s. o. .p.h.i.l.i.a.,. .c.o.r.t.i.c.a.l. .t.u.b.u. l. e. .s.,. .f.o.c.a.l. . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: KIDNE L--I-V-E-R End o dilatation. pelvi s (moderate) mineral 1 zation. pelvis (mi Id) hyperplasi a , pel vi c/papi 1 1 ary urothel i um (mi1d) basophilia, cortical tubules, focal (minimal) hyperplasia, tubul ar/ductul ar epi the1 i um, papi 1 1 a (minimal ) ---- . . . . . . .h.y.p.e.r.t.r.o.p.h.y.,. .h.e.p.a.t.o.c.e.l.l.u.l.a.r. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . Page 959 I 11-130 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p p e n d i x 111 I n a i v i d u a l A n i m a l Gross and H i s t o m a r p h o l o g y C a t a P Generation GROSS OE!SEQVATION(S): HISTOMOQPHOLOGIC OSSE9VATION( 51 . HISTOMORPHOLOG!C OBSERVATIONS: LIVER: inflamnation. chronic, focal/multifocal ( m i n i m a l ) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.la.m. .n.a.t.i.o.n... .c.h. .ro. .n.ic. . .( .m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE "!THIN NORMAL L I M I T S : ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .P.I T.U. .I T.A.R. .Y. . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. .S.T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f R e c o r d - 15531 Page 960 111-131 'ARGCS 4 1 S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix I 1 1 Individual Animai Gross and H i stomorphology Cata P Generation GQOSS OSSERL'ATION(SI: HISTOHORPYOLOCit OES5?VAT!CV(S). HISTOHORPHOLOGIC OBSERVATIONS: LIVER: vacuo1 ation. hepatocell ular. mu1 ti focal (miId) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.t.r.o.p.h.y. ,. .h.e.p.a.t.o.c.e.l.l.u.l.a.r. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 961 111-132 XRGL'S 4 18-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OSSERVATION(S): HIST030RPHOLOGIC O S S E R V A T I O N ( S ) : HISTOMORPHOLOGIC O S S E R V A T I O N S : KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r epi the1 iurn. paoi 11a (minimal ) LIVER: hematopoiesis. extramedullary (minimal) hypertrophy, hepatocellular (minimal ) .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.r.o.p.h.y... .f.o.c.a. .l . .( m. .i.l d. .) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: C. .O.A.G.U.L.A.T.I.N.G. .G.L.A.N.D. . . . . . . . . .E. .P.I D. .I D. .Y.M.I.S. . . . . . . . . . . . . . . . .S.E.M. .IN. .A.L. .V.E.S.IC.L.E. S. . . . . . . . . . . .T.E.S. .T.I S. . . . . . . . . . . . . . . . . End of Record- 15533 Page 962 I 11-133 .ARGUS 11S-011 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02: SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I11 Individual Animal G r o s s and Histomorphology Oara P Generation GROSS OBSERVATION(8): H!STOMORPHOLOGIC OESERVAT?@N!S! ' HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithelium. papilla (mild) LIVER: inflamnation. chronic, focal /mu1 ti focal (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.t.r.o.p.h.y.,. .h.e.p.a.t.o.c.e.l.l.u.l.a.r. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . End of Record- 15534 Page 963 I 11-134 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Anima: Gross and Hisromorpnoiogy D a t a P Generation ANIMA? NUF E R : 1 SEX: M GROSS OBSERVATION(S): H!STOMOAPHOLOG!C @3SERVd'I!lti(S\: H!STOMORPHOLOGIC OBSERVATIONS: KIDNEYS : basophilia, cortical tubules, focal (minimal ) .L.IV.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e. .rt.r.o.p.h.y. ., .h. .e.p.a.t.o.c. .e.l l.u.l.a.r. .(.m. .in.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . End of Record- 15535 Page 964 111-135 .-IRGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7465.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphology Data P Generation ANIMAL NUMBER: 15536 SEX: M DOSE GROUP: OEATH TYPE: V Scheduled (Ranoom) GROSS OBSEQVATIONf S) : H!STOMORPHOLOGIC OBSEQV&T!OV:S) : HISTOMORPHOLOGIC OSSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epi the1ium, papi 1l a (minimal ) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) .L.I V.E. .R.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e. .rt.r.o.p.h.y.,. .h.e. .p.a.t.o.c.e.l.l.u.l.a.r. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . Page 965 111-136 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 A N I C . NUMBER: 1553 SEX: M Aopendix III Individual Animal Gross and H i stomorphology Data P Generation GROSS OSSERVATION(5): HISTOMORPHOLOG!C OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithelium. papilla (mild) .L.IV.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p. .e.rt.r.o.p.h.y.,. .h.e. .p.a.to. .c.e.l .l u. .l a. .r. .(.m.i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15537 Page 966 III-137 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I 1 1 Individual Animal Gross and Hi stomorphoi ogy Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: LIVER: THYMUS : hyperplasia, pelvic/papillary urothel ium (mild) necrosis, papilla. focal (moderate) hemorrhage, pel vis (mi 1 d) basophilia, cortical tubules, focal (mild) hyperplasia, tubular/ductular epithelium, papilla hypertrophy, hepatocellular (miId) No microscopic change to correlate (moderate) Page 967 111-138 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY O F POTASSIUM PERFLUOROBUTANE SULFONATE (PiES) IN RATS PROTOCOL 41a-021 SPONSOR'S STUDY NLIMEER: T-7485. !3 Appendix I 1 1 I n d i v i d u a l Animal Gross and H:stomorphoiogj Caca P Generation GROSS OSSE?VATION(S): H!STOMORpHOLOGIC CSSE?VATiON(S). G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: EPIDIOYMIS: i n f i l t r a t i o n , mononuclear-cell, focal (minimal) KIDNEYS: hyperplasia. tubular/ductular epithelium. papilla (minimal) LIVER: hypertrophy, hepatocellul ar (minimal ) PROSTATE : i n f l a m n a t i o n , c h r o n i c (mi I d ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.tr.o.p. h. .y., . .fo. .c.a.l. .(.m.o.d. .e.ra. .te.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIHITS: Page 968 111-139 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY O F POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.1: Appendix 111 I n d i v i o u a l Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperpl a s i a , p e l v i c/papi 11a r y u r o t h e l ium ( m i 1d) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 ium. papi 1l a (mi I d ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a... .p.a. .p.i.l l.a.r.y. ., . .fo.c. .a.l . .(.m.i.n.i.m.a. .l). . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 969 I11-140 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFaS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 1 1 1 Individual Animal Gross and Histomorpnology Data P Generation GROSS 03SERVATION(S! : HISTOHORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epi the1 i um. papi 1 la (mi Id) edema, papillary, focal (mild) .L.I.V.E.R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.t.r.o.p.h. .y.,.h.e.p.a.t.o.c.e.l.l.u.l.a.r. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15541 Page 970 I 11-141 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i sromorphology Cara P Generation GROSS OBSERVAT!ON(S). HISTOMORPHOLOGIC OBSERV4TION( S 1 : .T.E.S.T.E.S.: . .R.i.g.h.t.-. .l.a.r.g.e... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o. .m.i.c.r.o.s.c.o.p.i.c. .c.h.a.n.g.e. .t.o. .c. .o.r.r.e.l.a.t.e... .T.E.S.T.I.S. . . HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : p y e l i t i s , chronic (moderate) h y p e r p l a s i a , p e l v i c / p a p i 1l a r y u r o t h e l i um (mi I d ) basophilia, cortical tubules, focal (minimal) hyperplasia, tubular/ductular epi the1ium, papi 11a (miI d ) LIVER: hypertrophy, hepatocellular (minimal) T. .E.S.T.I.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o. .m. .ic.r.o.s.c.o. .p.ic. .c.h.a.n.g.e. . .t o. . c. .o.r.r.e.l.a.t.e. . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 971 111-142 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and Hittomorphology Data P Generarion GROSS OBSERVATION(S): HISTOMORPHOLOGIC O@SERV&T!ON(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithe1 i urn, papi 1 1 a (miId) LIVER: hypertrophy, hepatocellular (minimal) --------------------------------------------------- TYE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE SEMINAL VESICLES Page 972 I 11-143 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross ana histomorphology Data P Generation HISTOMORPHOLOG!C O B S E Q V A T I O N S : KIDNEYS : LIVER: PROSTATE: ---- i n f i l t r a t i o n , mononuclear-cell, focal edema, p a p i l l a r y . f o c a l ( m i n i m a l ) hypertrophy, hepatocellular (minimal ) i n f l amnation. c h r o n i c ( m i 1d ) prostatitis, suppurative (minimal ) (minimal) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS PITUITARY S. .E.M.IN. .A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. .S.T.IS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15544 Page 973 I 11-144 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 1 1 1 Individual Animal Gross and Histomorohology Data P Generation ANIMAL NUMB R: 55 SEX: GROSS OESERVATION(S): HISTOYORPHOLOGIC 0SSERVATION:S). H!STOMORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductul ar e p i the1 i urn, papi 1 1 a (minimal) LIVER: i n f l amnation, chroni c , focal/mu1 ti focal (min i mal ) hypertrophy, hepatocellular (minimal ) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l.a.m.n.a.t.i.o.n... .c.h.r.o.n.i.c. . .(.m.i.ni.m.a.l. .). . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES COAGULATING GLAND TESTIS EPIDIDYMIS PITUITARY Page 974 111-145 ARGCS 118-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: 1-7485.13 Appendix 111 Individual Animal Gross and Histomorphology Dara P Generation GROSS OBSERVATION(S!: HISTOMORpHOLOGIC O@SERVAT!CN(S): HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS : LIVER: PROSTATE: THYMUS: i n f i l t r a t i o n , mononuclear-cell, focal (minimal) i n f i l t r a t i o n , mononuclear-cell, focal (minimal) hypertrophy, hepatocellular (minimal) prostatitis, suppurative (minimal ) ...h.e.m.o.r.r.h.a.g.e.,..f.o.c.a..l ..(.m.i.n.i.m.a..l).................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS TESTIS COAGULATING GLAND PITUITARY SEMINAL VESICLES Page 975 I 11-146 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.1: Appendix I 1 1 I n d i v i duai Animal Gross and H i stomorphoi ogy Data P Generation G R O S j OBSERVAT!ON(S) HISTOMORDHOLOGIC O @ S E R V A T I O N I S 1 . HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS : hyperplasia, tubular/ductular epithelium, papilla (minimal) edema. p a p i l l a r y , f o c a l ( m i n i m a l ) L. .IV.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p. e. .rt.r.o.p.h.y.,. .h. e. .p.a.t.o.c.e.l.lu. .l .a.r. .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . End of Record- 15547 Page 976 111-147 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7435.13 Appendix 111 I n d i v i a u a l Animal Gross and Histomorpnology Dara P Generation GROSS OBSERVATION!S) : H I STOMORDHOLOGI C 0's ER'JAT! C N [ S ' HISTOMORPHOLOGIC O B S E R V A T I O N S : ADRENAL GLANDS: vacuolation, cortex (minimal) LIVER: i n f l a m m a t i o n . c h r o n i c , f o c a l /mu1 t i f o c a l (minimal ) hypertrophy, hepatocellular (minimal ) .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . a. .tr.o.p.h. .y., . .f o. .c.a.l. .(.m.i.n.i.m.a. .l). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND EPIDIDYMIS KIDNEYS PITUITARY S. .E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. .S.T.IS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15548 Page 977 I I 1-148 ARGCS 41s-071 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: hyperplasia, tubular/ductular epithelium, p a p i l l a (minimal 1 .L.I V.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e. .rt.r.o.p.h.y.,. .h.e. .p.a.t.o.c.e.l.l.u.l a. .r . .(m. .in.i.m. .a.l .) . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15549 Page 578 I 11-149 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUM3EFi: T-7485.13 A p p e n d i x 111 I n d i v i d u a l A n i m a l Gross and H i stornorpnology C a r a P Generation GROSS OSSERVATION(S). HISTOYOR~HOLCGIC OBSERVAT!ON(S!: G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g. .e.s.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. o. .t .a.p. p. .l .ic.a.b.1. .e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: K. .ID.N. .E.Y.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.y.s.t.(.s.).,. .p.e.r.i.re.n. .a.l. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W!THIN NORM4L L I M I T S : LIVER Pase 979 I 11-150 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENER.ATiON! REPRODUCTION STUDY OF POTASSIUM PERFLUOROaUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: ;-7485.:3 Appendix 111 I n o i v i d u a l Animal Gross and H i sromorpholc;) S a t a P Generation HiSTOMOR3HO!OGIC OBSERVATIONS: K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a.r.y.,. .f.o.c.a. .l . .(m. .i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15551 Page 380 111-151 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEKATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 2 A o p e n d i x 111 I n d i v i d u a l Animal Gross a n d H l s t o m o r o n o i o g y b t z P Generation G2OSS OBSERVATION(S): HISTCMORPHOLOGIC OESERVA'!OR:S!. HISTOMORPHOCOGIC OBSEQVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: presence o f c o r p o r a l u t e a presence o f g r o w 1 n g / a n t r a l fol 11c l es PITUITARY: cyst(s) U. .TE. R. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.r o. p. .h .a.g.e.s., . .p.l.g.m.e.n.t.e.d. .(.m.i.1.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 981 I 11-152 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-74S5.13 A p p e n d i x 111 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y CaTa P Generation H!STOMORPHOLOtIC OBSERVATIONS: K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i .n.e.r.a.l.i.z.a.t.i.o.n.,. .m.u.1.t.i.f.o.c.a.l. .(.m. .i n.i.m.a.l. ). . . . . . . . . . . . . . . . . . . . . . . . E n d of Record- 15553 Page 982 I I 1-153 XRGCS 1 15-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: Page 983 I 11-154 ARGYS 1I S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF PDTASS IUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02i SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix I11 I n d i v i d u a l A n i m a l G r o s s and H i s t O m O r D n O i O g y Datz P Generation GROSS OeSEQVAT!ON(S) HISTOUORPYOLOGIC OSSE9VST:CN:S) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 984 111-155 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.1: Appendix 1 1 1 Individual Animal Gross and Histornorpholcgy Da:a P Generation GROSS OSSERVA'ION(S) : HISTOMORPHOLOGIC OBSERVATIONS: K. I. .D.N.E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t.u.b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.p.i.t.h.e.1. i.u.r.n.,. .p.ap.i. .1.1.a. .(.m.i.n.i.m.a.l.) End o f Record- 15556 Page 985 111-1516 XRGCS 4IS-02.1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUDY NUHBER: T-74E5.13 Aopendix 111 I n d iv i ddal Animal Gross and H i stomorphol ogy Cata P Generation HISTOYORPHOLOC!C OBSERVATIONS: KIDNEYS : pyelonephri t i s (mi 1d) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p. .e.r.p.la. .s.ia. ., .t.u.b.u. .l a. .r /.d.u. .c.t u. .l a.r. . .e.p.i .th.e. .1.i .u.rn.,. .p.a.p.i.1.1.a. .(.m.i.1.d.). . . . End o f Record- 15557 Page 986 111-157 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROCUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SCLFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Aopendix I11 I n d l v i dual A n l m a l G r o s s and H i s t o m O r o n o 1 Og): Car. P Generation T I S S U E ( S ) NCT AVAILABLE FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA OVARIES OVIDUCT( S) UTERUS VAG I NA LUTEA End o f R e c o r d - 15558 Page 987 111-158 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!8-021 SPONSOR'S STUDY NUMEER: T-7465.!5 Appendix I 1 1 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS: m i n e r a l i z a t i on, mu1t i f o c a l ( m i n i m a l ) OVARIAN FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s U. .TE.R.U. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.ig. .m.e.n.t.e.d. .(.m.o. .d.e.ra. .te.). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS CERVIX LIVER OVARIES O. .V.ID. .U.C.T.(.S.). . . . . . . . . . . . . . . . .P. .IT.U. .I.TA.R.Y. . . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15559 Page 988 I I 1-159 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-azi SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 2 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and Hi s t o m o r p h o l ogy D a t a P Generation GROSS O@SERVAT!ON(S)' HISTOMOR'JHOLOGIC OSSERVAT!OY!S'. THE FOLLOWING T I S S U E ( S ) WERE WITHIN NORMAL L I M I T S : Page 989 111-160 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOH) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-02: SPONSOR'S STUDY NUMBER: T-7465.13 A o p e n d i x 111 Inci v i d u a l A n i m a l Gross and H i s t o m o r p n o l o g y Daxa P Generation H I S T O M O R P Y C L O G I t @!SEQVS'!?Y'S! HISTOMORPHOL0G:C OBSERVATIONS: .K.ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i.n.e.r.a.l.i .z .a.t .i o. n. ., . .m.u.1.t.i.f.o.c.a.l. .(.m. .i n.i.m. .a.l .) . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 15561 Page 990 111-161 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.1; Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpnoiog. Data P Generation HISTOMORDHOLOGIC OBSERVATIONS: O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence of growing/antral f o l l i c l e s U. .TE.R. U. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.r.o.p.h.a.g.e.s.,. .p.ig. m. .e.n.t.e.d. .(.m. .o.d.e.r.a.te. .) . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX KI ONEY S LIVER O. .V.A.R.IE. S. . . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C. .T.(S.). . . . . . . . . . . . . . . . .P. I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . . .V.A.G.!N.A. . . . . . . . . . . . . . . . . . . End o f Record- 15562 Page 99i 111-162 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR S STUDY NUMBER: T-7485.13 A p p e n o i x 111 I n d i v i d u a l A n i m a l Gross and H i stomoronol o-,y D a t a P Generation ANIMAL NUMBER: 15563 SEX: F DOSE GROUP: DEATH TYPE: I Sacrifice-Schemled GQOSS OSSERV3T!ON(S): THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : ?age 992 I 11-163 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOti) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFGS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix 111 Individual Animal Gross and h i stomorpnology Data P Generation GROSS OESERVAT!ON(S): HISTOMORPHOLOGIC O?SSERV&TIOY(SI. HISTOMORPHOLOG!C OBSERVATIONS: O V A R I A N FOLLICLES/CORPORA LUTEA: presence of corpora l u t e a presence o f growing/antral f o l l i c l e s U. .TE. R. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.i.g.m.e.n.t.e.d. .(.m. o. .d.e.r.a.te.). . . . . . . . . . . . . . . . . . . . . . . . . . . . TYE FOLLOWING TISSUE(S) WERE WITHIN NORM4L L I M I T S : Page 993 II I - 164 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02i SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix 111 I n d i v i d u a l Anima7 Gross and H i s t o m o r p n o i o j y Cata P Generation HISTOMORPHOLOGIC OBSERVATIONS: O V A R I A N FOLLICLES/CORPQRA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s UTERUS : macrophages, pigmented (moderate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d.i.s.t.e.n.t.i.o.n.,. .l.u.m.e.n. . .(m. .o.d.e.r.a.t.e.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O. .V.ID. .U.C.T.(.S.). . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R. .Y. . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . End o f Record- 15565 Page 994 I 11-165 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 S P O N S O R ` S STUDY NUMBER: T-74B5.i; ANIMAL NUMBER: 15566 SEX: F Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Cata P Generation DOSE GRCUP: OEATH TYPE: I Scheduled (Reducec Fer:?ll:y) GQOSS OBSERVATION(S): G_E_N_ER_A_L:_N_o_g_ro_s_s_c_ha_n_g_es_. ____________________N_ot__ap-p-l-i-c-a-b-1-e--------------------------------------------------- TISSUE(S) NOT AVAILABLE FOR EVALUATION: Page 995 I 11-166 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROGUCTiON STUGY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: T-7485. 1; Appendix I11 I n a i v i dual Animal Gross and H i stornorpnoi ogy Dzta P Generation THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15567 Page 996 I 11-167 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-C2! SPONSOR ' S STUDY NUMBER: i - 7 4 8 5 . !3 A p p e n d i x 111 Individual A n i m a l G r o s s and Histomorpnoloc:/ P Generarion Cara GROSS OBSERVATION(S): HISTOMORPHOLOSIC OSSERVATIONS: .K.ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i n. .e.ra. .l .i.z.a.t.i.o.n.,. .m.u1. .t.i.f.o.c.a.l. .(.m.i.n.i.m.a.1.). . . . . . . . . . . . . . . . . . . . . . . . End of R e c o r d - 15568 Page 997 111-168 OilAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a P Generation GQOSS OSSERV9TION!S): HISTOHOf?PHO?OG!C OESEQV4TIONS: HISTOMORPYCLOGIC OSSERVST!OV'S\. Page 998 I I 1-169 .-\RGL*S4I F-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFON.4TE (PFBS) I N RATS PROTOCOL 418-021 SPOtiSOR'S STUDY NUMBER: T-7485.13 Appendix I11 Individual Animal Gross ana Histornorpnology Ea-a P Generation GROSS OESERVAT!OV:S). H!S TOMOQ PHOLCG IC O3S EQ V 4 TIObi '5 1 G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e. s. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. o. .t .a.p. p. .l .1c.a.b.1. .e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 999 I 11-170 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I11 Individual Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: O V A R I A N FOLLICLES/CORPORA LUTEA: PITUITARY: UTERUS : Dresence o f corDora l u t e a bresence o f growing/antral fo11 ic l es c y s t (s1 macrophages, pigmented (mi I d ) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.I .E.S. . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C.T. (.S. ). . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15571 Page loo0 I 11-171 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PF5S) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7465.13 Appendix I I I I n o i vi oual Animal Gross and iiistomorphol ogy Oata P Generation GROSS @BSERVAT!ON(S): HISTOMORDHOLOGIC 00SERV4T!3KrS' H!STOM@RPHOLOGIC OBSERVATION5: LIVER: OVARIAN FOLLICLESKORPOR`A LUTEA: inflammation. chronic, focal/multifocal (minimal) presence o f corpora lutea presence o f growing/antral f o l l i c l e s U. .TE.R. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.ro. .p.h.a.g.e.s., . .p.ig. m. .e.n.t.e.d. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS CERVIX KIDNEYS OVARIES O. .V.ID.U. .C.T.(.S.) . . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15572 Page 1001 111-172 ARGUS 116-02 1 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorpnology Caza P Generation GROSS 03SERVAT:ONIS): HISTOMORPHGL0G:C O ! S i R V 4 - ! G N ~ S ' : G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e. .s.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a. .p.p.l.i c. .a.b.l.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUF(S) WERE W I T H I N NORMAL LIMITS: .K.ID.N.E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15573 Page 1002 111-173 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTAhE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.1: Appendix 111 Individual Animal Gross and Histomorpnology Data P Generation GROSS OSSEQVATIONfS): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : basophilia, cortical tubules, focal (minimal) OVARIAN FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence of growing/antral follicles U. T.E.R. U. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.i.g.m.e.n.t.e.d. .(.m.o.d.e.r.a.t.e. ). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX LIVER OVARIES O. .V.ID.U. .C.T.(S. .) . . . . . . . . . . . . . . . . .P.I.T.U.1.T.A.R.Y. . . . . . . . . . . . . . . . . .V.A.G. .IN.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15574 Page 1003 111-174 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 1nd:vidual Animal Gross and Histomorpnclcgy Sara P Generation HISTOMORPHOLOG!C OESERVATIONS: O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora 1utea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p.re.s. e. .n.c.e. .o.f. .g.r.o.w.i.n.g./.a.n.t.r.a.l. .f.o.l.l.i.c.l.e.s. . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORM4L LIMITS: Page 1004 111-175 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS1 I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUHGER: T-7465.12 Appendix II! I n d i v i d u a l Animal Gross and H i stomorphology Datr P Generation GROSS OSSERVAT!OY(S): HISTOMORPHOLOrJ!C OSSERVATIONS: KIDNEYS : mi n e r a l iz a t i on, mu1t if o c a l ( m i n i mal ) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p.re. s. e. .n.c.e. .o.f. .g.r.o.w.i.n.g./.a.n. .tr.a.l. .f.o. .l l.i.c.l.e.s. . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: AORENAL GLANDS CERVIX LIVER O V A R I E5 O. .V.ID. .U.C.T.(.S.). . . . . . . . . . . . . . . . .P. I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . . .U.T.E.R.U.S. . . . . . . . . . . . . . . . . . . . . .V.AG. .I.N.A. . . . . . . . . . . . . . . . . End o f Record- 15576 Page 1005 111-176 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 Individual A n i m a l G r o s s and H i s r o m o r o h c l o g y C a t a P Generatlon GROSS CSSERVATION(S): HISTOHORPHCLOGIC OBSERVATIONS: SPLEEN: c y s t (s), capsul a r congestion, red pulp (moderate) ____________________^___________________--------------------------------------------------------------- T I S S U E ( S ) NOT AVAILABLE FOR EVALUATION: CERVIX K IDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT( S) UTERUS V_A_GI_NA_ _ _ _ _ _ _ _ _ - _ _ _ _ _ _ _ End o f Record- 15577 Page 1006 I I 1-177 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7 - 7 4 8 5 . 1 3 Appendix 111 I n d i v i a u a l Animal Gross and Histomorohology Czta P Generation GROSS CSSERVATION(S!: THE FOLLOWING TISSUE(S! WERE WITHIN NORMAL LIMITS: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15578 Page 1007 I 11-178 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOil'S STUDY NUMBER: 1-7485. i 3 Appendix 111 I n d i v i a u a l Animal Gross and Histomoronology Daca P Generation GROSS OSSERVAiIONIS): HISTOMORPHOLOG!C 355EQVCT!OYrS'. G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S! WERE W I T H I N NORMAL LIMITS: .K.ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Gecord- 15579 Page 1008 111-179 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E M I I O N ) REPROOUCTICN STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T - 7 4 9 5 . !3 Aopendix 111 I n o i v i d u a l A n i m a l Gross and H i stomorphologq G a ~ a P Generation GROSS OSSERVAT!ON(S): HISTOMCRPHOLOGiC OSSFSV\T:ON:S). THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1009 I 11-180 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p o e n d l x 111 i n c i v i aual Animal G r o s s and Hi stomorpnol ogq CaTa P Generalion GROSS OBSERVAT!ON(S): THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I M I T S : K. .I D.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15581 Page 1010 111-181 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPZOOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSCZ'S STUDY NUMBER: 1 - 7 4 8 5 . I? Appendix 111 I n d i v i d u a l Animal Gross and Histomorpnoiocjy Data P Generation THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1011 111-182 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p n o l ogy C a ~ a P Generation GROSS OSSERVAT!ON(S) HISTOMORPHOLOGIC OfSEW4'IOY( S 1 THE FOLLOWING T I S S U E ( S ) WERE WITH!N NORMAL L I M I T S : K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 15583 Page 1012 111-183 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p n o l o g y D a t a P Generation GROSS OSSE9VATIONfS): H!STOWOR~HO!OG!C 09SERVa-!?NfS). THE FCLLOWING T I S S U E ( S ) WERE W I T H I N NORM4L L I Y I T S : Page 1013 111-184 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRCOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i a u a l A n i m a l G r o s s and H i s t o m o r p h o i o g y D2:z P Generarion GROSS OBSERVATION(8): HISTOYORPHOLOG!C CSSERVATI3N!S!: G_E_N_ER_AL_: _N_o_g_r_os_s_c_ha_n_ge_s_. ____________________N _o t_a_p-p-l -i-c -a -b-1-e--------------------------------------------------- THE FOLLOWING T!SSUE(S) WERE W!THIN NORMAL L I M I T S : K. .ID.N.E.Y. S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 15585 Page 1014 111-185 ARGCS 1 1S-02 1 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 5 A p o e n d i x 111 I n d i v i d u a l Anima7 G r o s s and H i s t o m o r p h o l c g y Dara P Generation GROSS CBSERV4TION(S): HISTOMORPHOLOG!C CSSE'?VAT!ON!S~. THE FOLLOWING T!SSUE(S) WERE W!THIN NORMAL L I M I T S : Page 1015 111-186 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFaS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 i n o i v i ouai Animal Gross and H i sromorpnol ogy 3a;a P Generation GROSS OBSERVAT!ON(S): HISTOMORPHOLOGIC CBSERVATION(S!: HISTOMORPHOLOGIC OBSERVATIONS: K. .ID.N. .E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e. .t a. .l i.z.a. .t .i o.n.,. .m.u.1.t.i.f.o.c.a. .l . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15587 Page 1016 111-187 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRCOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1 - 7 4 8 5 . I t Appendix I11 I n d i v i d u a l Apimal Gross and Hi stomor?hol ogy Data P Generation HISTOM09PHCLOGIC OSSERVATIDNS: KIDNEYS : c y s t (s), papi 11a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e.r.a.l.i.z.a.t.i.o.n.,. .m.u.1.t.i.f.o.c.a.l. .(.m. .in.i.m.a. .l ). . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15588 Page 1017 II 1-188 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFOhATE (PFBS) I N RATS PROTOCOL 416-02! SPONSOX'S STUDY NUMBER: T-7465.13 Appendix I11 i n d i v i o u a l Animal Gross and H i stomorpnology Ca:a P Generation HISTOPORPHOLOGIC OBSEQVATIONS: KIDNEYS (1): hyperplasia, tubular/ductular epithelium, papilla (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a.r.y. ,. .f.o.c. .a.l . .(.m.i.n.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15589 Page io18 111-189 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-62 1 SPONSOR'S STUDY NUMBER: T-7485. 13 Appendix I I ! I n d i v i d u a l Animal Gross and H i s t o m o r p h c l c j y Data P Generation Page 1019 I 11-190 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUOY NUMBER: T-7485.13 Appendix 111 Inai v i dual Animal Gross and H i stomorohol ogy Data P Generation GRCSS OSSERVAT!ON(S): H!STOHORPHO?OG!C O ? 5 E ? V 4 T ! O N [ S ) : H!STOMORDHO?OG!C O B S E R V A T I O N S : K. .ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i.n.e.r.a.l.i .z.a.t.i o. .n... .m.u.1.t.i.f.o.c.a.l. .(.m. .in. i.m. .a.l .) . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15591 Page 1020 I 11-191 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTIOh STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 A p p e n d i x IiI I n d i v i o u a l A n i m a l G r o s s and H i s t o m o r p n o l o g y Oata P Generation GROSS OSSERVATION(SJ: H!STOHCRP~O?OGIC OESERVAT:CY(S\: THE FOLLOWING T I S S U E ( S ) WERE U ! T H I N NORMA! L I M I T S : K. .ID.N.E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f R e c o r d - 15592 Page 1021 111-192 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY O i POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL dl8-CZ1 SPONSOR'S STUDY NUMBER: ?-7485.!3 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpnoi c;y P Generation Daca GROSS OPSERVAT!ON!S): HISTOVORPHO?OS!C 03SERVA'!OV!S!. THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: .Page 1022 111-193 ARGL'S 4IS-02 i ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7485.1: Appendix 111 I n d i v i d u a l A n i m a l Gross and H i s t o m o r p n o l o S y D a t a P Generation THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I M I T S : K- -I D-N-E- Y_S- - - - - - - - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - E n d o f Record- 15594 Page 1023 I 1 1-194 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-OZ! S P O N S O R ' S STUDY NUMGER: 7-7485 .!3 Appendix I11 I n d i v i d u a l Animal Gross and Hi s:omorphoiogy P Generation Data GROSS OBSERVATION(S). HISTOPORPHOLOGIC OBSERV4T:OY(S). G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORPHOLOGIC OBSERVATIONS: K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .in.e. r.a.l.i.z.a.t.i.o.n. ,. .m.u.1.t.i.f.o.c.a. .l . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15595 Page 1024 111-195 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.12 Appendix 111 I n d i v i a h a l Animal Gross and Histomorphclogj Car? P Generation G-_EN_E_RA_L:__No__gr_os_s_c_n_an_g_es_. ____________________N_ot_a_p-p-l-i-c-a-b-l-e----------------------------------------------------- TPE FOLLOWING TISSUE(S) WEDE WITHIN NORMAL LIMITS: Page 1025 111-196 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Hi stomorpnol ogy o a t ? P Generation THE FOLLOWING TISSUE(S) WERE W I T H I N NOQY4L L!MITS: K- -ID-N_E-Y-S- - - _ _ _ _ _ _ _ _ _ _ _ - - _ - - - - _ - - _ _ _ _ - _ _ - _ - - - - - - - - - - - _ _ _ - - _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - End o f Record- 15597 Page 1026 I 11-197 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix 111 I n d i v i d u a ; Animal Gross and Histomorpholog? Caza P Generation Page 1027 111-198 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7385.15 Appendix Iii I n d i v: oual Animal Gross and H i stomorphol ooy Data P Generation GROSS OESERVAT!ON(S): HISTOYORpHOLOGIC C3SERV3T:ON:S!: G--E-N-E-R-A-L-: _N-o-_g-ro-s_s_c_h_an_g_es-.