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3 2> 445 H-25231: One-Generation Reproduction Study in Rats 3263 DuPont-9763 TRADE SECRET Study Title H-25231: One-Generation Reproduction Study in Rats Volume 1 of 3 Laboratory Project ID: DuPont-9763 Author: Eve Mylchreest, PhD . Study Completed on: January 31,2003 Performing Laboratory: E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Number: Service Code Number: Page 1 of 796 onipfryBanftfeqft Ues fio! eonlan TS'C08? H-25231: One-Generation Reproduction Study in Rats DuPont-9763 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles of Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17, except for the item documented below. The item listed does not impact the validity of the study. The bulk test substance characterization and stability analyses were performed at DuPont Regional Analytical Services (RAS), a non-GLP laboratory. These analyses were in compliance with regulatory guidelines. None of the aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with IS09002 regulations. All of the analyses are considered valid and sufficient for the purposes of this study. Applicant / Sponsor. E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Applicant / Sponsor DuPont Representative Date 2 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats QUALITY ASSURANCE STATEMENT DuPont-9763 Haskell Sample Number(s): 25231 Dates of Inspections: Protocol: February 25, 2002 Conduct: March 25, 2002; May 2, 2002; June 7,24, 2002; July 9,25, 2002; August 2,5,6,9, 2002 Records, Reports: August 23,25, 2002; September 30, 2002; October 1-4, 2002; December 10-13, 26,27,30,31, 2002; January 2,3, 2003 Dates Findings Reported to: Study Director: January 7, 2003 Management: January 31,2003 Reported by: Quality Assurance Au< Date 3 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Analytical Evaluations b y :______s '^ n c iz ^ * Janet C. Maslanka,. B.S,. Senior Staff Chemist Clinical Pathology Evaluations by: Nancy E. Everds, D.V.M. Diplomate A.C.V.P. Principal Research Clinical Pathologist Anatomic Pathology Evaluations by: / John F. Hansen, D.V.M., P1h.D. Diplomate A.C.V.P. Principal Research Pathologist Anatomic Pathology Evaluations Peer G. Tracy Makovec, D.\j0f. Diplomate A.C.V.P. Senior Research Pathologist Approved by * Scott E- Loveless, Ph.D. Research Manager and Director Issued by Study Director: Evejflyichreest, Ph.D. Senis/Kesearch Toxicologist So c Date 2 1 - T M 1 - & 03 Date 3 1 - 3tt.lL-00 3 Date C frt Date S l-T A O -U ? Date Date 4 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT............................................ 2 QUALITY ASSURANCE STATEMENT.......................................................................................... 3 CERTIFICATION...................................................................................................................................4 LIST OF TABLES..................................................................................................................................7 LIST OF APPENDICES........................................................................................................................9 STUDY INFORMATION.................................................................................................................. 11 STUDY PERSONNEL....................................................................................................................... 12 SUMMARY..................................................................................................................................... .....13 INTRODUCTION.................................................................................................................................16 OBJECTIVE......................................................................................................................................... 17 MATERIALS AND METHODS........................................................................................................ 17 A. Test Substance........................................................................................................................ 17 B. Test Species.............................................................................................................................17 C. Animal Husbandry...................................................................................................................17 D . Quarantine and Pretest Period....................................................................................... 18 E. Study D esign.............................................................................................................................19 F. Assignment to Groups and Study Start.................................................................................. 19 G. Analytical Methods - Test Substance Administration, Preparation, and Sampling........... 19 H. Body Weights - Pi R ats..........................................................................................................23 I. Food Consumption and Food Efficiency - Pi Rats...............................................................23 J. Detailed Clinical Observations and Mortality - Pi Rats...................................................... 24 K. Estrous Cycle Evaluation........................................................................................................24 L. Breeding................................................................................................................................... 24 M. Gestation Procedures..................................................................................... N. Lactation Procedures.............................................................................................................. .25 O. Fi Generation.............................................................................................................................25 P. Developmental Landmarks.....................................................................................................26 Q. Clinical Pathology Evaluation.......................................................................................... 26 R. Anatomic Pathology.................................................................................................................27 S. Sperm Assessment...................................................................................................................30 T. Statistical Analyses.................................................................................................................. 31 RECORDS AND SAMPLE STORAGE......................................................................... RESULTS AND DISCUSSION..........................................................................................................34 ANALYTICAL..................... :............................................................................ ................ ............... 35 A. Chromatography...................................................................................................................... 35 25 33 5 Company Sanitized. Does net contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 B. Dosing Solution Analyses....................................................................................................... 35 C. Analytical Conclusions........................................................................................................... 36 REPRODUCTIVE TOXICITY EVALUATIONS............ .............................................................. 37 IN-LIFE TOXICOLOGY................................................................................................................... 37 A. Pi Rats - Mean Body Weights and Body Weight G ains...................................................... 37 B. Pi Rats - Food Consumption and Food Efficiency...............................................................37 C. Pi Rats - Clinical Observations and Mortality...................................................................... 38 D. Sperm Param eters....................................................................................................................39 E. Estrous Cycle Parameters and Precoital Interval in Pi Fem ales..........................................39 F. Reproductive Indices............................................................................................................... 39 G. Fi Offspring D ata.....................................................................................................................40 H. Fi Rats - Mean Body Weights and Body Weight G ains...................................................... 41 I. Fi Rats - Food Consumption and Food Efficiency...............................................................41 J. Fi Rats - Clinical Observations and Mortality...................................................................... 41 K. Fi Rats - Developmental Landmarks.....................................................................................41 L. Reproductive In-Life Toxicology Conclusions..................................................................... 41 CLINICAL PATHOLOGY EVALUATIONS...................................................................................42 A. Hematology.............................................................................................................................. 42 B. Clinical Chemistry.................................................................................................................. 43 C. Plasma and Urine Fluoride......................................................................................................43 D. Clinical Pathology Conclusions............................................................................................. 44 ANATOMICAL PATHOLOGY.........................................................................................................45 A. Mortality................................................................................................................................... 45 B. Organ Weight D ata................................................................................................................. 45 C. Gross Findings.........................................................................................................................46 D. Microscopic Findings.............................................................................................. 46 E. Anatomic Pathology Conclusions.......................................................................................... 47 CONCLUSIONS............................ 48 TABLES................................................................................................................................................ 51 APPENDICES....................................................................................................................................127 VOLUME 2.........................................................................................................................................254 VOLUME 3.............. 456 6 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 LIST OF TABLES Page TABLE 1 SUMMARY OF DOSING SOLUTION ANALYSES.................................................................................... 53 TABLE 2 MEAN BODY WEIGHTS OF P, MALE RATS............................................................................................. 54 TABLE 3 MEAN BODY WEIGHT GAINS OF P, MALE RATS................................................................................. 56 TABLE 4 MEAN BODY WEIGHTS OF P, FEMALE RATS DURING PREMATING.............................................58 TABLE 5 MEAN BODY WEIGHT GAINS OF P, FEMALE RATS DURING PREMATING................. 59 TABLE 6 MEAN BODY WEIGHTS OF Pi FEMALE RATS DURING GESTATION............................................. 60 TABLE 7 MEAN BODY WEIGHT GAINS OF Pi FEMALE RATS DURING GESTATION................................. 61 TABLE 8 MEAN BODY WEIGHTS OF P, FEMALE RATS DURING LACTATION............................................ 62 TABLE 9 MEAN BODY WEIGHT GAINS OF P, FEMALE RATS DURING LACTATION................................ 63 TABLE 10 MEAN DAILY FOOD CONSUMPTION OF Pi MALE RATS DURING PREMATING....................... 64 TABLE 11 MEAN DAILY FOOD EFFICIENCY OF Pi MALE RATS DURING PREMATING..............................65 TABLE 12 MEAN DAILY FOOD CONSUMPTION OF Pt FEMALE RATS DURING PREMATING..................66 TABLE 13 MEAN FOOD EFFICIENCY OF Pi FEMALE RATS DURING PREMATING.......................................67 TABLE 14 MEAN DAILY FOOD CONSUMPTION OF Pj FEMALE RATS DURING GESTATION.................. .68 TABLE 15 MEAN FOOD EFFICIENCY OF P, FEMALE RATS DURING GESTATION....................................... 69 TABLE 16 SUMMARY OF CLINICAL OBSERVATIONS IN P, MALE RATS......................................................... 70 TABLE 17 SUMMARY OF CLINICAL OBSERVATIONS IN P, FEMALE RATS DURING PREMATING AND COHABITATION.................................................................................................................................................71 TABLE 18 SUMMARY OF CLINICAL OBSERVATIONS IN P, FEMALE RATS DURING GESTATION........ 72 TABLE 19 SUMMARY OF CLINICAL OBSERVATIONS IN P, FEMALE RATS DURING LACTATION........ 73 TABLE 20 SUMMARY OF SPERM PARAMETERS IN P, MALE RATS...................................................................74 TABLE 21 MEAN ESTROUS CYCLE PARAMETERS AND PRECOITAL INTERVAL IN P, FEMALE RATS 75 TABLE 22 SUMMARY OF REPRODUCTIVE INDICES: Pi GENERATION........................................................... 76 TABLE 23 MEAN PUP NUMBERS AND SURVIVAL: F, GENERATION................................................................77 . TABLE 24 MEAN PUP WEIGHTS: Fj GENERATION.............v..................................................................................78 TABLE 25 SUMMARY OF PUP CLINICAL OBSERVATIONS: F, GENERATION............................................. 79 TABLE 26 MEAN BODY WEIGHTS OF F| MALE RATS........................................................................................... 80 TABLE 27 MEAN BODY WEIGHTS GAINS OF F, MALE RATS............................................................................. 81 TABLE 28 MEAN BODY WEIGHTS OF F, FEMALE RATS....................................................................................... 82 TABLE 29 MEAN BODY WEIGHTS GAINS OF F, FEMALE RATS........................................................................ 83 TABLE 30 MEAN DALLY FOOD CONSUMPTION OF Fi MALE R A TS..................................................................84 TABLE 31 MEAN DAILY FOOD EFFICIENCY OF F, MALE RATS......................................................................... 85 TABLE 32 MEAN DAILY FOOD CONSUMPTION OF F, FEMALE RATS.............................................................. 86 7 Company Sanitized. Does net contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 33 MEAN FOOD EFFICIENCY OF Fj FEMALE RATS................................................................................... 87 TABLE 34 SUMMARY OF CLINICAL OBSERVATIONS IN F, MALE RATS..........................................................88 TABLE 35 SUMMARY OF CLINICAL OBSERVATIONS IN F, FEMALE RATS.................................................... 89 TABLE 36 SUMMARY OF DEVELOPMENTAL LANDMARKS IN F, RATS.......................................................... 90 TABLE 37 SUMMARY OF HEMATOLOGY VALUES FOR P, MALE RATS...........................................................91 TABLE 38 SUMMARY OF HEMATOLOGY VALUES FOR P| FEMALE R A T S..................................................... 93 TABLE 39 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR P, MALE RATS................... 95 TABLE 40 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR Pj FEMALE RATS...............96 TABLE 41 SUMMARY OF URINALYSIS VALUES FOR P, MALE RATS................................................................97 TABLE 42 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - P! ADULTS..........................98 TABLE 43 MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - P, ADULTS.................. 101 TABLE 44 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - F, ADULTS........................104 TABLE 45 MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - F, ADULTS.................. 107 TABLE 46 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - P! ADULTS.....................................110 TABLE 47 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - P, ADULTS................................ 111 TABLE 48 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - F, ADULTS..................................... 112 TABLE 49 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - F, ADULTS................................ 113 TABLE 50 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS - Pt ADULTS..................................................................................................................................118 TABLE 51 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - P, ADULTS..............................................................................................................................120 TABLE 52 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS - Fj ADULTS.................................................................................................................................. 122 TABLE 53 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - F, ADULTS..............................................................................................................................124 TABLE 54 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - F, WEANLINGS..................................................................................................................... 126 TABLE 55 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - F, WEANLINGS............................ 114 TABLE 56 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Fi WEANLINGS........................115 TABLE 57 INCIDENCES OF GROSS OBSERVATIONS IN GENERATION F, MALE PUPS................. 116 TABLE 58 INCIDENCES OF GROSS OBSERVATIONS IN GENERATION F, FEMALE P U PS........................117 8 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 LIST OF APPENDICES Page APPENDIX A ANALYTICAL D A T A ............................................................................................................................. 128 APPENDIX B INDIVIDUAL BODY WEIGHTS OF P, MALE RATS....................................................................... 136 APPENDIX C INDIVIDUAL BODY WEIGHT GAINS OF P, MALE RATS............................................................ 150 APPENDIX D INDIVIDUAL BODY WEIGHTS OF P, FEMALE RATS DURING PREMATING...................... 164 APPENDIX E INDIVIDUAL BODY WEIGHT GAINS OF Pi FEMALE RATS DURING PREMATING.......... 174 APPENDIX F INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF P, FEMALE RATS DURING GESTATION............................................................................................... ................................................184 APPENDIX G INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF P, FEMALE RATS DURING LACTATION................................................................................................................................................ 190 APPENDIX H INDIVIDUAL FOOD CONSUMPTION OF P, MALE RATS............................................................197 APPENDIX I INDIVIDUAL FOOD CONSUMPTION OF P, FEMALE RATS DURING PREMATING............207 APPENDIX J INDIVIDUAL FOOD CONSUMPTION OF P, FEMALE RATS DURING GESTATION.............217 APPENDIX K INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P, MALE RATS ..223 APPENDIX L INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P, FEMALE RATS DURING PREMATING AND COHABITATION.......................................................... 233 APPENDIX M INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P, FEMALE RATS DURING GESTATION........................................................................................................239 APPENDIX N INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P, FEMALE RATS DURING LACTATION.......................................................................................................245 v o l u m e 2 ............... ............................................................................................................................................................ 254 APPENDIX O INDIVIDUAL ANIMAL SPERM MOTILITY DATA IN Pj MALE RATS.................................... 255 APPENDIX P INDIVIDUAL ANIMAL SPERM MORPHOLOGY DATA IN P, MALE R A TS........................... 258 APPENDIX Q INDIVIDUAL ANIMAL SPERM AND SPERMATID COUNTS IN P, MALE RATS..................262 APPENDIX R INDIVIDUAL ANIMAL ESTROUS CYCLE PARAMETERS DURING PREMATING AND COHABITATION IN P, FEMALE R ATS................................................................................................................ 266 APPENDIX S INDIVIDUAL ANIMAL ESTROUS CYCLE STAGES DURING PREMATING AND COHABITATION IN P, FEMALE R A TS............................................................................................................... 272 APPENDIX T INDIVIDUAL MATING DATA AND GESTATION LENGTH: Pt GENERATION.................... 278 APPENDIX U INDIVIDUAL IMPLANTATION SITE DATA AND IMPLANTATION EFFICIENCY: P, GENERATION......................................................................................................................................................... 284 APPENDIX V INDIVIDUAL PUP SURVIVAL: Ft GENERATION...........................................................................289 APPENDIX W INDIVIDUAL PUP WEIGHTS: F! GENERATION............................................................................303 APPENDIX X INDIVIDUAL LITTER CLINICAL OBSERVATIONS: F, GENERATION..................................328 APPENDIX Y INDIVIDUAL BODY WEIGHTS OF F, MALE AND FEMALE RATS......................................... 333 APPENDIX Z INDIVIDUAL BODY WEIGHT GAINS OF F, MALE AND FEMALE RATS...............................343 9 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX AA INDIVIDUAL FOOD CONSUMPTION OF F, MALE AND FEMALE RATS............................353 APPENDIX BB INDIVIDUAL CLINICAL OBSERVATIONS, DEVELOPMENTAL LANDMARKS, AND MORTALITY DATA IN F, MALE AND FEMALE RATS....................................................................................363 APPENDIX CC INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA - P, ADULTS..................................379 APPENDIX DD INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS - P, A D U LTS..................... 406 APPENDIX EE INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS - Fi ADULTS.......................431 VOLUME 3 ..............................................................................................................................................................................456 APPENDIX FF INDIVIDUAL ANIMAL PATHOLOGY DATA - Pj ADULTS......................................................... 457 APPENDIX GG INDIVIDUAL ANIMAL PATHOLOGY DATA - F, ADULTS........................................................ 620 APPENDIX HH INDIVIDUAL ANIMAL PATHOLOGY DATA - F, WEANLINGS................................................764 APPENDIX II INDIVIDUAL ANIMAL GROSS OBSERVATIONS IN F, WEANLINGS AND P U T S................769 10 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats STUDY INFORMATION Substance Tested: DuPont-9763 Known Impurities: Physical Characteristics: Tan liquid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: March 15, 2002 / (see report cover page) 11 eompaqytanMzed rse* ear H-25231: One-Generation Reproduction Study in Rats DuPont-9763 STUDY PERSONNEL Study Director: Eve Mylchreest, Ph.D. Management: Scott E. Loveless, Ph.D. Robert M. Parker, Ph.D. Supervisor: Deborah L. Tyler Primary Technician: Kellie McDhatton Analytical Chemist: Janet C. Maslanka, B.S. Management: S. Mark Kennedy, Ph.D. Clinical Pathologist: Nancy E. Everds, Ph.D. Anatomic Pathologist: John F. Hansen, D.V.M., Ph.D. Peer Review Anatomic Pathologist: G. Tracy Makovec, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Toxicology Report Preparation: Mary K. LaRoe Maryanne M. Wilford, B.A. Wanda F. Dinbokowitz Management: Nancy S. Selzer, M.S. Laboratory Veterinarians: Thomas W. Mayer, D.V.M., A.C.L.A.M. William Singleton, D.V.M., A.C.L.A.M. a f , 12 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 SUMMARY mA one-generation ^production study was conducted with H-25231) involving the production of one set of litters. The test material was administered once daily by gavage to groups of male and female Crl:CD(SD)IGS BR rats (20/group), the Pi generation, at doses of 0,75, 500, or 3500 mg/kg/day. Following at least 70 days of dosing, the Pi generation rats were bred within their respective treatment groups, and allowed to deliver and rear their offspring until weaning (postpartum day 21). At weaning, 20 Fi rats/sex/group were randomly selected to produce the next generation. Unselected weanling pups underwent a gross pathological examination. The Fi generation rats were not exposed after weaning. The age of preputial separation and vaginal opening in the Fi generation rats were evaluated. A clinical pathology evaluation (hematology, clinical chemistry, plasma and urine fluoride in Pi males only) was conducted on week 10 on the first 10 Pi rats/sex/group. Estrous cycle and sperm parameters were evaluated in the Pi generation. At necropsy (Pi females on postpartum day 21; Pi males after siring litters [approximately 4 months of exposure], Fi generation at postnatal day 60), reproductive and target organs were weighed and retained for histopathological examination. Histopathological examination of reproductive organs (testes, epididymides, seminal vesicles, prostate, and uterus, ovaries, and vagina) was conducted only for Pi males and females with impaired reproductive performance. Liver, kidney, and thyroid were processed and evaluated microscopically in 10 randomly selected control and high-dose Pi males and females, and from all control and high-dose Fi males. Thyroid, the only target tissue in Pi females, was processed in all control and high-dose Fi adult females. Target tissues from Pi and Fi animals were subsequently processed and evaluated in lower dose groups as heeded to determine a no-adverseeffect level. At 3500 mg/kg/day, effects considered to be related to H-25231 treatment include: Adverse effects: Reductions in weekly mean body weights and body weight gains, overall mean body weight gain, weekly mean food consumption and food efficiency, overall food consumption, and overall food efficiency of Pi male rats. Reductions in weekly mean body weight gain and food consumption of Pi female rats during premating (test days 1-8) and on gestation days 0-7 and 7-14. Low incidences of clinical signs of toxicity in Pi males (lung noise, salivation, stained fur) and females (salivation), which were generally sporadic. Reduction in mean pup weight throughout the entire lactation period for Fi litters. Reductions in weekly mean body weights, body weight gains, and food consumption, overall body weight gain and food consumption of Fi males. Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Reduction in weekly mean body weights and body weight gains (test days 1-8) of Fj females. Increased mean age of preputial separation and vaginal opening in Fi rats, which were considered due to reduced body weights and body weight gain during the post-weaning period. Potentially adverse, thyroid follicular hypertrophy in Pi and Fi males and females. Hepatocellular hypertrophy in the liver in Pi males. Chronic progressive nephropathy in the kidney in Pi males. Non-adverse effects: Minimal decreases in red cell mass parameters (red cell count, hemoglobin, and/or hematocrit) and associated changes (red cell morphology and red cell distribution width) in Pi males. Increased liver and kidney weights in Pi males and females, and liver weights in Fi females. Increased plasma and urine fluoride in Pi males, indicating exposure to and metabolism o f a fluoride-containing molecule. At 500 mg/kg/day, effects considered to be related to H-25231 treatment include: Adverse effects: Reductions in-weekly mean body weight gains, overall weight gain and overall food consumption of Pi males. Potentially adverse, thyroid follicular hypertrophy in Pi and Fi males, and Pi females. Hepatocellular hypertrophy in the liver in Pi males. Chronic progressive nephropathy in the kidney in Pi males. Non-adverse effects: Minimal decreases in red cell mass parameters (red cell count, hemoglobin, and/or hematocrit) and associated changes (red cell morphology and red cell distribution width) in Pi males. Increased liver and kidney weights in Pi males, and kidney weights in Pi females. Increased plasma and urine fluoride in Pi males, indicating exposure to and metabolism of a fluoride-containing molecule. 14 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 At 75 mg/kg/day, effects considered to be related to H-25231 treatment include: Adverse effects: Potentially adverse, thyroid follicular hypertrophy in Pi and F males. Non-adverse effects: Increased liver and kidney weights in Pi males. Increased urine fluoride in Pi males, indicating exposure to and metabolism of a fluoridecontaining molecule. Under the conditions of this study, a no-observed-effect level (NOEL)a was not determined for Pi and Fi rats, based on thyroid follicular hypertrophy in Pi and Fi adult males at >75 mg/kg/day. The NOEL for reproductive effects was 500 mg/kg/day, based on reductions in m ean pup weights throughout the entire lactation period for Fi litters at 3500 mg/kg/day. a The NOEL for this study is defined as the highest dose at which toxicologically important effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL aS- defined by the United States Environmental Protection Agency (1985) and to the no-observed-adverse-effect ^evel (NOAEL) as defined by the European Union (1994). 15 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INTRODUCTION Thetest substance, H-25231, is a fluorosurfactant that contains^ N H I N T h e dose levels for this study were selected based on the results from a range-finding study with H-25156(1) in which rats were dosed by oral gavage with 100 mg/kg/day (20 mg/kg/day active ingredient), 500 mg/kg/day (100 mg/kg/day active ingredient), or 2000 mg/kg/day (400 mg/kg/day active ingredient) for 49 days. No body weight effects or clinical signs of toxicity were observed in either males or females at any dose level. Therefore, males exposed to 2000 mg/kg/day had their dose increased to 5000 mg/kg/day (1000 mg/kg/day active) on test day 52. Over an approximate 2-week period, the males dosed with 5000 mg/kg/day had a 10% decrement in body weight compared to control and were subsequently sacrificed on test day 64. The remaining female and male test substance treated groups were sacrificed on test days 49 and 50, respectively, and liver, kidney, and blood were collected from the 100 and 500 mg/kg/day male dose groups. The livers were evaluated histopathologically, while liver enzymes were measured in the blood. No histopathological changes in the liver nor elevated liver enzymes were observed in the 100 or 500 mg/kg/day male dose groups. In addition, kidney weights were not altered, while liver weights in the 500 mg/kg/day male dose group appeared to be increased. Data are also available from a 45-day range-finding(2) and 90-day gavage study(3) with a similar compound, H-24678, that contains the same active ingredient the range-finding study, r a t^ e r ^ a m in is te r e O T ^ ^ ^ ^ mg/kg/day (3 mg/kg/day active ingredient), 100 mg/kg/day (30 mg/kg/day active ingredient), 1000 mg/kg/day (350 mg/kg/day active ingredient), or 3000 mg/kg/day (1000 mg/kg/day active ingredient) H-24678. Males exposed to 3000 mg/kg/day exhibited statistically significant lower body weights and reduced body weight gain after 4 weeks of dosing and therefore had their dose lowered to 2000 mg/kg/day (700 mg/kg/day active) for the remaining 2 weeks of the study. Reductions in body weight gain (15% - 20% lower than controls) were also observed in rats exposed to 100 and 1000 mg/kg/day. Liver weights were significantly higher (40%-45%) compared to control rats administered 1000 and 3000/2000 mg/kg/day H-24678. No compoundrelated effects on organ weight were observed in rats administered 10 or 100 mg/kg/day. In the 90-day study with H-24678,1c3)rats were administered 10 mg/kg/day (3 mg/kg/day active ingredient), 60 mg/kg/day (20 mg/kg/day active ingredient), or 300 mg/kg/day (100 mg/kg/day active ingredient). Small, but statistically significant decrements in body weight parameters, food consumption, and food efficiency occurred in males administered 300 mg/kg/day. Kidney weights were significantly increased in rats administered 60 mg/kg/day H-24678 or higher. Liver weights were also increased in the 300 mg/kg/day female group, while males in the 60 and 300 mg/kg/day groups had elevated liver enzymes. The high-dose level of 3500 mg/kg/day (700 mg/kg/day active ingredient) was selected for this study and is expected to produce toxicity without excessive mortality. This was based on the results of the H-25156 range-finding study.(1) Rats in the high-dose level were able to tolerate 2000 mg/kg/day (400 mg/kg/day active) yet had a 10% decrement in body weight when compared with control when the dose was increased to 5000 mg/kg/day (1000 mg/kg/day active 16 Uampany 'SmMzed, Dobs not contain TSCA SB' H-25231: One-Generation Reproduction Study in Rats DuPont-9763 ingredient). The low dose of 75 mg/kg/day (15 mg/kg/day active) was expected to be the noobserved-effect-level, while the 500 mg/kg/day (100 mg/kg/day active) dose was expected to induce some toxicity. OBJECTIVE The objective of this study was to evaluate the effect of the test substance on the gonadal function, conception, parturition, and growth, and development of male and female Crl:CD(SD)IGS BR rats over one generation. MATERIALS AND METHODS A. Test Substance T hetetf substance was supplied by the sponsor as a tan liquid j U ^ T h e test substance appeared to be stable under the conditions of the study. No evidence of instability, such as a change in color or physical state, was observed. B. Test Species On March 5,2002,107 male and 109 female Crl:CD(SD)IGS BR rats, with an assigned birth date of January 21,2002 were received from Charles River Laboratories, Inc., Raleigh, North Carolina for use on this study. A subset of these animals (20 per sex) were used for a study of the time-course of blood fluorine, the results of which may be presented in a separate report. The rat was selected for this study because it is a preferred species for reproductive toxicity testing as recommended by the guidelines. The Crl:CD(SD)BR strain was chosen because extensive background information is available from the literature, the supplier, and previous studies with other compounds at DuPont Haskell Laboratory. This strain is also considered suitable relative to longevity, hardiness, and incidence of spontaneous disease. C. Animal Husbandry 1. Housing With the exception of the cohabitation periods, all rats were housed one per cage, sexes separate, in stainless steel, wire-mesh cages suspended above cage boards. Animal rooms were maintained on a 12-hour light/dark cycle (fluorescent light) and at a temperature of 22 3C and a relative humidity of 50% 20%. Occasional excursions outside the acceptable ranges were minor and did not affect the study. Rats were housed as breeding pairs during the cohabitation period. During the gestation period, female rats were housed individually until gestation day 20. Beginning on gestation day 20 for mated females, or at the end of the cohabitation period for females without evidence of Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 copulation, female rats were housed individually in polycarbonate pans with bedding. During the lactation period, adult female rats were housed with their litters in polycarbonate pans. 2. Feed and Water Tap water was provided ad libitum. All rats, except when fasted, were fed PMI Nutrition International, LLC Certified Rodent LabDiet 5002 ad libitum. 3. Identification Prior to assignment to groups, each rat was assigned a temporary cage identification. Subsequently, an individual identification number was tattooed on the tail of each rat. The information on the cage labels included the unique 6-digit Haskell animal number and the individual identification number assigned to each rat. Fj generation rats retained after lactation were tattooed when they were approximately 21 days old. 4. Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study. D. Quarantine and Pretest Period Upon arrival at Haskell Laboratory, the rats were quarantined for 9 days. The rats were observed daily for any clinically apparent signs of disease or injury and weighed 3 times. On the basis of acceptable body weight gains and clinical observations, all surviving rats were released from quarantine on test day -5 by the laboratory animal veterinarian designee. 18 Company Sanitized. Does not contain t s c a c b i H-25231: One-Generation Reproduction Study in Rats DuPont-9763 E, Study Design Treatment Groups and Daily Dosage Gtoud Number Pi Male Pi Female Number/ Group Daily Dosage (mg/kg/day)a 1-0 ni-o V-0 VII-0 II-O IV-0 VI-0 VIII-0 20 20 20 20 0 75 500 3500 a Weight of test substance per kg of animal body weight. Concentration (Control) (Low) (Intermediate) (High) Active Ingredient (mg/kg/day) 0 15 100 700 Generation Pi Fi Treatment Schedule Approximate Age at Start of Dosing (days) Approximate Number of Study Days Before Mating 55 Not applicable 70 Not applicable Duration of Dosing Until sacrifice No treatment Sacrifice Schedule Animals Schedule Adult Males After siring litters (at discretion of study director) Pregnant Females On day of weaning litters Nonpregnant Females With pregnant females Weanlings All unselected pups will be sacrificed on postnatal day 21 _____ Fj Adults_______________ _______At approximately postnatal day 60_________ F. Assignment to Groups and Study Start Hats of each sex were ranked by their most recently recorded body weight and randomly assigned to control and experimental groups. The randomization resulfed in a distribution in which the mean body weights for all groups within a sex were not statistically different (p > 0.05). G. Analytical Methods - Test Substance Administration, Preparation, and Sampling 1. Test substance Administration The test substance was administered by gavage in order to ensure delivery of known concentrations of the test substance. Animals were dosed once daily for approximately 70 days prior to cohabitation and during the cohabitation period (up to 2 weeks). Pi male and female rats showing no evidence of copulation continued to be dosed after the end of the cohabitation period 19 Company Saniiizsd. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 until sacrifice. Females showing evidence of copulation were dosed throughout gestation and lactation until their pups were weaned on postpartum day 21. Pregnant females in the process of delivery or showing signs of delivery were not dosed. From gestation day 18 until delivery, dose volumes were based on the gestation day 18 body weights. The volume of test substance or vehicle given to each rat was based on the most recently recorded body weight. D ose volumes were 5 mL/kg. Male and female control rats were similarly treated with deionized w ater at the same dose volume as used in the other groups. 2. Test Substance Preparation The test substance was a suspension of active ingredient in vehicle (deionized water). The material was further diluted with vehicle to prepare 3 different concentrations for dosing. Solutions of the test substance in the vehicle were prepared daily and stored at room temperature until used. The method of mixing the test substance with the vehicle is documented in the study records. 3. Sampling Samples containing H-25231 at the concentrations of 0,1 5 ,1 0 0 , and 700 mg/mL w ere collected on Test Day 2 for uniformity/concentration verification and 5-hour room temperature stability. Since homogeneity and concentration results for the 15 mg/mL samples were not w ithin acceptable ranges, samples containing H-25231 at the concentration of 15 mg/mL alo n g with a 0 mg/mL control were collected on Test Day 9 for repeat analysis of uniformity/concentration verification and 5-hour room temperature stability. Samples at all concentrations w ere collected on Test Day 46 and Test Day 114 for concentration verification analysis. All dosing solution samples were collected on the same day the solutions were prepared. The solution vehicle was deionized water. 4. Dosing Solution Treatment Each 1 mL dosing sample was diluted in 100 mL volumetric with high performance liquid chromatography (HPLC) grade water. The samples were further diluted with 50:50 methanol/water to final concentrations of 0.00045, 0.00050, or 0.00056 mg/mL (0 .4 5 , 0.50, or 0.56 ppm) H-25231. Prior to this final dilution, each aliquot was corrected with HPILC grade water so that all samples to be analyzed contained an equivalent amount of water. Samples submitted for analysis were analyzed the day the solutions were received. 