-------------------------------N-o-t--a-p-p-l-i-c-a-b-1-e-------------------------------------- Page 1028 I 11-199 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMGEi?: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation ANIMAL NUMBER: 15600 SEX: F DOSE GROUP: DEATH TYPE: 11 Sacrifice-Scheduleo GROSS CSSERVATION(S): H!STOMORPHO?OGIC OBSERVATION(S): THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 1029 111-200 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(5): HISTOHORPHOLOGIC OBSERV4T!ON(S): G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n. .g.e.s.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 1030 I 11-201 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTAjSIUH PERFLUOROBUTANE SULFOhATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I 1 1 Individual Animal Gross and H i stomorphology Data P Generation GROSS 09SERVA'!ON(S): H i STOMORPHOLOG! C 035 E ? V 4 T iON I S \ . Page 1031 I11-202 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFaS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o r n o r p n o i o g y 0a:a P Generatior: T I S S U E ! S ) NOT A V A I L A B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT( S) UTERUS V. A. G. .I .N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f R e c o r d - 15603 Page 1032 111-203 .ARGCS 41X-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRCDUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR' S STUCY NUMBER: T-7455.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Date P Generation ANIMAL NUMBER: 15604 SEX: F DOSE GROUP: DEATH TYPE: I1 Sacri fice-Scheduled GROSS OSSERVATION(S). HISTOWRPHOLCGIC O@SERV4TION(s!' G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t .a. p. .p.l .i.ca. b. .1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15604 Page 1033 111-204 ARGCS 418-02 1 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUDY NUMBER: T-7465.13 Appendix I11 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OFSERVATION!S) : HIST@M09t"@LOG!C O ~ S S E Q V A T ! O Y ( S ! ~ G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.l.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: Page 1034 111-205 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I11 I n d i v i d u a l Animal Gross and Hi stomorpnoi ogy DaTa P Generation GROSS OBSERVATIONIS]: HISTOMORpHOLOGiC OE!SE9VA?I@N:S'. G_E_N_ER_A_L:_N_o_g_ro_s_s_c_ha_n_ge_s_. ____________________N_ot_a_p-p-l -i-ca-b-1--e-------------------------------------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15606 Page 1035 I 11-206 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Aooendix 111 I n d i v i oual Animal Grass ana H i stomorphol ogy 0a:a P Generation GROSS OSSERVATION(S): HISTOMORPHOLOGIC OBSEQV4'!OY!S'. G. .E.N.E.R.A.L.:. .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.1.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15607 Page 1036 I 11-207 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!8-021 SPONSGR'S STUDY NUMBER: T-7485.!3 Appendix 111 I n d i v i d u a : Animal Gross ana Histomorpnoiogy CaTa F Generation GROSS OBSERVAT!OY(S): HISTOYORPHOLOGIC OSSE9VATION:S): HISTOMORPHOLOGIC OBSERV4TIONS: K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p. .e.r.p.la. .s.ia. ., .t.u.b.u. .l a. .r /.d.u. .c.t u. .l a. .r . .e.p.i.th. .e.] .i.ur.n... .p.a.p.i.1.1.a. .(.m.i.n.i.rn.a.l.). End o f Record- 15608 Page 1037 I 11-208 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Anlmal Gross and H i stomorpholcgy Data P Generation GQCSS OESERVATIOY(S): Page 1038 I I I -209 .\RGUS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION ( O N E L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Aopendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOCIC O B S E R V A T I O N S : KIDNEYS : cyst(s), medulla . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e. r.a.l.i.z.a. .t i.o.n.,. .m.u.1.t.i.f.o.c.a. .l . .(.mi. n. .i m. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15610 . Page 1039 111-210 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i dual A n i m a l G r o s s and H i s t o m o r p h o l ogy Cars P Generation THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : .K.ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 15611 Page 1040 111-211 OGAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENEZATION) REPRODUCTIOR STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS P R ~ T O C O L418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendlx 111 Individual Animal Gross and Histomarpnology Data P Generation GROSS OBSERVATION(S): HISTOMORPFOLOC!C OSSERVA'!OY(S' G--E-N-E_RA-L_: _N_o _g_ro_s_s _c_ha_n_ge_s_. ___________________N_o_t -a-p-p-l-i-c-a-b-1-e---------------------------------------------------- THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .K.ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15612 Page 1041 111-212 ORAL (GAVAGE) TWO-5ENEiWTION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCCL 4 18-02 1 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix 111 I n d i v i d u a l Animal Gross ana Histomorpnology Da:a P Generation G?OSS OSSEQVATION(S" P! STOMORPHCLOG! C OSS E Q V A T ! C N 5 ' ' G-_EN_E_RA_L:__No__gr_o-s_s _cn_a_n_ge_s_. ___________________N_o_t _a-p-p-l-1-c-a-b-1-e--------------------------------------------------- HISTOMORPYOLOG!C OBSERVATIONS: .K.ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i.n.e.r.a.l.i.z.a.t.i o. .n... .m.u.1.t.i.f.o.c.a.l. .(.m. .in.i.m. .a.l ). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15613 Page 1042 I 11-213 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SFONSOa'S STUDY NUMBER: T-7485.13 Appendix I 1 1 I n d i v i o u a l Animal Gross anc H i stomorpnolcgy Oa:? P Generation Page 1043 I 11-214 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PiBS) I N RATS PROTOC3L 4!8-021 SPONSOR'S STUDY NUMaER: T - 7 4 8 5 . 1 3 Appendix 111 I n d i v i a i i a l A n i m a l G r o s s and H i stornorphoi ogy Cars P Generation GROSS O a S E R V d T I O N i S ) : H!STOMORPHOLOG!C OBSE9V:'ION~SI: G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K. .ID.N.E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15615 Page 1044 111-215 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 Indiviaual Animal Gross and Histomorpnology Oat2 P Generation GROSS OSSERVAii3N(S): HISTOPORPHOLOGIC OBSERV4':ON:S'. E A R f S ) : Swollen and purple, bilateral. Tissue not avai 1 ab1 e __________----______----------------------------------------------------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: TISSUE(S) NOT AVAILABLE FOR EVALUATION: Page 1045 111-216 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix 111 I n d i v i o u a l Animal Gross anc H i stornoronology Ca:a P Generation THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1046 111-217 ORA? (GAVAGE) TVO-GENERATION ( O N E LITTER PE2 GENERATI3'i) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFSS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix III individual Animal Gross and H i stornorpnclcgy Cara P Generation GROSS OBSERVATION(S): THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: .K.ID.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15618 Pase 1047 I 11-218 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEgATIOh) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFOhATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 7-7485.!2 Apoendix I 1 1 I n d i v i a u a l Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): H!STOYORPHOLOG!t O S S E R V A T I O N S : K.I. .O.N.E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m. .a., . .p.a.p. i.l.l.a.r.y.,. .f.o.c.a.l. .(.m. .in.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15619 Page 1048 111-219 ORAL ( G A V A Z E ) TYO-GENERATION ( O N E LITTER PER GENER.:TION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i a u a l Animal G:oss and H i stomorpno:cg) P Generation Gata H!STOV@R'JHOLOGIC OESERVATIONS: K-_I D_N_EY_S _: _--__--__--______________d i_l a_t_a_t i_o _n ,__pe_l -v-i -s--(-m-i-1-d-)----------------------------------------------------- End of Record- 15620 Page I049 111-220 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENE8ATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SLILFONATE (PFBS) I N RATS PROTOCOL 418-G2! SPONSOR`S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix 111 I n c i v i o u a l Animal G r o s s ana Hi stomcrnno; ogy D a t a P Generation GROSS OBSERVA'IOYIS): THE FOLLOWING T I S S U E ( S ! WERE W I T H I N NORMAL L I M I T S : K. .ID.N.E.Y. S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15621 Page 1050 I11-221 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GEtiERATION) R i P R O D U C T I O N STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and histomorpncicg) Dara P Generation Page 1OS 1 I 11-222 ORAL ( G A V A G E ) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFESJ IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485. 13 Apoendix 111 I n d i v i d u a l Animai Gross and Histomorohology Cars P Generaxion GRClSS OSSERVATION(S): HIST0MOQPYOLOG:C OESE?VATION(S!. H!STOYOQDHOLOGIC OBSERVATIONS: K. .ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t u. .b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.o. .i t.h.e. .l .i.u.m.,. .p.a.p. .i l.l.a. .(.m. i.n.i.m. a. .l) End o f Record- 15623 Page 1052 111-223 .ARGCS 41 E-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR ' S STUDY NUMBER: T-7485.13 Appendix I11 Individual Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC O@SERVATION(S!, HISTOMORPHOLOGIC OSSERVATIONS: K. .I.D.N.E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e.r.a.l.i.z.a.t.i.o.n.,. .m.u.l.t.i.f.o.c.a.l. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15624 Page 1053 I 11-224 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 -- Appendix I 1 1 I n d i v i d u a l Animal Gross and Histomoroholoav Data P Generation Page 1054 111-225 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.13 A p p e n d i x I11 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S): ., Page 1055 111-226 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Hi stomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: K..ID.N.E..Y.S.:...................................m..i.n.e.r.a.l.i z.a..t i.o.n....m.u.1.t..i .fo..c.a.l ..(.m.i.n.im..a.l.)........................ End o f Record- 15627 Page 1056 I 11-227 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x I11 Individual A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a P Generation GROSS OBSERVATION(S) : HISTOMORPHOLOGIC OBSERVATION(S): t : Page 1057 I 11-228 - ~~ ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 Individual Animal Gross and Histomorphology Data P Generation GROSS OESERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): G.E.N.E.R.A.L.:...N.o..g.r.o.s.s..c.h.a.n.g.e.s.................................N..o.t .a.p.p.l.i.c.a.b.1.e................................. THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: -Page 1058 111-229 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation - Page 1059 I I 1-230 ORA! (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphology Oata P Generation GROSS OESERVATION(S): HISTOMORPHOLOGIC OBSERV4TIOY ( 5!' HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal ) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e 1 urn. p a p i l l a ( m i l d ) -----__-___---___--------------------e-d-e-m-a-,--p-a--p-i-l l-a-r-y-,--f-o-c-a-l--(-m--in--im--a-l)---------- End o f Record- 15631 Page 1060 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOFI'S STUGY NUMBER: 7-7485.13 A p p e n d i x 11: I n a i v i d u a : A n i m a l G r o s s and H i s t o m o r p h o l o g y Ea:; P Generation GROSS OESEQVAT!ON(S)~ H!STOYORPHO?OG!C CSSERVS`!ON:S'. THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORFAL L!MITS: Page 1061 I11-232 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMSER: T-7465.!3 Appendix I 1 1 Indiviaual Animal Gross and His~omorphology C a t a P Generation GROSS OSSERVATION(S). HISTOPORPHOLOGIC OSSERVATION ( S ) . Page 1062 I 11-233 ARGUS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 - AN IMAL NUMBER : !5634 SEX: r Appendix I11 I n d i v i d u a l Animal Gross ana Histomorphology Data P Generation DOSE GROUP: DEATH TYPE: I11 Sacrl fice-Scneauiea G?CSS CBSEQV4TION(S): HISTOHOQDHOLOGIC 03SERV\TI3N(3). , Page 1063 I I 1-234 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GRCSS CSSERVATION(S): H!STOFORL"OLOtIC OESFRV4TICY(S: : G--E-N_ER_4_L:_N_o-_gr_o_ss_-c-n-a-n-g-e-s_. ___________________-N-o-t--a-p-p-l-i-c-a-b-1-e------------------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMA! LIMITS: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15635 Page 1064 I 11-235 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS IUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i a u a i Animal Gross and Histomorphology Data P Generation THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1065 I 11-236 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S ANIMA? NUMBER: 15637 SEX: F GROSS O@SERVATION!S): Appendix I11 I n d i v i d u a l Animal Gross ana H i stomorphol ogy Cat? P Generation DOSE GROUP: DEATH TYPE: 111 Sacri fice-Scnedulec HISTOMORPHOLOGIC OESERVA'!ON:S' Page 1066 111-237 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROSUTANE SULFONATE (PFeS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7455.13 Appendix I 1 1 Individual Animal Gross and Histomorohology Dz:~ P Generation G-E-_NE_R_AL_:_N-o_g_r_os_s_c-h_a_ng_e-s-.____________________N_ot--a-p-p-l--i c-a-b-1-e---------------------------------------------------- HISTOMORPHOLCGiC OBSERVATIONS: .K.I.D.N.E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t.u.b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.p.i.t.h.e.l.i. u. .m.,. .p.a.p.i.l.l.a. .(.m.i.n.i.m.a.l.) End of Record- 15638 Page 1067 111-238 .ARGCS 41F-01I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7465.13 Appendix 111 I n d i v i d i l a l Animal Gross and Histomorphology Dara P Generation GROSS OSSERV4TION(S!: TAIC: T i p m i s s i n g . 16.0cm from base. HISTOMORPYOLOGIC OSSERVATION(S\. necrosis in f l amnation, c h r o n i c , focal HISTOMORPHOLOGIC O B S E R V A T I O N S : TAIL: necrosis (moderate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l.a.m.na.t.i. .o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l. .(.m. .o.d.e.r.a.t.e.). . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1068 I 11-239 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-74E5. i 3 Appendix I11 I n d i v i odal A n i m a l G r o s s and h i stomorpno! 05) D a r e P Generation GRCSS OSSEQVATICN(S): HISTOMOQPHCLCC!C 08SERVA'ICY:S': T I S S U E ( S ! NOT A V A I L A e L E FOR EVALUATION: CERVIX KIDNEYS OVAR I A N FOL LICLES/COR PORA LUTEA OVARIES OVIDUCT[ s 1 UTERUS .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15640 Page 1069 111-240 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOZ'S STUDY NUMBER: T-7485.13 Appendix 111 Indivioual Animal Gross and Hlstornorpnology Data P Generation GROSS OBSERVATION(S). HISTOMOQoHOLOG!C OSSERVZT:C&(S). G_E_N E_Q_A I_L :_N_o_g_r_os_s_c_h_an_g_es_._ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _N_ot_ _ap-p-l- i-c-a-b-1-e- - - - _ - _ - - _ - - - - - - - - - - - - - - - - - - - - - - - - - _ _ _ - - - - - - - - - - HISTOMORPHOLOGIC OBSERVATIONS: Page 1070 111-241 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i o u a l Animal Gross and Histomorphology DaKa P Generation HISTOHORPHOLOGIC OBSERVATIONS: KIDNEYS: hyperplasia, tubular/ductular epi the1 ium. papi1l a (mi I d ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m. .a.. . .p.a.p. .i l.l.a.r.y... .f.o.c.a.l. .(.m. .in.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15642 Page 1071 I 11-242 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.12 Appendix I11 I n d i v i d u a l Animal Gross and Histomorpnoiogy Cara P Generation GROSS OE5FRVATION(S): HISTOMORPHOLOG!C @BSERV4T!ON:S!- Page 1072 I11-243 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFGS) I N RATS PROTOCOL 418-02; SPONSOR'S STUDY NUMBER: T-7485.1: Appendix 111 Inaividual Animal Gross and Histomorpnology Dara P Generation Page 1073 I11-244 ORAL (GAVAGE] TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 1 1 1 Individual Animal Gross and H i stomcrphoiogy Da:8 P Generation ANIMAL NUMBER: 15645 SEX : F DOSE GROUP: DEATH TYPE: IV Sacri fice-Scnedulea HISTOMORPHOLOGIC OBSERVATIONS: Page 1074 I 11-245 XRGCS 118-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 Individual Animal Gross and histomorphology Data P Generation GROSS OSSERVATION(S): HISTOMOSPHOLOGIC OBSERVAT!ONS: KIDNEYS : hyperplasia, tubular/ductular epithelium, papilla (minimal) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e. .r .a.l i.z.a. .t i.o.n. ., .m. .u.l.t.i f.o. .c.a.l. .(.m.i.n.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15646 Page 1075 111-246 ARGCS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7485.13 Appendix I l l Individual Animal Gross and H i stomorphology Data P Generation GROSS OSSERV4TION(S): HISTOPOQDHOLOGIC OBSERV?T!ON:S). GENER.4L. No gross changes. Not appl icab1e ....................................................................................................... THE FOLLOW!NG TISSUE(S) WERE W I T H I N NORMAL LIMITS: K. .ID.N.E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15647 Page 1076 111-247 .-IRGLS 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE [PFBS) I N RATS PROTOC9L 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: K. .ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15648 Page 1077 I 11-248 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation Page 1078 I 11-249 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i a u a l Animal Gross and H i stomorphology Daza P Generation EXTREMITIES: KIDNEYS : ............................... End o f Record- 15650 ankylosi s osteochondritis (moderate) necrosis, papilla, focal (moderate) . . . .h.y.p.e. .r p. .l a. s. .i a. ,. .t.u.b. .u.l a. .r./ d. .u.c.t.u.l.a.r. .e.p. .i t.h.e. .l i.u.m , papi 1 1a (mi 1d) -- Page 1079 I 11-250 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 5 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 5 5 . 1 3 Appendix 111 I n d i v i d u a l A n i m a l G r o s s a n d H i s t o m o r p h o l o g y Daxa P Generation Page 1080 111-251 ARGLS 41S-02I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OSSERV4TION(S): H I STOMORPHOLOGIC O B S E R V A T I O N [ S ! : G..E.N.E.R.A.L.: ..N.o..g.r.o.s.s..c.h.a.n.g.e.s..................................N..o.t .a..p.p.l.ic.a..b.le................................ HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : hyperpl as ia, t u b u l a r / d u c t u l a r ep it h e ............................................m.i.n.e..ra..li.z.a.t.i.o.n....m.u.1.t.i..fo.c..a.l ..(.m.i.n.im..al ) End o f Record- 15652 Page 1081 111-252 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONS02'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix 111 Individual Animal G r o s s and H i stornorphol ogy Data P Generation Page 1082 111-253 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Data P Generation GROSS OBSERV4TION(S): HISTOMORPHOLOGIC OBSERVAT!ON [ S ) : T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: .K.I D.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d of R e c o r d - 15654 Page 1083 111-254 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTCCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix 111 Individua! Animal Gross and Histornorpnology Lata P Generation THE FOLLOWIYG T!SSUEIS! WERE W I T H I N NORMAL LIMITS: Page 1084 I 11-255 .ARGCS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 Inoi v i o u a l Animal Gross ana H i StomorDhology Dara P Generation GROSS OBSERVATION(S): HISTOHORPHOLOGIC OESiRVSTION(S!. HISTOMORPHOLOGIC O S S E R V A T I O N S : KI ONEY S : hyperplasia, tubular/ductular epithe1ium, papi 1l a (minimal ) ............................................e.d.e.m.a.,..p.a..p.i.l l.a.r.y.,..f.o.c..a.l ..(.m.i.n.i.m.a.l.).......................... End of Record- 15656 Page 1085 I 11-256 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation T ! S S U E ( S ) NOT A V A I L A B L E FOR E V A L U A T I O N : CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA OVARIES OVIDUCT ( S ) UTERUS LUTEA Page 1086 111-257 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 i n d i v i d u a l Animal Gross and Histomorpnoiogy Caza P Generation H!STOMORPHOLDG!C OBSERVATIONS: KIDNEYS : h y p e r p l a s i a . t u b u l a r / d u c t u l a r e p i the1 ium, papi 11a ( m i I d ) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e.r.a.l.i.z.a.t.i.o.n... .m.u.1.t. .i .f o. c. .a.l . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15658 Page 1087 111-258 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485. i2 Appendix 111 I nd iv id u a l A n 1mal Gross and H i stornorphol ogy D a r a P Generation ANIMAL NUMBER: 15659 SEX: F DOSE GROUP: DEATH TYPE: IV Sacri fice-Scnemlec GROSS OSSEQVCTIONfS): HISTOMORPHOLOGIC CSSEQV4'ION(S!: HISTOMORDHOLOGIC OBSERVATIONS: K. .ID.N.E. Y. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t.u.b.u.l.a.r./. d. .u.c.t.u.l.a.r. .e.p.i.t.h.e.l.i.u.m.,. .p.a.o.i.l.l.a. .(.m.i.n. i. .m.a.l.) End o f R e c o r d - 15659 Page 1088 111-259 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix 111 i n d i vioual Animal Gross and H i stomorphology Data P Generation GROSS OZSERVATION(S): HISTOMORpHOLOGIC 08SERV&T!ON(S): Page 1089 111-260 .ARGLS 118-02I ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBEG: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphol ogy Data P Generation GROSS OESERVATION(S): SPLEEN: Small. HISTOMORPHOLOG!C OBSERVATIONS: KIDNEYS : SPLEEN: --- HISTOMORPHOLOGIC O S S E R V A T ! O N ( S I : atrophy pigment necrosis, papi 11a , focal (moderate) dilatation, cortical tubules, focal (moderate) d i l a t a t i o n , medullary tubules (moderate) basophilia. cortical tubules, focal (moderate) h y p e r p l a s i a . t u b u l a r / d u c t u l a r epi the1 iurn, papi 11a atrophy (moderate) pigment (mild) (mi I d ) Page 1090 111-261 XRGCS 41 E-02 ! ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphology Caza P Generation GROSS OBSERVATION(5): HISTOHORPHOLOCIC O S S E R V A T I O N ( S ! : Page 1091 I 11-262 O X 4 L (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPXOOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTCCCL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and HistomorDho1ogy DaIa P Generation HISTOMORPHOLOGIC OSSERVATIONS: KIDNEYS : necrosis, papilla, focal (minimal) hyperplasia, tubular/ductular epithelium, papilla (mild) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p. .a.p.i.l.l a. .r y. ., . .fo.c. .a.l . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15663 Page 1092 111-263 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY O F POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorpnology Data P Generation - Page 1093 III -264 .?RGL-S 4 1E - O l ! ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) R E P R O D X T I O N STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PiiOTOCOL 418-021 SPOESOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d i v i d u a l Animal Gross anc H i stomorphoicgy Cata P Generation GROSS OBSERV4T!ON(S): HISTOMORPHO?OGIC O S S E Q V S T I O V( S I: -G-E_NE-R-A-L-:_N_o_g_ro_s_s _c_ha-n_g-e-s-. -----------------------------N-o-t--a-p-p--l i-c-a-b-1-e----------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIM!TS: .K.ID.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15665 Page 1094 111-265 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHSER: T-7485.13 Appendix 111 I n d i v i dual Animal Gross and H i stomorpnol ogy Data P Generation GRCSS OBSERVATION(S): HISTOMORPHOLOGIC 0SSERVA~:OY~S)~ HISTOM0RPHCLOG:C O B S E Q V 4 T I O N S : KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) hyperplasia, tubular/ductular epithelium, papilla (mild) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a.r.y. ., .f.o.c. .a.l . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15666 Page 1095 I 11-266 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.1; Appendix I11 Individual Animal Gross and Histmorphology Data P Generation GROSS OsSERVA-ION(S): HISTOMORPHOLOGIC 06SERVAriON!S). HISTOYORPHOLOGIC OBSERVATIONS: KIDNEYS: hyperplasia, tubular/ductular epithelium, papilla (minimal) m i n e r a l i z a t i o n , mu1t i f o c a l ( m i nimal ) S. .P.LE. .E.N.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.b.s.c.e.s.s. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15667 Page 1096 I 11-267 XRGC'S 118-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Aopendix 111 I n d i v i d u a l Animal Gross and Histornorpnology D a t a P Generation THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N.E.Y. S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15668 Page 1097 111-268 ORA? (GAVAGE) TUO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY -NUMBER: 1-7465.13 Appendix 111 I n d i v i d u a l Animal Gross and HisKOmorphology Dara P Generation ANIMAL NUMSER: 15669 SEX: F DOSE GROUP: DEATH TYPE: IV Sacri fice-Scheduiec GROSS OBSERVATION(S): HISTOMORPHOLOGIC OESERVAT!ON(S). HISTOMORPHOLOtIC OBSERVATIONS: K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a... .tu. .b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.D. .i t.h.e.1. i.u.m. .. . .p.a.p.i .1.1.a. .(.m.i.i.d.). . . End o f Record- 15669 Page 1098 I 11-269 ORAL (GAVACE) TWO-GENERATION (ONE LiTTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 4!6-021 SPCNSOR'S STUDY NUMBER: 1 - 7 4 8 2 . 1 3 Appendix 111 Inai v i oual Animal Gross and Hi stomorpnology Data P Generation GROSS OBSERVATIONIS): HISTOMORPYOLOG!C OPSERVS'!OY(S' G. .E.N.E.R.A.L.: . .N.o. .g.r.a.s.s. .c.h.a.n.g.e.s. ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l. i.c.a.b.1. .e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .K.IO.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15670 - Page 1099 I 11-270 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 416-02! S P O N S O R ' S STUDY NUMBER: 1-7485. !? Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphology Data P Generation GROSS OSSERVATION(S): HISTOYORDHCLOGIC 03SE9ViT!ON(SI. HISTOMORPHOLOGIC O B S E R V A T I O N S : K. .ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a., . .t .u.b.u.l.a.r./.d.u.c.t.u.l.a.r. .e. .p.i t.h.e. .l i.u.m. ... .p.a.p. .i l.l.a. .(.m. .i l.d.). . . End o f Record- 15671 Page 1100 111-271 ORAL (GAVAGE) TWC-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I 1 1 Individual Animal Gross and H i stomorphology 0a:a P Generation HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: KIDNEYS : OVARIAN FOLLICLES/CDRPORA LUTEA: .U.T.E.R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . degeneration, cystlc, cortex (minlmal) hyperplasia, tubular/ductul ar epl the1 1 um. edema, papillary, focal (minlmal) presence of corpora lutea presence of growl ng/antral fol1 i cl es ---- . . . .m.a.c.r.o.p.h.a.g.e. s. .,. p.i. .g.rn. e.n.t.e.d. . (. .m.o.d.e.r.a.t.e.). . . . . . pap i 1 1 a ( m i n i mal ) THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1101 111-272 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC OSSERVATIONS: KIDNEYS : O V A R I A N FOLLICLES/CDRPORA LUTEA: UTERUS : cyst(s). medulla m i n e r a l iz a t i on, mu1t i f o c a l ( m i nimal ) h y p e r p l a s i a . t u b u l a r / d u c t u l a r e p i t n e l i urn. pap i1 1a (mi nimal ) presence o f corpora lutea presence o f growing/antral f o l l i c l e s macrophages, pigmented (mild) --- -d_i-s_t e-n-t_i o--n-,-_lu_m_en__( m_i_l d_) _____________________-- THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX LIVER OVARIES O..V.IO..U.C.T.(.S.)..................P.IT.U..IT.A.R..Y..................V.A.G..I N.A............................................ End o f Record- 15673 Page 1102 111-273 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 I n d l v i a u a l Animal Gross and Histomorphology Oara P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: HISTOMORPHOLOGIC 08SEQVSTION:S). Page I103 I 11-274 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphol ogy Dara P Generation GRCSS OBSERVATION(S). HISTOMORDHOLOGIC 03SESV47!!X(S). HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS: h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e 1 iurn. p a p i 11a ( m i n i m a l ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .in.e. .ra. l.i.z.a.t.i.o.n... .m. .u1.t.i.f.o.c.a. .l . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15675 Page 1104 I 11-275 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T - 7 4 8 5 . 1 3 Appendix I11 I n d i v i d u a l A n i m a l G r o s s and H i s r o m o r p h o 1 o- g .y Dara P Generation OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIOUCT(S) UTERUS V.A.G. .I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f Record- 15676 Page 1 105 111-276 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: 1-7485.13 Appendix II! I n a i v i dual An imal Gross and Histomorpnology Da:a P Generation ANIMAL NUMBER: 15677 SEX: F GROSS OBSERVkTION(S): DOSE GROUP: DEATH TYPE: V Sacri fice-Scneouled H I S T O M O R P H O L O C I C O B S E R V A T I O N iS 1 : Page 1106 111-277 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: 1-7485.15 Appendix 111 Individual Animal Gross and Histomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : ---- di latation, medullary tubules (moderate) dilatation, cortical tubules, focal (mild) basophilia, cortical tubules, focal (mild) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 ium. papi 11a presence o f corpora lutea presence o f growing/antral f o l l i c l e s macrophages, pigmented (moderate) d i s t e n t i o n , lumen (moderate) (minirnal ) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX LIVER OVARIES O. .V.ID.U.C. .T.( .S.). . . . . . . . . . . . . . . . .P.I.T.U.IT. .A.R.Y. . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . COMMENTS : V.A.G. .I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .P.r.e.s.e.n. .t .o.n. .t.h.e. .s.e. .c.t t.o.n. .o. .f .c. .e.r.v.i x. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15678 Page 1107 111-278 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEUTION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a P Generation T I S S U E ( S ) NO' AVA!LABLE FOR E V A L U A T I O N : CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA OVARIES OVIDUCT(S) UTERUS LUTEA Page 1108 111-279 ARGUS 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorphology Data P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : m i n e r a l iz a t i on, mu1t i f o c a l (minimal ) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 iurn. papi 11a ( m i I d ) OVARIAN FOLLI CLES/CORPORA LUTEA: presence of corpora l u t e a presence o f growing/antral f o l l i c l e s U--TE-R-U-S--:----_______________-_--_-_.._.._m._.a._c.r._o.p.h.a.g.e.s.,..p.i.g.m..e.n.t.e.d..(m..o.d.e.r.a.t.e.)....................... ---- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 1109 111-280 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 i . 13 Apoendix 111 Individual Animal G r o s s and H i stmorphology Dara P Generation GROSS OBSERVATION(S): HISTOFORPHOLOCIC 02SEQVArIOY(S). HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : . hyperplasia, tubular/ductular epi the1 i um. papilla (minimal ) OVARIAN FOLLICLES/CORPORA LUTEA: presence of corpora lutea presence o f growing/antral follicles OVARIES : cyst (s), i ntraovarian U--TE-R--U-S-: ----________________--_-_-._._..d_.i_.s.t_.e._n.t.i.o.n....l.u.m.e.n..(.m.a.r..k.e.d.).................................. THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS VAGINA CERVIX OVIDUCT(S) P ITUITARY Page 1110 I 11-281 .ARGUS 4 1 S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTEQ PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.12 Appendix 111 I n d i v i d u a l Animal Gross and Histomorpnclogy DaTa P Generation GRCSS OSSERVATIOY(5): HISTOYORDYOLOG!C 09SEQV47!0Nf S' ' HISTOMORDHOLOGIC O B S E R V A T I O N S : K. .ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t.u.b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.p. .i t.h.e.1. .iu.m. ., . .p.a.p.i.1.l .a. .(.m.i.I.d.). . . End of Record- 15682 Page 1111 I 11-282 .ARGLS 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMSER: T-7485.13 Appendix I11 I n d i v i d u a l A n i m a l G r o s s and H i s r o m o r p n o i o g y Data P Generation GROSS OSSERVATION(S) : ' H I STOMORPHOLOG I C O5SERV4T IOSiS ' T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT(S) UTERUS V.A.G..I .N.A................................................................................................. E n d of R e c o r d - 15683 Page 1112 I 11-283 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: T-7485.13 Appendix I11 I n a i v i ouai Animal Gross and H i stomorpnol ogy Dara P Generation GROSS OESE4VAT!ON(S). HISTOMORPHOLOGIC OBSERV:';3N(S'. HISTOMORPHOLOGIC O B S E Q V A T I O N S : K. .ID.N. .E.Y.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p. .e.r.p.la. .s.ia.,. .t.u.b.u. l.a.r./.d.u.c.t.u.l.a.r. .e. .p.i t.h.e.1. .iu.m. ., . .p.a.o.i.i.l.a. .