20 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 5. Chromatographic Conditions LC/MS Method Method (Test Day 2/9) HPLC Instrument: Hewlett-Packard Model 1100 HPLC MS Instrument Micromass Quattro LC MS with "Z-spray" electrospray LC parameters: Column: XTerraMS C l8, 2.1mm x 30mm Mobile Phase (Time Table), flow rate: 0.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0 .25 mL/min. 10.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0 .2 5 mL/min. 16.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0 .2 5 mL/min. 16.01 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0 .3 0 mL/min. 23.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0 .3 0 mL/min. Run Time: 23.0 minutes Flow rate: (noted above with mobile phase) Injection Volume: 20 microliter Oven Temperature: 35C MS parameters: Ionization mode: Capillary voltage: Cone Voltage: Source Temperature: Desolvation Temperature: Scan function: Electrospray (ESI), negative ions 2.0 kV 40 V 120 300 SIR: 789, 889,989, and 1089 m/z time: 0-16 minutes 21 Company Sanitized. Does not contain TSCA CBE H-25231: One-Generation Reproduction Study in Rats DuPont-9763 LC/MS Method Method (Test Day 47/114) HPLC Instrument: Waters Model 2790 HPLC MS Instrument Micromass Quattro Micro LC MS with "Z-spray" electrospray LC parameters: Columns: XTerraMS C18, 2.1mm x 30mm and Phenomenex MercuryMS Luna C l8 (2), 2.0mm x 20mm Mobile Phase (Time Table), flow rate: 0.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.25 mL/min. 8.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 9.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 9.10 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.40 mL/min. 12.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.50 mL/min. 12.10 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.40 mL/min. 18.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.25 mL/min. Run Time: 18.0 minutes Flow rate: (noted above with mobile phase) Injection Volume: 20 microliter Oven Temperature: 35C MS parameters: Ionization mode: Capillary voltage: Cone Voltage: Source Temperature: Desolvation Temperature: Scan function: Electrospray (ESI), negative ions 3.5 kV 40 V 150 300 SIR: 789, 889, 989, and 1089 m/z time: 0-10 minutes 6. Calibration and Quantitation A stock solution of the H-25231 test material (separate samples of H-25231, used as analytical reference) was made in HPLC grade water. Appropriate aliquots of the stock were diluted with 50:50 methanol/water after a correction with HPLC grade water so that an amount equivalent to the dosing samples would be maintained in each diluted standard. These solutions were used as calibration standards that bracketed the target concentration of the diluted dosing samples. Mass to charge ratio (m/z) from LC/MS analysis using negative ion electrospray ionization and selective ion monitoring of these standards over the mass range of 789 to 1089 (m/z = 789, 889, 989,1089) were used to construct calibration curves by the appropriate regression (see Appendix A, Figure la - Id for representative calibration curves). Measured concentrations for dosing solutions were determined by applying the peak area from replicate injections of the 22 Compary Sanitized. Does not c'-ia in TSCA CBI Company Sanitized. Do _______________ '-'n H-25231: One-Generation Reproduction Study in Rats DuPont-9763 samples to each calibration curve. The mean result from the concentrations at all selected m/z (n = 4) is reported as the concentration for the sample. Test substance uniformity in the vehicle was evaluated by calculating the coefficient of variation (C.V. = standard deviation/mean x 100) of the measured concentrations in duplicate samples for each dosing level. A coefficient of variation of less than or equal to 10% is the standard criterion at Haskell Laboratory for acceptable distribution of the test substance throughout the solution. However, if the test substance has been shown to be difficult to disperse in the vehicle or the analysis has shown variability, a coefficient greater than 10 may be acceptable. The mean result of the duplicate samples for each dosing level was used to determine the concentration of the test substance for the respective dosing levels. Stability was evaluated by using the mean result of the duplicate samples from the concentration verification as the baseline for comparing the corresponding stability results. H. Body Weights - Pi Rats 1. Premating Feeding Period All Pi rats were weighed once per week. 2. Gestation and Lactation Periods Pi female rats were weighed on days 0 ,7 ,1 4 , and 21 of each period. Female rats without evidence of copulation, that copulated and did not deliver a litter, and male rats continued to be weighed on a weekly schedule. i. Food Consumption and Food Efficiency - Pi Rats 1. Premating and Cohabitation Dosing Periods Individual food consumption was determined weekly throughout the period, ending test day 75 (reported up to test day 71). Each feeder was weighed at the beginning and end of the interval and the final weight of the feeder and the amount of spillage from the feeder during the interval ivas subtracted from the initial feeder weight. From the food consumption and body weight data, the mean daily food efficiency was calculated. Food consumption was not determined during cohabitation. 2. Gestation and Lactation Periods Individual food consumption of pregnant Pj females was recorded on gestation days 0, 7, 14, and )1. Each feeder was weighed at the beginning and end of the interval and the final weight of the feeder and the amount of spillage from the feeder during the interval was subtracted from the 23 Company Sanitized. Does f contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 initial feeder weight. From the food consumption and body weight data, the mean daily food efficiency was calculated. Food consumption was not measured for females without evidence of copulation and for males. Food consumption was not measured during lactation. J. Detailed Clinical Observations and Mortality - Pi Rats Cage-site examinations were conducted at least once daily throughout the study. At least once weekly throughout the premating feeding, gestation, and lactation periods, each of the Pi parental rats were individually handled and carefully examined for abnormal behavior and/or appearance. K. Estrous Cycle Evaluation Vaginal lavage samples were collected daily from all Pi female rats in order to determine the stages of the estrous cycle. Vaginal lavage samples were collected beginning 3 weeks prior to mating, and continuing until copulation was confirmed, or the cohabitation period ended. Vaginal lavage samples were collected from all Pi parental female rats at the time of sacrifice. Vaginal lavage samples were examined microscopically for determination of the stage of the estrous cycle (diestrus, estrus, proestrus). L. Breeding 1. Start of Cohabitation After 2 weeks of exposure to the test substance 2. Duration of Cohabitation Period Until evidence of copulation was observed (designated as day 0 of gestation), or 2 weeks had (lapsed. 3. Cohousing fach female was continually housed on a 1:1 basis with a randomly selected, nonsibling male of lie same dosage level, in the male's cage. On the day copulation was confirmed, the female was ransferred back to individual cage housing. 4. Evidence of Copulation [jtravaginal copulation plug or sperm in vaginal lavage sample. Vaginal lavage samples were (Ollected daily from all Pi female rats that did not have an intravaginal copulation plug in order Ddetermine if there was sperm present in the vagina. Vaginal lavage samples were collected pring cohabitation and continued until evidence of copulation was observed or the cohabitation sriod ended. 24 Company Sanitized. Does not contain TSCACBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 M. Gestation Procedures After being transferred into polycarbonate pans (on day 20 of gestation for mated females, or at the end of the cohabitation period for females without evidence of copulation), female rats were observed at least twice daily for signs of delivery and offspring. N. Lactation Procedures The day when delivery was complete was designated day 0 postpartum. At each examination period, offspring were individually handled and examined for abnormal behavior and appearance; any dead, missing, or abnormal pups were recorded. 1. Day 0 Postpartum Live and dead pups in each litter were counted as soon as possible after delivery w as completed. Live pups in each litter were individually weighed. 2. Day 4 Postpartum Litters were culled randomly to 8 (4/sex when possible). Extra offspring were euthanized (by decapitation) and discarded without pathological examination. Litters of 8 offspring or fewer were not reduced. Litter counts were determined prior to and after culling. Individual pup weights were determined prior to culling. 3. Days 7 and 14 Postpartum Pups in each litter were counted by sex and individually weighed. 4. Day 21 Postpartum (Weaning) Pups in each litter were counted by sex and individually weighed. Randomly selected weanlings (one/sex/litter) were placed in individual cages and monitored for attainment of developmental landmarks. All unselected pups were then sacrificed and subjected to a gross pathological examination. O. Fj Generation 1. Body Weight Measurements All rats were weighed weekly until termination (approximately postnatal day 60). R ^ ts were also weighed on the day of preputial separation or vaginal opening. 2. Food Consumption and Food Efficiency Individual food consumption was determined weekly until termination (approximately postnatal day 60). Each feeder was weighed at the beginning and end of the interval and the filia l weight of the feeder and the amount of spillage from the feeder during the interval was subtracted frm 25 Company Sanitized. Does not contain TSCA CBf /*"*>. H-25231: One-Generation Reproduction Study in Rats DuPont-9763 the initial feeder weight. From these determinations and body weight data, individual daily food consumption and food efficiency were calculated. 3. Clinical Observations Cage-site examinations were conducted at least once daily. At least once weekly each rat was individually handled and carefully examined for abnormal behavior and/or appearance. P. Developmental Landmarks Developmental landmarks in the Fi generation male and female rats (one/sex/litter) were monitored on a daily basis until criterion was achieved. Animals were also weighed on the day the developmental landmark was achieved. 1. Vaginal Patency Female rats were examined once daily beginning on postnatal day 21 until achievement or postnatal day 43, whichever came first. 2. Preputial Separation Male rats were examined beginning on postnatal day 35 until achievement or postnatal day 55, whichever came first. Q. Clinical Pathology Evaluation A clinical pathology evaluation was conducted on week 10 prior to cohabitation on the first 10 rats/sex/group designated for the reproductive evaluation. The day before collection of blood samples for the clinical pathology evaluation, the male rats were placed in metabolism cages. The male rats were fasted overnight (approximately 16 hours) and urine was collected from each rat. Females were fasted, but were not placed in metabolism cages, and urine was not collected. Blood samples for hematology and serum chemistry measurements were collected from the orbital sinus of each animal while the animal was under light carbon dioxide anesthesia. Blood samples for fluoride analysis were collected at sacrifice from the abdominal vena cava of male rats only while the animal was under carbon dioxide anesthesia. 1. Hematology Blood samples were evaluated for quality by visual examination prior to analysis. Complete blood counts, including reticulocytes, were determined on a Bayer Advia 120 hematology analyzer, or determined from microscopic evaluation of the blood smear. Wright-stained blood smears from all animals were examined microscopically for confirmation of automated results and evaluation of cellular morphology. Blood smears, stained with new methylene blue, were prepared from each animal undergoing a hematology evaluation, but were not needed for evaluation. Bone marrow smears were prepared at the final sacrifice from all surviving animals. 26 Company Sanitized. Does not contain TSCA CBE H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Bone marrow smears were stained with Wright's stain and coverslipped, but analysis was not necessary to support experimental findings. The following hematology parameters were determined: red blood cell count hemoglobin hematocrit mean corpuscular volume mean corpuscular hemoglobin mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count platelet count white blood cell count differential white blood cell count microscopic blood smear examination 2. Serum Chemistry Serum clinical chemistry parameters were measured on a Roche Diagnostics (BMC)/Hitachi 717 clinical chemistry analyzer. Plasma fluorides were determined using a 012 pH meter and a fluoride-selective electrode. The following serum and plasma clinical chemistry parameters were determined: aspartate aminotransferase alanine aminotransferase sorbitol dehydrogenase plasma fluoride 3. Urinalysis Urine volume was measured. Urine fluorides were determined using a 0 1 2 pH meter and a fluoride-selective electrode. The following urinalysis parameter was determined: urine fluoride R. Anatomic Pathology 1. Pi Adults All Pi parental rats were sacrificed by carbon dioxide asphyxiation and exsanguination, and subjected to gross pathological examination, including those for which mating did not result in the production of offspring. The uteri of all cohabited females were examined for the presence and number of implantation sites. 