(.m.i.I.d.). . . . End o f Record- 15684 Page 1113 111-284 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRCDUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i S t O ~ r D h Oolgy Cata P Generation GQOSS CsSE?VAT!OV(S): HISTOMORPHOLOGIC O B S E R V A T I C N ( S 1 . HISTOMORPHO!OG!C OBSERVAT!ONS: KIDNEYS : hyperplasia, tubular/ductular epithelium. papilla (minimal) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l 1 i c l e s U. .T.E.R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. a. .cr.o.p.h.a.g.e.s.,. .p.i.g.m. .e.n.te. d. . .(m. .i.n.im. .a.l.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS CERVIX LIVER OVARIES O. .V.ID. .U.C.T.(.S.). . . . . . . . . . . . . . . . .P. .IT.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15685 Page 1114 111-285 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFSS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485. 13 Appendix 111 I n d i v i d u a l Animal Gross and Histomorohology Data P Generation GROSS OBSERV4T!ON(S): H!STOMORPHOLOGIC OBSERVATIONS: KIDNEYS: m i n e r a l iz a t i on, mu1t i f o c a l (minimal ) hyperplasia, tubular/ductular epi the1 ium, papi 1l a (mi I d ) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) OVARIAN FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s U. .TE.R. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a. .cr.o.p.h.a.g.e.s.,. .p.i.g.m. .e.n.te. d. . .(m. .o.d.e.r.a.t.e.). . . . . . . . . . . . . . . . . . . . . . . . . . . Page 1115 111-286 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix 111 I n d i v i d u a l Animal Gross and Histomorpnology Dara P Generation GROSS OBSERV,4TION(S): HISTOHORDHOLOGIC OBSERVSTiONiS!. G--E-N-E-2-A-L-: --N-o--g-r-o-s-s--c-h_an_g_es_.________________------N-o--t -a-p-p--l i-c-a-b-1-e-------------------------------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NOQMAL LIMITS: Page 1116 111-287 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 1 1 1 Inoividual Animal Gross and histomorphology Ca:a P Generation GROSS OBSERVA?ION(S): H!STOYORPHOLOG!C OSSERVA'ION!S!. HISTOYORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPQRA LUTEA: presence of corpora lutea presence of growing/antral follicles .U.T.E.R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r. .o.p.h.a.g.e.s.,. .p.i.g.m.e.n.t.e.d. .(.m. .in.i.m.a. .l ). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS CERVIX KI ON EYS LIVER .O.V.A.R.I.E.5. . . . . . . . . . . . . . . . . . . . O. V.I.D.U.C.T.(. .S.). . . . . . . . . . . . . . . . .P.I.T.U.I.T. A. R. Y. . . . . . . . . . . . . . . . . . .V.A.G. I.N.A. . . . . . . . . . . . . . . . . End of Record- 15688 Page 1I17 111-288 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY 0; POTASSIUM PERFLUOROEUTANE SLLFONATE (PFES) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 A p p e n d i x 111 I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Data P Generation GROSS O@SERVATION(S). T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT( S) UTERUS .V.A.G.I.N.A........................... E n d o f R e c o r d - 15689 HISTONIRPHO?OG!C OSSERVAT!O&{S' Page 1118 I 11-289 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR ' S STUDY NUMBER: T-7485.!3 Appendix 111 Individual Animal Gross and Hi stomorpnology Datz P Generation ANIMAL NUMBER: 15690 SEX: t DOSE GROUP: DEATH TYPE: V Sacri f1ce-Scnecsl ec FISTOYORPHCLOGIC OaSEQV4TIOY( S 1 . HISTOMORPHOLOGIC OESERVAT!ONS: KIDNEYS : hyperplasia, tubul ar/ductul ar epi the1 i urn. papi 1 1 a (minimal) edema, papillary, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e.r.a.l. .i.z.a.t.i.o.n.,. .m.u.1.t.i.f.o.c.a.l. .(.m.i.n.i.m.a.l. .) . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15690 Page 1119 111-290 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCCL 416-021 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix 111 Individual Animal Gross and Histomorphology Data P Generation GROSS OESERVATION!S): HI STOWRPHOLOGIC OBSERV4710N ( S . HISTO~ORPHOLOCIC O S S E Q V A T I O N S : KIDNEYS : dilatation, medullary tubules (minimal ) hyperplasia, tubular/ductular epi the1 ium, p a p i l l a (mild) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a.r.y.,. .f.o.c.a. .l . .(m. .i.n.im. .a.l.) . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15691 Page 1120 111-291 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF PDTASSIUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I11 i n d i v i d u a l Animal Gross and H i stomorphology Data P Generation HISTOMORPHOLOGIC OBSERVATTONS: KIDNEYS : ---- nephritis, chronlc. focal (minimal) basophilia, cortical tubules, focal (minimal) hyperplasia. tubular/ductular epithelium. papilla presence o f corpora lutea presence o f growing/antral f o l l i c l e s macrophages, pigmented (minimal ) (mild) THE FOLLOWING TISSUE(S) WERE W I T H I N NORMA? LIMITS: Page 1121 I 11-292 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: T - 7 4 8 5 . 1 3 A p D e n d i x 111 Individual A n i m a l G r o s s and H i s t o m o r p n o l o g y D a t a P Generation GR3SS OSSERV4TION[S): HISTOMORPHOLOGIC OGSERVST!OY(S). CERVIX KIDNEYS OVARIAN FDLLICLES/CORPORA OVARIES OVIDUCT (S) UTERUS VAG I NA LUTEA Page 1122 111-293 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEFATION) REPROOUCT!ON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.13 Apoendix 111 I n d i v i d u a l Animal Gross and Hi stomorphol ogy Data P Generation HISTOHORDt!OLOG!C 03SERVATIONS: KIDNEYS : h y p e r p l a s i a . t u b u l a r / d u c t u l a r epi the1 ium. paoi 1l a (mi I d ) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora 1utea presence o f growing/antral f o l l i c l e s U. .TE. R. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.i.g.m.e.n.t.e.d. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . TYE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1123 111-294 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE S u L i o N A i E (PFBS) I N RATS PR9TOCOL 418-02! SPONSOR`S STUDY NUMGER: 1 - 7 4 8 5 . 1 5 ApDendix 111 I n d i v i dual A n l r n a l G r o s s and H i s t o m o r p h o l ogy Ca:a P Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: Page 1124 111-295 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONS02,'S STUDY NUMBER: 1-7485.13 Appendix 111 I n d i v i oual Animal Gross and hi sTornorpnoi ogy Data P Generation GROSS OSSERVATIONISl: HISTOMORDHOLOGIC CSSEQL'?T!OV!S'. H I S T O ~ O R D H O L O G I CO S S E R V A T I O Y S : .K.ID.N. .E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d. .i l.a. t.a. .t i.o.n. .,. .p.e.l.v.i.s. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15696 Page 1125 111-296 ORA? (GAVAGE) TWO-GENERATION (ONE L I T T E i i PER GENERATION) REPRCDUCTION STUCY OF POTASSIUM PERFIUOROBdTANE SULFONATE ( p m s ) IN RATS ' PiiOTOCO? 4 1 6 - 0 2 1 SPONSOR'S STUCY NUMBER: 1-7485.1; Apoendix 111 I n d i v i d u a l Animal Gross and H i stomorpnci ogy Ca:a P Generation H!STOFORPHCLOGiIC CSSERVATIONS: \. Page I126 I 11-297 ARGL'S 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) RiPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorohology Data P Generation GRCSS OSSERV4T:CN(S!: HISTOMORPHOLOG!C OSSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithelium, papilla (minimal) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .in.e. .ra. .l i.z.a.t.i.o.n.,. .m. .u1.t. i. .fo.c.a. .l . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 15698 Page 1127 111-298 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFSS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix 111 I n d i v i d u a l Animal Gross and H i stomorphoiogy Card P Generation H!STOMORPHOLOG!C O S S E R V A T I O N S : K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p. .e.r.p.la. .s.ia. ., .t.u.b. u. .l a. .r /.d.u. .c.t u. .l a. .r . e. .p.i.t h. .e.l i.u.m. ... .p.a.p. .i l.l.a. .(.m. .i .l d. ). . . . End o f Record- 15699 Page 1128 I 11-299 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PGOTOCO? 4 1 8 - 0 2 1 SPONS02 ' S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix I11 Individual A n i m a l G r o s s and H i s t o m o r p n o l o g y D a t a P Generation ANIMAL NUMBER: 1 5 7 0 0 SEX : F DOSE GROUP: DEATH TYPE: V Sacrifice-Scheduled GQOSS OSSERVATION(S): HISTOMORPHOLOGIC 05SERVAT!3N(SI. T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 15700 Page 1129 I 11-300 0RAL (GAVAGE) TWO-GENERATION (ONE L I T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 HISTOPATHOLOGY REPORT APPENDIX IV INDIVIDUAL ANIMAL GROSS AND HISTOMORPHOLOGY DATA F1 Generation KEY TO CORRELATION OF HISTOMORPHOLOGIC OBSERVATIONS Not applicable = Microscopic evaluationkorrelation not appropriate or not required by protocol. Page 1130 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERAT!Oh) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PF8S) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: T-7485.13 Apoendix I V I n d i v i o u a l Animal Gross and H i stomorphology Ca-a F1 Generati on GRCSS OBSERVAT!ON(S). HISTOMORPYCLOGIC OSSEQVAT!ON!S' HISTOMORPHO?OC!C OBSERVATIONS: KIDNEYS : hyperplasia, tubul ar/ductul ar epi the ium, p a p i l l a (minimal) PROSTATE : inf l amnat ion, c h r o n i c ( m i 1d ) ............................................a.t.r.o.p.h.y.., ..fo..c.a.l..(.m.o..d.e.r.a.te.)......... TU! FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS LIVER SEMINAL VESICLES T. E. .S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3001 IV-1 Page 1131 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBEG: T-7485.13 Aooendix I V I n d i v i d u a l Animal Gross and Histornorpnology 0a;a F1 Generation HISTOMORDYOLOSIC CBSERViT:ON!S!: G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e. .s.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. .o.t.a. .p.p.l .i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H!STOMOR'JHO?OG!C OBSERVATIONS: PROSTATE : inflamnation. chronic (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.r o. .p.h.y.,. .f.o.c.a. l. . (.m. .i .n.i m. .a.l.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .LI.V.E.R. . . . . . . . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V. .E.S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . End o f Record- 3002 IV-2 Page 1132 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 5 - 7 4 8 5 . 1 3 Appendix IV I n a i v i dual A n i m a l G r o s s and H i stmoron01 ogy D a r a Fl Generation HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND EPIDIDYMIS K IONEY S LIVER S. .E.M.IN. .A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3003 IV-3 Page 1133 ORA? (GAVAGE) TWO-GENERATION (ONE L!TTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROSUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: i-7485.13 1ndiv:cual Anima: Appendix I V G r c s s anc H i s t o m o r p n o i o g y D a t a F I Generation - H E , D : P a l a t e - hole, 2 x 2m. fracture, PALATE hemorrhage, PALATE -_______________________________________----------------------------------------------------------- H!STOMORPYO?OGIC OBSERVATIONS: LIVER: in f l amnat ion, chroni c , focal /mu1 t i focal (min imal ) PALATE: fracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.e.m.o.r.r.h.a.g.e. . (.m.o.d.e.r.a.t.e. .) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : IV-4 Page 1134 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTAhE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUCY NUMBER: ? - 7 4 & 5 . 1 ? Appendix I V I n d i v i d u a l Animal Gross and Histomorphology 0z:a Fl Generation HISTOMORPHOLOG!C O S S E R V A T I O N S : EPIOICYMIS: microgranuloma(s) KIDNEYS: hyperplasia, tubular/ductular epithelium, papilla (minimal) edema, p a p i l l a r y , focal (minimal) .L.IV.E. R. .:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.1.a.m.n.a.t.i.o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./.m.u.1.t.i.f.o.c. .a.l . .(.m.i.n.i.m.a.l.). . . . . . . . . . THE FOLLOW!NG TISSUE(S) WERE W I T H I N NORMAL L I M I T S : C. .O.A.G.U.L.A.T.IN. .G. .G.L.A.N.D. . . . . . . . . .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V. .E.S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . End o f Record- 3005 IV-5 Page 1135 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i stomorpnology Oat; F i Generation HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f i l t r a t i o n . mononuclear-cell, focal (minimal) LIVER: hematopoie s i s , e x t ramedul 1a r y , mu1t 1 f o c a l ( m i n 1mal ) P. .R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .in. .fl.a.m. .n.a.t.io.n. .. . .c.h.r.o.n.i.c. .(.m.i.1.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : C. .O.A.G.U.L.A.T.IN. .G. .G.L.A.N.D. . . . . . . . . .K.I.D.N.E.Y.S. . . . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T. E. .S.T.I.S. . . . . . . . . . . . . . . . . End o f Record- 3006 IV-6 Page 1136 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 S P O N S O R ' S STUDY NUMGER: 7-7465.13 Appendix I V Individual Animal Gross and Histomorpno!ogy Caca F l Generation G_E_N_ER_A_L:_N_o_g_r_os_s_c_ha_n_g_es_. ____________________N_ot_a_p-p-l-i-c-a-b-1-e---------------------------------------------------- HISTOMORPHOLOGIC O B S E R V A T I O N S . ADRENAL GLANDS: vacuo1 a t 1 on, c o r t e x (mi 1d) EPIDIDYMIS: i n f i l t r a t i o n , mononuclear-cell I focal (minimal) .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.ro. .p.h.y.,. .f.o.c.a.l. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: IV-7 Page 1137 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFCUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix I V i n d i v i a u a l Animal Gross and Histomorphology Data il Generat io n GROSS OBSiRVkT!ON(S): H I S T O M O R P K I L O G I C OSSERVAT!OV(S!. LIVER: P a p i l l a r y process, f i r m t a n areas ranging necrosis, focal/multifocal --i -n--s_i z_e_f_ro_m_p_i_n p_o_i n_t_t_o_1__x _I_cm_.________________--------------------------------------------------------------- HISTOMORPHOLOGIC O B S E R V A T I O N S : LIVER: necrosis, focal/mul ti focal (moderate) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.r.o.p.h.y.,. .f.o.c.a.l. . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .P.IT.U. .IT.A. .R.Y. . . . . . . . . . . . . . . . . . .S.E.M.IN. .A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S. .T.IS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3008 IV-8 Page 1138 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PCBS) I N RATS PROTDCCL 418-021 SPONSOR'S STUDY NUMBER: 1-7465. I ? Appendix I V I n d i v i d u a : Animal Gross and H r s t m o r p n o i o g y DaIa F1 Generation GROSS O E S E R V A i I O N ( S ) : HISTOMORPHOLOGIC OBSERVATIONS: KIONEYS : hyperplasia, tubular/ductular epi the1 ium. paoi 1l a (minimal ) ---_----__-----_____-----------------------------------------------------------------------------*----- THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I M I T S : IV-9 Page 1139 ANIP L NUH9 SEX: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7385.13 Appendix IV I n d i v i o u a l A n i m a l Gross and H i s t o m o r p h o l o g y 0a:a F 1 G e n e r a t i on HISTOMORPHOLOGIC OBSERVATIONS: K. .ID.N. .E.Y.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d.i. l. a. .t.a.t.i.o.n.,. .p.e.l.v.i.s. .(.m.i.I.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : .L.I V.E..R.................................................................................................. End of R e c o r d - 3010 IV-10 Page 1140 ARGLS 4IS-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS IUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV Inoividual A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a Fl G e n e r a t 1 on HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : AORENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .L.I V.E. .R. . . . . . . . . . . . . . . . . . . . . .P.I.T.U.1.T.A.R.Y. . . . . . . . . . . . . . . . . .S.E. M. .IN. A. .L.V. .E.S.IC.L.E. S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . E n d of R e c o r d - 3011 IV-11 Page 1141 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02i SPONSOR'S STUCY NUMGER: T-7485.!2 Appendix IV i n d i v i d h a : A n i m a l G r o s s and H i s t o m o r p n o l o g y Oars F1 G e n e r a t i o n H!STOYORPHO?OG!C CESC?Va'!?U!C): THE FOLLOW!NG T!SSUE(S) WERE W I T H I N NORH4L LIMITS: IV-12 Page 1142 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix IV I n d i v l d u a l A n i m a l G r o s s an0 H i s t o m o r p h o l o g y Da?a F1 G e n e r a t ion GROSS O @ S E Q V A T ~ O N ( S ) ~ HISTOMORPYOLOG!C 09SERVAT!O+(S! HISTOYORPHOLOGIC DBSEQVATIOYS: ADRENAL GLANDS: vacuolation, cortex (minimal) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l.a.m.n.a.t.i.o.n... .c.h.r.o.n.i.c. .(.m.i.n.i.m.a. .l ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . T H E FOILOWING T I S S U E ( S ) WERE WITHIN NORMAL L I M I T S : COAGULATING GLAND EPIDIDYMIS KIDNEYS LIVER P. .IT. U. .I.TA.R. .Y. . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V.E. .S.IC.L.E. S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3013 IV-13 Page 1143 ARGUS 4 1$-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.1: Apoendix I V individual Animal Gross and h i stomorpnol ogy Cata FI Generat ion ANIMAL NUMBER: 3014 SEX: M DOSE GROUP: DEATH TYPE: I Scheduled ( R GROSS OBSERVATION(S): H!STOYOQPHO?OG!C OSSERVAT!C!Y!S!. H!STOMORPHOLOGIC OESERVATIONS: LIVER: inflamnation. chronic, focal/mul t i focal (minimal ) PROSTATE: in f l amnat i on, c h r o n i c (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.tr.o.p.h. .y., . .fo. .c.a.l. .(.m. .in.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS KIDNEYS SEMINAL VESICLES T. .E.S.T.I .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3014 Page 1144 IV-14 X R G L S 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix IV I n d i v i o u a i A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F! G e n e r a t i o n THE FOLLOWING T!SSUE(S) COAGULATING GLAND PROSTATE WERE W I T H I N NORMAL L I M I T S : . EPIDIDYMIS SEMINAL VESICLES KIDNEY S TESTIS LIVER IV-15 Page 1145 ARGC'S 41S-07 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUDROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i a u a l Animal Gross and Histomorphology Data F I Generation GROSS O@SERVbT!ON(S): HiSTOMORPHOLOGiC O@SEQV4T!ON(S). HISTOPORPHOLOGIC OESERVATIONS: KIDNEYS : cyst(s). medulla LIVER: inflamation. chronic, focal/mul ti focal (minimal) P. .R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.r.o.p.h.y.,. .f.o.c.a.l. .(.m. .i I.d. .) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : C. .O.A.G.U.L.A.T.IN. .G. .G.L.A.N.D. . . . . . . . . .E.P.I.D.I.D.Y.M.I.S. . . . . . . . . . . . . . . . .S.E. M. .IN. A. .L.V. E. .S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . End o f Record- 3016 IV-16 Page 1 146 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-74,05.!3 Appendix IV I n d i v i d u a i A n i m a l G r o s s and Histomorpnology Da:a F1 G e n e r a t ion HISTOMORPHOLOGIC OBSERVATIONS: .L.I V.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l a. .m. .a.t.i o. .n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./.m.u.1.t.i.f.o.c.a. .l . .(.m.i.n.i.m.a.l.). . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K.I.O. .N.E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3017 IV-17 Page 1147 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomoronclogy Data F1 Generation GROSS 03SERVA'!Oi4(S): HISTOWQPYOLOGIC OESERVAT!OM(S). HISTOHORPHOLOGIC OBSERVATIONS: LIVER: infl amnat ion, c h r o n i c , f o c a l /mu1 t i f o c a l ( m i ni mal ) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p.r.o.s.t.a. .t i.t.i.s.,. .s.u.p.p. .u.r.a.t.iv.e. .(.m. .in. i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(8) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS KIDNEYS SEMINAL VESICLES IV-18 Page 1148 ORAL (GAVAGE) TWO-GENEGATION (ONE L I T T E R PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV Individiia: Animal G r o s s and H i s t o r n o r p n o l o g y Data F1 G e n e r a t i o n GOO85 OESERVAT!ON(S): G_E_N_ER_AL_: _N_o_g_r o_s_s _c_ha_n_ge_s.____------_----_-----_----N-_ot_a-p-o-l-i-c_ab_1-e-------_------_--_----------------------------- THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : -K-ID_N_EY_S___________. __L_IV_ER____________________-------_________-----------------------__----------- End o f R e c o r d - 3019 I v.- 19 Page 1149 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o i o g y D a t a FI Generation GROSS OSSERVAT!ON(S) : H!STOMORPHOLOG!C OBSERVAT!ON(S! : HISTOMORPHOLOGIC OBSEQVATIONS: ADRENAL GLANDS: vacuolation, cortex (minimal) P. .I T.U. .I T.A. .R.Y.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c. .y.s.t(.s.1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S I WERE W I T H I N NORMAL L I M I T S : COAGULATING GLANO EPIDIDYMIS KIDNEYS LIVER P. .R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. S. .T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV-20 Page I 150 ARGUS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMEER: T-70eS. 1 3 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o i o g y D a t a F1 Generation GQOSS OSSERVAT!ON(S). H!STOYORPH@LOGIC O@SERVAT!Oh'?!. THE FOLLOWING T I S S U E f S ) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND TESTIS . EPIDIDYMIS PROSTATE SEMINAL VESICLES IV-21 Page 1151 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCT!ON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: 1-7485.13 ADDendix I v I n d i v i d u a l Animal Gross and H i stomorohol ogy Data F l Generation HISTOMORDHOLOGIC O B S E R V A T I O N S : K. .ID.N.E. .Y.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.i.l.t .r .a.t.i .o.n.,. .m. .o.n.o.n.u. c. .le.a.r.-.c.e.l.l,. . .fo.c. .a.l . .(.m.i.n.im. .a.l.). . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: .L.IV.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3022 IV-22 Page 1152 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 Appendix I V I n o i v i a u a l Animal Gross and hi stomorphology Dara F1 Generat ion GROSS OBSERVATION(S): HISTOMOR!"OLOGIC OBSERV&ii3Y(SI. G--E_NE_R_AL_: -N_o_g_r_os_s_c_h_an_g_es_. ____________________N_o_t -a-p-p-l-i-c-a-b-l-e----------------------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: vacuolation, cortex (moderate) PITUITARY: hyperplasia, pars distalis, focal (mild) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l.a.m. .a.t.i.o.n. .. .c.h. .ro. .n.ic. . .(m. .i.n.im. .a.l.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS KIDNEYS LIVER .S.E.M.IN. .A.L. .V.E.S.IC. .L.E.S. . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3023 IV-23 Page 1153 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i stornorpnol ogy Ca:a Fl Generation GROSS OESEQVAT!ON[S): HISTOMOSPPOLOGIC OSSEQV.ATISY(S!: HISTOMORDHOLOGIC OBSERVATIONS: .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.1.a.m. .n.a.t i.o.n. ,. .c.h.r.o.n. i.c. . .( m. .i n. .i m. .a.l .) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(5) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .L.I V.E. .R. . . . . . . . . . . . . . . . . . . . . .P. .IT.U. .I T.A.R.Y. . . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V.E. .S.IC.L.E. .S. . . . . . . . . . .T.E.S.T. .I S. . . . . . . . . . . . . . . . . End of Record- 3024 IV-24 Page 1154 ORAL (GAVAGE) TWO-GENEWTION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485. I ? Append1 x I V I n d i v i o u a l A n i m a l G r o s s and Histornoronology Data F l Generation GSCSS OSSESVfiTION(S): HISTOYOSPPOLOGIC C?SEQVCT!C'T!S!. THE FOLLOWING T!SSUE(S) WERE W!THIN NORMAL L I M I T S : IV-25 Page 1155 ARGUS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Indivioual Animal Gross and Histomorpnology Oaza F1 Generat 1 on H!STOMORPHOLOG!C CSSERVATIONS: KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) .L.IV.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n. .f l.a. .m. . .t i.o.n... .c.h. .r o. .n.i.c., . .f o. c. .a.l ./m.u.1. .t.i.f.o.c.a.l. .(.m. .in.i.m.a.l.). . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS PITUITARY .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . . .S.E.M.IN. .A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S. .T.IS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3026 IV-26 Page 1156 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERAT!Ok) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANi SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix IV Indivlouai A n i m a l G r o s s and H i s t o m o r p n o i o g y D a t a F i G e n e r a t ion THE FOLLOU!NC: T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : .K.I.O.N.E.Y.S. . . . . . . . . . . . . . ... . . . .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of R e c o r d - 3027 IV-27 Page 1I 57 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Apoendix IV I n d i v i o u a l A n i m a l G r o s s and H i s r o m o r p n o l o g y D a t a F1 Generation THE FOLLOWING T I S S U E ( 5 ) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND EPIDIDYMIS KIDNEYS LIVER .P.I T.U. .I T.A.R. .Y. . . . . . . . . . . . . . . . . .S.E.M. .IN.A. .L.V. E. .S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3028 IV-28 Page 1158 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFOKATE (PFBS) I N RATS PROTOCOL 416-CZI SPONSOR`S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross ana Histomorphoiogy Data F l Generation GROSS OBSERVATION(S). HISTOMOQPHOIOGI: O?SEQiIaT!CV`S" H!STOMORPHOLOGIC OBSERVATIONS: KIDNEYS : basophilia, cortical tubules, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.i.l.t.r.a.t.i.o.n.,. .m. .o.n.o.n. .u.c.le.a. .r-.c.e.l.l., . .fo. .c.a.l. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: IV-29 Page 1159 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Apoendix IV I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o i o g y Data F1 G e n e r a t i o n GRCSS O!SERVAT!ON(S): H!STOMORPHOLOG!C @ESE?VkT!3Y!S'. THE FOLLOW!NG T I S S U E ( S 1 WERE W I T H I N NOQM4i L I M I T S : IV-30 Page 1160 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 6 - 0 2 1 S P O N S O R ' S STUDY NUMBER: T - 7 4 E 5 . 1 3 Appendix I V I n d i v i d u a l Animal Gross and H i stomorpnoiogy Cz:a F 1 Generation H!STOMORPHOLOGIC O B S E Q V A T I O N S : KIDNEYS : m i n e r a l i z a t i o n , mu1t i f o c a l (minirnal ) .L.IV.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l a. m. .n.a. .t i.o.n... .c.h.r.o.n.i.c.,. .f.o.c.a.l./m. .u.1.t.i.f.o.c.a.l. .(.m. i.n.i.m.a. .l ). . . . . . . . . . . . End of Record- 3031 IV-31 Page 1161 ANIMAL NUMBER: 3 0 3 2 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFGS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 1nd:vidual ADDendix Iv A n i m a l G r o s s and histomorpho sgy Dara F1 G e n e r a t i o n DOSE GROUP IV-32 Page 1162 XRGL'S f 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOC3L 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Apoendix I V I n d i v i o u a l A n i m a l Gross and Hisrorno-pnology Data F1 Generation GROSS @@SERVAT!ON(S): IV-33 Page 1163 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i stomorphology Data F l Generation GROSS OPSERVATION(S): HISTOHORt"OLOG1C 0!5EQV4:1@V!S!: H!STOHORPHOLOGIC O B S E R V A T I O N S : .K.ID.N. .E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .b.a.s.o.p. .h.i l.i.a.,. .c.o.r.t.i.c.a.l. .t.u.b.u.l.e.s.,. .f.o.c.a. .l . (.m. .in. .im. .a.l.) . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL LIMITS: IV-34 Page 1164 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix IV I n d i v i dual A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a FI G e n e r a t i o n GROSS CSSERV4TICN(S!: HTSTCMCRPHCLCGIC OSSERVATICN(SI: IV-35 Page 1165 ORSL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUCROBUTANE SULFONATE (PFBS) I N RATS PRCTOCOi 418-021 SPONSOR'S STUOY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV Inoiviaual A n i m a l Gross an3 H i stomorpnoiogy 0a:a F! G e n e r a t i o n GROSS O@SERVATION(5): THE FOLLOWING T!SS!JE(S) WERE W I T H I N NORMAL L I M I T S : IV-36 Page 1166 ARGUS 4I S - 0 2 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.!3 Appendix I V Indivicual Animal Gross and Histomorphoiogy Oara FI Generat 1on TFE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIFITS: IV-37 Page 1167 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7465. i3 Appendix I V I n d i v i d u a l Animal Gross and Histomorphoiogy Dara F1 Generation ESOPHAGUS. P e r f o r a t i o n . 1.3cm i n l e n g t h . GASTROINTEST!N4L T R A C T , Stomach and i n t e s t i n e s distenaed with gas. HEART Pericardium- yellow, t h i c k . f i r m . distention bacterial colonies No m i c r o s c o p i c change t o c o r r e l a r e . distention, INTESTINES p l e u r i t i s , f i b r i n o p u r u l e n t . LUNG abscess ----. . . .p.e.r.i.c.a. .r .d.i.t i.s... . .f.i b. .r.i n. .o.p.u. .r.u.l.e.n.t. . . . HISTOMORPHOLOGIC OBSERVATIONS: ESOPHAGUS: HEART : INTESTINES: LUNG: STOMACH: distention (moderate) bacterial colonies abscess p e r i c a r d i t i s , f i b r i n o p u r u l e n t (marked) distention (moderate) p l e u r i t i s , f i b r i n o p u r u l e n t (marked) No m i c r o s c o p i c change t o c o r r e l a t e COMMENTS : TISSUE(S) NOT AVAILABLE FOR EVALUATION: IV-38 Page 1168 `ARGCS 1I S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i o n GROSS OBSERVAT!ON(S): HISTOMORPHOLOGIC O!SEQVA:ION(S): .E.A.R.(.S.).: . .S.w.o. .l l.e.n.,. .r.i.g.h. .t .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .T.i.s.s.u.e. .n. .o.t . .a.v.a.i.l.a.b.l.e. . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : K. I.D.N.E.Y.S. . . . . . . . . . . . . . . . . ... . .L.I .V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: EAR(S) IV-39 Page 1169 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PEQ GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SVLFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485. i 3 Appendix IV Individual A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t ion THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : IV-40 Page 1170 ARGL'S 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY O i POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 Apoendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generation GROSS OBSERVATIONIS). HISTOMORPHOLOGIC OSSERV:T!ON(S). K_I_DN_E_Y_S:_L_e_f t_-_o_i _t t_e d__on__ca_p_su_l_e.________________No__m_ic-ro--s-c-o-p-ic---ch-a--n-g-e--t o---c-o-r-r e--; a--t e--------------------------------- HISTOMORPHOLOG!C OBSERVATIONS: K. .ID.N.E.Y. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o. .m. .ic.r.o.s.c.o. .p.ic. .c.h.a.n.g.e. .t.o. .c. o. .r.r .e.l .a.t.e. . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N.E. .Y.S. . . . . . . . . . . . . . . . . . . .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3041 IV-41 Page 1171 ARGUS 4 IS-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V i n d i v i a u a l Animal Gross and H i s t m r o n o l o g y D a t a F1 Generati on ANIMA? NUMBER: 3042 DOSE GROUP: I 1 SEX: ..... . . . . . . . . . . P .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DEATH ...... TYPE: ..... . . . . Sacri fi ....... c . e . . Schedu ....... lec ... . . _. ._. ._. _. ._. ._ _ _ - - - GROSS OBSERVAT!OY(S): H!STOMORPHOLOGIC O S S E Q V A T I O N ( 8 ) : HISTOHORPHOLOG!C O B S E R V A T I O N S : KIDNEYS : basophilia, cortical tubules, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n. .f .i l.t.r.a.t.i.o.n. ., . .m.o.n. .o.n.u.c.l.e.a.r.-.c.e.l.l,. .f.o.c.a.l. . .(m. .i.n.im. .a.l.). . . . . . . . . . . . IV-42 Page 1172 .ARGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n a i v i d u a l Animal Gross and H i stomorphoi ogy Da:a F l Generat 1 on HISTOYORP?OLOGIC 03SE9VSTiCV!5' G-_EN_E_RA_L_: _No__gr_o_ss__ch_a_ng_e_s.____________________N_o_t _ap-p--l i-c-a-b-1-e----------------------------------------------------- H!STOHORPHOLOGIC OBSEQVATIONS: EPIDIDYMIS: i n f i l t r a t i o n . mononuclear-cell, focal (minimal) KIDNEYS : cyst(s). cortex i n f i l t r a t i o n , mononuclear-cell, focal (minimal) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.r.o.p.h.y.,. .f.o.c.a. l. . (.m. .in. .im. .a.l.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: IV-43 Page 1173 .ARGLS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485. :? Appendix I V I n d i v i a u a l Animal Gross and Histomorphology Data F1 Generati on HISTOMORPHOLOGIC O S S E R V A T I O N S : L. .IV.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n.f.l.a.m. .n.a.t.i o. .n.,. .c.h.r.o.n.i.c... .f.o.c.a.l./.m.u.1.t.i.f.o.c.a. .l . .(m. .i.n.im. .a.l.). . . . . . . . . . IV-44 Page 1174 .ARGUS 41S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix I V Individual Animal Gross and H i stornorphoiogy Oata F1 Generation HISTOMORPHOLOGIC O B S E R V A T I O N S : .L.IV.E. .R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .in. .f.l .a.rn.n.a.t.i .o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./m. .u.1.t.i.f.o.c.a. l. . .(.mi.n. .ir.n.a.l.). . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: IV-45 Page 1175 ARGUS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix IV Individual Animal Gross ana Hi stomoronology Data F1 G e n e r a t i o n G90SS OSSERVATION(S) : T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: KION EYS -L I-V-E-R- - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - _ - - _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - E n d of R e c o r d - 3046 IV-46 Page 1176 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix I V I n d i v i d u a l Animal Gross and Histomorphoiogy Data F1 Generation GROSS OBSEQVATION(S). HISTOMORPHOLOG!C OESERV4i!OY!S', HISTOMORPHOLOGIC O B S E R V A T I O N S : EPIDIDYMIS: i n f i l t r a t i o n . mononuclear-cell, focal (minimal) KIDNEYS: mineralization, multifocal (minimal) .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .in. .fl.a.m. .n.a.t.i.o.n.,. .c.h.r.o.n.i.c. .(.m.o. d. .e.ra. .te.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: IV-47 Page 1177 ARGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i stomorphoi ogy C a r d F1 G e n e r a t i o n AN IAL NUMBER: 304 SEX: v GROSS OBsEQV.4??ON(S): HISTOM0RPHOLOG:C OBSERV?TION(S). G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o.t. .a.p.p.l.i.c.a.b.1.e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H!STOMORPHOLOGIC OBSERVATIONS: .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.la. .m.n.a. .ti.o.n... .c.h.r.o.n. .ic. . .( m. .i n. .i m. .a.l ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND EPIDIDYMIS KIDNEYS LIVER S. .E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S. T. .I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3048 IV-48 Page 1178 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix IV I n d i v i d d a l A n i m a l G r o s s and H i s t o m o r p n o i o g y D a r a F1 G e n e r a t 1on ANIMAL NUMBER: 3 0 4 9 FFX. M DOSE GROUP: DEATH TYPE: I1 S c h e d u l e d ( R e d u c e d Fe7:ll i:yj GROSS OSSERVAT!ONfS): HISTOMORPHOLOGIC OF!SERVAT!CS!S). H!STOYORPHOLOCIC OBSERVATIONS: .E.P.I D. .I D.Y. .M.I.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n. .f .i l.t.r.a.t.i.o.n. .,. .m.o.n.o. n. .u.c.l e. .a .r -.c.e.l.l., . .f.o.c.a. .l . .( .m.i.n.i .m.a.l.). . . . . . . . . . . . IV-49 Page 1179 .ARGUS 4 IS-07 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.1: Appendix I V Inoivi dual Animal Gross ana Hi sromorpnol ogy Daza F1 Generation GRSSS OSSERVATION(S): HISTOMORPHOLOGIC C?SERV:';CN!S': HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS : LIVER: TESTIS: infiltration, mononuclear-cell, focal (minimal) infiltration, mononuclear-cell, focal (minimal) 1 ipidosis. tension, focal retained Step 19 spermatids, Stage IX/X tubules --------d-e-g_e_ne_r_at_io_n_. _m_u1_ti_f_oc_a_l _(_mi_I_d)________________-------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: C. O. .A.G.U.L.A.T.I.N.G. .G.L.A.N.D. . . . . . . . . .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3050 IV-50 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUV PERFLUOROBUTANE SLLFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.13 Appenaix I V i n d i v i d u a l Animal Gross and H Istomorpnology Cara F l Generation THE FOLLOWING T!SSUE(S! WERE WITHIN NORHAL LIMITS: .K.IO.N.E.Y. S. . . . . . . . . . . . . . . . . . ... .L.IV.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3051 IV-51 Page 1181 ORAL (GAVAGE) TWO-GENERATION (ONE L!TTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix I V IndividuaT Anlmal Gross and Histornorpnoiogy Daxa F1 Generation GROSS OBSERVATIONIS): H!SIOYORPHOLOG!C OSSERVATIONS: K_I_ON_E-Y-S_: _------_________________d_i l_a t_a_t i_o n_,__p e_l_v i-s--(-m-a-r-k-e-d-)--------------------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: .LI.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3052 IV-52 Page 1182 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7385.13 Appendix IV I n d i v i d u a ; A n i m a l G r o s s and H i s t o m o r p n o l o g y DaT2 F 1 G e n e r a t i on THE FOLLOWING T I S S U F ( S , WERE W I T H I N NORMAL L I M I T S : IV-53 Page 1183 ARGCS 11S-02I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485.13 Appendix I V !naiviaual Animal Gross and histomorpnoiogy Data F1 Generat 1on THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . .'. .L.IV.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Recoro- 3054 IV-54 Page 1 184 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.1j Appendix I V Individual Animal Gross and Histomorpnolcgy C a r d Fi Generati on GRCSS OSSERVATION(S\: HISTOWORDHOLOGIC !?SSERVAT12N(S'. HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: exfoliated spermatogenic cells (minimal) LIVER: hyperplasia, bile duct, focal (minimal) infl amnati on, chroni c , focal/mu1 ti focal (min i mal ) ....................................................................................................... TPE FOLLOWING TISSUE(S) WERE U!THIN NORMAL LIMITS: IV-55 Page 1185 ORAL (GAVAGE) TWO-GENERATION ( O N E L I T T E R PER GENERATION) REPRODUCTION STUDY O f POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUHBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i stomorphol ogy Data F1 Generati on GQOSS OBSEQVATION(S) HISTOMORP~OLOG!C OSSERV4T!ON(S). HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: K IDNEYS : PROSTATE: TESTIS: atrophy (moderate) hypospermia (marked) dilatation. pelvis (minimal) a t r o p h y , f o c a l (mi I d ) _---.....a.t.ro..p.h.y.,..d..i f.f.u.s..e..(.m..a.rk..e.d.).... THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: IV-56 Page 1186 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFeS] I N RATS PRCTCCOL 418-02! SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i o u a i Animal Gross ana Histomorpholog) Data i l Generation HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : dilatation, pelvis (mild) h y p e r p l a s i a . p e l v i c / p a p i 1l a r y u r o t h e l i um (mi I d ) m i n e r a l iz a t 1on, p e l v i s [ m i n i m a l ) cyst(s), cortex ---- _____i n_f l_a_m_n a_t i_o_n .__c h_r o_n_i c_,_f_o c_a_l /_mu_1_t _i f_o c_a_l _(m_i_n_im_a_l ) _____------------------_-- IV-57 Page 1187 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.;3 Appendix IV Indiviobal A n i m a l G r o s s and H i s t o m o r p n o l c g > DaCa F l Generation H!STOMORPHOLCSIC OSSE9VATIONS: IV-58 Page 11SS ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7465.13 Appendix I V i n d i v i o u a l Animal Gross ana H i s t m o r p h o l o g y Data F1 Generation GROSS OESERV4T!ON(S): HISTOMORPHOLOG!C OBSESV4T!ON(SI. HISTOMORPHCLOGIC O B S E R V A T I O N S : .L.IV.E.R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i .n.f.l.a.m. .t.i.o. n. ... .c.h.r.o.n.i.c.,. .f.o.c.a.l./.m.u. .l t.i.f o. .c.a.l. .(.m. .in. i.m. .a.l). . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL LIMITS: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3059 IV-59 Page 1189 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i o u a l Animal Gross and Histomorpnology Data F1 Generation THE FOLLOWINE T I S S U E ( S ) WERE W I T H I N NORMAL LIMITS: IV-60 Page 1190 XRGLS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PRCTOCOL 418-021 S P O N S O R ' S STUOY NUMBER: T-7485.13 Aopendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generat 1on G?OSS OSSERVA'!ON(S): H!STOMORPHOLOG!C OBSERVA'!DN(S!. HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f i l t r a t i o n . mononuclear-cell, focal (minimal) .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.l a. .m.a. .t .i o. .n.,. .c.h.r.o.n.i.c. .(.m. .in.i.m. .a.l ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: COAGULATING GLAND KIDNEYS LIVER SEMINAL VESICLES T. .E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3061 IV-61 Page 1191 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i s t m o r p h o l o g y D a r a F1 Generation GROSS OBSERVATICN(5): HISTOMORPHOIOGIC OESERVAT!3N(Sl: T I S S U E ( S ) NOT A V A I L A B L E FOR EVALUATION: KIDNEYS .L.I V.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3062 IV-62 Page 1192 .ARGL'S 4 1 S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.1 Append1 x I V I n d i v i a u a l Animal Gross and Histomorphology Data F1 Generation GROSS @?SERVaT!OK(S): T Y E FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: IV-63 Page 1193 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUM6ER: T-7485.!2 Apoendix IV I n d l v l d u a l A n i m a l G r o s s and Histmorpnoiogy Cata F1 G e n e r a t i o n HISTOMOQDHO!CGIC OBSERVATIONS: THE FOLLOWING ?!SSUE(S) COAGULATING GLAND SEMINAL VESICLES WERE W I T H I N NORMAL L I M I T S . EPIDIDYMIS TESTIS K I ONEY S LlVER IV-64 Page 1194 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION S T C O Y OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.17 I n d i vidua: Appendix I V Animal Gross and H i stomorphology Data F i Generati on IV-65 Page 1195 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) R i P R O D U C T I O N STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Indiviaual Animal Gross and Histomorohology Data F1 Generat ion G90SS CSSERVQT!ON(S): HISTOHORPHOLOGIC O B S E R V A T I O N S : KIDNEYS: m i n e r a l i z a t i o n , p e l v i s (mi 1d ) _____------__-________________ed_e_ma_,_p_a_p_i l_l a_r y_,--f-o-c-a-l--(-m-i-n-i-m-a-l-)---------------------------------------------- TPE FOLLOWING TISSUE(S) WERE W I T H I N NORVAL LIMITS: Page 1196 IV-66 ARGCS 1 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N R A i S PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.12 Appendix I V I n d i v i d u a l Animal Gross anc Histomcrphciogy Data F1 Generat 1 on G--E-N-E-R-A-L_: _No__gr_o_ss_c_n_an_g_es_. ____________________N_ot--a-p-p-l-i c--a-b-l-e--------------------------------------------------- THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: IV-67 Page 1197 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERA:!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PGOTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.!3 Aooendix I V Indi vi oual Animal G r o s s and Hi S t o M r p h o l ogy Cat? F 1 Generation GROSS O@SERVAT!ON(5) : G_E_N_ER_A_L: _N_O_g_r_os_s_c_h_an_g_es_.____________________N_ot__ap-p-l-i-c-a-b-1-e---------------------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : cyst(s). papilla infiltration. mononuclear-cell , focal (minimal') LIVER: inflamnation. chronic, focal/mul ti focal (minimal) T. E. .S.T.I.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . .a.t.r. o. .p.h.y.,. .f.o.c.al. . .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMA? L I V I T S : C. .O.A.G.U.L.A.T.I.N.G. .G.L.A.N.D. . . . . . . . . .E. .P.I D.I.D.Y.M. .I S. . . . . . . . . . . . . . . . . .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . E n d of R e c o r d - 3068 IV-68 Page 1198 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-74&5.!: Apoendrx I V I n d i v i a u a l Animal Grass a n a H r s r o m o r p n o i o g j Cata F1 Generation GROSS 03SERVATIOV(S): HISTOHORDHOlOGiC 0ESERVAT:ON:S): THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : IV-69 Page 1199 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUIANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 Aopendix I V I n o i v i d u a : Animal Gross and H i stomorphology Oaca F1 Generation TFE FOLLOWING ' I S S U E ( 5 ) WERE W I T H I N N O R M U L I M I T S : IV-70 Page 1200 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.12 Appendix I V I n d i v i d u a l Animal Gross ana H i stomorpnology Data F l Generation KIDNEYS: mineral i z a t i o n . pelv i s (mi I d ) dilatation, pelvis (mi I d ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t.u.b.u.l.a.r./.d.u.c. .t u. .l a.r. .e. .p.i t.n. e. .l i.u.m. ... .o.a. o. .i l.l.a. .(.m. .i.l d. .) . . THE FOLLOWING T!SSUE(S) WERE WITH!N NORMAL L I M I T S : IV-71 , Page 1201 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOil'S STUDY NUMBER: T-7485.13 Appendix IV I n d i v i o u a l Animal Gross and Histomorpnology Data FI Generati on THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: K. .ID.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3072 IV-72 Page 1202 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Individual Animal Gross and Histomorpnology Daca Fl Generation GQCSS OSSERVAT!@N(S): HISTOHOPPH@LOG!C OSSEQVATI@N(S'. HISTOHORPHOLOGIC OSSEQVATIONS: KIDNEYS : dilatation, pelvis (mi L-I-V-E-R-:----_--_-_________________i_n_fl_a_mn_a_ti_on_,_c-h-r-o-n-i-c-.----------------- End o f Record- 3073 IV-73 Page 1203 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOi7'S STUDY NUMEER: T-7485. i j Appendix I V Indiviaual Animal G r o s s and H i s t m r p h s l o g y D a t a F1 Generati on GROSS OBSERVATION(S). HISTOYORDYOLOGIC OSSEQVl'!Oh(S! HISTOHORPHOLOG!C OESERVAT!ONS: KIDNEYS : hyperplasia, pelvic/papillary urothel ium (minimal) infiltration. mononuclear-cell, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d. i. .l.a.t.a.t.i.o.n.,. .p.e.l.v.i.s. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV-74 Page 1204 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATC (PFBS) I N RATS PROTOCOL 413-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d 1 x !V I n d i v i d i i a l Animal G r o s s and H i s t m o r o n c i o g y Data F1 G e n e r a t 1 on IV-75 Page 1205 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTiON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 i ~ - a z i SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . !j Appendix IV I n o i v i duai A n l m a l G r o s s ana HI s t o m o r p n o i og? CaIa F 1 G e n e r a t l on IV-76 Page 1206 ORA! (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7485. i 3 Appendix I V I n d i v i d u a l Animal Gross and His:omorono1ogy F1 Generaxi on Data F!STOYORPHZ!CGIC O E S E R V A T I O N S : K--ID-N-E--Y-S-: -_--------________________d_i l_a t_a_t i_o_n .--p--e-l -v-i s---(m--i-n-im--a-l-) --------------------------------------------- THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL LIMITS: LIVER ....................................................................................................... End o f Record- 3077 IV-77 Page 1207 XRGLS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I V l n a i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y O a z a F1 G e n e r a t 1 on GROSS OSSERVPi!ON(SI: HISTOYOR~HOLOGIC OBSERVATIONS: HIST@FOQ'JH@LOG!C OSSERVATIChiS' IV-78 Page 1208 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 7 - 7 4 8 5 . 1 3 Appendix IV Individual A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i o n G40SS OBSEQVAT!CY(S): HISTOMOQPHO?OG!C OESERVATIO%IS'. HISTOMORPHOLOGIC CJSERVATIONS: K--IO-N-E--Y-S-:------___________________b_a s_o_p_h i_l i_a_, -c-o-r-t-i -c-a-l--t -u-b-u-l-e-s-,--f-o-c-a-l--(-m--i n-i-m--a-l )------------------------------ THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : IV-79 Page 1209 ORAL (G,AVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONS3R'S STUDY NUMBER: T-7485. :3 Apoendix I V I n d i v i d u a l Animal Gross and Histomorphology Dats F1 Generation GROSS OBSERVATION(S): H!STCMORWOL@C!C C?SSERV:':~?NiS'. G--E-N_ER_A_L: _N_o_g_ro_s_s_c_h_an_g_es_. ____________________N_ot_a-p-p-l-i-c-a-b-1-e--------------------------------------------------- THE FOLLOWING TISSUE(8) WERE W I T H I N NORMAL LIMITS: K. .ID.N.E.Y. .S. . . . . . . . . . . . . . . . . .* . .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3080 IV-80 Page 1210 OR.iL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROCUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!E-021 SPONSOR'S STUDY NUMBER: 1-7485.1: Appendix I V Indiviaual Animal Gross and nistomorphology Da;a F; Generation H!STOMORPHOLOGIC OSSEQVATIONS: KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) -------------------------------------------d-i-l-a-t-a-t-i o--n-,--p-e--l v-i-s--(-m--in-i-m--a-l)--------------------------------- IV-81 Page 1211 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 2 Appendix I V I n d i v i d i i a : A n i m a l G r o s s and Histomorpnoiogy Dasa Fl Generation H!STOHORPHO?OG!C OBSERVATIONS. THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMA!. L I M I T S : COAGULATING GLAND EPIDIDYMiS K I DNEYS LIVER .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. .S.T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3082 IV-82 Page 1212 ORAL (GAVAGE) TKO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i a u a l Animal Gross and tiistomorphology Oat? F1 Generation HISTOH0QpUOLOG:C O S S E Q V 4 T ! O Y ` S ) t'IST0YORt"OLOSIC O P S E R V A T I O N S . .L.IV.E. .R.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.fl.a.m. .n.a.t.i.o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./m. .u.l.t.i.f.o.c.a.l. .(.m. .in.i.m. .a.l ). . . . . . . . . . . . THE FOLLOWING TISSUEfSI WERE W I T H I N NOQMAL LIMITS: K IONEYS ....................................................................................................... End o f Record- 3083 IV-83 Page 1213 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S?ONSOR'S STUDY NUMGER: 1 - 7 4 8 5 . 1 2 Appendix I V I n d i v i d u a l Animal Gross and Histornorpnoiogj Lata F1 Generati on PISTOMORPHOLOGIC O B S E R V A T I O N S : K. .ID.N.E.Y. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i n. .f .i l.t.r.a.t.i.o.n. .. . .m.o.n. .o.n.u.c.l.e.a.r.-.c.e.l.l,. .f.o.c.a. .l . .( .m.i.l.d.). . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMA? LIMITS: Page 1214 IV-84 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 18- 02 1 SPONSOZ'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorpnology Data Fl Generation A N I M A ? NUP E R : 3 0 SEX: M GROSS O?SE?VA?!!lN(S): EXTREt(!T!ES: Hind l e g - l e f t ankle swollen. osteoarthritis, chronic ____________________--------------------------in-f-l-a-m-m--a-t-io-n--, --s-u-p-p-u-r-a-t-i-v-e-.--j o--i -n-t--c-a-o-s-u-l-e------------------ HISTOMORPHOLOGIC O S S E R V A T I O N S : EXTREMITIES: osteoarthritis. chronic (moderate) ----------______________________i n_f l_a_m_n a_t_i o_n_, -s-u-p--p-u-r-a-t-iv-e-,--j-o-i-n-t---c-a-p-s-u-l-e--(-m-o--d-e-r-a-te-)------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND EPIDIDYMIS KI ON EYS LIVER .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E.S. .T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3085 IV-85 Page 1215 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PfBS) IN RATS PROTOCOL 416-021 SPONSOR'S STUOY NUMBER: 1-7485.13 Appendix IV I n d i v i o u a l Animal Gross and Histomorpnoiogy Data F1 Generation GROSS O@SERVAT!ON(S\: HISTOMOROH3COGIC SSSERVST!9N(S). HISTOMORpHOLOGIC OBSERVATIONS: .L.I.V.E.R.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .in. .f.la. m. .n.a.t.i.o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./m. .u.1.t.i.f.o.c.a. .l . .( m. .i .ni.m.a.l. .). . . . . . . . . . THE FOLLOWING TISSUE!S) WERE WITHIN NORMAL LIMITS: .K.I.D.N.E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3086 Page 1216 IV-86 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PES GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SL'LFONATE (PFBS) IN RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: T-7485.13 Apoeqdix I V I n d i v i d u a l Animal Gross and H i s t o m o r ~ h o l c g yDara F1 Generation H!ST@MCRPHC?OGIC 03SERVQTIONS: K. .ID.N.E.Y. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .b. .a.s.o.p.h. .il.ia. ., . .c.o.r.t.i .c.a.l. .t.u.b.u.l.e.s.,. .f.o.c.a.l. . .(m. .i.n.im. .a.l.). . . . . . . . . . . . . . THE FOLLOWING TISSUErS) WERE W I T H I N NORMAL LIMITS: Page 1217 IV-87 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.15 Appendix I V Indivioua: Animal Gross ana Histomorphology Dara F1 Generari on H:STOHOROYO:OG!C OESERVATIONS: -K_ID_NE_Y_S:___________-___________d_i_l a_t a_t_i o_n_. _p_e_l v_i s_-(-m--i l-d-)-------------------------------------------------------- T M FOLLOW!NG T I S S U E I S ) WERE W!THIN NORMAL LIMITS: Page 1218 IV-88 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix I V I n d i v i d u a l Animal Gross and H i stoncrpnoi oay Oaza F l Generation IV-89 Page 1219 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: i - 7 4 a s . :3 Appendix I V Individual Animal Gross and Histornorpnoiogy D a t a F1 Generation G9CSS OBSERVST!ON(S): GEhlE94L. No gross changes HISTOMORDHOLOG!t OeSERVATIONS: KIDNEYS : p y e l o n e p h r i t i s , mu necrosis. papilla, IV-90 Page 1220 ARGL'S 1IS-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFaS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Indi viaual Animal Gross and H i stomorpnoiogy Data F l Generat 1on NUMBER: DOSE GROUP: I V A N I M A L 309! SEX: w T Y P E : Scheduled (Reduced Kerf1 1 t y ! DEATH i --. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . G90SS CBSERVP'ION(S): H!STOMORPMOLOGIC OBSE?VATION(S:. G E N E i l A L : No gross changes. Not apol icab1e K-_ID-N-E-Y_S-:--R-i_gn_r----p-e-l-v-i_s _d_i l _a t_e_d ,__s l_i g_h_t_. _________---d--i l-a-t-a-t-i-o-n--, -p--e-l -v-i s------------------------------------------- H!STOM~RPHO?@G!C OBSERVATIONS: KIDNEYS : dilatation, pelvis (mild) LIVER: hypertrophy, hepatocellular (minimal ) PROSTATE : inflamnation. chronic (mild) -------------------------------------------a-t-r-o-p-h-y-,--f-o-c-a-l--(-m--i-l d-)---------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: C. .O.A.G.U.L.A.T.IN. .G. .G.L.A.N.D. . . . . . . . . .E.P. I.D.I.D.Y.M. .I S. . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. .S.T.I.S. . . . . . . . . . . . . . . . . End o f Record- 3091 IV-91 Page 1221 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM pERFLUORO6UTANE SULFONATE (PF6S) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1 - 7 4 9 5 . 1 3 Appendix I V I n d i v i d u a l Animal Gross and H i stomorohol ogy Da:a F1 Generation HISTOMORPHOLOGIC OBSERVATIONS: L-I-V-E-R--: --_______________________hy_p_e_rt_ro_p_hy_, _h_e-p-a-t-o-c-e-l-l-u-l -a-r--(m--i-n-im--a-l -)----------------------------------------- THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL LIMITS: .K.ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3092 IV-92 Page 1222 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROaUTANE SULKONATE (PFBS) I N RATS PROTOCOL 413-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i a u a l Animal Gross and Histornorohoiogy Data F1 Generation ANIMAL NUMSER: 3093 six: M DOSE GROUP: DEATH TYPE: IV Schedui d (Geduced F IV-93 Page 1223 ORA! (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Indiv i aual Animal Gross and H i stomorohoiogy Gala F l Generat 1 on HISTOMOR~HOLOGICOBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular e p i t n e l ium, p a p i l l a (minimal) .P.R.O.S.T.A.T.E.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.tr.o.p.h. .y.. . .fo. .c.a.l. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS LIVER SEMINAL VESICLES IV-94 Page 1224 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHBER: 1 - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l Animal Gross ana Histomorpnology Data F 1 G e n e r a t 1 on GQCSS 09SERV4'ION(S1: H!STOMORPYO?OG!C O?SSEQV4TIONS: PROSTATE: atrophy, f o c a l ( m i l d ) .S.K.I N. . .(G. R. .O.S.S. .L.E.S.I.O.N.).:. . . . . . . . . . . . . . . . . . . . . . . .d.e.r.m.a. .t i.t.i.s.,. .c.h.r.o.n. i.c.,. .f.o.c.a. l. . .( m. .o.d.e.r.a.t .e.) . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : COAGULATING GLAND SEMINAL VESICLES EPIDIDYMIS TESTIS KIDNEYS LIVER IV-95 Page 1225 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Indiviaiia' Animal Gross and Histomorphology Cata F l Generati on _ES_OD_H_AS_-U_S_: _P_e r_f o_r_a_t i o_n_. _1_.3_c_m _i _n _l e_n_g_t h_. ___________p e_r_f o_r-a-t-i -o-n-------------------------------------------------------- H!STOMORPHOLOG!C O B S E R V A T I O N S : -E-SO--P-H-A-G_US-:--__--_-_-______________p_e_r f_o_r a_t _i o_n--------------------------------------------------------------- TISSUEfS) NOT AVAILABLE FOR EVALUATION: KIDNEYS LIVER ....................................................................................................... End o f Record- 3096 IV-96 Page 1226 XRGUS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV Individual Animal Gross and Hi stomorphol ogy Data FI Generation ESOPHAGUS: 0.5cm tear (trimning observation). necrosis Derforation abscess, THORACIC CAVITY HEART: Pericardium- distended with approximately pericarditis. fibrinopurulent - 3cc of thin red fluid. SKIN: Left axilla- 4.5 x ' 2 . 5 x 1.8cm, soft, tan. abscess, SKIN (GROSS LESION) cut surface reveals green caseous and green . .g.r.a.n.u.l.a.r. .m.a.t.e.r.i.a.1... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTOMORpHOLOGIC OBSERVATIONS: ESOPHAGUS : HEART : SKIN (GROSS LESION) : THORACIC CAVITY: necrosis (marked) perforation pericarditis, fibrinopurulent (marked) abscess abscess COMMENTS : TISSUE(S) NOT AVAILABLE FOR EVALUATION: IV-97 Page 1227 ARGYS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV I n d i v i d u a l Animal Gross and Histomorphology Data FI Generation GROSS OSSERVATION(S): H I STOMORPHOLOGIC O B S E R V A T I O N S ) . HISTOMORPHOLOGIC OBSERVATIONS: LIVER: in f l amnati on, c h r o n i c , f o c a l /mu1 t i f o c a l ( m i n i mal ) T.R.A.C. .H.E.A.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .A.d.v.a.n.c.e.d. .a.u. .t o. .l y. s. .i s. .p. .re. .c.lu.d. .e.s. .e.v.a.l.u.a.t.i.o.n. . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : K. .ID.N.E. Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV-98 Page 1228 ARGCS 11s-02I ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUiANE SULFONATE (PFBS) I N RATS Pt?OTOCCL 418-021 SPONSOR'S STUDY NUMBER: ?-7465.13 Appendix IV I n a i viOua1 A n i m a l G r o s s and Hi s t o m o r p h o l o g y Da:a F1 G e n e r a t 1on IV-99 Page 1229 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Aooendix I V I n c i v i d u a l Animal Gross and Histomorpnology Dara F l Generation HISTOMORPHO?OGiC O B S E R V A T I O N S : KIDNEYS : hyperplasia, p e l v i c / p a p i 1l a r y u r o t h e l ium (mi I d ) hemorrhage, p e l v i s ( m i l d ) necrosis, papilla. focal (minimal) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e 1 ium. p a p i 1l a (mi I d ) m i n e r a l iz a t i on, p e l v i s (mi 1d ) ' _ _ _i n_f_l a_m_a_t i_o n_,_c_h_r o_n_i c-,_f_oc_a_l/m- -u-l _t i-f-o-c-a~l -(-m-i-n-im- -a-l )- - - - - - - - - - - - - - - - - - - - - - - - Page 1230 IV-100 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d a a i A n i m a l G r o s s and H i s t o m o r p n o i o g y OaTa F1 G e n e r a t i o n GRlrSS OSSERVAT!ON(S): H!STOMORD~OLOC!C 09SERV4r!OV(S \ . H!STOMORPHOLOG!C OSSERVATIONS: EPIDIDYMIS: in f i 1 t r a t i on, m o n o n u c l ear-cel 1 , f o c a l ( m i n i m a l ) .P.R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .a.t.ro. .p.h.y.,. .f.o.c.a.l. .(.m.i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE W I T H I N NORFAL LIM!TS: COAGULATING GLAND TESTIS KIDNEYS LIVER SEMINAL VESICLES Page 1231 IV-101 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I V I n d i v i a u a l A n i m a l Gross and Histomorpholo~D~a:a F l G e n e r a t i on HISTOWIQpHCLOGIC OESE?V;':OY:S' THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 1232 IV-102 XRGCS 41S-02 1 ORAL (GfiVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02; SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV Individual Anlmal Gross and Histomorphology Data F1 Generation 5ROSS OSSERVAT!ON(S! : HISTOMORPHOL0G:C OSSERVA'!ZV(S: : _E4_R(_S_) _: _Sw_o_l1_e_n,__bi_1_ar_er_a_l _. ___________________d_er_m_at-i-t-i-s-,--c-h-r-o-n-i-c-,--f-o-c-a-l--------------------------------------- HISTOYORPHOLOGIC OBSERVATIONS: EAR( S) : dermatitis, chronic, focal (minimal) KIDNEYS : infiltration, mononuclear-cell, focal (minimal) - - - - _ _ _ _ _ - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _m_in_e_ra_l_iz_at_i_on_._p_e-l-v-i-s- -(-m-i-n-i-m-al- -) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - THE FOLLOWING TISSUE(S) WERE W!TH!N NORMAL LIMITS: LIVER ....................................................................................................... End o f Record- 3103 Page 1233 IV-103 .-\RGCS -1!S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFSS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV Indi v i aual A n i m a l Gross and H i stomcrDnol ogy D a t a F 1 Generation THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I V I T S : Page 1234 IV-104 XRGL'S 1IS-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 7 - 7 4 8 5 . 1 3 Appendix I V !ndividual Animal G r o s s and Histomorphology D a t a F1 Generat1on HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 1235 IV-105 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTIOh STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix IV i n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F1 Generation F I S T O H O R ~ Y O L O G I CD S S E R V A T I O N S : THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1236 IV-106 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION S T U D Y OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I h RATS PROTOCOL 415-02! SPONSOR'S STUDY NUHGER: i-7465.!3 Appendix I V i n a i v i a d a i A n i m a l Gross and Histomorpnoicgy Ca:a F l G e n e r a t 1on H!STOMOR'JHO!OG!C O E S E Q V ? ' ! 3 Y ( S ) G--E-N_ER-A-L_: -N--o-g_r_os_s_c_h_an_g_es_. ------------------------------N--o-t -a-p--o-l i-c-a-b--l e---------------------------------------- THE FOLLOWING TISSUE(8) WERE W!THIN NORMAL L I M I T S : K. .ID.N.E. .Y.S. . . . . . . . . . . . . . . . .'. . .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d of R e c o r d - 3107 Page 1237 IV-107 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41@-021 SPONSOR'S STUDY NUMBER: T-7485.17 Appendix I V I n d i v i a u a l Animal Gross and H i stornorohoiogj 3a:a F i Generation H!STOYORDHO!OGIC OSSERVCTIONS: K--I -O-N-E-Y_5 :--_--_-_-________________i_n_f i_l t_r _a t_i _o n_,--m--o-n-o-n-u-c--le-a-r---c-e-l-l,---fo--c-a-l --(-m-i-n-i-m-a-l-)---------------------------- THE FOLLOWING T I S S U E ( S ) WERE WITH!N NORMAL LIMITS: Page 1238 IV-108 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY O F POTASSIUM PERFLUOROBUTAN E SULFONATE (PFSSI I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix I V I n d i v i d u a l Animal Gross ana Histomorphoicg) Dd'id F1 Generation GROSS O B S E R V A T I O N f S l : H I S T O M O Q D H O L O G I C OSSERVATION[S!: G--E-N-E-R-A_L:_N_o_g_r_os_s_c_h_an_g_es_. ____________________N_o-t -a-p--p-l l-c-a--b-l -e--------------------------------------------------- HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS: hemorrhage, p e l v i s (moderate) h y p e r p l a s i a , p e l v i c / p a p i 11a r y u r o t h e l i urn (mi n imal ) necrosis, papilla, focal (minimal) hyperplasia, tubular/ductular epithelium, papilla (minimal) mineral ization. pelv i s (moderate) inflamnation, chronic, focal/multifocal (minimal) -___-______--___________________________----------------------- Page 1239 IV-109 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUCY OF POTASSIUM PERFLUOROBUTANE SULFONATE ( p i a s ) IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix I v IndividJal Animal Gross and Histomorphologj L a t a F 1 Generation HISTOMORPHOLOGIC OBSERVATIONS: LIVER: necrosis, focal/multifocal (minimal) i nf 1amnat ion, chron i c , foca 1 /mu1 r i f oca 1 ( m i n 1Tal ) ------------------------------------------------------------------------------------------------------- Page 1240 IV-110 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1e- 021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV i n d i v i d d a l A n i m a l Gross and H i s t o m o r p n o l q y D a t a Fl G e n e r a t i o n HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWrNG TISSUE(SJ WERE W I T H I N NORYAL L I M I T S : -L-I V-E-_R ________-----______________________--------------------------------------------------------------- End o f R e c o r d - 3111 Page 1241 IV-111 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENER.ATION) REPRODUCTION STUSY 3F POTASSIUM PERFLLOROSUTANE SULFONATE (PFBS) I N RATS PR3T3CCL 415-C2! SPONSC2'S STUOY NUMSER. i - 7 4 8 5 . I t Appendix IV In31 vi ouai Aninai Gross and Hi storncrow'c;) Cata F1 Generari on EP!DIDYM:S: infiltration. mononuclear-cell, focal (minimal) KIDNEYS : cyst(s). p. ap. illa nephritis, chronic, focal (minimal) hyperplasia, tubular/ductul ar epi the1 iurn. paoi 1 1 a (minimal ) dilatation. pelvis (minimal) -L -I V-E-R-:-_----___-----_-------------------c-e-l-l-u-l-a--r-a-1-t-e-r-a-t-i-o-n--.-e-o-s-i-n-o-p-h-i-1-I--C-,-f-o-c-a-l--(-m-i-I-d-)------------------ THE FOLLOWING TISSUE(8) WERE W I T H I N NORMAL L I M ! T S : .C.O.A.G.U.L.A.T.I.N.G. .G.L.A.N.D. . . . . . . . . .P.R.O. S. .TA.T.E. . . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . . . .T.E. .S.T.I S. . . . . . . . . . . . . . . . . . End of Record- 3112 Page 1242 IV-112 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTIOh STUDY OF POTASSIUH PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 419-021 SPONSOR'S STUDY NUMBER: 1-7465.12 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i stmorphol cgy D a l a F1 G e n e r a t i o n H!STOKORPHOLOG!C OSSEQVS'IO'iiS): THE COLLOWING T I S S U E [ S ) WERE W I T H I N NORMAL L I M I T S : Page 1243 IV-113 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTIOh STUDY OF POTASSIUM PERFLUORO3UTANE SCLFONATE (PFBS) I N RATS PROTCCOL 418-021 S P O N S O R ' S STUDY NUMBER: 1-7485. :t Appendix I V I n d i v i d u a l Animal Gross and Histomorpno'iogy Dala F1 Generation F!STCWRPYOLOGIC OBSEQVATIONS: EAR(S): dermatitis, chronic, focal (minimal) .K.ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d.i.l a. .t a. .t .i o. .n... .p.e.l.v.i.s. .(.m.i.I.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 1244 IV-114 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 6 5 . 1 3 Appendix I V I n d i v i d u a l Animal Gross and Histomorphoiogy DaLa F1 Generation GROSS OSSERVATIONIS!: ~ I S T O M O R ~ Y O L O G IOCB S E R V A T I O N S : KIDNEYS: hyperplasia, pelvic/papi 1l a r y urothel ium (minimal ) hyperplasia, tubular/ductular epi the1ium. papi 1l a (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .in.e. r.a.l.i.z.a. .t i.o.n. ., . p. .e.l.v.i.s. .