27 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 The following table lists tissues that were weighed and/or collected from Pi adults: M ale Testes Epididymides Seminal Vesicles (with Coagulating glands) Prostate Tissues Weighed from Pj Adults Female Both Sexes Uterus (with oviducts and cervix) Ovaries Thyroid Gland8 Liver Brain Kidney M ale Tissues Collected from Pj Adults Female Both Sexes Testes'5 Epididymides'5 Prostate Seminal Vesicles (with Coagulating Gland) Ovaries Uterus (with cervix and oviducts) Vagina Thyroid Gland8 Gross Observations"5 Pituitary Gland Liver Kidney a Thyroid glands were weighed after fixation. b The right testis and epididymis collected from male rats were placed in Bouin's solution. The left testis and epididymis were frozen for sperm assessment. All other tissues (reproductive and non-reproductive) collected from male and female rats were placed in formalin, c Gross lesions observed at necropsy for which histopathology was not appropriate or would not be additive were generally not collected. 2. Offspring Offspring that were found dead during the lactation period underwent a gross pathological evaluation. 3. Fi Weanlings Ml unselected pups, litter size permitting, were sacrificed by carbon dioxide asphyxiation and underwent a gross pathological evaluation on postnatal day 21. Gross lesions were preserved. 4. Fi Adults' Ml Fj generation rats were sacrificed by carbon dioxide asphyxiation and exsanguination, and pceived a gross pathological examination, including Fj rats that died (found dead, accidentally tilled) or were sacrificed in extremis prior to postnatal day 60. Selected tissues and all gross lesions were preserved in appropriate fixative for possible future histopathological examination. 28 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 The following tables lists tissues that were collected and/or weighed from Fi adults: Male Testes Epididymides Seminal Vesicles (with Coagulating glands) Prostate Tissues Weighed from Fi Adults Female Both Sexes Uterus (with oviducts and cervix) Ovaries Thyroid Gland2 Liver Brain Kidney M ale Tissues Collected from Fi Adults Female Both Sexes Testesb Epididymides0 Prostate Seminal Vesicles (with Coagulating Gland) Ovaries Uterus (with cervix and oviducts) Vagina Thyroid Gland2 Gross Observations" Pituitary Gland Liver Kidney a Thyroid glands were weighed after fixation. b The testes and epididymides were placed in Bouin's solution. All other tissues (reproductive and non- reproductive) collected from male and female rats were placed in formalin, c Gross lesions observed at necropsy for which histopathology was not appropriate or would not be additive were generally not collected. 5. Microscopic Evaluations - Pi and Fi Rats Histopathological examination of reproductive organs (testes, epididymides, seminal vesicles, prostate, and uterus, ovaries, and vagina) was conducted only for Pi males and females with impaired reproductive performance. Gross lesions were saved and evaluated microscopically if they might have been additive to the interpretations of the study. Selected gross observations for which a microscopic diagnosis would not be additive (e.g., osteoarthritis, pododermatitis, tail chronic dermatitis, calculus, and deformities of the teeth, toe, tail, or ear pinnae) were saved, but not processed for microscopic evaluation. hiver, kidney, and thyroid were processed and evaluated microscopically in 10 randomly selected control and high-dose male and female Pi rats, and from all Fi control and high-dose adult males. Thyroid, the only target tissue in Pi females, was processed in all control and high-dose Fi adult females. Target tissues from Pi and Fi animals were subsequently processed and evaluated in lower dose groups as needed to determine a no-adverse-effect level. Selected tissues representing gross lesions from 3 Fi Weanlings were also processed and evaluated microscopically. 29 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 S. Sperm Assessment Sperm parameters for all Pi parental males were evaluated. The right epididymis was removed and weighed. The right cauda epididymis was weighed, excised, and placed in 32C phosphate buffered saline with 10 mg/mL bovine serum albumin, pricked with a needle to facilitate the release of sperm, and placed in an incubator at 32C for 5 minutes. After incubation, an aliquot was placed in a sample chamber which was loaded into a Hamilton Thome Integrated Visual Optical System (IVOS). The percentage of motile cells among at least 200 cells examined per animal were determined. After removal of an aliquot of sampling for videotaping, the right cauda epididymis was further incubated for approximately 15 minutes. An aliquot was stained with eosin, and smears were prepared on microscope slides. Sperm smears were examined to determine the frequency of morphologically abnormal sperm, expressed as percentage of normal cells among a t least 200 cells examined per animal. The specific types of abnormal morphologies, if any, were not categorized. The excised right cauda and the right caput and corpus epididymis w ere then placed in Bourn's solution. The left epididymis and left testis, following removal, were flash frozen in liquid nitrogen and stored at -65 to -85C until analyzed. After thawing, the cauda epididymis was excised, weighed, and homogenized. After thawing, the testis was weighed and homogenized. Sperm count per cauda epididymis and per gram cauda epididymis, and spermatid count p e r testis and per gram testis were determined using the IVOS. Company Sanitized. Does not contain TSCA CBI 30 Company Sanitized. Does not TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 T. Statistical Analyses The following table lists the indices of reproductive function that were calculated for the Pi and Fi adults. Reproductive Function Calculations Mating Index (%) Fertility Index (%) = = Gestation Index (%) = Implantation Efficiency (%)c - Pups Bom Alive (%)c - Viability Index (% )c,d = Lactation Index (% )c,d = Litter Survival (% )d = Number Copulated Number Cohabited Number Pregnant^ Number Copulated Number of Litters with at Least One Live Pun Number of Litters Number of P uds Bom Number of Implantation Sites Number of Pups Bom Alive Number of Pups Bom Number of Pups Alive Dav 4 Preculling Number of pups bom alive Number of pups alive at weaning (Dav 21 postpartum) Number of pups alive Day 4 Postculling Number of litters weaned Number of viable litters delivered x 100 x 100 x 100 x 100 x 100 x 100 x 100 x 100 a Evidence of copulation = intravaginal copulatory plug, sperm in vaginal lavage sample, found dead pregnant, or delivery of a litter. b Including those found dead pregnant during gestation. c To be determined for each litter. Mean and standard deviation for each dose level will be calculated. d Excluding litters sacrificed due to death of dam during lactation. 31 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Parameter Body Weight Body Weight Gain Food Consumption Gestation Length Implantation Site Numbers Implantation Efficiency Mean Number of Pups Per Litter Percent Bom Alive Precoital Interval Vaginal Patency Preputial Separation Litter Survival 0-4 Day Viability Lactation Index Organ Weight Statistical Methods Preliminary Test Test for lack of trend(4) Method of Statistical Analysis If preliminary test is not If preliminary test is significant significant Sequential application of the JonckheereTerpstra trend test Preliminary tests for pairwise comparison ORa Levene's test for homogeneity0**and Shapiro-Wilk test for normality1* One-way analysis of variance and Dunnett's test00* Kruskall-Wallis test0 1* and Dunn's test02* Food Efficiency Clinical Pathology Incidence of Clinical Observations Mating Index Fertility Index Gestation Index Viability Index Mean Pup Weights (Covariates: litter size, sex ratio) Sex Ratio Vaginal Patency (covariates: body weight) Preputial Separation (covariates: body weight) None Levene's test for homogeneity and Shapiro-Wilk test for normalityb None None Shapiro-Wilk test for normality One-way Analysis of Variance followed with Dunnett's test00* One-way analysis of variance followed with Dunnett's test00* Kruskall-Wallis test01* followed with Dunn's test02* Cochran-Armitage test for trendc Linear contrast of least squares means1il3>; Analysis of covariance404* Dunn's test02* Dunnett-Hsu05* a Pairwise comparisons and associated preliminary tests are only conducted if the test for lack of trend is significant. b If the Shapiro-Wilk test is not significant but Levene's test is significant, a robust version of Dunnett's test will be used. c If the incidence is not significant, but a significant lack of fit occurs, then Fisher's Exact test(16) with a Bonferroni correction is used. d A stepwise regression was used to determine which variables (body weight parameters) in addition to dose were significantly explanatory)/4* 32 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 For each parameter analyzed with a trend test, the test was applied to the data sequentially. If a significant dose-response was detected, data from the top dose group was excluded and the test repeated until no significant trend was detected.(5) For litter parameters, the proportion of affected fetuses per litter or the litter mean was used as the experimental unit for statistical evaluation.(I7) The level of significance selected is p < 0.05. Additional statistical tests were used, and other parameters analyzed, as deemed necessary. Where the data were tied and the standard large sample version of Jonckheere's test(6) was not applicable, exact p values were calculated using permutation methodology.0 8) RECORDS AND SAMPLE STORAGE Laboratory-specific or site-specific raw data, such as personnel files and equipment records will be retained by the facility where the work was done. A sample of the test substance was collected for archive purposes and retained at Haskell Laboratory. Specimens, raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. Raw data will be retained at Haskell Laboratory, Newark, Delaware. Characterization data (percent purity, composition, and known impurities) will be stored at Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. Characterization data used to support test substance stability will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. 33 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 RESULTS AND DISCUSSION 34 Company Sanitized. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 ANALYTICAL A. Chromatography (Appendix A) H-25231 eluted from the HPLC column as resolved peaks over mass to charge ratio (m/z) range of approximately 789 to 1089. For the purpose of quantitation, the m/z ratios of 789, 889,989, 1089 for the "bis" substituted c o m p o n e n t s M H M ^ ^ M M S H H B H i H were determined to be representative of the H-25231 in the dosing matrix. Representative LC/MS chromatograms are shown in Appendix A, Figures 2(a - c). Test substance was not detected in the 0 mg/mL control. B. Dosing Solution Analyses (Table 1, Appendix A) 1. Concentration Verification and Stability Samples Analytical results from dosing solutions prepared Test Day 2 and Test Day 9 (15.0 mg/mL, only) analyzed for uniformity/concentration verification and stability are shown in Summary Table 1 and Appendix A, Table I. The following table summarizes the results for uniformity/concentration verification and stability analyses for the H-25231 sample preparation on Test Days 2 and 9. I . . . - ........................ ........ ....... .................................... .1111 ........ Preparation Nominal3 Measured Day mg/mL mg/mL .l.llll.l........................... ............ Average CV %% Nominal ...... , . l l Stability0 % Nominal Test Day 2 15 100 700 8.72d, 12.8 91.6, 97.2 715,668e 72.0 94.4 98.8 27 72.0d 4 87.7 5 108.46 Test Day 9 15 12.7d, 15.6e 94.7 14 110.0 a Dosing solution concentration mg H-25231/mL, based on 5 mL dose volume. H-25231 is approximately b Duplicate samples analyze c Stability samples held for 5 hours at room temperature. Percent Nominal based on measured. d Reported result based on all analysis from the original samples. e Reported result based on duplicate reanalysis of the original sample. The results for H-25231 samples prepared on Test Day 2, show that the test substance was adequately mixed (CV's less than 10) except at the 15 mg/mL level (CV = 27), at the targeted levels (target = 5.6% of nominal) except for the 15 mg/mL level (72% of nominal), and stable in the vehicle when held 5 hours at room temperature. An additional sample of the 15 mg/mL level was taken on Test Day 9 for repeat analysis since the results for the Test Day 2 sample did 35 Company Sanitized. Does not contain TSCA CBf H-2S231: One-Generation Reproduction Study in Rats DuPont-9763 not meet concentration and homogeneity acceptability criteria. The results for H-25231 sample prepared on Test Day 9 of the 15 mg/mL level, show that the test substance was adequately mixed (CV = 14), at the targeted levels (target = 5.3% of nominal), and stable in the vehicle when held 5 hours at room temperature. Test substance was not detected in the 0 mg/mL samples. 2. Concentration Verification Samples Analytical results from dosing solutions prepared Test Day 46 and Test Day 114 and analyzed for concentration verification are shown in Summary Table 1 and Appendix A, Table II. The following table summarizes the results for concentration verification analyses for the Test Days 46 and 114 of the H-25231 sample preparation. Preparation Day Nominal2 mg/mL Measured*5 mg/mL Average % Nominal CV % Test Day 46 15 100 700 15.1,16.6 112,113 749,666 106.0 113.0 101.1 7 1 8 Test Day 114 15 100 700 1 6 . 