(.m.i.I.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOW!NC T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : LIVER Page 1245 IV-115 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i o u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i o n CROSS O@SERVATION(S): HISTOMOSPHOLOGIC OSSERVATIONS: HISTOHORPHOLOiIC OSSEQVAT:34[S\ ' Page 1246 IV-116 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41E-CZ1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I V I n c i v i d u a l A n i m a l G r o s s and h i s t o m o r p h o l o g y Data Fl Generation H!STOMORPHOLOGIC OBSERVATIONS: Page 1247 IV-117 ORAL (GAVAGE] TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUGY NUMBEii: 1-7485.15 Apoendix I V I n o i v i d u a l Animal Gross and Histomorphology Data F l Generation HISTOYOQDHOLOGIC OBSEQV4TIONS: KIDNEYS : nephritis, chronic, focal (minimal) basophilia, cortical tubules. focal (minima dilatation, pelvis (minimal ) THE FO?LOW!NG TISSUEfS) WE?E WITFIN NORMAL LIWITS: L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3118 Page 1248 IV-118 O?AL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41a-oil SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix I V Individtia; Animal Gross ana Histornoronoiogy Data F1 Generation H!STOMOR'Jt'O?06IC OESEQVATIONS: KIDNEYS: hyperplasia, pelvic/papi 1lary urothel 1urn (minimal ) di latati on. pel vis ( m i Id) L. .I V.E. R. .: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i.n.f.1.a. .m. .t.i.o.n.,. .c.h.r.o.n.i.c.,. .f.o.c.a.l./.m.u.1.t.i.f.o.c.a.l. . .(.m.i.n.i .m.a.l.). . . . . . . . . . End o f Record- 3119 Page 1249 IV-119 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Amendix I V I n d i v i d u a l Animal Gross and Histomorphoiog) D a t a F I Generation GROSS C?SSERV,ATION(S!: H!STOMORDHOLOG!C OSSERVAT!ONS: K--ID-N_E_Y-S_: ______________________b_a_s_op_h_il_ia_, _c_o_r t_i c-a-l--t-u-b-u--le-s-,---fo-c-a--l --(-m-i-n-im--a-l-)--------------------------------- THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL LIMITS: LIVER ....................................................................................................... End o f Record- 3120 Page 1250 IV-120 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i o u a l Animal Gross and Histomorpnology Oata F1 Generatlon GR9SS OSSEQVArION(S!. HISTOMORPHOLOGIC 03SEQVATI04:S'. HISTOMORPHOLOGIC OESEQVATIONS: KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 1 urn, p a p i l l a ( m i l d ) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) ------------------------------------------------------------------------------------------------------- Page I251 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 E - 0 2 i SPONSOR`S STUDY NUMBER: 1 - 7 4 8 5 . 1 2 Appendix I V Individual Animal G r o s s and Histomorphology Cata F1 GeneraIion GROSS O B S E R V A T I O N ( S ) : HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS : PROSTATE: TESTIS: hypospermi a (mi1 d) exfoliated spermatogenic cells (moderate) basophilia. cortical tubules, focal (minimal) hyperplasia. tubular/ductular epi the1 i um. papi 1 la (miId) 1 nflamnati on, chronic (minimal ) atrophy, focal (minimal) degeneration. multifocal (mild) . . . . . . . . .r.e.t.a.i.n.e.d. .S.t.e.p. .1.9. .s.p.e.r.m.a.t.i.d.s... .S.t.a. g. .e. .I X. ./ X. . .t.u.b.u.l.e.s. . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : C. .O.A.G.U.L.A.T.I.N.G. .G.L.A.N.D. . . . . . . . . .L.I.V.E.R. . . . . . . . . . . . . . . . . . . . . .P. .I T.U.1.T.A.R.Y. . . . . . . . . . . . . . . . . . .S.E.M.I.N.A.L. .V.E.S.I.C.L.E.S. . . . . . . . End of Record- 3122 Page 1252 IV-122 .-IRGCS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i o u a l Animal Gross and Histomorphology Data F1 Generation GROSS OBSERVATIONfS): HISTOHORpHOLOGIC OESE9VATICN(S)' HISTOMOQPYOLOG!C O B S E R V A T I O N S : KIDNEYS: basophilia, cortical tubules, focal (minimal) -L-IV-E-R--: ------------------------------------h-y-p--e-rt-r-o-p-h-y-,--h-e--p-a-t-o-c-e-l-l u--l a--r -(-m--in-i-m-a--l)------------------------- End o f Record- 3123 Page 1253 IV-123 ORAL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODUCTIOfi STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N KATS PROTOCOL 418-021 SPONSOR'S STUDY NUHGER: 7-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorpnoiogy Card F1 Generation HISTOMORPHOLOGIC OSSERVATIONS: KIDNEYS : dilatation, cortical tubules, focal (mild) h y p e r p l a s i a . t u b u l a r / d u c t u l a r e p i t h e 1 1 urn. p a p i 11a (mi 1d ) -L-IV-E_R_: ___------_________________n_e_c_ro_s_is_. _fo_c_a-l -/m-u-1--t-i-fo--c-a-l--(-m-i-n-i-m-a-l-)----------------------------------------- THE FOLLOWING TISSUE(S1 WERE W I T H I N NCRMAL LIMITS: ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS P ITUI TARY .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S. .E.M.IN. .A.L. .V.E.S.IC. .L.E.S. . . . . . . . . . .T.E.S. .T.I S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3124 Page 1254 IV-I24 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02: SPONSOR'S STUDY NUMBER: 1-7485.1: Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Da:a F1 Generation ANIMAL NUMBER: 3 1 2 5 DOSE GROUP: V SEX: M DEATH TYPE: Sacri fice-Schemled ......................................................................................................... GR@SS @SSE?VATIONIS): HISTOMORPFOLOGIC O R S E R V S T ! @ Y ( S ! . G_E_N_ER_4_L:_N_o_g_ro_s_s_c_ha_n_g_es_. ____________________N_ot_a_p-p--l i-c-a-b-l-e--------------------------------------------------- HIST@MORDH@LOG!COBSERVATIONS: KIDNEYS : hemorrhage, p a p i l l a ( m i l d ) basophilia, cortical tubules, focal (mild) hyperplasia, t u b u l a r / d u c t u l a r epi the1 ium. papi 1l a (mi I d ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m. .a,. . .p.a.p.i.l.l a. .r.y.,. .fo. .c.a.l . .(.m. .in.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N N3RMAL LIMITS: .L.IV.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3125 Page 1255 IV-125 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOh) REPRODUCTIOh STUDY OF POTASSIUM PERFLUOROGUTANE SCLFONATE (PFGS) Iti RATS PROTOCOL 418-021 SPOkSOR'S STUDY NUM3ER: T-7465. i t ApDendix I V I n a i v i a u a ' Animal Gross and H i stornorpnoiogh Da?a F1 Generati on HISTOMO?pHOLOG!C OSSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithel iun, papilla (mild) edema, p a p i l l a r y . f o c a l ( m i n i m a l ) -L-IV-E--R-:--_______________________hy_p_e_rt_ro_p_hy_, _h_e-p-a-t-o-c--e-l l-u-l-a-r--(-m-i-n-im--a-l------------------------------------------ THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M ! T S : Page 1256 IV-126 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: T-7485. I ? Appendix I V I n d i v i d u a l Animal Gross and Histornorpnolcgy Ca:a F! Genera t 1on GRQSS ?SSERVAT!@N(S!: HIST@M@RPVILOS!C OSSERVATIONS: KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r eoi the1 ium. papi 1 1 a ( m i l d ) -L-IV-E--R-:-----------_________________h_y_pe_r_tr_op_h-y-,--h-e-p--a-t-o-c-e-l-l-u-l a--r -(-m--in--im--a-l-) ----------------------------------- End of Record- 3127 Page 1257 IV-127 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV Individual A n i m a l G r o s s and H i s t o r n o r o h o l o g y Data F1 G e n e r a t ion GROSS CSSERVATION(5): HISTOHORPHOLCCIC CFSEQVS'!O&!S'. H!STOMOSDHOLOGIC OBSERV4TIONS: ADRENAL GLANDS: LIVER: vacuolation, c o r t e x (moderate) hypertrophy, hepatocellular ( m i n i m a l ) THE FOLLOWING T I S S U E ( 5 ) WERE W!THIN NORMAL L I M I T S : COAGULATING GLAND PROSTATE EPIDIDYMIS SEMINAL VESICLES KIDNEYS TESTIS PITUITARY Page 1258 IV-128 ORAL ( G A V A G ET)WO-GENERATION ( O N ELITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE ( p i a s ) IN R A T S PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7465.1: Apoendix I V I n d i v i d u a l Animal Gross and Histomorphology Dara Fl Generation HISTOMORPHOLOGIC OBSEQVATIONS: ADRENAL GLANDS: vacuolation. cortex (moderate) K--ID-N--E-Y-S-:----____________________h_y_p_e r_p_l a_s_i a_, -t-u-b-u--l a-r-/-d-u--c-t u--l a--r -e--p-i -th-e--1-i-u-rn-. --p-a-p-1-1-l-a--(-m--in-i-m--a-l )---------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS LIVER PITUITARY P. R. .O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E. .M.IN. A. .L. .V.E.S.IC. .L.E.S. . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3129 Page 1259 IV-129 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROSUTANE SULiOhATE ( P i a s ) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 7 - 7 4 8 5 . 1 3 Appendix I V Inaiviauai Animal G r o s s and H i sromcrpnoiogj 3ara F l Generati on Y!STOPOR~HO?OGIC OSSERVATIONS: LIVER: necrosis, focal/multifocal (mild) hypertrophy. hepatocell ul ar (minimal -P-R-O-S-T_AT_E_: __-___________________a_t_ro_p_hy_,_f_oc_a_l _(-m-i-n-i-m-a-l-)----------------------------------------- THE FOLLOWING TISSUE!S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS KIDNEYS .P.I T.U. .I T.A.R. .Y. . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V.E. .S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3130 Page 1260 IV-130 ORAL (GAVASE) TWO-GENERATION (ONE L!TTER PER GENER4TION) REPRODUCTION STUDY Or POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02: SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix I V Indiviauai Animal Gross and H i stomorpnology Data F1 Generation P!STOMORPH@LOG:C 05SERVATIONS: KIDNEYS : hemorrhage, p a p i l l a ( m i l d ) hemorrhage, p e l v i s (mi 1d ) hyperplasia, tubular/ductular epithelium, papilla (mild) atrophy, focal (mild) __No__m_ic_ro_s_co_p_ic_c_h_an_g_e _t _o _c_o r_r_e l_a_t e_________________-------------------- THE FOLLOWING TISSUE(S) WE95 W I T H I N NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS LIVER SEMINAL VESICLES T. .A.IL. . . . . . . . . . . . . . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3131 Page 1261 IV-131 ARGCS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generation GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OSSERVATION(S): GENERAL: No gross changes. Not appl icab1 e ------______________----------------------------------------------------------------------------------- HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: KIDNEYS : i n f i l t r a t i o n , mononuclear-cell, focal (minimal) i n f i l t r a t i o n , mononuclear-cell, focal (minimal 1 h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 ium. papi 1l a (minimal ] edema, p a p i l l a r y , f o c a l ( m i n i m a l ) __h_yp_e_rt_ro_ph_y_. _h_e_p a_t_o c_e_l l_u l_a_r _(m_i_ni_m_al_) _______________------------------ Page 1262 IV-132 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Data Fl Generation KIDNEYS : hemorrhage, p a p i l l a (minimal) pyelonephritis (minimal ) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 iurn. hypertrophy, hepatocellular (minimal ) papilla (mild) Page 1263 IV-133 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a F1 G e n e r a t ion GROSS OBSERVATION(S1 : HISTOMORPHOLOGIC OBSERVATIONS: H ISTOMORPHOLOGIC OBSERVATION (S1 : Page 1264 IV-134 ~~ ARGUS 4 18-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i stomorphol ogy Data F1 Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: HISTOMORPHOLOGIC OBSERVATION(S): h y p e r p l a s i a . p e l v i c / p a p i 1l a r y u r o t h e l ium (minimal ) h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i the1 iurn, papi 11a (mi I d ) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) Page 1265 IV-135 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i stomorphol ogy Data F1 G e n e r a t i o n ANIMAL NUMBER: 3136 SEX : M DOSE GROUP: DEATH TYPE: V Spont neous (Gr ss Le GROSS DBSERVATION(S): ESOPHAGUS: P e r f o r a t i o n , 1.5 x 0.2cm; t h o r a c i c c a v i t y c o n t a i n s a p p r o x i m a t e l y 40ml of dark r e d fluid. HISTOMORPHOLOGIC OBSERVATION(S): perforation hemorrhage HISTOMORPHOLOGIC OBSERVATIONS: ESOPHAGUS: perforation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h. e. .m.o.r.rh. .a.g.e. .(.m.o.d. e. .r a.t.e.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . TISSUE(S) NOT AVAILABLE FOR EVALUATION: KIDNEYS LIVER End o f Record- 3136 Page 1266 1'4-136 ' ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i o n GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S): T I S S U E ( S 1 NOT A V A I L A B L E FOR EVALUATION: KIDNEYS .L .I V.E. .R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3137 Page 1267 IV-137 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Hi stomorphology Oata F1 Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIONEYS : hyperplasia, tubular/ductular epithelium. papilla (mild) .L.IV.E.R..: .....................................h.y.p.e..rt.r.o.p.h.y.,..h.e..p.a.t.o.c.e.l.l.u.la..r ..(m..i.n.im..a.l.)....................... End o f Record- 3138 Page 1268 IV-138 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV Individual A n i m a l Gross and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i o n GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: HISTOMORPHOLOGIC OBSERVATION(S): THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : LIVER E n d o f R e c o r d - 3139 Page 1269 IV-139 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Individual Animal Gross and H i stornorphology Data F1 Generat ion HISTOMORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: adenoma, c o r t i c a l , benign KIDNEYS : hemorrhage, p e l v i s (mild) h y p e r p l a s i a , p e l v i c / p a p i 1l a r y u r o t h e l ium (mi nimal ) basophilia, cortical tubules, focal (minimal) hyperplasia, tubular/ductular epithelium. papilla (mild) ...........................................m..in..e.r.a.l .i.z.a.t.i.o.n.,..p.e.l.v.i.s..(.m.i.I.d.)............................... THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : .L.IV.E. R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NEOPLASMS: A.D.R..E.N.A.L..G.L.A.N.D.S.............................a.d.e.n.o.m..a., ..c.o.r.t.i.c.a.l.,..b.e.n.i.g.n................................... End o f Record- 3140 Page 1270 IV-140 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphol ogy Oata F1 Generation GROSS OBSERVATION(S1: HISTOMORPHOLOGIC OBSERVATION(S1: .G.E.N.E.R.A.L.:..N.o..g.r.o.s.s..c.h.a.n.g.e..s.. ................................N.o.t..a.p.p..li.c.a.b..le............................... HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f i l t r a t i o n . mononuclear-cell, focal (minimal) KIDNEYS : hyperplasia, tubular/ductular epithelium, papilla (mild) edema, p a p i l l a r y , f o c a l (minimal) .L.IV.E..R.:.....................................i.n.f.l.a.m..n.a.ti.o.n....c.h.r.o.n..ic.,..f.o.c.a.l./m..u.l.t.i.f.o.c.a..l ..(m..i.n.im..a.l.)........... THE FOLLOWING TISSUEIS) WERE WITHIN NORMAL LIMITS: ADRENAL GLANDS SEMINAL VESICLES End o f Record- 3141 COAGULATING GLAND TESTIS PITUITARY PROSTATE Page 1271 IV-141 ARGUS 4 18-02I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V Individual Animal Gross and H i stomorphology Data F1 Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : LIVER: hemorrhage, p e l v i s (moderate) mineralization, p e l v i s (moderate) hypertrophy, hepatocell u l a r (mi 1d) THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL L I M I T S : ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS PITUITARY .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V. E. .S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3142 Page 1272 IV-142 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Hi stomorphology Data F1 Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONIS): HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: i n f i l t r a t i o n . mononuclear-cell , focal (minimal) K..ID.N.E.Y..S.: ...................................h.y..p.e.r.p.la..s.ia.,..t.u.b..u.l.a.r./ .d.u.c.t.u.l.a.r..e.p.i.t.h.e.1.i.u.r.n,..p.a..p.i 1.l.a...(.m.i.n.im..a.l.) THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS LIVER PROS TAT E SEMINAL VESICLES Page 1273 IV-143 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generation HISTOMORPHOLOGIC OBSERVATIONS: Page 1274 IV-144 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i s t m o r p h o l ogy Data F1 Generation GROSS OBSERVATION(S): HISTOMORPHOLOGIC OBSERVATION(S): basophilia, cortical tubules, focal (mild) hyperplasia, tubular/ductular epithelium, papilla (mild) in f l a m n a t i on, c h r o n i c , f o c a l /mu1 t i f o c a l (minimal ) hypertrophy, hepatocell u la r (minimal ) hyperplasi a/hyperkeratosi s (moderate) .........d.e.r.m..a.t.i.t i.s.,...c.h.r.o.n.i.c..(.m..i l.d.).................................. THE FOLLOWING TISSUE(S1 WERE WITHIN NORMAL LIMITS: COAGULATING GLAND TESTIS EPIDIDYMIS PROSTATE SEMINAL VESICLES End o f Record- 3145 Page 1275 IV-145 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PEX G E N E R A T I O N ! REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCCL 418-021 S P O N S O R ' S STUOY NUMBER: T-7485. I t Appendix I V I n d i v i d u a l Animal Gross and H i stomorpnologh DaIa F1 Generation GRCSS OESE9VATIOt~iSI: F!STOMORPYCLOGIC O E S E R V A T I O N S : ADRENAL GLANDS: vacuolation, cortex (minimal) LIVER: congestion, acute (moderate) -----__-____________--------------h--y-p-e-r-tr-o-p-h-y-,--h-e--p-a-t-o-c_e-l l-u-l-a-r-_(m-i-n-i-m-a-l-)---------------------------------- THE FOLLOWING TISSUE(5) WERE W I T H I N NORMAL LIMITS: COAGULATING GLAND EPIDIDYMIS KIDNEYS PITUITARY .P.R.O.S.T.A.T.E. . . . . . . . . . . . . . . . . . .S.E.M. .IN.A.L. .V.E. .S.IC.L.E.S. . . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3146 Page 1276 IV-146 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOk) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: 1-7485.13 Appendix IV Individual Animal Gross and Histomorpnology Data F! Generation THE FOLLOWING TISSUE(8) WERE.WITHIN N O W A L LIMITS: .L.IV.E.R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3147 Page 1277 IV-147 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.1: ApDendix I V I n d i v i o u a l Animal Gross and histomorpnology Da:a F1 Generation GRCSS C'?SERVATION(S): HISTOMORPHOLCGIC OESERV'TION!S!. HISTOMORDHOLOGIC OESERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epithelium. papilla (minimal) LIVER: inflamnation. chronic, focal/multifocal (minimal) hypertrophy, hepatocellular (minimal) P. .R.O.S.T.A.T.E.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . a. .tr.o.p. h. .y., . .fo. .c.a.l. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . T Y E F9LLOWINS T!SSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS COAGULATING GLAND EPIDIDYMIS PITUITARY S. .E.M.IN. .A.L. .V.E.S.IC. .L.E.S. . . . . . . . . . .T.E.S.T.I.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3148 Page 1278 IV-148 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOi?'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Apoendix IV Inai v i dual A n i m a l G r o s s anc H i s t o m o r p n o l ogq C a t a F l Generation H!STOuORDKYLOGIC OSSERVATIONS: THE FOLLOW!NG T!SSUE(S) WERE W I T H I N NORMAL L!Y!TS: . Page 1279 IV-149 .ARGUS 4IS-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUDY NUMBER: 1-7485. I? Apoendix IV Individual Animal G r o s s and Histomorpnology Cata F1 Generati on HISTOMORPHOLOGIC OBSERVATIONS: EPIDIDYMIS: infiltration, mononuclear-cell, focal (minimal) KIDNEYS : hyperplasia, tubular/ductul ar epi the1 1 um. pap1 11a (minimal ) edema, papillary, focal (minimal) -P-R_OS_T_AT_E:_______________________in_f_la_m_na_t_io_n.__ch_r_on-i-c--(-m-i--n-i-m-a-l-)------------------------------------------------ THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1280 IV-150 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!CN) REPRODUCTION STUDY OF POTASj IUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!S-021 SPONSOR'S STUDY NUMBER: 1-7465.I; Appenoix I v I n d i v i d u a l Animal Gross ana H i stomorpnolcg) 2a:a Fl Generation HISTOMORPHOLOGIC O S S E R V 4 ' i O h ( S ' . HISTOMOQDHOLOGIC O S S E R V A T I O N S : LIVER: cytoplasmic vacuolation, diffuse (moderate) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f g r o w i n g / a n t r a l follicles U. .T.E.R.U.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.i.g.m.e.n.t.e.d. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page iL81 IV-151 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) R E P R O O U C T I O N STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOZ'S STUDY NUMBER: T-7485.13 Appendix I V Individual Animal Gross and hi stomorphoiogy Dara F1 Generati on H!STOMORPHOLOGIC OSSERVATIONS: MAMMARY GLAND: adenocarcinoma. malignant O V A R I A N FOLLICLES/CORPORA LUTEA: presence of corpora lutea presence o f growing/antral f o l l i c l e s U. .TE.R. U. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.r.o.p.h.a.g.e.s., . .p.ig. m. .e.n.t.e.d. .(.m. i.n.i.m.a.l.). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(8) WERE WITH!N NORMAL L I M I T S : ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C.T. (.S. .) . . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . .V.A.G. .I N. A. . . . . . . . . . . . . . . . . . COMMENTS : NEOPLASMS: Page 1282 IV-152 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41P-021 SPONSOR`S STUDY NUMBER: 1-7485.13 Aooendix IV I n d i v i d u a l A n i m a l G r o s s and H i s t o r n o r p n o i o g y C a t a F1 Generation GPOSS OSSERVOTIOV!S): TISSUErSI NOT 9 V A I L A S L E FOR E V A L U A T I O N : CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT(S) UTERUS V-A-G- -I -N-A- - _ _ - - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ E n d o f R e c o r d - 3153 HISTOP!ORPHO?OGIC OESERV4T!C!V(S). Page 1283 IV-153 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 16-02 1 SPONSOR'S STUDY NUMBEX: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i s t m o r p n o l ogy Daza F! G e n e r a t i on HISTOMORPHOLOGIC OSSE4VATIONS: K--ID-N-E-Y--S-:-----------------------------------m--in-e-r-a-l-i-z-a--t i-o-n-,--m-u-1-t-i-f-o-c-a-l---(m-i-n-i-r-n-a-l -) ------------------------ End o f Record- 3154 Page 1284 IV-154 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i stomorpnology D a t a F1 Generation T ! S S t i E ( S ) NO? A V A I L A B L E FOR E V 4 L U 4 T I O N : CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT ( S) UTERUS V.A.G. .I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3155 Page 1285 IV-155 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix IV Indiviaual Animal Gross and Histomorphology Data F l Generation GROSS OBSERVATION(S). t!ISTOMORPHOLOtIC OBSERVATIONS: EYES: KIDNEYS : H!STOHORPHO?OG!C OL?SSEQVST!OY'fi cataract, bilateral dilatation. cortical tubules, focal (moderate) p y e l i t i s , chronic (moderate) Page 1286 IV-156 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix I V Individual Animal Gross and Histomorpnology Data F! Generat ion GROSS OSSERVATION(S): HISTOMORPHOLOGIC OSSE9VA'!Ch'[S' G-_EN_E-R-A-L-:--N-o--g-r-o-s-s_c-h_a-n_ge_s_. _________________----N--o-t-a--p-p-l-i c--a-b-l-e--------------------------------------------- THE FOLLOW!NG TISSUE(S) WERE WITHIN NORMAL LIMITS: .K.ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3157 Page 1287 IV-157 OR.AL ( G A V k G E ) TWO-GENERATION (ONE L I T T E R PER GENERATION) RiPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTAtiE SULFONATE (PFBS) I N RATS PROTOCOL 4iB-D2! SPONSOZ`S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l Animal G r o s s ana h i s t o m o r p n o l o g y D a t a F1 G e n e r a t i o n THE FOLLOW!NG T I S S U E ( 8 ) WERE W I T H I N NORMAL L I M I T S : Page 1288 IV-158 O R i i (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION] REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFOhATE (PfES) I N RATS PROTOCOL 4 1E - 0 2 1 SPONSOR'S STUDY NUMBER: T-74E5.13 Indivioual Anima: ADDendix IV Gross anc Historncrpnoiogy Data F1 G e n e r a t 1 on Page 1289 IV-159 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.!3 Aopendix I V I n d i v i d u a l A n i m a l Gross and H i stornorohology D a r a F1 G e n e r a t i on THE FOiLOWING T!SSUE(S) WE9E W I T H I N NO?MAL L I H I T S : Page 129Q IV-160 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4i8-0~1 SPONSOR'S STUDY NUMEER: T-7485.!3 Apoendix I V i n d i v i d u a l Animal Gross and Histomorphclogy Data Fl Generation GlCSS O?SSERVAT!CN(S). HISTOMOQWCLOG!C O@SERVC7!CN!S!: H!STOHORPHOLOGIC O B S E Q V A T I O N S : O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora 1utea presence of growing/antral f o l l i c l e s .U.T.E.R.U.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.ig. .m.e.n.t.e.d. .(.m. o. .d.e.r.a.te. .) . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 1291 IV-161 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41P-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . l : Appendix IV Individua: A n i m a l Gross and Histomorpnology Dara F1 G e n e r a t i o n G--E-bi_EQ_A_L._N_o_g_r_os_s_c_n_a n_g_e s_. ____________________N_o _t -a-o-p-l-1-c-a-b-i-e---------------------------------------------------- T!SSUE(S) NOT A V A I L A B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CCRPORA LUTEA OVARIiS OVIOUCT( S) UTERUS VAGINA ....................................................................................................... E n d of R e c o r d - 3162 Page 1292 IV-162 .4RCLS -4 1 S-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 5 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i stornorpnol ogy Data F1 Generation T I S S U E ( S ) NOT A V A I L 4 B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT (S) UTERUS V. .A.G.IN. .A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f Record- 3163 Page 1293 IV-163 -4RGL.S 41S-02 I OR:i (GAVAGE) TUG-GENERATION (ONE L I T T E R PER G E N E R A T i O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 3 6 5 . i? Appendix IV I n o i v i d u a l A n i m a l G r o s s and H l s t o m o r p h o i o g y Oar; F1 G e n e r a t i o n ANIMAL NUMBER: 3164 DOSE GROUP: I ON TEST: GROSS OSSERV:TION(S): TISSUE(S) NOT AVAILP.8LE FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT ( S ) UTERUS .V.A.G.IN. .A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of R e c o r d - 3164 Page 1294 IV-164 O R A L (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (FFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: i - 7 4 8 5 . 1 3 Appendix I V I n d i v i d u a l Animal Gross and Histomorpkclcgy C a r 2 F1 Generarion H!STOMOQPHOLOG!C OBSEQV4TIONS: ADRENAL GLANDS: degeneration, cystic, cortex (mild) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p.r.e.s.e.n.c.e. .o.f. .g.r.o.w.i.n.g./.a.n.t.r.a.l. .f.o.l.l.i.c.l.e.s. . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOW!NG T!SSUE(S) WERE V ! T Y I N NORMAL LIMITS: CERVIX KIDNEYS LIVER OVARIES O. .V.ID. .U.C.T.(.S.). . . . . . . . . . . . . . . . .P. .IT.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . . .U.T.E.R.U.S. . . . . . . . . . . . . . . . . . . . .V.A.G. .I .N.A. . . . . . . . . . . . . . . . . End o f Record- 3165 Page 1295 IV-165 ORAL (GAVAGE) TWO-GENERATION (ONE LITTEG PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSDR'S STUDY NUMBER: i-7485.!3 Apoendix IV Inoiviaual Animal Gross an0 Histornorpnology Cata F i Generation HISTOt!ORPHOLOG!C OOSERVAT!OYS: K-I--D-N-E-Y-S-:------------_______________m_i_ne_r_al_i-z-a-t-i-o-n-,--m-u-l-t-if-o-c-a-l---(-m-i-n-i-m-a-l--)---------------------------------- End o f Record- 3166 Page 1296 IV-166 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Aopendix IV Ind: v i o u a l A n i m a l G r o s s ana Hi s t o m o r p h o i ogy D a t a F1 G e n e r a t i o n F!STCY3RpHOLOE!C OPSERVATIONS: -K-ID-N-E_Y_S-: _----___________________d_i_1a_t_a _t i_on_,_p_e-l-v-i-s--(-m-i-n-i-m-a-l-)------------------------------------------------- End of R e c o r d - 3167 Page 1297 IV-167 ORAL (GAVAGE) TWO-GENERATION (ONE LITTEG PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMEER: T - 7 4 8 5 . 1 3 Indiviaua! Animal Appendix IV G r o s s and H i s t o m o r p h o l o g y Dara F 1 G e n e r a 1 1 on H!STOYORPHOLOG!C CSSEQVATIONS. T`E FOLLOWING '!SSUE!S) WERE W!THIN NORMAL L I M I T S : Page 1298 IY-168 ORA! (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS I U M PERFLUOROEUTANE SULFONATE IPFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMEER: T-7485. I? Appenaix I V 1ndiv:aual Animal Gross and Histomorphoiogy Cata F i Generation ANIMAL NUMEER: 3i6C SEX: F DOSE GROUP: DEATH TYPE: I Schedul :: (Rana H!STOMCRDHO?OG!C O S S E R V A T I O N S : O V A R I A N FOLLICLESiCORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s U_T_ER_U_S:_______________________m_a_c_ro_ph_a_ge_s_. _p_ig_m_en_te-d--(-m--o-d-e-r-a-te-)----------------------------------------------- Page 1299 IV-169 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 . ApDendix I V I n d i v i d u a l Animal Gross and Histomorphoiogy D a t a F l Generation GROSS 09SEQV4T!ON!S): H!STOHORPHOLOGIC O B S E R V A T I O N S : distention (moderate) presence o f corpora lutea presence o f growi ng/antral f o l l ic l es cystic bursa(e) cyst(s), intraovarian ----____d_i s_t e-n--t -i o_n_, _1_um_e_n_(_m_ar_ke_d_) __________________--------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1300 IV-170 .ARGCS 41s-071 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'SSTUDY NUMBER: T - 7 m . 1 3 Appendix I V i n d i v i d u a l Animal Gross and H i stomorpnoiogy Oara F; Generat ion P!STOMOQPHO?OG!C OSSERVATIONS: KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e 1 1 urn. p a p i 11a ( m i n i m a l ) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s UTERUS : macrophages, pigmented (moderate) ------------------------------------------------------------------------------------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1301 IV-171 ARGVS 1I s-011 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION! REPROOUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHaER: T-7465.1; Appendix I V I n o i vioua: Animal Gross ana H i stomorpnoiogk Card Fi Generation G_E_N_EG_S_L:_N_o_g_r_os_s_c_h_an_g_es_. ____________________N_ot_a_p-o-l-i-c-a-b-l-e--------------------------------------------------- HISTOYORPHOLOGIC O B S E R V A T I O N S : O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f g r o w i n g / a n t r a l f o l 1 ic l es U. .TE. .R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.r.o.p.h.a.g.e.s., . .p.ig.m. .e.n.t.e.d. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1302 IV-172 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Apoendix I V I n d i v i d u a l Animal Gross and Histomorpnology Data F1 Generation Page 1303 IV-173 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER G E N E R A T i O h ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTAhE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: 1 - 7 4 5 5 . !3 Appendix IV Inai v i o u a l A n i m a l G r o s s and H i s t o m o r c n c l oay Ca:a Fl Generation ANIMAL NUMBER: 3 1 7 4 SEX: F DOSE GRCUF: DEATH TYPE: 1 S a c r i C:ce-S;wa-'ec T Y E F@LLOW!NG T I S S U E I S ) WERE W I T H I N NORMAL L ! l r I T S : Page 1304 IV-174 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOK) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.13 ADpendix I V I n o i v i d d i a l Afiimal Gross and Histomorpnology Da:a F1 Generation G. .EN.E.R.A.!.. . . .N.o. .g.r.o.s.s. .c.h.a.n.g.e. s. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N. o. .t .a.p. p. .l i.c.a.b.1. .e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSLIE(S\ WERE WITHIN NORMAL LIMITS: Page 1305 IV-175 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOK) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: T-7485.13 Appendix IV Individual Animal Gross and Histomorpnology DaTa F 1 Generati on HISTOMORPHOLOGIC OBSERVATIONS: K-I-D_N-E-Y_S-:-__-_______-____________h_yp_e_rp_l_as_i_a,_t_u-b-u-l-a-r-/d-u-c-:-u-la-r----e-p-i-t-h-e-1--i -u-m-.--p-aD-i--1-1-a--(-m-i-n-i-m-a-l-)------------------ End of Record- 3176 Page 1306 IV-176 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SLILFONTE (PFBS) I N RATS PROTOCOL 418-021 S P O N S O R ' S STUDY NUMBER: T - 7 4 8 5 . 1 : ADpendix I V I n d i v i d u a l Animal Gross and Hi stomorDno~ogyDala F1 Generat 1 on HISTOPORJ!KJ?OGICOOSE9VATIONS: .E.A.R.(.S.).:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.h.o.n.d.r.o.p.a.t.h.y.,. .a.u.r.i.c.u. l.a. r. .(.m. a. .rk.ed THE FOLLOUIYG TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3177 Page 1307 IV-177 OR41 (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!5 1ndiv:aual Animal Appendix I V Gross and Histomorphology Data F1 Generation GQOSS O!SEQVAr!3N(S) HISTCWQPHOLOG!C O?SEQV4T!C!Y:S' HISTOMORPHOLOG!C O B S E R V A T I O N S : O V A R I A N FOLLICLES/CORPURA LUTEA: presence o f corpora lutea presence o f growi ng/antral f o l 1ic l es U. .TE.R. U. .S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s.,. .p.ig. m. .e.n.t.e.d. .(.m. .i l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMA? L!MITS: ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.IE. .S. . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C. .T.(S.). . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . End o f Record- 3178 Page 1308 IV-178 .ARGCS 4I S-02 1 ORAL (GAVAGE) TJC-GENERATION (ONE LITTER P E i l GENERATION 1 REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n a i v i d u a l Animal Gross ana Hi stomorpnol o g j Daxa F i Genera t ion HISTOMORPHOLOGIC O B S E R V A T I O N S : O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s .U.T.ER. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.r.o.p.h.a.g.e.s... .p.i.g.m.e.n. t.e.d. .(.m. .o.d.e.r.a.t.e.). . . . . . . . . . . . . . . . . . . . . . . . . . THE FO!LOW!NG TISSUE(S) WERE W!THIN NORMAL LIMITS: ADRENAL GLANOS CERVIX KIDNEYS LIVER O. .V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O.V. .ID.U.C. .T.(S.). . . . . . . . . . . . . . . . . .P.IT. .U.IT.A. .R.Y. . . . . . . . . . . . . . . . . .V.A.G. .I N. A. . . . . . . . . . . . . . . . . . End o f Record- 3179 Page 1309 IV-179 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOGOBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBE?: 1 - 7 4 8 5 . 1 3 Apoendix IV I n d i v i d u a l A n i m a l G r o s s and Hi s t o m o r p n o l o g y D a h F1 G e n e r a t i on GQOSS OFSERVAT!ON(S): H!STOYOGWCLGG!C C!SEYVr'IOY ( 5 ' HISTOYOQPHOLOS!C OBSERVATIONS: .K.ID.N. E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.i.n.e.r.a. .l i.z.a.t.i.o.n... .m.u.1.t. i. .f o. c. .a.l . .(.m.i.n.i m. .a.l.). . . . . . . . . . . . . . . . . . . . . . . E n d of R e c o r d - 3180 Page 1310 IV-180 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix IV I n d i v i d u a l A n i m a l Gross and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i on GROSS OSSERVATIOY(5): T!SSUE(S) NCT AVA!LAa?E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIOUCT(S) UTERUS V. .A.G.I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3181 HISTOMORDHOLOGIC 05SEQVAT!ON(S) Page 1311 IV-181 .ARGCS 1 1F-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTAHE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR`S STUDY NUMBER: 7-7485.13 Appendlx I V I n d i v l c u a l Animal Gross and h i s t m o r p n o l o g y Data F i Generation Page 1312 IV-182 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTAhE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 6 5 . 1 3 A p ~ e n d i xI V I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F1 G e n e r a t i o n THE COLLOWING T I S S U E ! S ) WERE W I T H I N NORMAL L I M I T S : -K-I D-N- E- -Y -S- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - E n d of R e c o r d - 3163 Page 1313 IV-183 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I v I n d i V I c u a l Anlrnal Gross and HI stornorphol ogy Data F! Generarlon THE FOLLOWING T I S S U E ( S ) WERE WITHIN NORWAL L I M I T S : Page 1314 IV-184 O W L (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASS I U H PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . 1 3 Indivloual Anima: Appendix I V G r o s s and H i s t o m o r p h o l o g y DaTa F1 G e n e r a t i o n GSCSS OSSERV4TION'S): H:STO~ORWOLOG!C @!!SERVLT:ON:S' Page 1315 IV-185 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d l v i d u a l Animal Gross and histomorpnology Data F1 Generation Page 1316 IV-186 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCT [ON STUDY OF POTASS I UM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PR3TOCOL 418-021 S P O N S O K ' S STUDY NUMBER: i - 7 4 6 5 . 1 3 Appendix I V Individual Animal Gross anc Histomorpnology Daza F1 Generation HISTOMORPHOLOGIC OPSSERVATIONS: O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s OVARIES: cyst(s), intraovarian U-_TE_RU_S_: ____-----_---_------------------d-i s-t-e-n--t i-o-n-,---lu-m-e-n--(-m--in--im--a-l)----------------------------------------- THE FCLLOWIKG T!SSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1317 IV-187 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUCY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!8-021 SPONSOR'S STUOY NUMBER: 1-7485.13 Appendix I V Individual Animal Gross and Histornorpnology Data F1 Generation THE FOLLOWING TISSUE(8) WERE WITH!N NORMAL L!MITS: K--I-D-N-E-Y-S---_____--__-____________________-------------------------------------------------- End o f Record- 3188 Page 1318 IV-188 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: T - 7 4 8 5 . 1 3 Appendix I V I n d i v i a u a l Animal Gross and H i stomorpnology Dara F1 Generation GROSS OBSERVATION(S): H!STOMORDHOLOGIC O S S E R V i T ! O Y ( S ) ' Page 1319 IV-189 .ARGL'S 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02: SPONSOR'S STUDY NUMBER: 1-7485.13 Appenaix I V I n o i v i a u a l Animal Gross and Histornorpnology Cat2 F1 G e n e r a t i on ANIMAL NUHSER: 3190 DOSE GROUP: I 1 SEX: .... . . . . . . . . . . . F .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DEATH ...... T . Y . P . E: .. . . . . Sa ... c . ri f .. ic .. e . -S .. cneau ...... iec ... . . . . . . . . . -. -. - - HISTOY@RPY@LOG!C OSSERV4'!OC:S' THE FOLLOWING TISSUE(S) UEqE W I T H I N NORMAL LIM!TS: Page 1320 IV-190 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.1: Aooendix I V Indiviaual Animal Gross and HlstomorDnologj Data F 1 Generation GROSS OBSERV4TION(S): H!STOMOQPHOLOG!C OBSEQV~':CJV( S ' ' THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 1321 IV-191 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E P PER GENERATION) REPR3OUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 7 - 7 4 8 5 . 1 2 Appendix IV I n c i k i d l i a l Animal Gross anc Histomorpnology Oata F1 Generati an GQOSS O?SiSVAi!ONiSI HISTOHORPHOLOG!C OSSERVATIONS: K. .ID.N. .E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d.i.l.a.t.a.t.i.o.n... .p.e.l.v.i.s. . .(.m.i.l.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of R e c o r d - 3192 Page 1322 IV-192 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Apoendix I V I n d i v i d u a l Animal Gross and Histomorphoiogy D?:a F1 Generation Page 1323 IV-193 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41P-021 SPONSOR'S STUDY NUMBER: T-7485.!3 AoDendix I V I n d i v i d u a l Animal Gross and Histomorpnology Data F l Generat ion HISTOMORPHDLOGIC O B S E R V A T I O N S : -K-ID-N-E--Y-S-:-------__--_______________m_i_n_e r_a_l i_z a--t i-o-n--. -m--u--l t-i-f-o-c-a-l--(-m--in-i-m--a-l-) ----------------------------------- End o f Record- 3194 Page 1324 1'4-194 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T - 7 4 8 5 . 1 3 Apoendix IV I n d i v i o u a l A n i m a l Gross and H i s t o m o r p n o l o g y D a t a Fl Generation H!STOHORPHOLOGIC OE!SERVc'!ON!S) ' G_E_N_ER_A_L:_N_o_g_r_os_s _c_ha_n_ge_s_. ___-------------------------N-o-t--a-p-p-l-1-c-a-b-1-e--------------------------------------------- T!SSUE(S) NOT AVAILASLE FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT( S) UTERUS V- -A-G-I N- -A - - - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ E n d of Record- 3195 Page 1325 IV-195 XRGCS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Aopendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F I Generation HISTOMORPHOLOGIC O B S E R V A T I O N S : K. .ID.N.E.Y. .S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i.n.e.r.a.l.i .z.a.t.i o. .n.. . .m.u. .l t.i.f .o.c.a.l. .(.m. .in.i.m. .a.l). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3197 Page 1326 IV-196 .ARGUS 11F-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: T - 7 4 8 5 . 1 3 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l ogy D a t a F1 G e n e r a t i o n GROSS OBSERVATION(S): HISTOMORPHOLOG!C OBSERVATIONS: H!STOMORPHOLOGIC OeSERVATION ( S ) : Page 1327 IV-197 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFBS) I N RATS P R ~ T O C O L418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n o i v i d u a i Animal Gross and histomorpnoicgy Data F1 Generation GPCSS CESSE?VAT!ON(S). HISTOYORL"CL06IC C3SERV4T!0N'S\. THE FOLLOWING T!SSUE(S) WERE WITH!N NORMA? LIMITS: Page 1328 IV-198 ORAL (GAVAGE) TVO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S S'TUDY NUMSER: 1-7485.13 Appendix I V I n d i v i d u a : Animal Gross and Histomorpnolocjy Cata F1 Generat 1on EARIS): Discolored. bilateral, purple; swollen, cnonaropathy. auricular -b-i--1a--re--ra-_l .__------------------------------------------------------------------------------------------- HISTOMORPHCLOGIC OBSERVATIONS: THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL L I M I T S : Page 1329 IV-199 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV I n d i v i d u a l A n i m a l G r o s s and Histomorpnology L a t a F l G e n e r a t 1on GROSS OBSERVATIONfS)' HISTOM0RPHOLOG:C OSSERV4'!O+'S) TWE FOLLOWING T I S S U E ( S ) WEFE W I T H I N N0W4L L I M I T S : Page 1330 IV-200 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Anlmal Gross and H i stomorphology Data F1 Generation HISTOMORPHOLOGIC OBSERVATIONS: End o f Record- 3202 a Page i331 IV-201 .ARGCS 11I-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SCLFONdTE (PFBS) IN RATS PRCTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Aooendix I V icoiviaua! Animal Gross and Histmorpnology Data F1 Generat1on THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIH!TS: K. .I.D.N.E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3203 Page 1332 IV-202 ARGCS 418-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.15 Apoendix I V i n d i v i d u a l Animal Gross and Histomorpnology Data F1 Generation GQOSS @SSERVCTION(S): H!STOWRPH@LOG!C OBSERV4T!ON:S': G_E_NE_R_A!:__N_o_g_ro_s_s_c_ha_n_g_es_. ____________________N_ot_a_p-p-l-i-c-a-b-1-e--------------------------------------------------- Page 1333 IV-203 .ARGVS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SGLFONATE (PFeS) IN RATS PROTOCOL 41a-02; SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix IV Inoi v i a l r a l Animal Gross and Hi s t m o r p h o i o g y Car2 F1 Generation G70SS O?SSERVA?!ON(S). H!STOMORDHOLOG!C CSSERV4TION(S!. ?YE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: .K.I.D.N.E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3205 Page 1334 IV-204 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.12 Appendix I V I n d i v i a u a l Animal Gross and Histomorpnology CaZ3 F1 Generation EPR(S): Discolored. b i l a t e r a l , purple; swollen. chondropathy, auricular --b-i -l a--t e-_r a_l_. ______________________________--------------------------------------------------------------- HISTOYORPHOLOGIC O B S E R V A T I O N S : Page 1335 IV-205 .ARGCS 4I S-0111 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F! G e n e r a t i o n GROSS OBSERVATION(S). HISTOMORPHOLOGIC O?SERV3'13N(S\ HISTOMORPHOLOGIC OBSERVATIONS: THE FOLLOWING T I S S U E ( S 1 WERE W I T H I N NORMAL L I M I T S : .K.ID.N.E.Y. S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f R e c o r d - 3207 Page 1336 IV-206 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROSUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4!8-OZ! SPONSCR`S STUDY NUMGER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r o h o l o g y Data F! G e n e r a t i o n GROSS OSSERVATION(S) T!SSUE(S) NOT A V A I L A Q L E FOR E V A L U A T I O N : CERVIX KIDNEYS OVARIAN FOLLICLES/CORPDRA OVARIES OVIDUCT ( S ) UTERUS LUTEA H!STOMORPHOLOGIC OESERV4T!3N'?' Page 1337 IV-207 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generat ion THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: K. .ID.N.E. Y. .S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3209 Page 1338 IV-208 .ARGUS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-02: SPONSOR'S STUDY NUMGER: T-7485.13 Appendix I V i n d i v i d u a l Animal Gross and Histomorpnoiogy Data F1 Generation THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L!M!TS: .K.ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3210 Page 1339 IV-209 ARGUS 11$02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix I V individual A n i m a l Gross and H i s t o m o r p n o l o g y D a t ? Fl GeneFation Page 1340 IV-210 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPONSOR'S STUDY NUMBER: i - 7 4 8 5 . 1 3 Appendix I V I n d i v i d u a l Animal Gross and Histomorpnoiogy Da:a Fl Generation THE FOLLOWING TISSUE(S) WERE W!THIN NOQMAL L!M!TS: Page 1341 IV-211 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7 - 7 4 8 5 . 2 Appendix IV Indiv~dual Animal Gross and H i s t o m o r p n o l ogy Dala F1 G e n e r a t i on GROSS OBSERVATION(S!: THE FOLLOWING T I s S U E ( S ) WERE W!TH!N NORMAL L I M I T S : K- -I D-N- E- -Y -S- - - - - - - - _ _ - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - End of Record- 3212 Page 1342 IV-212 ARGCTS 418-02 1 ORAL ( W A G E ) lW-6ENERATION (ONE L I T T E R PER CENERATION) REPROOUCTION STUOY OF P O T A S S I W PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l Smss and H i s t a n o r p h o l o g y D a t a F1 Generation GROSS OBSERVATIONfS): HISTOMORPHOLOGIC OBSERVATIONIS): - Page 1343 IV-213 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY 0; POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCGL 4!6-021 S P O N S O R ' S STUDY NUMBER: T-7485.12 Appendix I V I n d i v i o u z l Animal Gross and Histomorphoiogy Cat2 il Generation G 2 C S S OSSEQVAT!ON(S): H!STCYORpHOLOS!C OSSERVATIONS: EYES: atrophy, retinal (mild) -------------------------------------------k-e--r a--t-i t-i-s-,--c-h-r-o-n--lc-.--f-o-c-a--l --(m--i-n-im--a-l-) ------------------------- THE FOLLOWING TISSUE(S) WERE W I T H I N NOQMAL LIMITS: K. .ID.N. .E.Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3214 Page 134-4 IV-214 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENER.4TION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41E-021 SPONSOR'S STUDY NUMBER: T-7485. i j Appendix I V I n a i v i d u a l Animal Gross and H i s t m o r o h o l o g j Data F1 Generation T K E FOLLOW!NC T ! S S U E ( S ) WERE W!THIN NOQMAL LIMITS: Page 1345 IV-215 OR&L (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION: REPR30UCT:ON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFaS) I h RATS PfiOTOCOL 418-021 SPONSOii'S STUDY NUMGER. 1 - 7 4 8 5 . 1 3 Appendix I V I n d i v i d u a l A n i m a l Gross and Histomorphology D a t a F1 G e n e r a t ion Page 1346 IV-216 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTiDN STUDY OF POTASSIUM PERFLUOROBUTAhE SULFONATE (OFBS) I N RATS PROTKC? 416-DZi SPONSOQ'S STUDY NUMBER. T - 7 4 6 5 1 3 Amendix IV I n d i v i c d a i A n i m a l G r o s s and Hisromorohoiogy Car? F 1 Generation HISTOMORPUOLOGIC OSSERVATIONS: K--ID-N-E--Y-S-: ---__----------------------------d-i-l-a-t-a-t-i-o-n-.--p-e-l-v-i-s--(-m-i-n-i-m-a-l-)----------------------------------- End o f Record- 3217 Page 1347 IV-217 ORAL (GAVAGE) TUG-GENERATION (ONE LITTER PE2 G E N E R A T I O N ) REPRC3UCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (FFBS) I N RATS PROTOCOL 4!8-02! SPONSOX'S STUDY NUHGER: 1-7485.13 Appendix I V I n a i v i d u a l Animal Gross and Histornorpnology Gaia F1 Generat 1on GROSS O@SERVATION(S~: THE FOLLOWING T I S S C E ( 8 ) WERE W I T H I N NOQMAL LIMITS: Page 1343 IV-218 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) ( v a s ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE IN RATS PROTOCOL 416-02: SPONSOR'S STUDY NUHPEi?: T - 7 4 8 5 . 1 2 ApDenoix Iv I n o i v i d u a l A n i m a l Gross a n d h i s t o m c r p n o l o g i D a t a F l Generation THE FOL?OW!NG T!SSUE(S) WERE W I T P I N hlORY?L L I M ! T S : Page 1349 IV-219 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERkT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 6 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7465.!2 Appendix I V Indivioual Animal G r o s s and histomorphoiogy Daza F i Generation GROSS CSSERV4T!CY(S): HISTOMORPHOL@G!C @ ? S E ? V 4 T I C V ( S ) . Tt'E CCLLOW!NG T1SSUE:S) WERE W I T H I N NORMAL L I V I T S : -K -I D-N- E- -Y -S- - - - - - - - - - - - - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - End o f R e c o r d - 3220 Page 1350 IV-220 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEPATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUORO8UTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSCR'S STUDY NUMBER: 7-7485.12 ADoendix IV Individual Animal Gross and histomorpnolog) Data il Generat 1 on t!!STOMORPHOLOC!C OE!SERVAT!OYS: KIDNEYS : hyperplasia, t u b u l a r / d u c t u l a r e p i t h e l ium, pap -------------------------------------------m--in-e-r-a-l-i-z-a-t-i-o-n-,--m-u-1-t-i-f-o-c-a-l--(-m--in-i-m--a-l -) -------- End of Record- 3221 Page 1351 IV-221 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER P E R GENERATION) REPRODUZTION STUDY Or P O T A S S I U M PERFLUOROSUTANE SULFONATE (PFBS) I N RATS PROTOLOL 418-021 SPONSO?'S STUDY NUMBER. 1-7465.13 Apoendix I V Inaivicual Animal Gross an3 HiStOmOrDnOiOg:+ D a t a F1 Generation HISTOMORWSLOGIC OPSE9VATIONS: K--ID-N-E--Y-S-:-----____________________hy_p_e_rp_la_s_ia_, --t u--b-u-l-a-r-/-d-u-c-t-u-l-a-r--e-p-i-t-h-e-1-i-u-m-.--p--a-o-i1--1-a--(-m-i-n-i-m-a--l)--------------- End o f Record- 3222 Page 1352 IV-222 .ARGCS 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.1; Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i s t o r n o r p n o l o g y Daca F1 G e n e r a t i o n GROSS OSSERVfiTION(S): HISTOMORPHOLOG!C O@SERVST!ON(S): THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1353 IV-223 ARGUS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l A n i m a l G r o s s and H i stornorphol ogy D a t a F1 G e n e r a t 1 on GROSS OBSERVATION(8): HISTOMORPHOLOGIC OSSERVATION( S 1 : G. .E.N.E.R.A.L.: . .N.o. .g.r.o.s.s. .c.h.a.n.g.e.s... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N.o. .t .a.p.p. .l i.c.a.b. .1e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 1354 IV-224 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION 1 REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.!3 Aopenaix IV i n a i v i a u a l A n i m a l Gross and Histomorpnology O a c a F1 G e n e r a r i o n GR"S O E S E Q V A T I O N ( S ) : HISTOHORPYOLOGIC OESEQVA`I3QjS' T I S S U E ( S ! NOT AVAILABLE FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVAR I ES OVIDUCT ( S ) UTERUS VAG I NA ....................................................................................................... End o f R e c o r d - 3225 Page 1355 IV-225 ARGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (DFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: 7-7485.13 Apoendix I V I n d i v i o u a l Animal Gross and Histornorphoiogy Data F1 Generation GROSS OSSEQVAi!ON(S). H!STOMORPrOLOGIC 03SE9VCTIOY!5'. T l i E FOLLOWING TISSUE(S1 WERE W I T H I N NORMCL LIMiTS: Page 1356 IV-226 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Appendix I V Individual A n i m a l G r o s s and H i s t o m o r p h o ! o g y F1 G e n e r a t i o n Data GSOSS OESERVAT!ON(S). HISTOVORDHOLOGIC OBSERVST!OY(S' THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : Page 1357 IV-227 .4RGCS 1IS-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFeS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1-7465.13 Aopendix IV I n d i v i d u a l A n i m a l G r o s s and H i S t G m G r U h O l O g y Data Fl Generation Gn3SS OESERVFT!ON:S). HISTOMORPHOLOGiC OSSE?VATION(S' Page 1358 IV-228 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCCL 418-021 SPONSOR'S STUDY NUMSER: 1-7485.13 Appendix I V I n d i v i c u a l Animal Gross and Histomorphology Oata F1 Generation THE WLLOWING T I S S U E ( 5 ) WERE WITHIN NORMAL LIMITS: Page 1359 IV-229 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-OZ! SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 ADpenaix I V Individual A n i m a l G r o s s and H i s t o r n o r p h o l o g y D z r a F 1 G e n e r a t i on GRCSS O@SEQV4TION(SI: HISTOMORPHOLOGIC OBSERVATIONS: Page 1360 IV-230 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEUTION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and H i stornorpnology Data F l Generat ion Page 1361 IV-231 ANIMAL NUMEEK: 2 SEX: F ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER G E N E R A T I O N ) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.12 Apoendix IV Individual Animal Gross and histomorpnoiogy Data F1 Generat 1on H!STOMORPHOLOE!C OESERVATIONS: KIDNEYS : basophilia, cortical tubules, focal (minimal) i n f i l t r a t i o n . mononuclear-cell, focal (minimal) --____--____________----------------------------------------------------------------------------------- End of Record- 3232 Page 1362 1V-232 XRGL'S 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 7-7485.13 Appendix I V Inaividual An:rnai Gross a n d Histornorpnoiogy Cata F1 Generation THE FOLLOWING T!SSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1363 IV-233 ORAL (GAVAGE) TWO-GENERATION (ONE L!TTER PEQ GENERATION) REPROCUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-02! SPONSOR'S STUDY NUMBER: 7 - 7 4 6 5 . 1 3 Appendix IV I n d i v i d u a l Anima! Gross and Histomorpnoiogy Dara F1 Generation Page 1363 IV-234 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-74E5.13 Appendix Iv I n d i v i o u a l A n i m a l Gross and H i stomoronoiogy Ea:. FI G e n e r a t i on GQOSS OESE?VFT!CN!S) : H!STOMORDHC?CGIC OSSERVATION(5': Page 1365 IV-235 ORAL (GAVAGE) TWO-GENERATION (ONE L!TTER PER GENERATION) REPRODUCTION STUDY OF POTASSiUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4:a-ozi SPONSGZ'S STliDY NUMBER: 7-7485.13 Appendix IV i n c t i v i o u a : Animal Gross and Histomorcnology CaTa F1 G e n e r a t i o n Page 1366 IV-236 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PEG GENERAT!ON) REPRODUCTION STUDY OF POTASSIUM PERFLUORO3UTANE SULFONATE (PFSS) I N RATS PROTOCOL 418-021 SPONSO2'S STUDY NUMBER: T - 7 4 6 5 .!3 Append:x I V Inoi vidual A n i m a l Gross and liistornorphoicgy Ozta F! G e n e r a t i o n T I S S U E ( S ) NC' A V A I L A S L E FOR E V A L U A T I O N : CERVIX K IDNEYS OVARIAN FOLLICLES/CORPORA OVAR I ES OVIDUCT ( S ) UTERUS VAG I NA LUTEA E n d of R e c o r d - 3237 Page 1367 IV-237 ORAL (GAVAGE) TWD-GENERATION (ONE LITTER PE2 GENERATION) REPROOUCTiON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (Pies) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Apoendix I V Individual Animal Gross and Hisrornorpnoiogy Da:a F i Generation Page 1368 IV-238 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHSER: T-7485.13 Appendix I V Indiviaual Animal Gross and Histomorphology Data F1 Generation HISTOMORDHCLOGIC C?SEQV:'!3h(S) H!STOMORPHOLOG!C OSSERVATIONS: K--ID_N_EY_S_:_______________________d i_l a_t_a t_i o_n_,_p_e_l v_i_s -(-m--i I-d--) ------------------------------------------------------ End o f Record- 3239 Page 1369 IV-239 OM: (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROCUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-02: SPONSOR'S STUDY NUMGER: 1-748i.13 Apoendix I v I n d i v i aual A n i m a l G r o s s and Hi stornorpnoi ogy Data Fl Generation GQOSS O@SEQVAT:ON(S): HISTOMOQoHOLOG!C OBSEQV&"ION`S\. V E FOLCOWING TISSLIE(S) WERE W I T H I N NOQMAL LIMITS: Page 1370 IV-240 ORAL (GAVAGE) TWO-GENERfiTION (ONE LITTER PER GENERATION) REPROCUCTION STUD'! OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS P ~ O T O C O4~18-azi S P O N S O R ' S STUOY NUHBER: 1-7485.15 Appendix I V InCi v i d i l a l Animal Gross and Hi stomorpnology C a t ? F l Generat 1 on G-_EN_E_RA_L_: _No__g r_o_s s__cn_a_ng_e_s.____________________N_o_t _a p--p-l i-c-a-b--l e---------------------------------------------------- HISTOYORPHOLOS!C O B S E R V A T I O N S : Page 1371 IV-241 A N I M A L NUM ER: SEX: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER DER GENE34TION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE S U L F O h 4 i E (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Anpendix I V i n d i v: dJa1 A n i m a l G x s s and H i stomorohol o g D a t a F1 G e n e r a t i o n Page 2372 IV-242 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATIOk) REPRODLETION STUDY OF POTASSIUM PERFLUCROBUTANE SliLFONATE (PFBS) IN RATS PROTOCOL 416-021 SPONSO2'S STUDY NUMBER: T-7485.13 Appenoix I V Inzi v i z d z ; Animial Gross and Hi s t o n c r p n o l cgy Car6 F l Generation IJISTOMORPHOLOG!C OESERVl'i3ViS): HISTOWORPHOLOGIC OFSERVATIONS: EAR( 8) : chondropathy, auricular (marked) KIDNEYS: hemorrhage, papi 1 la (minimal ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.,. .t.u.b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.p.i.t.h.e.1. i. .u.m.,. .p.a.p.i.l.l.a. .(.m.i.I.d.). . . End o f Record- 3243 Page 1373 IV-243 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUH PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . i 3 Appendix I V I n d i v i a u a l A n i m a l G r o s s and H i s : o m o r p n o l o g y Da:a F1 Generation G?OSS OSSC?VATIOU(S): k!!S?OMORpHOLOGIC OBSERVATIONS: Page 1374 IV-244 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV i n d i v i d u a i Animal Gross ana Histomorphoiogy D a t a F i Generati on HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS: h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e l i u m , pap l l a ( m i l d ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a.r.y. ,. . f.o.c. a. .l . .(.m.i.l.d.). . . . . . . . . . . . . End o f Record- 3245 Page 1375 IV-245 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 ApDendix I V I n o i v i d u a ! A n i m a l G r o s s and Hi stornorphology D a t a F1 G e n e r a t i on HISTDMDRDHOLOC!C OsSEQVA710Y!S!. 'age 1376 IV-246 ORAL (GAVAGE) TWO-GENERATION (ONE LITTEil PER GENERATION) REPR3OUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHEER: T-7485.13 Apoendix I V I n d i v i d u a l Animal Gross arid H i stomorpnoiogy Oar? F1 Generation C9OSS OSSESVCTION(S): Page 1377 IV-247 ORAL (G4VAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFON4TE (PCRS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 2 Aooendix I v Individual Animal G r o s s and H i S t O m O r D n O 3gy 0a:a F1 G e n e r a t i o n Page 1378 IV-248 XRGL-S 4 I S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PE2 GENERATION) REPROOUCTION STUDY OF POTASSIUH PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 2 Appendix IV I n o i v l o u a l Anima7 G r o s s and Histomorpnology Gat2 Fl Generation GROSS OSSERVATIONIS' H!STONIRPHOLOGIC GESERV4'!C4iS' ' ?HE FOLLOWING ?!SSUE(S) WERE W!TH!N NORM,4L L I M I T S : Page 1379 IV-249 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PGOTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.12 Appendix I V I n o i v i d u a l Animal Gross and Histomorphology Data F I Generation GQOSS OESEQVATION(Si : H!STOYOQDHC!OG!C C B S E R V S T I O NiS ) ' EAR(S): Swollen, b i l a t e r a l : discolored, chondropathy, auri cu?ar _b_i i_a_t e_r_a l_,_p_u_rp_l e_,____________________________---------------------------------------------------------- H!STOMORPHOLOG!C O B S E R V A T I O N S : .E.A.R.(.S.).:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .c.h.o.n.d. .ro.p.a. .th.y... .a.u. .r.i c. .u.l a. .r. .(m. .a.r.k.e.d.). . . . . . . . . . . . . . . . . . . . . . . . . . . . Page 1380 IV-250 ARGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Aopendix IV Individual A n i m a l Gross and H i s t o m o r p h o l o g y D a t a F i G e n e r a t i on GROSS OBSERVAT!OV(S): HISTOMORPHOLOGIC OSSERVATIONS: HISTOHORPHOLOGIC OBSERVAT!OV(S): IV-251 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.1; Appendix IV I n d i v i a u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Dara i l G e n e r a t i on GROSS OBSERVATION(S). HISTOMORDHOLOGIC OSSERVATIONS: T I S S U E ( S ) NOT A V A I L A B L E FOR E V A L U A T I O N : CERVIX K I ONEY S OVARIAN FOLLICLES/CORPORA OVARIES OVIDUCT(S) UTERUS LUTEA HISTOMORPHOLOGIC OFSEQV?TI3N(S\. Page 1382 IV-252 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFeS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7465.13 Appendix I V I n a i v i d u a l Animal Gross and Histomorphology Data F l Generation Page 1383 IV-253 ORAL (GAVAGE) TWO-GENERATION (ONE LITTEli PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorohclogy Data F1 Generation GROSS OSSERVATION(S): ADRENAL GLANDS: L e f t - 1a r g e ; r i g h t - a r g e . L!VER: L e f t l a t e r a l l o b e , r e d , d a r k e a i s e d area 1 . 5 x l.Gcm. HISTOMORPHOLOGIC OBSE?VATI@N(S): vacuolation, cortical, focal hypertrophy, cortex, diffuse hemorrhage, acute, focal HISTOYORPHOLOGIC OBSERVATIONS: ADRENAL GLANDS: vacuolation, cortical, focal (minimal) hypertrophy, cortex, diffuse (moderate) KIDNEYS : p y e l i t i s , chronic (minimal) .L.IV.E. R. .:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.e.m.o.r.rh. .a.g.e.. . .a.c.u.t.e.,. .f.o.c.a.l. .(.m. .o.d.e.r.a.te. ). . . . . . . . . . . . . . . . . . . . . . . . . COMMENTS: LIVER The hemorrhage i n t h e l i v e r appears t o be o f t r a u m a t i c . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .o.r.i.g.i.n... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3254 Page 1384 IV-254 ARGCS 11S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animzl Gross and Histomorphology Data F1 Generat ion G?OSS @ ~ S ~ Q V A T I O V ( S ) : HISTOMORWOLOG!C OBSEQV&TIOY(S)' GENERA!: No gross changes. Not appl icab1e --------____________----_--------_----__--__-_-----------_--------------_------------------------------ HISTOMORPHOLOGIC OBSERVATIONS: KIDNEYS : -______-------_--------- End o f Record- 3255 dilatation. cortical tubules, focal (mild) necrosis. papilla, focal (mild) basophilia, cortical tubules, focal (mild) _ _ _ _hy_p_er_pl_a_si_a._ _t u_b u_l_a r_/ d_u_c t_u_l a-r- -e-p-i _th-e-1-iu-m- -.- _p a-p- -i l-l-a- -(m- -o-d-e-r-a-t-e--)- - - - - Page 1355 IV-255 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: T - 7 4 8 5 . 1 3 A p p e n d i x !V I n d i v i d u a l A n i m a l Gross and H i s t o m o r p n o 1 o g y D a t a Fl Generation GROSS OSSERVAT!@N(S): t!!STOMORPHOL@GIC OBSERVAT!ONS: Page 1386 IV-256 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUGY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUGY NUMBER: 1-7485.13 Appendix I V Individua: Animal Gross and H i stomorpnology GaIa F1 Generation GROSS OBSERVC:!ON!SI. . EAR(S): Swollen, b i l a t e r a l ; b i 1a t e r a l p u r p l e . discolored. HISTOMORPHOLOGIC OBSERVAT!ON(S). Page 1387 IV-257 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTI O N STUDY OF POTASS I UM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorpnology Data F l Generat ion GROSS OBSERVATION(S): HISTOMOQPHOLOGIC O B S E R V A T I O N ! S ) . HISTOMORPHOLOGIC O S S E R V A T I O N S : K--ID_N-E-Y_S-:___-___________________h_yp_e_rp_l_as_ia_,_t_u_b-u-l-a-r-i d--u-c-t-u-l-a-r--e-p-i-t h--e-l -i u-m--,--p-a-p-i-1-l-a--(-m--i l-d-)----------------------- End o f Record- 3258 Page 1388 IV-258 ORAL (GAVAGE) TWO-GENERATION (ONE LITTEG PER GENERATION) REPRODUCTION STUOY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBE~: 7-7485.15 Appendix IV I n o i v i o u a l A n i m a l Gross and H i s t o m o r p h o i o g ) D a t a F1 G e n e r a t l on GROSS OSSEQV4TION!S) HISTOMOGPHOLOGIC OBSEFVATIONS: H I S T O W R ~ P O L O G I C OSSEQVAT!3Y!S) Page 1389 IV-259 -4RGC.S 4 1S-02 I ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHGER: 1-7485.1: Appendix IV I n o i v i a u a l A n i m a l G r o s s and Histomoroho.Iogy D a r a Fl G e n e r a t 1 on r,?OSS 09SERV4i!ON(S!. HISTOMORPHOLOGIC @ 3 S E R V 4 T ! O Y ( SI : THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL LIMITS: Page 1390 IV-260 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF P O T A S S I U M PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: T-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generation GSOSS 09SERV4:1ON(S): HISTOHORWOLOC!C OBSERVAT!ON(S): EXTREM!TIES: R i g h t f r o n t paw- m i s s i n g d i g i t . 3 r d dermatitis. chronic, focal dig]t . tendonitis, chronic -___________________----------------------------------------------------------------------------------- HISTOMORPHOLOG!C O B S E R V A T I O N S : Page 1391 IV-261 XRGCS 41I-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STU3Y OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: T-7485.1; Apoendix I V Individkal Animal G r o s s and Histomorpnology Data F1 Generation GROSS OBSERVATION(8I: V!STOHOQPHOLOGIC OBSERVATIONS: KIDNEYS : hyperplasia, tubular/ductular epi the1 ium, pap ila (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a.p.i.l.l.a.r. y. .,. .f.o.ca.l. . .(.m.i.n.i.m.a.l.). . . . . . . . . . End o f Record- 3262 Page 1392 1V-262 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUDROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix IV I n d i v i d u a l A n i m a l Gross and Histomorpnology D a t a F 1 Generation GROSS OBSERVATION(8): HISTOMORPHOLOG!C O?SE?V:T!C'4!s): T I S S U E ( 8 ) NOT A V 4 I L A B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT(S) UTERUS .VA.G. .I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E n d o f R e c o r d - 3263 Page. 1393 IV-263 .ARGUS 418-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUOY NUMBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorphology Data F1 Generation HISTOMCRPHOLOGIC O B S E R V A T I O N S : KIDNEYS : h y p e r p l a s f l . t u b u l a r / d u c t u l a r e p i t h e l i u m , pap l l a (minimal) edema, p a p i l l a r y , f o c a l ( m i n i m a l ) ....................................................................................... End o f Record- 3264 Page 1394 IV-264 ARGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 Appendix I V I n d iv i dual Animal Gross and Hi stomcrphcl ogy Data F1 Generation GROSS OSSERVATION(5): HISTOMOR~HOLOGIC 095EGVAT!3N( 5 ) : G--E-N_ER_A_L:_N_o_g_ro_s_s_c_ha_n_ge_s_. __--------------------------N--o-t -a-p--p-l i-c-a-b-1-e-------------------------------------------- THE FOLLOWING TISSUE(S) WERE WITHIN NORMAL LIMITS: Page 1395 IV-265 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GEHERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41E-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Apoendix I V I n a i v i a u a l Animal Gross and Histomorphology Cata F1 Generati on HISTOWRPHOLOGIC O B S E R V A T I O N S : K. .I D.N. .E.Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .i.n.e.r.a.l .i.z.a.t.i.o.n.,. .m.u.1.t.i.f.o.c.a.l. .(.m. .in.i.m. .a.l ). . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3266 Page 1396 IV-266 XRGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV I n d i v i d u a l A n i m a l G r o s s and H i stmorphology D a t a F 1 G e n e r a t i on GQOSS OSSEQVSTION(S): HISTOMORPHOLOGIC OBSERVATIOY: SI ' HISTOMORPHOLOGIC OBSERVATIONS: OVARIAN FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growi n g / a n t r a l f o l 1ic l e s U. .TE.R. .U.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .d.i.s.t.e.n.t.i.o.n.,. .l.u.m.e.n. .(.m. .i n. i.m. .a.l ). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T I S S U E ( 5 ) WERE W I T H I N NORMAL L I M I T S : C. .E.R.V.I.X. . . . . . . . . . . . . . . . . . . . .O.V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C.T. .(.S.). . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . T I S S U E ( S 1 NOT A V A I L A B L E FOR E V A L U A T I O N : K. .I D.N. E. .Y.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3267 Page 1397 IV-267 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUDROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix I V I n o l v l c u a l Animal Gross and HistomorphcloGg Data F! Generation GQQSS OBSERVA7!@N(S): HISTOMORPHOLOGIC O!?SE9V?'!OY!S': H!STOMOQDHOLOGIC O B S E R V P T I O N S . KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e 1 i um, p a p i 11a ( m i n i m a l ) -------____---_________________ed_e_m_a,_p_a_p_i l_l a_r y--, --fo-c--a-l --(m--i-n-im--a-l-) --------------------------------------------- End o f Record- 3268 Page 1398 IV-268 ARGUS 418-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROSUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 ApDendix I V I n d i v i d u a i Animal Gross and H i stomorphol ogy Oars F1 Generati on HISTOMORPHOLOGIC O B S E R V A T I O N S : K--ID-N-E-Y-S--: -_____________________e_d_em_a_. _p_a p_i_l l_a r_y-.--fo--c-a-l --(-m-i-n-i-m-a-l-)--------------------------------------------- End o f Record- 3269 Page 1399 IV-269 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 7-7465.13 Appendix I V Individual Animal Gross and Histomorpnology Data F 1 Generat i on - TA!?. Tip missing. 16.0cm from base. necrosis abscess H I S T O ~ O Q ~ Y C L O G IOCBSERV4TIONS: TAIL: necrosis (mild) abscess inflamnation, chronic (moderate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y.p.e.r.p.l.a.s.i.a.l.h.y.p.e.r.k.e.r.a.t.o.s.i.s. .(.m.o. d. .e.r.a.t.e.). . . . . . . . . . . . . . . . . . . . . . . T I S S U E ( S ) NOT A V A I L A B L E FOR E V A L U A T I O N : CERVIX KIDNEYS OVARIAN FOLLICLES/CDRPDRA LUTEA Page 1400 IV-270 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTAS jIUH PERFLUOROBUTANE SULFONATE ( P F B S ) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUHBEK: 1-7485.13 Appendix I V I n a i v i d u a l Animal Gross and Histomorpho1ogy Oa:a F1 Generation GROSS 09SEWVATION(S): HISTOHORPHOLOGIC 09SERV4T!ON:S): EAR(S): Swollen, b i l a r e r a l : discolored, chondropathy, auricular _b_i l_a_t e_r_a _l , _p_u_r p_l_e .____________________________----------------------------------------------------------- H!STOM09DYOLOGIC O B S E R V A T I O N S : EAR(S): chondropathy, auricular (mild) -K-ID-N--E-Y-S_: ______________________h_y p_e_r p_l_a s_i a_,_t_u b_u-l-a-r-/-d-u-c_t u--l a_r--e-p-i-t h--e-l i-u-m--. --p-a-p--i l-l-a--(-m-i-n-im--a-l-)-------------------- End o f Record- 3271 Page 1401 IV-271 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOG'S STUDY NUMBER: T-7485.13 Apoendix I V I n d i v i d u a l Animal Gross and Hlstomorpnology Oar2 F1 Generation G70SS OBSERV4TION(S). HISTOMORDHOLOGIC OBSERV47I@N(S): HISTOMORW!OLOGIC OBSERVATIONS: EAR( S ) : chondropathy, auricular (moderate) O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .p.re. s. e. .n.c.e. .o.f. .g.r.o.w.i.n.g. /.a.n. .tr.a.l. .f.o. .l l.i.c.l.e.s. . . . . . . . . . . . . . . . . . . . . . . . TFE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1402 IV-272 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR`S STUDY NUMBER: 1-7485.13 Appendix I V I n o i v i d u a i Anlmal Gross and HI stomorpnology Data F1 Generation HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS : O V A R I A N FOLLICLES/CORPORA LUTEA: U. .T.E.R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . necrosis, papilla, focal (mild) hyperplasia, tubular/ductular epithel lum. papilla (mild) presence o f corpora lutea presence o f growing/antral f o l l i c l e s ---- . . . m. .a.c.r.o.p.h.a.g.e.s... .p.i.g.m. .e.n.t.e.d. .(.m.o. .d.e.r.a.te. .) . . . . . . . . . . . . . . . . . . . . . . . --- Page 1403 IV-273 .ARGCS 4 1S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCT!ON STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 ApDendix IV Indi v i dua: A n i m a l G r o s s ana H i stornorpnol ogy b r a Fl Generation GQOSS OBSERVPT!Oh`(S): T!SSUE(S) NOT A V A I L 4 B L E FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA LUTEA OVARIES OVIDUCT ( S ) UTERUS V. A. G. .I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3274 Page 1404 IV-274 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUF PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . !3 Appendix I V I n d i v i d u a l Animal Gross and Histomorpno12gy Ea:? F1 Generat ion G!?CSS C3SERVC?!ONfS\: H!STOMORPHOLOCIC OBSERVATIONS: KIDNEYS : hyperplasia, p e l v i c l p a p i l l a r y u r o t h e l ium (minimai) cyst(s), medulla hemorrhage, papi 11a (minimal ) hyperplasia, tubular/ductular epithelium. papilla (minimal) Page 1405 IV-275 .ARGCS 4 IS-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROEUTANE SULFOSATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMEER: 1-7485.13 Appendix I V i n d i v i d u a l Animal Gross and Histomorpholog) Oara Fi Generation G R O S S OBSERVATION(S). HISTOMORWOLOGIC OBSEQVFTIOY!S! HISTOMORPHOLOGIC O B S E R V A T I O N S : KIDNEYS : hyperplasia, tubular/ductular epithelium, papilla (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ed.e.m. .a., . .p.a.p. .i l.l.a.r.y... .f.o.c.a.l. .(.m. .in. .im. .a.l.) . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3276 Page 1406 IV-276 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE ( P F B S ) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.12 Appendix I V I n d i v i d d a l Animal Gross and H i stomorpnologj Daca F! G e n e r a t i o n H!STOMORPHCLOG!C 03SERVATIONS: K-_ID_NE_Y_S_: ___-__________------------h-y-p--e-r-p-la-s-i-a-,--t-u-b-.-u-la--r/-d-u-c-t-u-l-a-r--e-p-i-t -h-e-l i-u-m--.--p-a-p--i l-l-a--(-m-i-n-i-m-a-l-)------------- End o f Record- 3277 Page 1407 IV-277 XRGUS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROEUTANE SULFONATE (PFGS) I N RATS PROTOCOL 318-021 SPONSOR'S STUDY NUMBER: 1-7465.13 Apoendix I V I n d i v i d u a l Aninal Gross and Histomorphology Data F1 Generati on HISTOMORPYOLOGIC O B S E R V A T I O N S : KIDNEYS : h y p e r p l a s i a , t u b u l a r / d u c t u l a r e p i t h e i urn, p a p i 11a (moderate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e.d.e.m.a.,. .p.a. .p.i.l l.a. r.y. ., . .fo.c. .a.l . .(.m.i.l.d.). . . . End o f Record- 3278 Page 1408 O2AL (GAVAGE) TWO-GENERATION (ONE L i T T E 9 PER GENERATION) REPRODUCTION STUDY OF POTASS!UM PERFLUOROEUTANE SULFONATE (PFES) I N RATS PROTOCOL 418-021 SPONSCR'S STUDY NUMBER: T - 7 4 8 5 . 1 3 Apoendix IV I n d i v i o u a l A n i m a l Gross and H i s t o m o r p n o 1 o g y Data F l Generation CROSS 3SSERVATION:S). HISTOYORPHOLOtIC OeSiRVATION(S). Page 1409 IV-279 XRGUS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRCDUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE ( P F B S ) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-7485.13 Appendix IV Individual A n i m a l G r o s s and H i s t o m o r p h o l o g y D a t a F1 Generation GROSS CBSERVATIONfS): HISTOMORPHOLOG!C OSSERVATIONS: HISTOMORPHOLOGIC O@SERVAT!ON(S): Page 1410 IV-280 ORAL (GAVAGE) TUO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 2 Appendix I V inaivioua1 A n i m a l Gross and tiistomorpnoiogy D a r a F1 Generation HISTOMORPHOLOGIC OESERVATIONS: KIDNEYS: basophilia, cortical tubules, focal (minimal) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . h. .y.p.e.r.p.l.a.s.i.a... .t u. .b.u.l.a.r./.d.u.c.t.u.l.a.r. .e.p. .i t.h.e.1. .iu.m. ... .D.a.p.i.l.l.a. .(.m. .in.i.m. .a.l) End o f Record- 3281 Page 1411 IV-281 ARGCS 115-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDEUTANE SULFONATE (PFaS) I N RATS PROTCCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 6 5 . :3 A p p e n d i x IV I n o i v i d u a l A n i m a l G r o s s and t i i s t o m o r o n o l o g y E z r a Fi Generation G--E-N-E-R-A-L-: -_No__gr_o_ss__ch_a_ng_e_s.____________________-N--o -t -a-p-p--l -ic-a--b -1-e------------------------------------------------ T!SSUE(S) NOT A V A I L A B L E FOR EVALUATION: Page 1412 IV-282 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.15 Aooendix I V individual A n i m a l G r o s s and Histomormology D a t a F i G e n e r a t i on GROSS O@SERV4T!@N(S): Page 1413 IV-283 .hRGLS 11s-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENEUTION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTAhE SULFONATE (PFBS) I N RATS PROTOCOL 4 1 8 - 0 2 1 SPONSOR'S STUDY NUMBER: T-74ES. 1 3 Appendix I V Indi viaual Animal Gross and hi stomoronoiogy Data F i Generation HISTONIRPPOLOGIC OSSERV:':ClY(S). H!STOMO?PYO?CSIC OBSERVATIONS: EXTREMITIES: dermatitis, chronic, focal (mild) OVARIAN FOLLICLES/CORPORA LUTEA: presence of corpora 1 utea presence of growl n g / a n t r a i fol iicl es -U-TE-R-U-S--:-----------------------------------m--a-c-ro-p-h-a-g-e-s-,--p-i-g-m--e-n-te-d--(-m--i-l d--) -------------------------------- THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C.T.(.S. ). . . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . . V. .A.G.IN. .A. . . . . . . . . . . . . . . . . End o f Record- 3284 Page 1414 IV-284 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPROCUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 41e-02 1 SPONSOR'S STUDY NUMBER: T-7485.1: Apoendix I V ! n d i v i c l u a ? A n i m a l G r o s s and H i s t o r n o r p n o i o g y Data F1 G e n e r a t 1on HISTOMOQPHOLOGIC OESEQV4T!ON:S!: THE FOLLOWING T!SSUE(S! WERE W I T H I N NORMAL LIM!TS: -K-ID-N-E_Y_S ___-__-___________________________---------------------------------------------- End of Record- 3285 Page 1415 IV-285 .ARGCS 41I-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSCR'S STUDY NUMBER: 1-7485.13 Appendix I V I n d i v i d u a l Animal Gross and Histomorpnoiogy Cata F l Generati on SqOSS 02SEQV4T!9N(S:. AESOMINAL C A V I T V Mass, 0 . 5 x 0 2 x 0 lcm. y e l l o w i n c o l o r , connecred proximal t o the spleen and pancreas. ' HISTOMORPHOLOGIC O S S E R V A T I O N ( S ' Tissue not available HISTOHORPHOLOGIC O E S E R V A T I O N S : O V A R I A N FOLLICLES/CORPORA LUTEA: presence of corpora 1utea presence o f growing/antral f o l l i c l e s U. .T.E.R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.c.r.o.p.h.a.g.e.s.,. .p.i.g.m.e.n.t.e.d. .(.m. .o.d.e.r.a.t.e.) . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL L I M I T S : ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O.V.I.D.U.C.T.(.S.). . . . . . . . . . . . . . . . .P. .IT.U. .I T.A.R.Y. . . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . TISSUE(S) NOT AVAILABLE FOR EVALUATION: .A.B.D.O.M.I.N.A.L. .C.A.V. I.T.Y. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3286 Page 1416 IV-286 .qRGUS 11F-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROGUTANE SULFONATE (PFSS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: T-7485.12 Apoendix I v Individual Animal Gross and hlstomorproicgy Dzrz F1 Generation G--E-E-iE_R._4L_: _No__gr_o_ss__ch_a_ng_e_s.____________________N_o_t -a-p-p-l-i-c-a-b-i-e--------------------------------------------------- H!STOMORDHOLOGIC O B S E R V A T I O N S : O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l 11 c l es U. .T.E.R.U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m. .a.cr.o.p.h.a.g.e.s.,. .p.i.g.m. .e.n.te. .d. .(m. .o.d.e.r.a.t.e.). . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS CERVIX KIDNEYS LIVER O. .V.A.R.I.E.S. . . . . . . . . . . . . . . . . . . .O.V. I.D.U.C. .T.(S.). . . . . . . . . . . . . . . . .P.I.T.U. .I T.A.R.Y. . . . . . . . . . . . . . . . . . .V.A.G.I.N.A. . . . . . . . . . . . . . . . . . End of Record- 3287 Page 1417 IV-287 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY O F POTASSIUM PERFLUOROEUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7465.12 Appendix I V I n d i v i d u a l Animal Gross and H i stornorohology Ca;a F1 Generatl on H!STOflORPHOLOGIC O B S E R V A T I O N S : O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora 1utea . presence o f g r o w i n g / a n t r a l f o l l i c l e s U. .TE.R. .U.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s. . .p.i.g.m.e.n.t.e.d. .(.m. .o.d.e.r.a.te.). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING T!SSUE(S) WERE WITHIN NORMAL LIMITS: Page 1418 IV-288 ORAL (GAVAGE) TUO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUORDBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMSER: 7-7485.13 Appendix I V I n d i v i o d a l Animal Gross ana H i stomorpho'ogy Dara il Generation GROSS CESERVAT!ON(Sf: HISTOMORPHOLOGIC OSSERVAT:ON!S'. H!STOMOQoHOLOGIC S S S E R V A T I O N S . O V A R I A N FOLLICLES/CORPORA LUTEA: UTERUS: presence o f corpora lutea presence o f growl ng/antral f o l 1ic l es macrophages, pigmented (moderate) TEE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: ADRENAL GLANDS KIDNEYS LIVER OVARIES O. .V.ID. .U.C.T.(.S.). . . . . . . . . . . . . . . . .P.I.T.U.I.T.A.R.Y. . . . . . . . . . . . . . . . . .V.A.G. .IN.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . COMMENTS : CERVIX The c e r v i x was r e c e i v e d damaged and t h e s e c t i o n t h a t c o u l d be . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .o.b.t.a.i.n.e.d. .w.a.s. .n. .o.t.a. .d.e.q.u.a.t.e. .f.o.r. .e.v.a.l.u.a. .t i.o.n. .. . . . . . . . . . . . . . . . . . T!SSUE(S) NOT AVAILABLE FOR EVALUATION: C. .E.R.V.I .X. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End o f Record- 3289 Page 1419 IV-289 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPROOUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFOhATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T - 7 4 8 5 . i? Aopendix IV I n d i v i d u a l A n i m a l G r o s s and H 1 s : o m c r p n o i o g y 0a:a Fi Generation GROSS O?SEPV4TION(S' HISTOHORPHOLGGIC OBSERVATIONS: Page 1420 IV-290 XRGCS 41S-02 1 ORAL (GAVAGE) TWO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSDZ'S STUDY NUMBER: T-7485.13 Appendix IV Individual Animal Gross and h i sromorphoiogg CaKa F1 Generati on HISTOMOP~HOLOCIC OSSERVATIONS: KIDNEYS : LIVER: OVARIAN FOLLICLES/CORPORA LUTEA: hemorrhage, papi 1 la (mi Id) infiltration, mononuclear-cell, focal (minimal) basophilia, cortical tubules, focal (mild) hyperplasia, tubular/ductular epi the1 ium. papilla inflamnation, chronic, focal/rnulti focal (minimal) presence of corpora lutea presence of growing/antral follicles (mi Id) THE FOLLOWING T I S S U E ( S ) WERE W I T H I N NORMAL L I M I T S : AORENAL GLANDS CERVIX OVARIES OVIDUCT ( S ) .P.IT. .U.1.TA.R. Y. . . . . . . . . . . . . . . . . . .U.T.E.R.U.S. . . . . . . . . . . . . . . . . . . . .V.A.G. I.N.A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . End of Record- 3291 Page 142 1 IV-291 ORA? (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1-7485.13 Appendix I V Inai v i a u a l Animal Gross and H i stomorpnology Data F1 Generation G--E-N-E_RA_?:__No_g_r_os_s_c_ha_n_ge_s_. __--------------------------N--o-t -a-p-p--l i-c-a-b-l-e-------------------------------------------- H!STOYOR~YOLOOIC OBSERVATIONS: K. .ID.N.E. .Y.S.:. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .h.y. p. .e.r.p.la. .s.ia. ., .t.u.b.u.l.a.r./.d.u.c.t.u.l.a.r. . .e.p.i.th. e. .1.i.u.m... .p.a.p.i.1.l.a. .(.m. .i I.d. ). . . . End of Record- 3292 Page 1422 IV-292 ORAL (GAVAGE) TVO-GENERATION (ONE L I T T E R PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N GATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: 1 - 7 4 8 5 . 1 3 ApDendi x I V I n d i v i d u a l A n i m a l G r o s s and H i s t o m o r p h o l o g y Cata F1 G e n e r a t i o n GROSS OBSE9VCTION(S). HISTOMORPHOLOGIC OBSERVATIONS: HISTOMORPHOLOGIC OBSERVA'!ON(S\ Page 1423 IV-293 .ARGTS -118-021 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMGER: T-7435.1; Appendix I V Indivioual Animal Grass and Hi stomorpnology DaTa F l Generarion C?OSS OESERVZTION(SI. HISTOYOQPHOLG6!C OSSERVATIONS: HISTOM09DHOLOGIC OESERV?T!GN(S!, Page 1424 IV-294 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) I N KATS PROTOCOL 418-021 SDONSOR'S STUDY NUMBER: T-7485.13 Aopendix I V I n d i v i d u a l A n i m a 1 G r o s s and H i s t o m o r p n o i o g y O a r a F1 G e n e r a t i on GQOSS C5SERVArIOY(S): H!STOMCRWOLOGIC C?S!SVA-ION(S). G_E_NE_R_AL_: _N_o_g_ro_s_s_c_ha_n_g_es_. ____________________N _o t_a_p-p-l -i-c-a-b1--e---------------------------------------------------- T I S S U E ( S ) NOT AV$!L4BLE FOR EVALUATION: CERVIX KIDNEYS OVARIAN FOLLICLES/CORPORA OVARIES OVIDUCT(S) UTERUS VAG INA LUTEA Page 1425 IV-295 ORAL (GAVAGE) TWO-GENERATION (ONE LITTEG PER GEhERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-621 S P O N S O R ' S STUDY NUMBER: T-7485.13 Appendix I V I n d i v i d a a i Animal Gross and Histomorpnology DaKa F1 Generat 1 on HISTCMOQPHOLOG!C O B S E R V A T I O N S : O V A R I A N FOLLICLES/CORPQRA LUTEA: presence o f corpora lutea presence o f growl n g i a n t r a l f o l 1i c l es U. .TE. R. .U.S.: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .m.a.c.r.o.p.h.a.g.e.s... .p.i.g.m.e.n.t.e.d. .(.m. .o.d.e.r.a.te. ). . . . . . . . . . . . . . . . . . . . . . . . . . . . THE FOLLOWING TISSUE(S) WERE W I T H I N NORMAL LIMITS: Page 1426 IV-296 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) R i P R O D U C T I O N STUDY OF P O T A S S I U M PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.13 Aopendix I V I n d i v i d u a l Animal Gross and Histomorphology Da:a F1 Generation G R O S S OBSERV4T!ON(S): H!STO~OR~HCLOGICOSSERVATION(S): HISTOMORPHOLOGIC OBSERVATIONS: O V A R I A N FOLLICLES/CORPORA LUTEA: presence o f corpora lutea presence o f growing/antral f o l l i c l e s U--TE-R--U-S-:-------___---______________m_ac_ro_p_ha_g_es-,--p-i-g-m-e-n--te-d--(-m--o-d-e-r-a-te--) ---------------------------------------- THE FOLLOWING TISSUE(S1 WERE W I T H I N NORMAL L I P I T S : COWENTS: CERVIX The c e r v i x was r e c e i v e d damaged and t h e s e c t i o n t h a t c o u l d be . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .o.b.t.a.i.n.e.d. .w.a.s. .n. .o.t.a. .d.e.q.u.a.t.e. .f.o.r. .e.v.a.l.u.a.t.i.o.n... . . . . . . . . . . . . . . . . . TISSUE(S) NOT AVAILABLE FOR EVALUATION: Page 1427' 1V-297 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 416-021 SPONSOR'S STUDY NUMBER: T-7485. I? Appendix I V I n d l v l a u a l Animal Gross and Histomorpnology Data F1 Generation Page 1428 IV-298 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF P O T A S S I U M PEGFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTCCOL 418-021 SPCNSOR'S STUDY NUMSER: T - 7 4 6 5 . 1 3 Appendix I V I n d i v i o m l Animal Gross and Histomorphology Data F I Generation Gil9SS CSSERV*'ION(S): HISTOMORPHOLOG!C OESERVAT!O+(S'. Page 1429 IV-299 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) I N RATS PROTOCOL 418-021 SPONSOR'S STUDY NUMBER: T-7485.1: Apoenaix IV I n a i v i dual A n i m a l Gross and Hi s t o m o r p n o i ogy O a r a F i Generation G9CSS OESERV4TIONfS): T ! S S V E ( S ) NOT AVA!LASLE FOR EVALUATION: Page 1430 IV-300 APPENDIX L SPERM EVALUATION CHARLES RIVER MBORATORIES SPEREl ANALYSIS REPORT FOR ORAL, (GAVAGE) TWO-GENERATION (ONE LITTER PER GZNERATION) FSPRODUCTION STUDY OF POTASSIUM PEFSLUOROBUTANE SULFONATE (PFBS) IN RATS PRIMEDICA-ARGUS STUDY NUMBER: 418-021 PREPARED FOR PRIMEDICA-ARGUS RESEARCH LABORATORIES, INC. 905 SHEEHY DRIVE, BUILDING A HORSHAM, PA 19044-1297 PREPARED BY PATHOLOGY ASSOCIATES (PA11 A DIVISION OF CHARLES RIVER LABORATORIES, INC. 15 Worman's Mill Court, Suite I, Frederick, MD 21701 301.663.1644 FAX: 301.663.8994 www.criver.com/products/pathology Page 1432 Primedica-Argus S t u a y No . . 418-021 TABLE OF CONTENTS Section Paae No . I. QUALITY ASSURANCE STATEMENT . . . . . . . . . . . . . . . . . . . . . . . . . . 4 II. MATERIALS AND METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 A.. Sample Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 B . Sperm Motility Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . 5 C . Total Sperm Count Determination . . . . . . . . . . . . . . . . . . . 5 D . Sperm Morphology Evaluation . . . . . . . . . . . . . . . . . . . . . . 6 E . Statistical Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 F . GLP Compliance Statement . . . . . . . . . . . . . . . . . . . . . . . . . . 6 111. RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 A . Sperm Motility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 B . Total Sperm Count . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 C . Sperm Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 IV. DISCUSSION AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 V . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2 Page 1433 Primedica-Argus Scuay NO.: 418-021 INDEX OF TABLES AND APPENDICES Table Paae No. 1. Summary of P Generation Sperm Analysis Paraiieters . . . . . a 2 . Summary of F. Generation Sperm Analysis Parameters . . . . 10 Paae No. A. Individual P Generation Male Sperm Motility and Count Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 B. Individual Fi Generation Male Sperm Motility and Count Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 C. Individual P Generation Male Sperm Morphology Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 D. Individual F, Generation Male Sperm Morphology Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3 Page 1434 ARGCS 41S-02 I _ _ CHARLES RIVER LABORATO~ES Discovery and Dweioprnent Senices htholcgy .%wJcidres Sperm Analysis Report Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Potassium Perfluorobutane Sulfonate (PFBS) in Rats Primedica-Argus Study Number: 418-021 QUALITY ASSURANCE STATEMENT This sperm analysis project has been inspected and audited by the PAI Quality Assurance Unit (QAU) as required by the Good Laboratory Practice (GLP) regulations promulgated by the U.S. Environmental Protection Agency (EPA) and the Organization for Economic Cooperation and Development (OECD). The sperm analysis report is an accurate reflection of the recorded data. The following table is a record of the inspections/audits performed and reported by the QAU. Date of InsDectiOfl 06R5/01 1 1/05.06/01 1 1/05.OW01 03/20/03 Phase insDected Date Findings Reported to Reproductive Toxicologist/ PA1 Management Date Findings Reported to Study DirectorIStudy Director Management Sperm Motility Individual Animal Data Draft Sperm Analysis Report Final Sperm Analysis Report 06/25/01 1 1/OfdO1 1 1/06/01 03/20/03 11/07/01 11/07/01 11/07/01 03ROI03 Karen E. Butler Quality Assurance Manager 4 Page 1435 XRGLS 11$02 1 ?rirnedica-hrgus S:udy No.: 418-021 Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Potassium Perfluorobutane Sulfonate (PFBS) in Rats 11. MFITERIALS AhD METHODS A . Samnle Collection Following compieLion of their respective cohabitation periods, all surviving adult male rats from the P and F. generations were euthanized by carbon dioxide asphyxiation. F o r all animals, a gross necropsy of the thoracic, abdominal and pelvic visceral was performed. PA1 technicians using PRL Standard Operating Procedures conducted the necropsy. The sperm analysis, including motility assessment, was conducted by PA1 using PA1 Standard Operating Procedures. For motility assessment, the right vas deferens was dissected away from the testis and immediately placed in a petri dish containing 10 ml of a solution consisting of 1% Bovine Serum Albumin dissolved in Phosphate Buffered Saline. The solution was prewarmed to a temperature of approximately 38oC. A minimum 3minute period was allowed for the sperm to disperse from the vas deferens . The right epididymis was then removed, weighed and divided in half by cross sectioning at the middle. The cauda and distal midsection was placed on dry ice and transferred to Pathology Associates, A Division of Charles River Laboratories, Inc. (formerly known as Pathology Associates International until January 8, 2001), Frederick, MD and stored frozen at -70C until evaluation for caudal epididymal sperm and testicular spermatid counts (total sperm counts). B. SDerm Motilitv Evaluation Following the dispersal period, a sperm sample was obtained using a 100 deep cannula. The cannula was immediately loaded into the prewarmed stage of the Hamilton Thorne IVOS automated sperm analyzer. Five fields were automatically selected by the analyzer and each motion image was recorded and stored digitally. The images were subsequently analyzed for percent motility. The images were permanently stored to optical media. C. Total SDerm Count Determination Each frozen epididymis was removed from the freezer, thawed and the caudal section was trimmed and weighed. Each frozen testis was removed from the freezer, thawed, the tunica removed and the testicular parenchyma weighed. The cauda epididymis and 5 Page 1436 Prineaica-Argus Study No.: 418-021 testicular parenchyma were homogenized in deionized water and the suspensions were transferred to plastic test tubes and vortexed. A 100 p1 sample was transferred to a violet reaction vial containing a Hoechst dye ( H 3 3 3 4 2 ) that uniquely stains the head of the sperm. A sample of the stained sperm was placed into a 20 I,lm deep Cell-Vu glass slide that was loaded into the analyzer. TwenKy fields were automatically selected by the analyzer for each animal and the number of cauda epididymal sperm and testicular spermatids determined. The counts reported were adjusted for caudal epididymal or testicular weight. D. SDerm Momholouv Evaluation Two Eosin stained slides were prepared for each animal from the caudal epididymis count preparation. The slides were evaluated and a minimum of 200 sperm cells/animal was examined f o r morphological development. E. Statistical Analyses The means and standard deviations for the sperm motility, caudal epididymal sperm count, testicular spermatid count and sperm morphology data were calculated and compared across groups using the Kruskal-Wallis nonparametric ANOVA test. If a significant effect occurred (p<O.O5),the Mann-Whitney U test was used for pair-wise comparisons of each treated group to the control group. Statistical analyses were performed using an IBMm compatible computer with SAS computer programs (SAS/STAT User's Guide, 1989). F. GLP ComDliance Statement The portion of this study performed by PA1 was conducted in compliance with Good Laboratory Practice Regulations cited below: 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 16O/Part 792. Organization for Economic Cooperation and Development (1988). The Revised OECD Principles of Good Laboratory Practices [ C ( 9 7 ) 186/Final]. 6 Page 1437 Primeaica-Argus Study No.: 418-023. ARGYS 4 1 S-02 1 111. RESULTS A. SDe-m Notility Table 1 and 2 (Summary Data) Appendix A and B (Individual Data) No apparent treatment-related effects were observed in the percent motility data for either generation. Group mean values were comparable between the study groups and ranged from 94% to 95% and 92% to 95% for the P and the F, generations, respectively. KO evidence of reduced motility due to treatment with PFBS was observed. B. Total Sperm Count Table 1 and 2 (Summary Data) Appendix A and B (Individual Data) The number of sperm/gram of cauda epididymis was comparable between the study groups for both generations. Group mean values ranged from 956.7 to 1033.2 million sperm/gram for the P generation and 769.8 to 928.4 million sperm/gram for the F, generation. No treatment-related differences were observed. A statistically significant reduction in the number of spermatids/gram of testis was observed in the 1000 mg/kg/day dose group of the P generation. The difference was not considered biologically meaningful since there was not a similar statistical reduction observed in the F, generation. Group mean values for the F, generation ranged from 106.6 to 124.0 million spendgram of tissue. C . Sperm Morpholoav Table 1 and 2 (Summary Data) Appendix C and D (Individual Data) A low incidence of head and/or tail abnormalities was observed for animals in all treatment groups of both sacrifice periods. No treatment-related differences were observed. Group mean values were comparable between the study groups and ranged from 1.5 to 2.0 percent abnormal sperm for the P generation. An incidental but statistically significant increase in the percent of abnormal sperm in the 1000 mg/kg/day dose group of the F, generation was observed. This increase was not considered biologically meaningful since the mean percent of abnormal sperm in the P and F, 1000 mg/kg/day dose groups was equivalent. 7 Page 1438 Prirredica-Argus Study No.: 4 1 8 - 0 2 1 .ARGUS -1I S-@2I IV. DISCUSSION AND CONCLUSIONS Sperm motility, epididymal sperm count, testicular spermatic cocint and sperm morphoiogy were not affected by treatment with PFSS at dosage levels of 30, 100, 300 and 1000 mg/kg/day in t h e P or F, generations. No biologically meaningful differences were groups of either generaEion. Reproductive Toxicologist Pathology Associates A Charles River Company Date: 3/zo/oa V. REFERENCES SAS Institute Inc., SAS/STAT User's Guide, Version 6 , Fourth Edition, Cary, NC:SAS Institute Inc., 1989. Vol. 2 p . 1195-1210. 8 Page 1439 .ARGUS 4 1S-011 PRIMEDICA-ARGUS STUDY NO.: 4 1 8 - 0 2 1 TA3LE 1 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PEP. GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SLZFONATE (PFBS) IN FSTS SUMMARY OF P GENERATION S P E M ANALYSIS PfiRAMETEiiS Group : Level: PFBS (MG/KG/DAY) MOTILITY ( % ) Mean SD K EPIDIDYMAL COUNT (MILLION SPEFUUGRAM) Mean SD N TESTICULAR COUNT (MILLION SPERM/GRAM) Mean SD N SPERM MORPHOLOGY ( % ABNORMAL) Mean SD N I TI I11 I v v 0 30 100 300 io00 96 95 94 95 95 4 5 12 4 5 30 30 30 30 28 1030.4 209.1 30 1033.2 226.2 30 956.7 217.1 30 1018.9 181.3 30 969.4 274.7 29 147.9 38.9 30 135. I 34.0 30 146.4 36.1 30 132.3 20.5 30 121.8* 35.7 29 1.7 2.0 1.6 1.5 2.0 1.5 1.3 1.0 0.6 0.6 30 30 30 30 29 "MEAN AND STANDARD DEVIATIONS WERE CALCULATED USING THE TOTAL NUMBER OF ABNORMAL SPERM AS A PERCENTAGE OF THE NUMBER OF SPERM EXAMINED. SIGNIFICANTLY DIFFERENT FROM CONTROL ( p < 0 . 0 5 ) . 9 Page 1440 '2RIMEDICA-ARGUS STUDY NO.: 4 1 8 - 0 2 1 TABLE 2 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) RZPRODUCTION STL3Y OF POTASSIUM PERFLUOROBUTANE SULFONATE (PPBS) IN M T S SUMMARY OF F1 GENERqTION SPERM ANALYSIS PARUlETERS Group : Level: PFBS (MG/KG/DAY) MOTILITY ( % ) Mean SD EPIDIDYMAL COUNT (MILLION SPERM/GRAM) Mean -93 N TESTICULAR COUNT (MILLION SPERM/GRAM) Mean SD N SPERM MORPHOLOGY ( % ABNORMAL) Mean SD N I I1 111 IV v 0 30 100 300 1000 92 92 94 95 92 10 10 6 3 10 29 26 29 27 27 836.6 257.2 29 769.8 282.4 27 839.9 261.5 29 856.6 221.6 27 928.4 n3.3 27 124.0 32.8 29 109.4 33.7 27 107- 0 29.2 29 109.5 24.2 27 106.6 31.7 27 1.5 1.3 1.4 1.5 1.9* 0.7 0.6 0.5 0.6 0.5 29 27 29 27 27 dMEAN AND STANDARD DEVIATIONS WERE CALCULATED USING THE TOTAL NUMBER OF ABNORMAL SPERM AS A PERCENTAGE OF THE NUMBER OF SPERM EXAMINED. 'SIGNIFICANTLY DIFFERENT FROM CONTROL ( p c o .0 5 ) . ~ 10 Page 1441 .ARGCS 4 1S-0111 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX A O W L (GAVAGZ)TWO-GENERATION (ONE LITTER PER GEIERATION) REPROCUCTION ST'JDY OF POTASSIUM PERFLUOROBWANE S'ULFONATE (PFBS) IN RATS INDIVIDUAL P GENERATION SPERM MOTILITY C0LTF.T DAT.4 Group I: 0 MG/KG/DAY (PFBS) Animal No. Mo tillty (8) SPERM COUNT Homogenization Resistant Caudal Testicular Ep1dldymal (million sperm/gran) 0-15401 94 0-15402 99 0-15403 97 0-15404 100 0-15405 99 0-15406 98 0-15407 76 0-15408 98 0-15409 96 0-15410 97 0-15411 97 0-15412 99 0-15413 98 0-15414 100 0-15415 . 