5 , 12.9C 107,120 765,681 98.0 114.0 103.3 17 8 8 a Dosing solution concentration mg H-25231/mL,Jjgsed on 5 mL dose volume. H-25231 is approximately! b Duplicate samples per level were analyzed. C.VTcalculated to verify uniformity of mixture. c Reported result based on duplicate reanalysis of the original sample. The results for samples prepared on Test Days 46 and 114 indicate that the test substance was adequately mixed except for the 15 mg/mL level on Test Day 114 which was marginal and at the targeted levels (target = 14.0% of nominal) for all H-25231 samples. Test substance was not detected in the 0 mg/mL sample. C. Analytical Conclusions Results from the analysis of the test substance dosing solutions during the study indicate that the test substance was mixed properly except for the 15 mg/mL level on Test Day 2 but was acceptable on Test Day 9,46, and marginally acceptable on Test Day 114, at the targeted levels except for the 15 mg/mL level on Test Day 2 and stable under the conditions of the study. Test substance was not found in the 0 mg/mL samples. The results obtained on Test Day 2 are not believed to have impacted the study since the repeat sampling on Test Day 9 and subsequent samplings showed acceptable results. Company S a n lta i. Does nof ^ 36 ^^ H-25231: One-Generation Reproduction Study in Rats DuPont-9763 REPRODUCTIVE TOXICITY EVALUATIONS IN-LIFE TOXICOLOGY A. Pi Rats - Mean Body Weights and Body Weight Gains 1. Pi Males: (Tables 2-3, Appendices B-C) There were test substance-related reductions in body weights at 3500 mg/kg/day and body weight gains at >500 mg/kg/day. At 3500 mg/kg/day, mean body weight gain was reduced for much of the dosing period. As a result, weekly mean body weights were consistently reduced throughout the dosing period, and mean final body weight (test day 113) and overall weight gain (test days 1-113) were 80% and 64% of the control mean, respectively. At 500 mg/kg/day, there were transient reductions in body weight gain; the most evident of these occurred on test days 1-8,1522,43-50, 85-92, and 92-99. As a result, mean final body weight (test day 113) and overall weight gain (test days 1-113) were 94% and 88% of the control mean, respectively. 2. Pi Females: (Tables 4-9, Appendices D-G) There were test substance-related reductions in body weight gain at 3500 mg/kg/day. Mean body weight gain was reduced during premating, on test days 1-8 and 36-43, and on gestation days 0-7 and 7-14. These sporadic reductions in weight gain did not affect overall weight gain during premating (95% of control mean on test days 1-71) or gestation (95% of control mean on gestation days 0-21). Overall mean body weight gain during lactation was increased at 3500 mg/kg/day (226% of control mean on lactation days 0-21) and was mainly due to a mean body weight change that was 165% of control on lactation days 14-21. This finding was considered spurious and not biologically meaningful. B. Pi Rats - Food Consumption and Food Efficiency 1. Pi Males: (Tables 10-11, Appendix H) There were test substance-related reductions in food consumption and food efficiency at 3500 mg/kg/day. Mean food consumption was reduced (89%-98% of the control mean) for much of the premating period. As a result, overall food consumption for this period (test days 171) was 93% of the control mean. Mean food efficiency was reduced (89%-98% of the control mean) for much of the premating period. As a result, overall food consumption for this period (test days 1-71) was 93% of the control mean. 37 ftim Htr SanRIzed. Does no! contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 2. Pi Females: (Tables 12-15, Appendices I-J) There were test substance-related reductions in food consumption at 3500 mg/kg/day. Mean food consumption was reduced during premating, on test days 1-8, and on gestation days 0-7 and 7-14. These sporadic reductions in food consumption did not affect overall food consumption during premating (98% of control mean on test days 1-71) or gestation (93% of control mean on gestation days 0-21). C. Pi Rats - Clinical Observations and Mortality 1. Pi Males: (Table 16, Appendix K) There was no test substance-related mortality. Two animals died as a result of gavage trauma; one in the 3500 mg/kg/day group on test day 42 and one in the 500 mg/kg/day group on test day 86. One animal in the 3500 mg/kg/day group was found dead on test day 66. This death was considered possibly due to gavage trauma since the lungs had red discoloration and congestion, and prior to sacrifice this animal did not display any significant reduction in body weight gain or food consumption, or show any overt signs of toxicity except for intermittent salivation. One animal in the control group was sacrificed in extremis on test day 60; prior to sacrifice this animal displayed reduced body weight gain and body weight loss as a result of a sore on shoulders/neck. There were test substance-related clinical observations at 3500 mg/kg/day that consisted of low incidences of "lung noise," "salivation," "stained nose," and "stained perineum," which were generally sporadic. The salivation occurred after dosing and was not considered indicative of neurological effects since previous studies with this active ingredient showed no signs of neurotoxicity. 2. Pi Females: (Tables 17-19, Appendices L-N) There was no mortality at any dose level. There were test substance-related clinical observations during premating at 3500 mg/kg/day that consisted of low incidences of sporadic salivation. There were no test substance-related clinical observations during gestation or lactation at any dose level. The salivation occurred after dosing and was not considered indicative of neurological effects since previous studies with this active ingredient showed no signs of neurotoxicity. / " 'v 'C om pany Sanitized. Does not contain TSCA CBI 38 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 D. Sperm Parameters (Table 20, Appendices O-Q) There were no test substance-related effects on sperm motility, morphology, epididymal sperm or testicular spermatid numbers at any dose level. The percent normal sperm was statistically significantly reduced at 500 and 3500 mg/kg/day (98.3% and 98.3% vs. 99.1% for the control group). These changes were considered spurious due to their small magnitude and values were within the historical control range at Haskell Laboratory. Historical Control Data for Haskell Laboratory 1999-2001 Studv Start Date Mar-01 Dec-00 Sep-00 Jun-00 Jan-00 Mar-99 Apr-99 Jul-99 Soerm Mornholoev (% Normal! 98.3 98.8 98.6 98.0 97.7 98.0 96.1 99.2 Mean Standard Deviation Minimum Maximum 98.1 0.9 96.1 99.2 E. Estrous Cycle Parameters and Precoital Interval in Pi Females (Table 21, Appendices R-S) There were no test substance-related effects on percent days in estrus, diestrus, or proestrus, mean cycle length, or precoital interval at any dose level. F. Reproductive Indices (Table 22, Appendices T-U) There were no test substance-related effects on mating, fertility, gestation length, number of implantation sites, or implantation efficiency at any dose level. The Pi generation fertility index was lower (not statistically significant) than the control group at 3500 mg/kg/day (75% vs. 90% for the control group). Implantation efficiency was statistically significantly reduced at 3500 mg/kg/day (93% vs. 96.9% for the control group). These changes were considered spurious due to the small magnitude, the unusually high implantation efficiency in the control group, and values were within the historical control range at Haskell Laboratory. These findings were not associated with any test substance-related change in other reproductive parameters in affected animals (implantations, litter size, pup viability, estrous cycle or sperm parameters, or reproductive organ histopathology). W jrnm w ^m m m d. Does ,,c? s cw 39 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 H istorical Control Data for Haskell Laboratory 1994-2002 Study Start Date Feb-02 Mar-01 Dec-00 Sep-00 Jan-00 Oct-98 Mar-97 Jul-95 Apr-94 Jan-94 Fertility Index (%) 100.0 85.0 72.2 90.0 87.5 75.0 90.0 93.3 93.1 82.1 Implantation Efficiency! %) 93.8 90.0 96.6 91.2 92.1 84.4 93.4 90.2 90.7 86.3 Mean Standard Deviation Minimum Maximum 86.8 8.5 72.2 100.0 90.9 3.5 84.4 96.6 G. Fi Offspring Data 1. Litter Size, Sex Ratio and Pup Survival (Table 23, Appendix V) There were no test substance-related effects on the number of pups bom, bom alive, alive on day 4 ,7 ,1 4 , or 21, nor were there any effects on sex ratio, or survival indices during the lactation period. 2. Pup Weights (Table 24, Appendix W) There was a test substance-related effect on pup weights at 3500 mg/kg/day. Mean pup weights i/ere reduced during the lactation period and were 91%, 86%, 77%, and 76% of the control mean un lactation days 0 ,7 ,1 4 , and 21, respectively. There was a test substance-related increase in the incidence of small whole body in Fi pups that were sacrificed at weaning (5 vs. 0 pups in the (ontrol group) (see Gross Pathology Tables and Appendices for weanling rats). 3. Clinical Observations in Fj Pups (Table 25, Appendix X) fhere were no test substance-related clinical observations at any dose level. y 40 Company Sanitized. Does not contain TSCA CBI ffi-25231: One-Generation Reproduction Study in Rats DuPont-9763 H. Fi Rats - Mean Body Weights and Body Weight Gains (Tables 26-29, Appendices Y-Z) There were test substance-related reductions in body weights and body weight gain in males and females at 3500 mg/kg/day. Consistent with the reduction in pup weight at the end of lactation, mean body weights on the day of weaning (test day 1 or postnatal day 21) were also reduced (76% and 79% of control in males and females, respectively). Weekly mean body weight gains were reduced throughout much of the post-weaning period in males (76%-91% of control mean). As a result, weekly mean body weights were consistently reduced throughout the post-weaning period, and mean final body weight (test day 36) and overall weight gain (test days 1-36) were 87% and 89% of the control mean, respectively. Weekly mean body weight gain was reduced for the first week after weaning in females (86% of control mean on test days 1-8); however, mean final body weight and overall body weight gain were unaffected. 1 F] Rats - Food Consumption and Food Efficiency (Tables 30-33, Appendix AA) There were test substance-related reductions in food consumption in males at 3500 mg/kg/day. Mean food consumption was reduced (81%-91% of the control mean) for the first 3 weeks of the post-weaning period in males. As a result, overall food consumption for this period (test days 136) was 91% of the control mean. Mean food efficiency was not affected at any dose level. J. Fi Rats - Clinical Observations and Mortality (Tables 34-35, Appendix BB) There was no test substance-related mortality nor were there any clinical signs of toxicity in any jroup. One female in the 3500 mg/kg/day group was found dead on test day 7 (postnatal day27); on the day prior to death this animal was weak and hunched over. One male in the 3500 mg/kg/day group was also weak and hunched over on test day 6. The mortality and clinical sgns were considered spurious due to the low incidence. p. Fi Rats - Developmental Landmarks (Table 36, Appendix BB) There were no test substance-related effects on developmental landmarks. The mean age of peputial separation (45.333 days for the 3500 mg/kg/day group vs. 42.778 days for the control poup) and vaginal opening (33.786 days for the 3500 mg/kg/day group vs. 31.772 days for the (Ontrol group) were increased in the 3500 mg/kg/day groups. These changes were not considered tjbe due to the test substance but rather an indirect effect of the reduced body weights and body weight gain during the post weaning period. I Reproductive In-Life Toxicology Conclusions -tieNOEL for reproductive toxicity in this study was 500 mg/kg/day, based on reductions in Fj jjp weights during lactation at 3500 mg/kg/day. 41 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 CLINICAL PATHOLOGY EVALUATIONS A. Hematology (Tables 37-38, Appendix CC) There were no adverse changes in hematology parameters in rats dosed with the test substance. All statistically significant changes in hematology parameters were considered unrelated to treatment and/or non-adverse (not toxicologically significant). These changes are detailed below. Red cell mass parameters (red cell count, hemoglobin, hematocrit) were minimally decreased in males dosed with 75, 500, or 3500 mg/kg/day (variable statistical significance). There was a lack of a dose-response relationship in red cell mass effects despite the nearly 50-fold difference in dose between the low and high dose, and the presence of a clear doserelationship in other parameters indicating exposure to the compound (plasma and urine fluoride). However, the changes at 500 and 3500 mg/kg/day were considered to be probably related to treatment because there was a minimal increase in red cell morphologic changes (anisocytosis, microcytosis, and hypochromasia) in males dosed with 500 or 3500 mg/kg/day, and mildly increased red cell distribution width at 3500 mg/kg/day, indicating a possible dose-related effect. The magnitude of change in all red cell parameters was small, and therefore, was considered to be non-adverse White cell counts were minimally increased in females dosed with 75, 500, or 3500 mg/kg/day (statistically significant only at 3500 mg/kg/day). Increased white cell counts were the result of statistically increased lymphocytes (females dosed with 75 or 3500 mg/kg/day only) and eosinophils (females dosed with 3500 mg/kg/day only). There was a lack of a dose-response relationship in white cell effects despite the nearly 50-fold difference in dose between the low and high dose. There were no other clinical pathology or histologic changes (e.g. inflammation) that correlated with these minimal changes. In addition, for those mean leukocyte counts (total and individual cell types) that were statistically significant, individual counts were generally within or just outside the reference range for individual control rats.3 Therefore, these changes were considered unlikely to be related to treatment and non-adverse. iThe 2.5-97.5 percentile counts for female rats aged 19 weeks, reported as cells/uL, are WBC 4.92-13.25; ALYM 3.83-10.41; AEOS 0.06-0.22).