100 0-15416 98 0-15417 97 0-15418 100 0-15419 92 0-15420 99 0-15421 94 0-15422 98 0-15423 94 0-15424 97 0-15425 96 0-15426 92 0-15427 97 0-15428 97 0-15429 95 0-15430 98 104.4 127.1 140.3 177.9 106.3 185.o 146.8 132.9 104.5 152.1 196.8 136.1 224.9 167.7 127.1 155.3 122.8 134.6 164.7 122.1 112.8 107.8 192.1 202.3 157.7 105.5 128.6 259.4 131.5 108.9 706.6 921.8 1481.8 1318.2 1376.0 946.7 853.3 857.8 1230.4 1012.4 1115.8 1008.3 1377.3 801.4 1110.1 918.7 1069.5 906.4 1059.2 871.7 798.0 802.5 1171.5 1135.4 1295.9 917.7 1000.5 667.5 1221.4 957.6 11 Page 1442 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX A ORAL (GAVAGE)TWO-GENERATION (ONE LITTZR PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL P GENENITION MALE SPERM MOTILITY AND COUNT DATA Gro-p 11: 30 MG/KG/DAY (PF3S) Ilrlimal No. Motility (%) SPERM COUKT Homogenization Resistant Caudal Tes t'icu 1ar E;, 1didyma 1 (million spe-m/gram) 0-15431 99 0-15432 82 0-15433 95 0-15434 95 0-15435 96 0-15436 98 0-15437 98 0-15438 98 0-15439 96 0-15440 99 0-15441 98 0-15442 97 0-15443 98 0-15444 95 0-15445 96 0-15446 97 0-15447 100 0-15448 89 0-15449 94 0-15450 98 0-15451 98 0-15452 85 0-15453 92 0-15454 98 0-15455 78 0-15456 97 0-15457 98 0-15458 93 0-15459 98 0-15460 95 172.0 128.8 123.4 120.9 107.1 160.6 143.9 127.2 103.6 110.4 97.9 115.7 124.1 167.4 105.0 222.4 159.5 153.3 125.1 213.8 135.8 110.2 98.5 166.0 101.1 146.6 108.4 103.5 197.2 122.7 948.8 1500.6 1255.7 655.7 756.0 1261.6 1050.3 1190.1 1157.1 983.5 806.3 882.3 1011.5 542.6 704.5 1201.9 952.4 1045.5 1174.1 782.2 912.8 1106.9 921.5 1217.3 1269.1 1013.4 1468.3 1225.7 965.4 1032.8 12 Page 1443 .ARGCS 41S-02 1 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX A ORAL (GAVAGE) T W O - G W ~ R ~ T I O(NONE LITTER PER GENZRATION) RZTRODUCTION STL?Y OF POTASSIUM PERFLUOROBUTANE: SULFONATE (PFES) IN FLATS INDIVIDUAL P GZNERATION SPERM MOTILITY DATA Group III: 100 MG/KG/DA'I (IFBS) A n i m + l No. Mot111ty (%I SPERM COUNT Homogenizatron Resistant Caudal Testicular 2p 1didyma1 (mi11ion sperm/gram) 0-15461 99 0-15462 94 0-15463 97 0-15464 100 0-15465 95 0-15466 98 0-15467 88 0-15468 96 0-15469 96 0-15470 94 0-15471 97 0-15472 100 0-15473 99 0-15474 36 0-15475 95 0-15476 97 0-15477 93 0-15478 99 0-15479 93 0-15480 97 0-15481 98 0-15482 98 0-15483 96 0-15484 91 0-15485 98 0-15486 97 0-15487 92 0-15488 98 0-15489 76 0-15490 100 120.3 167.6 150.3 157.9 93.8 139.9 148.0 110.8 110.5 197.9 116.4 126.4 160.0 143.6 105.7 116.4 111.8 147.8 158.7 132.7 161.4 166.4 261.3 154.5 191.0 167.1 89.7 202.2 130.5 152.7 665.3 724.2 810.0 776.2 1228.9 1193.0 1232.7 906.4 1157.1 1188.6 942.2 955.7 975.3 1172.5 794 * 5 1259.9 835.7 1403.4 540.0 825.1 727.3 1070.3 674.3 1076.1 731.3 925.7 1115.0 731.4 1066.2 995.9 13 Page 1444 ARGUS 41S-02 1 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX A ORFLL (GAVAGE) TWO-GENERATION ( O N E LITTER PER GEKiRATION) REPRODCCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN R*.TS INDIVIDUAL P GENZRATION MALE SPERM MOTILITY FAT COUNT DATA Gro,Ap I\/3: 00 MG/KG/DXY (PFBS) A n i m a l No. Motility (8) SPERM COUNT Homogenization Resistant Cauda 1 Tescicular Ep1didyma 1 (million spem/gram) O-i5491 0-15492 0-15493 0-15494 0-15495 0-15496 0-15497 0-15498 0-15499 0-15500 0-15501 0-15502 0-15503 0-15504 0-15505 0-15506 0-15507 0-15508 0-15509 0-15510 0-15511 0-15512 0-15513 0-15514 0-15515 0-15516 0-15517 0-15518 0-15519 0-15520 97 96 98 97 99 93 97 87 94 97 93 99 100 99 97 83 96 94 93 98 92 100 98 100 96 88 94 97 100 92 124.4 144.8 117.1 120.6 152.0 129.0 137.2 128.4 18s.5 174.4 104.4 119.3 134.2 154.0 149.9 134.2 127.1 131.0 133.3 106.0 120.3 134.1 129.3 117.9 136.2 107.2 129.6 123.2 93.2 170.0 1359.6 1057.9 821.2 1025.4 686. o 785.2 983.5 1059.9 948.8 1111.6 1136.4 852.4 1330.6 948.1 729.5 747.7 996.1 1053.3 885.8 1432.4 1234.2 1054.7 1070.3 994.2 884.3 985.8 1091.5 971.2 1131.4 1199.2 14 Page 1445 .ARGUS 118-02 I PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX A ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION ST'VDY OF POTASSIUM PEWLUOROBUTANE SULFONATE (PFSS) IN FATS INDIVIDUAL P GENERATION MALE SPERM MOTILITY AND COUNT DATA Group V: 1000 MG/KG/DAY (PFBS) Animal No. Mot ill ty (6) SPERM COUNT Homogenization Resistant Caudal Testicular E pidiayma 1 (million sperm/gram) 0-15521 O-i5522 0-15523 0-15524 0-15525 0-15526 0-15527 0-15528 0-15529 0-15530 0-15531 0-15532 0-15533 0-15534 0-15535 0-15536 0-15537 0-15538 0-15539 0-15540 0-15541 0-15542 0-15543 0-15544 0-15545 0-15546 0-15547 0-15548 0-15549 0-15550 96 83 99 94, 94 97 94 99 a 99 89 95 98 97 94 98 98 99 99 94 96 81 96 97 100 97 b a5 97 97 101.5 134.4 104.4 138.6 175.3 167.5 132.6 110.7 0.0 106.4 119.6 96.4 102.4 168.2 101.5 121.1 175.2 141.9 119.6 123.4 102.1 92.6 100.1 117.7 100.1 193.3 126.3 130.0 128.1 941.6 1123.1 754.0 874.8 1055.3 1108.1 991.3 697.9 0.0 900.9 1016.6 974.6 805.8 1121.2 1109.2 655.7 678.8 1119.8 1283.6 1628.5 1133.9 925.7 1071.4 1137.1 921.0 1002.8 1018.2 1250.5 810.0 'NO SPERM PRESENT FOR ANALYSIS. bA.NIMAL DIED PRIOR TO SCHEDULED NECROPSY. 15 Page 1446 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX B ORAL (GAVAGE) TWO-GENEFATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PEWLUOROBUTANE SULFONATE (PFBS) IN .RATS INDIVIDUAL F:GENEII\TION MALE SPERM MOTILITY AND COUNT 3ATA Group I: 0 MG/KG/DAY (3FBS) Animal No. Motility (%) SPERM C O U N T Homogenization Resistant Cauaal Testicular E p 1diayma1 (million sperm/gram) 0-03001 54 0-03002 94 0-03003 96 0-03004 97 0-03005 91 0-03006 95 0-03007 59 0-03008 99 0-03009 94 0-03010 99 0-03011 97 0-03012 98 0-03013 91 0-03014 97 0-03015 89 0-03016 95 0-03017 95 0-03018 90 0-03019 95 0-03020 96 0-03021 a 0-03022 99 0-03023 94 0-03024 91 0-030 2 5 97 0-03026 98 0-03027 90 0-03028 94 0-03029 83 0-03030 88 94.2 102.6 205.6 114.2 141.3 82.0 131.6 137.9 146.8 128.7 156.8 108.8 150.5 105.4 91.8 82.0 101.8 90.4 90.2 127.0 136.6 120.1 112.7 140.2 223.6 105.6 110.2 117.0 139.3 734.3 844.7 475.2 925.7 480.6 495.4 933.9 907.0 661.9 567.0 703.5 600.8 772.6 1108.6 854.7 1085.3 781.0 447.7 567.7 937.6 983.5 1045.1 1135.4 1203.4 778.0 1037.1 972.0 1349.9 871.9 'ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 16 Page 1447 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX B ORAL (GAVAGE)TWO-GENEFATION (ONE LITTER PER GENERATION) REPRODUCTION STLiiY OF POTASSIUM PERFLUOROBUTFNE SULFONATE (PFBS) IN RATS INDIVIDUAL F:GENERATION MALE SPERM MOTILITY AND COUNT DATA Group 11: 30 MG/KG/DAY (PFBS) Animal No. - 0-03031 0-03032 0-03033 0-03034 0-03035 0-03036 0-03037 0-03038 0-03039 0-03040 0-03041 0-03042 0-03043 0-03044 0-03045 0-03046 0-03047 0-03048 0-03049 0-03050 0-03051 0-03052 0-03053 0-03054 0-03055 0-03056 0-03057 0-03058 0-03059 0-03060 Motility (8) 96 92 85 ai 97 94 98 a 99 91 98 98 92 a7 94 a 97 96 99 66 89 92 98 94 54 b 96 96 100 a SPERM COUNT Homogenization ResistanC Caudal Testicular E p id idyma1 (million sperm/grarn) 116.4 181.2 75.0 139.7 73.6 109.6 103.6 81.6 125.0 94.4 150.9 103.0 86.1 107.1 92.2 90.8 178.7 92.6 110.4 102.0 93.9 124.2 96.7 27.6 109.5 112.9 175.0 647.1 721.5 636.4 797.1 665.3 1004.1 569.3 848.5 865.3 911.2 697.8 959.4 574.4 526.7 752.1 772.6 1 2 06 10 . 68 702.8 1192.1 1268.5 591.4 703.2 0.0 1028.0 8 9 1 10 997.5 "ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. b~~~~ THAN 25 SPERM CELLS COUNTED; EXCLUDED FROM STATISTICAL A N A L Y S I S . 17 Page 1448 PRIXEDICA-ARGUS STUDY NO.: 4 1 8 - 0 2 1 APPEKTDIX a O W L (GAVAGE) TWO-GENERATION ( O N E LITTER PER GENERATION) REPRODCCTI3N STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFES) IN RATS INDIVIDUAL F;GENEmTION MALE SPERM MOTILITY AND COUl:T DATA Group 111: 100 MG/KG/DAY (PFES) Azinal No. Mot ilicy (8) SPERM COUNT Homogenization ResisLant Caudal Testicular Ep161ayma1 (million sperm/gram) ~ 0-03061 0-03062 0-03063 0-03064 0-03065 0-03066 0-03067 0-03068 0-03069 0-03070 0-03071 0-03072 0-03073 0-03074 0-03075 0-03076 0-03077 0-03078 0-03079 0-C3080 0-03081 0-03082 0-03083 0-03084 0-03085 0-03086 0-03087 0-03088 0-03089 0-03090 96 a 99 94 98 92 94 9s 9s 98 84 91 93 96 95 9s 100 95 100 99 99 96 93 98 71 92 95 96 90 87 99.7 108.0 61.6 102.2 89.7 105.4 62.9 173.2 90.7 139,O 73.9 74.8 112.0 93.6 101.3 112. a 99.5 117.3 85.4 140.2 147 .5 105.6 90.6 165.7 103.0 95.0 165.1 107.4 80.0 918.0 703.2 1250.4 640.5 801.1 603.3 727.3 1049.6 752.1 636.4 536.9 907.2 664.3 599.2 841.9 634.3 1179.3 735. 9 502.7 894.5 640.8 876.7 888.3 874.2 1817.3 799.4 925.7 990.5 967.0 "ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 18 Page 1449 - .ARGCS 418-02 1 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX B ORrzL (GAVAGE)TWO-GENERATION (ONE LITTER PER GPNERATION) REPRODUCTION STUDY OF POTASSIUM PEFGLUOROBUTANE SULFONATE IPFBS) IN RATS INDIVIDUAL F.GENERRTION W E SPERM MOTILITY AND COLTNT DATA Grcup IV: 300 MG/KG/DAY (PFBS) Animal No. Mot ii1ty (8) SPERM COUNT Homogenization Resistant Caudal Testicular E p ididyma1 (millior. sperm/gram) 0-03091 0-03092 0-03093 0-03094 0-03095 0-03096 0-03097 0-03098 0-03099 0-03100 0-03101 0-03102 0-03103 0-03104 0-03105 0-03106 0-03107 0-03108 0-03109 0-03110' 0-03111 0-03112 0-03113 0-03114 0-03115 0-03116 0-03117 0-03118 0-03119 0-03120 96 91 .90 94. 94 a a a 93 94 93 94 97 87 99 95 98 98 97 92 94 95 95 87 99 97 91 99 99 97 98.9 82.9 149.7 69.2 108.9 98.3 95.4 87.1 145.6 71.5 156.0 111.9 102.5 89.5 133.3 120.3 134.5 99.4 100.5 147.3 79.5 106.8 109.4 140.9 103.5 112.0 100.8 1157.1 596.1 907.2 670.3 544.3 1065.5 975.3 407.7 801.4 1072.5 737.6 880.2 824.9 743.8 934.9 505.7 1002.8 734.5 956.8 685.0 941.6 1265.1 1243.9 582.5 942.8 918.0 1031.7 "ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 19 Page 1450 ARGCS 41S-02 I PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX B 0% (GAVAGE) TWO-GENER4TION (ONE LITTER PER GENZRATION) REPRODUCTION STUDY Or" POTASSIUM PZRFLUOROBUTANE SULFONATE (PFBS) IN KATS INDIVIDUAL F.GENERATION MALE SPERM MOTILITY COUNT DATA Group TI: 1000 MG/KG/DAY (PCBS) Zillirnal No. Moti1ity (8) SPERM COUNT Homogenization Resistant Caudal Testicular Ep ididyma 1 (million sperm/gram) 0-03121 0-03122 0-03123 0-03124 0-03125 0-03126 0-03127 0-03128 0-03129 0-03130 0-03131 0-03132 0-03133 0-03134 0-03135 0-03136 0-03137 0-03138 0-03139 0-03140 0-03141 0-03142 0-03143 0-03144 0-03145 0-03146 0-03147 0-03148 0-03149 0-03150 94 67 94 98. 96 98 95 95 94 93 53 90 91 99 94 a a 87 98 9a 97 94 98 99 95 a 89 94 99 ai 158.5 157.3 84.2 83.8 81.7 86.2 90.3 86.2 110.5 199.1 114.2 65.5 loa. 5 90.4 107.7 115.7 104.7 107.6 109.7 151.7 99.5 105.1 66.1 77.9 82.3 85.2 149.8 789.3 211.0 970.5 640.a 959.4 921.2 1019.0 590.5 1276.a 1027.5 1095.1 942.a 562.6 1049.6 937.6 511.a 913.3 657.2 1020.7 817.7 1142.2 1004.2 993.2 1344.0 1330.6 925.7 1412.4 "ANIMAL DIED PRIOR TO SCHEDULED NECROPSY 20 Page 1451 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX C ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN wrs 1NI)IVIDUAL P GENERATION MALE SPERM MORPHOLOGY DATA GROUP I: 0 MG/KG/DAY (PFBS) 0-15401 197 0-15402 195 0-15403 197 0-15404 197 0-15405 196 0-15406 198 0-15407 199 0-15408 197 2 0-15409 196 0-15410 200 % 0-15411 188 c P 0-15412 199 VI 0-15413 192 td 0-15414 197 0-15415 200 0-15416 196 0-15417 198 0-15418 189 0-15419 196 0-15420 198 0-15421 200 0-15422 200 0-15423 197 0-15424 198 0-15425 196 0-15426 194 0-15427 198 0-15428 197 0-15429 194 0-15430 199 3 0 0 0 5 0 0 0 3 0 0 0 3 0 0 0 2 2 0 0 2 0 0 0 1 0 0 0 3 0 0 0 4 0 0 0 0 0 0 0 2 2 8 0 1 0 0 0 3 0 5 0 3 0 0 0 0 0 0 0 4 0 0 0 2 0 0 0 8 0 3 0 4 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 2 0 0 0 4 0 0 0 6 0 0 0 2 0 0 0 3 0 0 0 3 0 3 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 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 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 21 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX C ORAL (GAVAGE TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL P GENERATION MALE SPERM MORPHOLOGY DATA GROUP 11: 30 MG/KG/DAY (PFBS) 0-15431 0-15432 0-15433 0-15434 0-15435 0-15436 0-15437 0-15438 3 0-15439 09 0-15440 CD 0-15441 c P 0-15442 wl 0-15443 w 0-15444 0-15445 0-15446 0-15447 0-15448 0-15449 0-15450 0-15451 0-15452 0-15453 0-15454 0-15455 0-15456 0-15457 0-15458 0-15459 0-15460 196 198 197 197 191 198 197 199 197 196 199 198 198 200 197 196 191 194 195 196 196 189 197 190 198 199 196 196 195 197 4 0 0 0 2 0 0 0 3 0 0 0 3 0 0 0 3 0 6 0 2 0 0 0 3 0 0 0 1 0 0 0 3 0 0 0 4 0 0 0 1 0 0 0 2 0 0 0 2 0 0 0 0 0 0 0 3 0 0 0 4 0 0 0 9 0 0 0 3 0 3 0 5 0 0 0 4 0 0 0 4 0 0 0 11 0 0 0 3 0 0 0 10 0 0 0 2 0 0 0 1 0 0 0 4 0 0 0 4 0 0 0 5 0 0 0 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 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 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 22 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX C ORAL (GAVAGE) TWO-GENERATION (ONE LITTEH PEK GENERATION) REPHOUUC'I'ION S'I'UDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL P GENERATION MALE SPERM MORPHOLOGY DATA GROUP 111: 100 MG/KG/DAY (PFBS) 0-15461 196 0-15462 197 0-15463 198 0-15464 199 0-15465 194 0-15466 196 0-15467 197 0-15468 198 w 0-15469 199 P, 09 0-15470 197 0 0-15471 199 R c 0-15472 197 0-15473 198 P 0-15474 200 0-15475 199 0-15476 191 0-15477 197 0-15478 193 0-15479 196 0-15480 196 0-15481 194 0-15482 197 0-15483 198 0-15484 195 0-15485 198 0-15486 196 0-15487 197 0-15488 198 0-15489 197 0-15490 198 4 0 0 0 3 0 0 0 2 0 0 0 1 0 0 0 4 0 2 0 4 0 0 0 3 0 0 0 2 0 0 0 1 0 0 0 4 0 0 0 1 0 0 0 3 0 0 0 1 1 0 0 0 0 0 0 1 0 0 0 9 0 0 0 3 0 0 0 6 1 0 0 4 0 0 0 4 0 0 0 6 0 0 0 3 0 0 0 2 0 0 0 5 0 0 0 2 0 0 0 4 0 0 0 3 0 0 0 2 0 0 0 3 0 0 0 2 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 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 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 23 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX C ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION s ' r u w OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL P GENERATION MALE SPERM MORPHOLOGY DATA GROUP IV: 300 MG/KG/DAY (PFBS) 0-15491 196 0-15492 194 0-, 15493 197 0-15494 195 0-15495 195 0-15496 196 0-15497 196 F 0-15498 197 0-15499 197 0-15500 198 % 0-15501 197 CL P 0-15502 199 tn 0-15503 197 VI 0-15504 198 0-15505 197 0-15506 196 0-15507 198 0-15508 198 0-15509 198 0-15510 197 0-15511 199 0-15512 198 0-15513 196 0-15514 196 0-15515 198 0-15516 199 0-15517 199 0-15518 197 0-15519 197 0-15520 198 4 0 0 0 6 0 0 0 3 0 0 0 5 0 0 0 5 0 0 0 4 0 0 0 4 0 0 0 3 0 0 0 3 0 0 0 2 0 0 0 3 0 0 0 1 0 0 0 3 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 2 0 0 0 1 0 1 0 2 0 0 0 3 0 0 0 1 0 0 0 2 0 0 0 4 0 0 0 4 0 0 0 2 0 0 0 1 0 0 0 1 0 0 0 3 0 0 0 3 0 0 0 2 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 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 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 24 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX C ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STIJDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL P GENERATION MALE SPERM MORPHOLOGY DATA GROUP V: 1000 MG/KG/DAY (PFBS) 0 -15521 0-15522 0-15523 0-15524 0-15525 0-15526 0-15527 0-15528 2 0-15529 OQ 0-15530 0 0-15531 + P 0-15532 VI 0-15533 o\ 0-15534 0-15535 0-15536 0-15537 0-15538 0-15539 0-15540 0-15541 0-15542 0-15543 0-15544 0-15545 0-15546 0-15547 0-15548 0-15549 0-15550 193 195 196 197 197 198 196 196 196 197 195 194 195 196 197 196 197 196 197 197 194 197 196 195 197 195 a 197 198 196 7 0 0 0 5 0 0 0 4 0 0 0 3 0 0 0 3 0 0 0 2 0 0 0 3 1 0 0 4 0 0 0 4 0 0 0 3 0 0 0 4 1 0 0 6 0 0 0 5 0 0 0 4 0 0 0 3 0 0 0 3 1 0 0 3 0 0 0 4 0 0 0 3 0 0 0 3 0 0 0 5 1 0 0 3 0 0 0 4 0 0 0 2 0 3 0 4 0 0 0 5 0 0 0 3 0 0 0 2 0 0 0 3 1 0 0 'ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 25 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 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 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 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX D ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL F, GENERATION MALE SPERM MORPHOLOGY DATA 0-03001 0-03002 0-03003 0-03004 0-03005 0-03006 0-03007 0-03008 F 0-03009 09 0-03010 CD 0-03011 R c 0-03012 0-03013 4 0-03014 0-03015 0-03016 0-03017 0-03018 0-03019 0-03020 0-03021 0-03022 0-03023 0-03024 0-03025 0-03026 0-03027 0-03028 0-03029 0-03030 196 198 197 196 197 199 198 197 198 191 197 196 197 198 197 197 199 198 198 197 a 196 198 197 195 198 197 196 197 198 3 0 1 0 2 0 0 0 3 0 0 0 4 0 0 0 3 0 0 0 1 0 0 0 1 1 0 0 3 0 0 0 2 0 0 0 3 0 6 0 3 0 0 0 3 1 0 0 2 1 0 0 2 0 0 0 3 0 0 0 3 0 0 0 1 0 0 0 2 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 2 0 0 0 3 0 0 0 5 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 3 0 0 0 2 0 0 0 'ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 26 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 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 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 PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX D ORAL (GAVAGE TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL F, GENERATION MALE SPERM MORPHOLOGY DATA GROUP 11: 30 MG/KG/DAY (PFBS) 0-03031 197 0-03032 200 0-03033 196 0-03034 197 0-03035 198 0-03036 2 00 0-03037 199 0-03 038 a 0-03039 198 2 0-03040 196 w 0-03041 199 w P 0-03042 197 VI 0-03043 196 00 0-03044 196 0-03045 198 0-03046 a 0-03047 197 0-03048 197 0-03049 198 0-03050 196 0-03051 198 0-03052 198 0-03053 196 0-03054 197 0-03055 197 0-03056 195 0-03057 198 0-03058 197 0-03059 197 0-03060 a 2 1 0 0 0 0 4 0 0 2 1 0 2 0 0 0 0 0 1 0 0 2 0 0 4 0 0 1 0 0 3 0 0 4 0 0 4 0 0 2 0 0 3 0 0 3 0 0 2 0 0 2 0 2 2 0 0 2 0 0 4 0 0 3 0 0 3 0 0 5 0 0 2 0 0 2 1 0 3 0 0 'ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 27 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 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 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 0 0 0 ~~ ~~~ PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX D ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUC'PION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL F, GENERATION MALE SPERM MORPHOLOGY DATA GROUP 111: 100 MG/KG/DAY (PFBS) 0-03061 198 0-03062 0-03063 198 0-03064 197 0-03065 197 0-03066 196 0-03067 198 2 0-03068 196 0-03069 197 % 0-03070 0-03071 198 196 w c 0-03072 196 VI 0-03073 197 \o 0-03074 197 0-03075 196 0-03076 196 0-03077 195 0-03078 197 0-03079 199 0-03080 198 0-03081 198 0-03082 197 0-03083 198 0-03084 199 0-03085 197 0-03086 196 0-03087 198 0-03088 198 0-03089 196 0 - 03090 197 2 0 0 0 2 0 0 0 3 0 0 0 3 0 0 0 4 0 0 0 2 0 0 0 4 0 0 0 3 0 0 0 2 0 0 0 3 1 0 0 4 0 0 0 3 0 0 0 3 0 0 0 3 1 0 0 4 0 0 0 2 0 3 0 3 0 0 0 1 0 0 0 2 0 0 0 2 0 0 0 3 0 0 0 1 1 0 0 1 0 0 0 3 0 0 0 4 0 0 0 2 0 0 0 2 0 0 0 4 0 0 0 3 0 0 0 'ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 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 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 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 2a I PRIMEDICA-ARGUS STUDY NO.: 418-021 APPENDIX D ORAL (GAVAGE TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS INDIVIDUAL F, GENERATION MALE SPERM MORPHOLOGY DATA GROUP IV: 300 MG/KG/DAY (PFBS) 0-03091 0-03092 0-03093 0-03094 0-03095 0-03096 0-03097 7 0-03098 0-03099 019 0-03100 CD 0-03101 c. P 0-03102 o\ 0-03103 0 0-03104 0-03105 0-03106 0-03107 0-03108 0-03109 0-03110 0-03111 0-03112 0-03113 0-03114 0-03115 0-03116 0-03117 0-03118 0-03119 0-03120 199 198 196 195 199 a a 1 196 197 197 198 196 196 196 196 197 196 196 198 198 198 197 196 197 197 199 195 197 198 1 0 0 0 2 0 0 0 3 0 0 0 4 1 0 0 1 0 0 0 3 0 0 0 3 0 0 0 3 0 0 0 2 0 0 0 3 1 0 0 2 2 0 0 4 0 0 0 4 0 0 0 3 0 0 0 3 0 1 0 4 0 0 0 2 0 0 0 2 0 0 0 2 0 0 0 3 0 0 0 4 0 0 0 3 0 0 0 2 1 0 0 1 0 0 0 4 1 0 0 3 0 0 0 1 1 0 0 `ANIMAL DIED PRIOR TO SCHEDULED NECROPSY. 29 0 0 0 0 0 0 0 0 0 1 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 m 00 00 00 00 %. 0 0 0 0 0 0 0 0 0 r 0 0 0 0 vi PRIMEDICA-ARGUS STUDY NO.: 4 1 8 - 0 2 1 APPENDIX D ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STIJDY OF POTASSIUM PERFLUOROBUTANE SULFONATE ( P F R S ) IN RATS INDIVIDUAL F, GENERATION MALE SPERM MORPHOLOGY DATA 'GROUPV : 1000 MG/KG/DAY (PFBS) 0-03121 196 0-03122 196 0 -03123 196 0-03124 195 0-03125 195 0-03126 196 0-03127 197 0-03128 195 2 0 - 0 3 129 197 0-03130 196 % 0-03131 198 L P 0-03132 197 E 0-03133 0-03134 199 196 0-03135 198 0-03136 0-03137 a 0-03138 196 0-03139 196 0-03140 197 0-03141 195 0-03142 195 0-03143 196 0-03144 198 0-03145 196 0-03146 a 0-03147 196 0-03148 195 0-03149 195 0-03150 196 4 0 0 0 3 1 0 0 4 0 0 0 5 0 0 0 3' 2 0 0 3 1 0 0 3 0 0 0 3 2 0 0 2 1 0 0 4 0 0 0 2 0 0 0 3 0 0 0 1 0 0 0 4 0 0 0 1 0 0 0 4 0 0 2 2 0 2 1 0 4 1 0 3 2 0 4 0 0 2 0 0 4 0 0 2 1 0 0 3 2 0 0 5 0 0 0 4 0 0 0 'ANIMAL D I E D PRIOR TO SCHEDULED NECROPSY. 30 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 0 0 0 0 0 0 0 0 0 0 0 - 0 1 0 0 j, 35 0 0 0 0 0 0 0 0 0 r 0 0 0 0 vi - 4- - I PI, 1 5 IJ 1 ARGUS 11S-02 1 APPENDIX M QUALITY ASSURANCE STATEMENT Page 1462 905 Sheehy Drive, Bldg. A Horsharn, PA 19044 Telephone: (2 7 5) 443-871 0 Telefax: (215) 443-8587 ARGCS 41S-02 1 -x/ ARGUS RESEARCH Charles River Laboratories Discovery and Development Services QUALITY ASSURANCE STATEhIEST Argus Protocol: 318-02 1 Sponsor's Study ru'umber: T-7385.13 Study Director: Raymond G. York. Ph.D., DABT The protocol, critical phases, raw data and final report were inspected by the Quality Assurance Unit (QAU), to assure conformance with: U.S. Environmental Protection Agency. Federal Insecticide. Fungicide and Rodenticide Act/Toxic Substances Control Act (FIFRA/TSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160Part 792. Organisation for Economic Co-operation and Development ( 1998). The Revised OECD Principles of Good Laboratory Practices [C(97)186Finall. The undersigned indicate that the 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 1463 V-10.25.00 The QAU inspection and report audit dates are listed below: Inspection Phase Date(s) Finding Submitted to Stud\, Inspection Date(s) Director Date(s1 Findinss Submitted to Alanaoenienr Protocol TS Administration TS Preparation Natural Delivery/ Litter Observations Dam/Litter Sacrifice Male Sacrifice/ Sperm Evaluations Preputial Separation Vaginal Patency F1 Natural Delivery/ Litter Observations F1 D a d i t t e r Sacrifice F1 Male Sacrifice/ Sperm Evaluations In-Life Data Necropsy Data Formulations Data 18.19 DEC 00 28 DEC 00 18 JAN 01 19 DEC 00 02 J A i i 01 29 J . W 01 30 MAR 01 20 APR 01 30 M A R 01 01 MAY 01 27 APR 01 02 MAY 01 03 MAY 01 04 MAY 01 11 MAY 01 11 MAY 01 08 AUG 01 29 AUG 01 08 AUG 01 14 SEP 01 07 SEP 01 14-17 AUG 01 and 20-22 AUG 01 23-24 AUG 01, 27-3 1 AUG 01 and 04 SEP 01 04-07 DEC 01 and 10-14 DEC 01 19 DEC 01 through 09 JAN 02 17-18 DEC 01 08-10 JAN 02 26-27 SEP 01 12 DEC 01 and 10-11 JAN 02 14 SEP 01 23 AUG 01 04 SEP 01 14 DEC 01 09 JAN 02 18 DEC 01 10 JAN 02 28 SEP 01 11 JAN 02 19 DEC 00 02 J.4S 01 29 JAS 01 30 M.4R 01 01 h l A Y 0 1 04 M.4Y 01 1 1 MAY 01 11 MAY 01 08 AUG 01 14 SEP 01 14 SEP 01 23 P.UG 01 04 SEP 01 14 DEC 01 09 JAN 02 18 DEC 01 10 JAN 02 28 SEP 01 11 JAN 02 Page 1464 V-10.25.00 Inspection Phase Report Tables Report Text Revised Report ' ARGUS 418-02 1 Date(s) Findings Submitted to Study Inspection Date(s) Director Dare(s) Findings Submitted to klanaoemen t 23-25 SEP 01 05-06 SEP 01 and 21-26 SEP 01 09-1 1 & 14 JAN 02 15-18 JAN 02 and 21-22 JAN 02 24 & 26 SEP 01 27 SEP 01 28 SEP 01 28-30 JAN 02 30-31 JAN 02 03 JUL 02 25 SEP 01 26 SEP 01 22 JAN 02 22 JAN 02 27 SEP 01 28 SEP 01 28 SEP 01 30 JAN 02 31 J A N 02 03 JUL 02 3 SEP 01 26 SEP 01 22 JXN 02 22 JAN 02 27 SEP 01 28 SEP 01 28 SEP 01 30 JAN 02 31 Jm 02 03 JUL 02 Page 1465 V-10.25.00 SANITIZED FOR MAY 06 2004 3M CORPORATE TOXICOLOGY Study Title ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE SULFONATE (PFBS) IN RATS SPONSOR'S STUDY NUMBER: T-7485.13 Data Requirement ~~ US:EnvironmentalProtection Agency. a i Health Effects Test Guidelines; Reproduction and Fertility Effects. Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3800. U.S. Environmental Protection Agency. Toxic Substances Control Act (TSCA) Test Guidelines; Final Rule. Reproduction and Fertility Effects, 799.9380. Study Director Raymond G. York, Ph.D., DABT Study Completed On 5 May 2004 (Report Amendment 1) Performing Laboratory Argus Research 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044 Laboratory Project ID Argus Research, Protocol Number: 418-021 Page 1 of 5 ARGUS 418-021 This page to be supplied by the Sponsor. Page 2 ARGUS 418-021 SANITIZED GOOD LABORATORY PRACTICE STATEMENT MAY 0 6 2004 This study was conducted according to U S . Environmental Protection Agency. Federal Insecticide, Fungicide and Rodenticide Act/Toxic Substances Control Act (FIFMTSCA); Good Laboratory Practice Standards; Final Rule. 40 CFR Part 160/Part 792 and The Organisation for Economic Co-operation and Development (1998). The Revised OECD Principles of Good Laboratory Practices [C(97)186/Final]. Any areas of noncompliance are documented in the study record. No deviations existed that affected the validity of the study. Submitter : Study Director: Sponsor: Page 3 r ARGUS 418-021 .. Page 4 ARGUS 418-021 905 h h y Dive, 5Hg. A Horzham, PA 19044 Tckphont: (2 15) 443-8 7IO Ta[eii: (2is) c13-8587 ARGUS RESEARCH Chorles River Laboratories Discovery and Development Services =PORT AMENDMENT 1 5 MAY 2004 PROTOCOL 418-02I SPONSORS STUDY NUMBER: `T-7485.13 ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATION) REPRODUCTION STUDY OF POTASSIUM PERFLUOROBUTANE (PFBS) IN RATS FINAL REPORT 1. Page 20 - Section 1.2.4. F1 Generation Female Rats was replaced with the correct information. In paragraph 4, sentence 2, was changed to+Terminal body weights of the'F1generation female rats were significantly increased in the four treatment groups, compared to the control group value." rather than "Terminal body weights . of the F1 generation female rats were significantly increased in the five respective dosage groups." 2. Page 2 1 - Section 1.3. In paragraph 1, sentence 2 "The maternal NOAEL is 300 mg/kg/day (the 1000 mg/kg/day dosage had a significantly reduced brain weight)." rather than "The maternal NOAEL is 300 mg/kg/day (the 1000mgkg/day dosage significantlyreduced liver weight and liver weight to terminal body weight and to brain weight ratios)." 3. Pages 49 and 50 - Section 3.2.7.Natural Delivery and Litter Data for P Generation Female Rats was replaced with the correct information. Assoc?idte Director o w e a r c h and , Study Director Senior Manager, Regulatory Compliance 5 Original page 20 - amended on May 5, 2004 ARGUS 418-02I Absolute and relative feed consumption values during the precohabitation, gestation and lactation periods were unaffected by dosages of the test substance as high as 1000 mg/kg/day. The age of vaginal patency for the F1 generation female rats was comparable among the dosage groups and did not significantly differ. The average numbers of estrous stages per 21 days were comparable among the five dosage groups and did not significantly differ. All mating and fertility parameters were unaffected by dosages of the test substance as high as 1000 mg/kg/day. All necropsy observations were considered unrelated to the test substance. Terminal body weights of the F1 generation female rats were significantly increased in the five respective dosage groups. Terminal body weights were 106%, 107%, 105% and 105% for the 30, 100, 300 and 1000 mg/kg/day dosage groups, respectively, above the control group. The absolute organ weights and the ratios of the organ weights to the terminal body weights and to the brain weights were cornparable to control values and did not significantly differ. Microscopic examination of the kidneys of female rats revealed treatment-related effects similar to those in the P generation female rats. No treatment-related microscopic changes were observed in the reproductive organs of any female Fl generation rat selected for histopathologic evaluation that had been given 1000 mg/kg/day of the test substance. Pregnancy occurred in 24 to 28 rats in each.dosage group. Natural delivery observations were unaffected by dosages of the test substance as high as 1000 mg/kg/day. 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. No clinical or necropsy observations for F2 generation pups were attributable to dosages of the test substance as high as 1000 mgkg'day. F2 generation weanling rats had comparable terminal body weights on DL 22; the values did not significantly differ. None of the significant differences in organ weights or organ weight ratios for the F2 generation pups were considered treatment-related because they were not dosagedependent. Page 20 Original page 21 - amended May 5, 2004 ARGUS 418-021 1.3. Conclusion On the basis of these data, the P generation paternal no-observable-adverse-effect-level (NOAEL) for Potassium Perfluorobutane (PFBS) is less than 300 mg/kg/da): (the 300 mg/kg/day dosage caused significant increases in the liver weight to the brain weight to the terminal body weight ratios). The maternal NOAEL is 300 mgkglday (the 1000 mg/kg/day dosage significantly reduced liver weight and liver weight to terminal body weight and to brain weight ratios). 'The reproductive NOAEL in the males and female P generation rats is greater than 1000 mg/kg/day (the 1000mg/kg/day dosage had no effect on mating, fertility or maternal delivery parameters). The F l generation paternal no-observable-adverse-effect-level (NOAEL) for (PFBS) is 300 mg/kg/day (the 1000 mgkg/day dosage caused a significant increase in excess salivation and significant decrease in terminal body weight, organ weights and body weight gain and delayed sexual maturation). The F1 generation maternal NOAEL is 300 mg/kg/day (the 1000 mg/kg/day dosage caused a significant increase in excess salivation and terminal body weights and delayed sexual maturation) increased postweaning mortality, decreased postweaning body weight, body weight gain and feed consumption. The reproductive NOAEL in the males and female Fl generation rats is greater than 1000rng/kg/day (the 1000 mg/kg/day dosage had no effect on mating, fertility or maternal delivery parameters). The F2 generation terminal body weights did not differ among the groups. None of the significant differences in organ weights or organ weight ratios for the F2 generation pups were considered treatment-related. Alan M. Hoberman, Ph.D., DABT Date Director of Research AssoUte Director b&earch and Study Director Page 21 Original page 49 - amended May 5, 2004 ARGUS 418-02I Treatment-related microscopic changes were observed in the kidneys of female rats in the 300 and 1000 mg/kg/day dosage groups. The primary treatment-related microscopic change consisted of an increased incidence and severity of hyperplasia of the tubular and ductular epithelium of the inner medulla/papilla region. The affected tubules were more densely cellular with variable-sized nuclei. Also, there was an increased incidence of minimal or mild focal papillary edema in the 300 and 1000mgkglday dosage groups. Focal necrosis of the papilla occurred in three female rats in the 300 mg/kg/day dosage group and medullary tubular dilatation was seen in one 300 rng/kg/day dosage group rat and two 1000 mg/kg/day dosage group rats. No treatment-related microscopic changes were observed in the reproductive organs of any female P generation rat selected for histopathologic evaluation that had been given 1000 mg/kg/day of the test substance. 3.2.6. Terminal Body Weights and Organ Weight Ratios (9%) of Organ Weight to - Terminal Body Weight and Brain Weight P Generation Female Rats - (Summary - 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. All organ weights (pituitary, liver, left and right adrenals, left and right kidneys, spleen, thymus, left and right ovary and uterus with oviducts) 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 1000 mg/kg/day. The weight of the brain was significantly decreased (p50.01) in the 1000 mg/kg/day dosage group. Although this reduction occurred in the highest dosage tested it was not considered toxicologically important because: 1) the value was 96% of the control group value; and 2) brain weights were not similarly reduced for the male rats. - 3.2.7. Natural Delivery and Litter Data P Generation Female Rats - - (Summaries Tables C19 and C20:;Individual Data Tables C35 through C38) Pregnancy occurred in all 15 rats (100%)assigned to the 0, 10 and 50 mg/kg/day dosage groups and 13 rats (86.7%) assigned to the 250 mgkglday dosage group. All pregnant rats delivered a litter. Natural delivery observations were unaffected by dosages of the test substance as high as 250 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;, stillborn pups, pup sex ratios and body weights were comparable among the four dosage groups and did not significantly differ. Page 49 Original page 50 - amended May 5, 2004 ARGUS 4 18-021 The number of pups found dead or presumed cannibalized on day 1 and days 2 to 5 postpartum were significantly increased (p:;O.Ol) in the 250 mg/kg/day dosage group. This resulted in the viability index being significantly reduced (pI0.05)in the 250 mg/kg/day dosage group, compared to the control group value. The average number of surviving pups per litter on DL 5 was also significantly reduced in the 250 mg/kg/day dosage group. These reductions were considered related to the test substance. - 3.2.8. Clinical and Necropsy Observations - F1 Generation Litters (Summaries - Tables C21 and C22; Individual Data Tables C39 and C40) No clinical or necropsy observations in the F1 generation pups were attributable to dosages of the test substance as high as 1000mgkglday 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, not nursing, umbilical hernia, not nesting, alopecia on back or head, abrasion on back, scab on the back or head, dehydration, missing or black tip of tail, decreased motor activity, corneal opacity, bruised eye or back and absent portion of tail. Necropsy observations included no,milk in stomach, liver adhered to diaphragm, pedunculated areas of the liver, dilation of ureter, opaque tan material in anterior chamber of the left eye, large spleen, diaphragmatic hernia, moderate dilation of the renal pelvis and extreme dilation of the lateral ventricles of the brain. 3.2.9. 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 Fl generation pups selected for organ weight evaluation were comparable among the five dosage groups and did not significantly differ. The weights of the brain, spleen, liver, kidneys 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 1000 mg/kg/day. Page 50