(19> 42 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 B. Clinical Chemistry (Tables 39-40, Appendix CC) There were no adverse changes in serum clinical parameters in rats dosed with the test substance. Statistically significant changes in serum clinical chemistry parameters were considered unrelated to treatment and/or non-adverse (not toxicologically significant). These changes are detailed below. Alanine aminotransferase activity was minimally increased in males dosed with 75, 500 (not statistically significant), or 3500 mg/kg/day. There was a lack of a dose-response relationship in this effect despite the nearly 50-fold difference in dose between the low and high dose, and the presence of a clear dose-relationship in other parameters indicating exposure to the compound (plasma and urine fluoride, hepatocellular hypertrophy). In addition, the control mean is near the low end of the laboratory historical range for mean alanine aminotransferase activity in males of approximately the same age.8 Therefore, although it is possible that the changes in alanine aminotransferase activity are related to treatment, it is more likely that the apparent increased activity in the treated group was due to the unusually low mean activity in the control group. C. Plasma and Urine Fluoride (Tables 39 and 41, Appendix CC) Plasma and urine fluoride were measured in males only. Plasma fluoride was increased in males dosed with 500 or 3500 mg/kg/day, while urine fluoride was increased in males dosed with 75 (not statistically significant), 500, or 3500 mg/kg/day (Clinical Pathology Text Table 1). These changes occurred in a dose-related manner. Increases in plasma and urine fluoride indicate exposure and metabolism of a fluoride-containing molecule. Clinical Pathology Text Table 1: Mean urine and plasma fluoride for males Parameter (units) Dose (mg/kg/day) 0 75 500 'PELU (ug/mL) 0.1 0.1 % of control mean NA 100% JFLU (ug) 12.1 53.9 % of control mean NA 445% ' Statistical significance is indicated by bold italicized type. 0.2 200% 176.1 1455% 3500 0.4 400% 512.4 4235% (Means alanine aminotransferase activity for younger males (12-14 weeks old) is 28-50 U/L, while that for older males (30-65 weeks old) is 30-65 U/L.(20> 43 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 D. Clinical Pathology Conclusions There were no adverse changes in clinical pathology parameters. Therefore, under the conditions of this study and for the clinical pathology parameters measured, the no-adverse-effect level was 3500 mg/kg/day for males and females, the highest dose administered, based on the lack of adverse findings at this dose. Treatment related but non-adverse changes included minimally decreased red cell mass parameters, increased red cell distribution width (3500 mg/kg/day only), and increased red cell morphology in males dosed with 500 or 3500 mg/kg/day. In addition, increased plasma and urine fluoride measurements were observed in males dosed with 75 (urine fluoride only), 500, or 3500 mg/kg/day; the presence of fluoride in plasma and urine indicates exposure to and metabolism of a fluoride-containing molecule. 44 Company Sanitized. Does not contain TSCA CBt H-25231: One-Generation Reproduction Study in Rats DuPont-9763 ANATOMICAL PATHOLOGY A. Mortality (Pi Adult Rats - Appendices K, L-N, and FF) (Fi Adult Rats - Appendices BB and GG) There were no test substance-related deaths in the study. B. Organ Weight Data (Pi Adult Rats - Tables 42-43, Appendix DD) (Fi Adult Rats - Tables 44-45, Appendix EE) There were statistically significant test substance-related higher mean liver and kidney weights in male and female Pi rats as listed in the following table: Test Substance-Related Organ Weight Effects In Pt Males and Females Dose Group: Organ Liver (absolute weight) 75 mg/kg/day Male Female ---- 500 mg/kg/day Male Female ---- 3500 mg/kg/day Male Female tT Liver (relative to body) T -- -- T T Liver (relative to brain) -- -- T-- TT kidneys (absolute) -- ---- -- kidneys (relative to body) T -- t t kidneys (relative to brain) -- -- TT Higher liver weights in Pi rats correlated with microscopic hepatocellular hypertrophy and was considered non-adverse (see discussion in Microscopic Findings). There was no microscopic correlate for higher kidney weight. Higher kidney weight was most likely due to hypertrophy, which was below the threshold of microscopic detection, and was considered non-adverse. Other statistically significant organ weight changes (lower absolute,'relative to brain and/or higher relative to body) in the epididymides, seminal vesicles, prostate and/or brain in Pi males from the high dose group were interpreted to be the result of lower final body weight in that group and not test substance-related. The mean relative (to body) liver weight was significantly higher than the control in the high dose female Fi adults, and was considered a test substance-related effect. There was no microscopic correlate and the small weight increase was most likely due to hepatocellular hypertrophy that was below the threshold of microscopic detection. This weight change was considered a non-adverse finding (See discussion of hepatocellular hypertrophy in Microscopic findings section). 45 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 There were no other test substance-related organ weight effects in Fj adult rats. Other significant organ weight changes (lower absolute, relative to brain and/or higher relative to body) in the testes, epididymides, and/or prostate in Fi males from the high dose group were interpreted to be the result of lower final body weight in that group and not test substance related. Prostate weight from one high dose male rat (Animal No. 660638) was removed from the weight calculations due to a weighing error. C. Gross Findings (Pi Adult Rats -Tables 46-47, Appendix FF) (Fi Adult Rats - Tables 48-49, Appendix GG) (Weanlings - Table 50-51, Appendix HH and II) (Pups - Tables 52-53, Appendix II) There were no test substance-related gross observations in adult Pi, Fi, or in weanling rats. Gross observations occurred in low incidences and were randomly distributed across control and treatment groups. Observations in pups of "lungs not expanded," and "no milk spot in the stomach," are nonspecific lesions that are commonly seen in all pups that are bom dead, and thus are not considered to be compound-related. Pup viability and mortality are discussed elsewhere in this report. D. Microscopic Findings (Pi Adult Rats - Tables 54-55; Appendix FF) (Fi Adult Rats - Tables 56-57, Appendix GG) (Weanling Female Rats - Table 58, Appendix HH) 1. Pi Adult Rats (Pi Adult Rats - Tables 54-55; Appendix FF) Hepatocellular hypertrophy in the liver and chronic progressive nephropathy in the kidney were increased in incidence in Pi males from the 500 and 3500 mg/kg/day dose groups, and were interpreted to be test substance-related. Hepatocellular hypertrophy depicted hepatocytes with tnlarged eosinophilic cytoplasm with intact hepatic cords and was interpreted to be an adaptive physiological response to exposure to a xenobiotic, and not biologically adverse. Chronic progressive nephropathy depicted basophilic staining of tubular epithelium, often with enlarged juclei, sometimes accompanied by a minimal inflammatory component and minimal peritubular tromal thickening. Chronic progressive nephropathy occurs commonly as a spontaneous lesion inrats and the increased incidences noted in the current study represent a compound-related (arlier onset of a typical age-related finding. The severity of this lesion was minimal in treated nd in control animals and was unaccompanied by any correlative adverse clinical pathology jndings (see Clinical Pathology portion of this report). Kidney changes in Pi males administered |00 mg/kg/day and above were considered adverse findings. fhyroid follicular hypertrophy was increased in incidence in all dose groups of Pi males (75mg/kg/day and higher) and in females in the intermediate and high (500 and 3500 mg/kg/day) y" 46 Company Sanitized. Does not contain TSCA CBl 0-25231: One-Generation Reproduction Study in Rats DuPont-9763 dose groups. Hypertrophy was generally minimal in severity with moderate severity diagnosed in 2 males (one 500 mg/kg/day and one 3500 mg/kg/day). Follicular hypertrophy was diagnosed when the follicular epithelium was tall columnar with a finely granular cytoplasm. Thyroid hypertrophy was considered test substance-related and potentially adverse. Thyroid follicles containing altered colloid were found in thyroids from controls as well as treated animals. An increase in incidence and/or an increase in the number of affected follicles, and thus grade, was interpreted to be treatment-related. Altered colloid described as clumped or granular has been reported to occur spontaneously in Sprague-Dawley rats with increasing incidence with increasing age.(2I> Thus, alterations in colloid are known to occur spontaneously in the Sprague-Dawley rat. In the present study, there was only a treatment-related increase in grade and not in incidence of the observation for Pj males at all dose levels. There was an increase in the incidence of altered colloid in the 500 and 3500 mg/kg/day group Pi females. There was no consistent association between the presence or absence of altered colloid with follicles that were lined by hypertrophic or non-hypertrophic follicular cells. Because altered colloid occurs spontaneously in healthy Sprague-Dawley rats, and because increases in its grading score did not correlate with degenerative morphologic observations, altered colloid was interpreted in the present study as not biological meaningful and not adverse. 2. Fi Adult Rats (Fi Adult Rats - Tables 56-57, Appendix GG) Minimal hypertrophy of thyroid follicular epithelium was increased in incidence in Fi adult males at all test substance dose groups and in one Fi adult female from the 3500 mg/kg/day dose group. Altered colloid was detected in very few animals across dose groups and was not considered to be test substance-related in the Fj adults. Thyroid hypertrophy was considered test substance-related and potentially adverse. The character and severity of thyroid hypertrophy was very similar between affected Pi and Fi animals. In females, the NOEL for thyroid changes was ligher in the Fi generation compared to the Pi generation. 3. Fi Weanlings (Weanling Female Rats - Table 58, Appendix HH) there were no test substance-related findings in the weanlings examined. The few lesions resent (hydronephrosis, bone fracture, urinary bladder inflammation with mucosal hyperplasia) ire commonly observed spontaneous or incidental lesions in this age and strain of rat. f. Anatomic Pathology Conclusions the no-observed-adverse-effect level (NOEL) for this study is defined as the highest dose at ihich toxicologically important effects attributable to the test substance were not detected. I'nder the conditions of this study, based on hypertrophy of thyroid epithelium, the NOEL for jathology was not determined in Pi and Fi adult males, was 75 mg/kg/day for Pi adult females, ifidwas 500 mg/kg/day for Ft adult females. 47 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 CONCLUSIONS Under the conditions of this study, a no-observed-effect level (NOEL)3was not determined for Pi and F] rats, based on thyroid follicular hypertrophy in Pi and Fi adult males at >75 mg/kg/day. The NOEL for reproductive effects was 500 mg/kg/day, based on reductions in mean pup weights throughout the entire lactation period for Fi litters at 3500 mg/kg/day. 1 The NOEL for this study is defined as the highest dose at which toxicologically important effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency(22) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(23) 48 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 REFERENCES 1. DuPont Haskell Laboratory^JRepeated Dose Oral Toxicity, Gavage Range-Finding Study in Report. 2. DuPont Haskell LaboratoryJRepeated Dose Oral Toxicity, Gavage Range-Finding Stud^jj Rats. Unpublished R eport.________ 3. DuPont Haskell Laboratory (2002). Jjubchronic Toxicity, 90-Day Oral Gavage Study in Rats. Unpublished Report,i 4. Draper, N.R. and Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. Wiley, New York. 5. Selwyn, M.R. (1995). The use of trend tests to determine a no-observable-effect level in animal safety studies. Journal o f the American College o f Toxicology 14(2), 158-168. 6. Jonckheere, A.R. (1954). A distribution-free K-sample test against ordered alternatives. Biometrika 41,133-145. 7. Levene, H. (1960). Robust test for equality of variances. Contributions to Probability and Statistics (J. Olkin, ed.), pp 278-292. Stanford University Press, Palo Alto. 8. Shapiro, S.S. and Wilk., M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611. 9. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th edition, pp 246-248 and 349-352. The Iowa State University Press, Ames. 10. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50,1096-1121. 11. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Auner. Statist. Assoc. 47, 583-621. 12. Dunn, O J. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. 13. Dempster, A.P., Selwyn, M.R., Patel, C.M., and Roth, A.J. (1984). Statistical and computational aspects of mixed model analysis. The Journal o f the Royal Statistical Society, Series C (Applied Statistics) 33(2), 203-214. 14. Milliken, G.A. and Johnson, D.A. (1984). Analysis o f Messy Data, Volume 1.: Designed Experiments. Lifetime Learning Publications, Belmont. 15. Hsu, J.C. (1992). The Factor Analytic Approach to Simultaneous Inference in the General Linear Model. Journal o f Computational and Graphical Statistics 1,151-168. 16. Fisher, R.A. (1985). Statistical Methodsfo r Research Workers, 13th edition. Haffner, New York. 17. Haseman, J.K. and Hogan, M.D. (1975). Selection of the experimental unit in teratology studies. Teratology, 12, 165-171. 18. Patefield, W. (1982). Exact tests for trends in ordered contingency tables. Applied Statistics 31, 32-43 49 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 19. DuPont Pharmaceuticals Company. (April 3, 2000). Clinical Pathology Reference Ranges . The 2.5-97.5 percentile counts for female rats aged 19 weeks, reported as cells/uL, are WBC 4.92-13.25; ALYM 3.83-10.41; AEOS 0.06-0.22). 20. DuPont Haskell Laboratory. Clinical Pathology Reference Ranges. The Haskell historical range of means for younger males (12-14 weeks old) is 28-50 U/L, while that for older males (30-65 weeks old) is 30-65 U/L. 21. Rao-Rupanagudi, S., Heywood, R., and Gopinath, C. (1992). Age-related Changes in Thyroid Structures and Function in Sprague-Dawley Rats. Vet. Pathol., Vol. 29, No. 4, pp. 278-287. 22. Hazard Evaluation Division, Standard Evaluation Procedure, Toxicity Potential: Guidance for Analysis and Evaluation of Subchronic and Chronic Exposure Studies Paynter, O. E. et al., United States Environmental Protection Agency, Office of Pesticide Programs, Washington, D.C., 20406. EPA-540/9-85-020. (June 1985). 23. Risk Assessment of Notified New Substances. Technical Guidance Document (XE283/94-EN), Chapter I, Sections 2.24 and 2.25. 1994. 50 Company Sanitized. Does no? contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLES 51 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats TABLES EXPLANATORY NOTES Notes Test Days 1-75 Test Days 76-90 Premating period Cohabitation period Abbreviations - Clinical Pathology Summary of Hematology Values RBC - red blood cell count HGB - hemoglobin HCT - hematocrit MCV - mean corpuscular volume MCH - mean corpuscular hemoglobin MCHC - mean corpuscular hemoglobin concentration RDW - red cell distribution width ARET - absolute reticulocyte count PLT - platelet count WBC - white blood cell count ANEU - absolute neutrophil (all forms) ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absolute eosinophil ABAS - absolute basophil ALUC - absolute large unstained cell Summary of Serum and Plasma Chemistry Values AST - aspartate aminotransferase ALT - alanine aminotransferase SDH - sorbitol dehydrogenase PFLU - plasma fluoride Summary of Urinalysis Values UFLU - urine fluoride DuPont-9763 52 Company Sanitized. Does n->t contain TSCA CBI -!*},,__l H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 1 SUMMARY OF DOSING SOLUTION ANALYSES Sample Type___________________ Dosing Concentrations and Stability of H-25231 (mg/mL)a Test Day 2 Concentration Verification Nominal:_________ 15_______________ 100______________ 700 8.72b 91.6 715 (58.1) (91.6) (102.1) 12.8 97.2 668d (85.3) (97.2) (95.4) Average M easured Conc.e Average Percent Nominale Standard Deviation Coefficient of Variation Stability 0-Day Room Temperature!" 5-hour Room Temperatureg Test Day 9 Concentration Verification A verage M easu red Cone. A verage P ercen t Nominal S tandard Deviation Coefficient of Variation Stability 0-Day Room Temperature^ 5-hour Room Temperatureg 10.8 (72.0) 2.9 27% 10.8 (72.0) 10.8 (72.0) 12.7b (84.7) 15.6^ (104.0) 14.2 (94.7) 2 .0 . 14% 14.2 (94.7) 16.5 (110.0) 94.4 (94.4) 4 .0 4% 94.4 (94.4) 87.7 (87.7) ...Ja __ h __ h 691 (98.8) 33 5% 691 (98.8) 759 (108.4) __ h __ h __ h Concentration Verification! Test Day 46 Test Day 114 15.9 (106.0) 14.7b, (98.0) 113 (113.0) 114 (114.0) 708b (101.1) 723 (103.3) a Dosing solution concentration mg H-25231/mL based on 5 mL dose volume. b Mean result for all analysis on the original sample, c Numbers in parentheses are the respective percent of nominal values, d Mean result for duplicate reanalysis of the original sample. e Mean, S.D. and C.V. for duplicate samples calculated to verify uniformity of mixture, f Mean result for Test Day 2/9 concentration verification samples used for baseline for stability samples, g Samples (Test Day 2/9) held at room temperature for 5 hours, h Samples not submitted at 100 mg/mL and 700 mg/mL levels, i Duplicate samples submitted. Mean result reported. 53 Company Sanitized, Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats TABLE 2 MEAN BODY WEIGHTS (grams) OF Pi MATE RATS Group: Dose (mg/kg/day): Test Day 1 1-0 0 280.705 11.038(19 ) 8 328.795 15.689(19 ) 15 372.779 19.979(19 ) 22 413.263 23.642(19 ) 29 443.800 26.475(19 ) 36 469.489 29.543(19 ) 43 48 9 . 2 1 6 31.089(19 ) 50 513.721 35.429(19 ) 57 528.600 39.702(19 ) 64 545.063 42.339(19 ) 7ia 555.321 43.764(19 ) Data summarized a s : Mean S t a n d a r d D e v i a t i o n (n) III-O 75 282.150 16.254(20 ) 325.915 25.132(20 ) 370.265 33.315(20 ) 407.190 41.592(20 ) 441.255 46.750(20 ) 469.295 52.089(20 ) 491.340 58.499(20 ) 513.150 61.580(20 ) 529.720 67.382(20 ) 546.940 71.181(20 ) 559.630 74.515(20 ) V-0 500 280.095 17.039(20 ) 320.525 22.059(20 ) 362.720 28.615(20 ) 396.845 34.923(20 ) 426.585 42.624(20 ) 453.710 48.275(20 ) 474.150 53.150(20 ) 489.045 55.908(20 ) 503.435 58.367(20 ) 519.430 59.740(20 ) 530.605 60.329(20 ) VII-0 3500 280.950 13.073(20 ) 310.775# 22.865(20 ) 344.930# 27.306(20 ) 373.410# 36.048(20 ) 398.090# 41.213(20 ) 414.360# 41.010(20 ) 425.484# 45.959(19 ) 432.121# 44.357(19 ) 448.100# 47.730(19 ) 461.721# 54.438(19 ) 468.300# 57.872(18 ) # Statistically significant differences at p < 0.05 b y Jonckheere-Terpstra trend test, a Day 71 = last weigh day of premating period. DuPont-9763 54 Company Sanitized. Does not contain TSCA CB1 TABLE 2 (Continued) MEAN BODY WEIGHTS (grams) OF Pj MALE RATS Group: Dose (mg/kg/day): Test Day 1-0 0 III-O 75 V-0 500 VII-0 3500 78 547.558 553.160 520.755 456.039# 46.367(19 ) 74.282(20 ) 63.036(20 ) 65.794(18 ) 85 564.232 564.635 532.850 463.533# 48.458(19 ) 72.682(20 ) 63.070(20 ) 62.448(18 ) 92 578.274 576.615 543.611 470.222# 52.989(19 ) 75.452(20 ) 64.062(19 ) 64.983(18 ) 99 591.011 55.185(19 ) 106 598.047 58.160(19 ) 113 607.016 62.443(19 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) 591.630 80.024(20 ) 602.035 83.343(20 ) 610.145 83.184(20 ) 552.537 66.185(19 ) 560.816 67.011(19 ) 567.916 70.567(19 ) 478.028# 63.958(18 ) 479.383# 69.104(18 ) 487.822# 69.251(18 } # Statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test, a Day 71 = last weigh day of premating period. ' 55 Company Sanitized. Does not contain TSCA CB{ H-25231: One-Generation Reproduction Study in Rats TABLE 3 MEAN BODY WEIGHT GAINS (grams) OF P! MALE RATS Group: Dose (mg/kg/day): Test Day 1- 8 8-15 15-22 22-29 29-36 36-43 43-50 50-57 57-64 64-719- 1-0 III-O 0 75 k 48.089 7.967(19 ) 43.765 10.656(20 ) 43.984 8.906(19 ) 40.484 7.324(19 ) 30.537 6.024(19 ) 25.689 6.818(19 ) 19.726 6.921(19 ) 24.505 6.326(19 ) 14.879 6.263(19 ) 16.463 4.380(19 ) 44.350 9.785(20 ) 36.925 9.346(20 ) 34.065 7.000(20 ) 28.040 7.232(20 ) 22.045 8.210(20 ) 21.810 5.398(20 ) 16.570 7.025(20 ) 17.220 5.935(20 ) 10.258 4.406(19 ) 12.690 7.114(20 ) V-0 500 40.430# 8.179(20 ) 42.195 8.538(20 ) 34.125# 8.605(20 ) 29.740 9.663(20 ) 27.125 8.299(20 ) 20.440 8.060(20 ) 14.895# 13.058(20 ) 14.390 8.331(20 ) 12.995 5.464(20 ) 14.175 5.531(20 ) VII-0 3500 29.825# 14.964(20 ) 34.155# 12.675(20 ) 28.480# 14.058(20 ) 24.680 10.372(20 ) 16.270# 11.550(20 ) 14.505 10.179(19 ) 6.637# 16.356(19 ) 15.979 7.392(19 ) 13.621 13.185(19 ) 5.894 14.734(18 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant difference at p < 0.05 by Jonckheere-Terpstra trend test. Significant difference from control at p < 0.05 (Nonparametric comparison to control (Dunn's Te s t ) . a Day 71 - last weigh day of premating period. DuPont-9763 56 Company Sanitized. Does not contain TSCACBi H-25231: One-Generation Reproduction Study in Rats TABLE 3 (Continued) MEAN BODY WEIGHT GAINS (grams) OF Pi MATE RATS Group : Dose (mg/kg/day): Test Day 1-0 0 III-O 75 V-0 500 V II-0 3500 71- 78 -7.763 8.408(19 ) -6.470 9.986(20 ) -9.850 12.715(20 ) -12.261 18.049(18 ) 78- 85 16.674 8.621(19 ) 11.475 6.644(20 ) 12.095 7.849(20 ) 7.494 16.349(18 ) 85- 92 14.042 6.456(19 ) 11.980 5.709(20 ) 7.789# 5.763(19 ) 6.689# 18.139(18 ) 92- 99 12.737 6.001(19 ) 15.015 7.964(20 ) 8.926# 4.684(19 ) 7.806# 13.370(18 ) 99-106 106-113 7.037 7.134(19 ) 8.968 6.536(19 ) 10.405 7.792(20 ) 8.110 6.573(20 ) 8.279 6.690(19 ) 7.100 7.016(19 ) 1.356 16.965(18 ) 8.439 10.013(18 ) 1- 71a 274.616 40.730(19 ) 1-113 326.311 59.368(19 ) Data summarized as: Mean. S t a n d a r d D e v i a t i o n (n) 277.480 60.742(20 ) 327.995 69.415(20 ) 250.510 47.575(20 ) 287.584 57.687(19 ) 188.122# 49.577(18 ) 207.644# 63.272(18 ) # Statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test, a Day 71 = last weigh day of premating period. DuPont-9763 57 Company Sanitized. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats______________ DuPont-9763 TABLE4 MEAN BODY WEIGHTS (grams) OF FEMALE RATS DURING PREMATING Group: Dose (mg/kg/day): Test Day II-O 0 IV-0 75 VI-0 500 VIII-O 3500 1 190.645 192.125 193.240 191.415 11.679(20 ) 7.975(20 ) 13.359(20 ) 10.097 (20 ) 8 202.980 207.440 205.760 198.185 15.412(20 ) 12.385(20 ) 15.346(20 ) 16.377 (20 ) 15 218.500 225.075 220.025 217.505 20.790(20 ) 10.786(20 ) 19.231(20 ) 16.277(20 ) 22 232.910 239.230 236.390 228.785 17.997(20 ) 12.880(20 ) 21.861(20 ) 15.883 (20 ) 29 240.970 248.710 244.290 238.450 20.965(20 ) 15.671(20 ) 23.601(20 ) 16.032(20 ) 36 248.045 256.675 249.475 244.370 27.027(20 ) 14.961(20 ) 18.756(20 ) 16.711(20 ) 43 253.980 263.320 253.155 245.075 25.693(20 ) 16.137(20 ) 23.097(20 ) 19.170(20 ) 50 263.255 270.095 263.680 254.645 24.699(20 ) 16.542(20 ) 24.975(20 ) 21.093(20 ) 57 267.210 275.480 269.725 260.960 24.368(20 ) 19.726(20 ) 28.046(20 ) 19.295(20 ) 64 269.360 282.950 273.760 263.620 25.755(20 ) 20.187(20 ) 25.351(20 ) 17.951 (20 ) 7ia Data summarized a s : Mean 271.995 26.534(20 ) 284.265 17.044(20 ) 277.280 27.763(20 ) 268.875 21.619(20 ) S t a n d a r d D e v i a t i o n (n) There were no statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test. a Day 71 = last weigh day of premating period. 58 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats TABLE 5 MEAN BODY WEIGHT GAINS (grams) OF Pi FEMALE RATS DURING PREMATING Group : Dose (mg/kg/day): Test Day II-O 0 IV-0 75 VI-0 500 VIII-0 3500 1- 8 8-15 15-22 22-29 29-36 36-43 43-50 50-57 57-64 64-71a 12.335 8.862(20 ) 15.520 9.015(20 ) 14.410 6.897(20 ) 8.060 7.211(20 ) 7.075 10.654(20 ) 5.935 7.448(20 ) 9.275 5.662(20 ) 3.955 6.646(20 ) 2.150 7.222(20 ) 2.635 6.379(20 ) 15.315 7.371(20 ) 17.635 3.898(20 ) 14.155 6.973(20 ) 9.480 6.791(20 ) 7.965 6.215(20 ) 6.645 5.562(20 ) 6.775 3.803(20 ) 5.385 6.507(20 ) 7.470* 6.847(20 ) 1.315 8.729(20 ) 12.520 7.395(20 ) 14.265 8.160(20 ) 16.365 7.878(20 ) 7.900 6.097(20 ) 5.185 7.037(20 ) 3.680 7.416(20 ) 10.525 7.005(20 ) 6.045 6.258(20 ) 4.035 6.109(20 ) 3.520 6.552(20 ) 6.770# 12.508(20 ) 19.320 9.604(20 ) 11.280 5.488(20 ) 9.665 7.050(20 ) 5.920 11.719(20 ) 0.705# 10.099(20 ) 9.570 11.353(20 ) 6.315 5.111(20 ) 2.660 5.692(20 ) 5.255 7.678(20 ) l-71a Data summarized as: Mean' 81.350 19.056(20 ) 92.140 14.033(20 ) 84.040 20.207(20 ) 77.460 16.322(20 ) J , S t a n d a r d D e v i a t i o n (n) statistically significant differences at p < 0.05 b y Jonckheere-Terpstra trend test, igni icant difference from control at p < 0.05 {Parametric comparison to control {D u n n e 1 1 / T a m h a n e - D u n n e 1 1 ) a Day 71 - last weigh day of premating period. DuPont-9763 59 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE MEAN BODY WEIGHTS (grams) OF P! FEMALE RATS DURING GESTATION Group : Dose (mg/kg/day): Gestation Day 0 II-O 0 IV-0 75 VI-0 500 VIII-0 3500 274.439 25.755(18 ) 283.094 18.471(17 ) 279.818 32.087(17 ) 272.046 20.011(13 ) 7 309.156 313.306 310.253 300.069 27.639(18 ) 18.932(17 ) 31.104(17 ) 19.939(13 ) 14 339.844 340.629 337.506 326.823 28.876(18 ) 19.600(17 ) 31.107(17 ) 20.255(13 ) 21 414.767 409.529 415.344 406.015 39.163(18 ) 35.439(17 ) 33.925(16 ) 29.016(13 ) Data summarized a s : Mean S t a n d a r d D e v i a t i o n (n) There were no statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test. 60 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 7 MEAN BODY WEIGHT GAINS (grams) OF Pi FEMALE RATS DURING GESTATION Group: Dose (mg/kg/day): Gestation Day 0- 7 II-O 0 34.717 6.415(18 ) IV-0 75 30.212 5.374(17 ) VI-0 500 30.435 7.430(17 ) VIII-0 3500 28.023# 5.485(13 ) 7-14 30.689 6.823(18 ) 27.324 7.178(17 ) 27.253 5.010(17 ) 26.754# 4.861(13 ) 14-21 74.922 16.698(18 ) 68.900 24.377(17 ) 76.856 12.826(16 ) 79.192 16.018(13 ) 0-21 140.328 23.109(18 Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant differences at p 126.435 134.950 133.969 ) 31.681(17 ) 16.886(16 ) 16.292(13 < 0.05 b y Jonckheere-Terpstra trend test. ) 61 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 8 MEAN BODY WEIGHTS (grams) OF P, FEMALE RATS DURING LACTATION Group : Dose (mg/kg/day): Lactation Day 0 7 II-O 0 IV-0 75 VI-0 500 VIII-0 3500 318.594 27.523(18 ) 329.228 28.567(18 ) 311.437 20.333(19 ) 331.405 19.893(19 ) 314.526 30.933(19 ) 326.968 29.573(19 ) 301.613 25.254(15 ) 324.627 20.497(15 ) 14 344.989 341.879 343.395 331.780 24.884(18 ) 19.219(19 ) 25.400(19 ) 17.720(15 ) 21 332.356 332.521 327.205 329.240 24.069(16 ) 19.168(19 ) 24.010(19 ) 19.590(15 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) There were no statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test. 62 .Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 9 MEAN BODY WEIGHT GAINS (grams) OF P, FEMALE RATS DURING LACTATION Group : Dose (mg/kg/dy): Lactation Day 0- 7 7-14 II-O 0 10.633 14.482(18 ) 15.761 10.754(18 ) IV-0 75 19.968 20.495(19 ) 10.474 13.692(19 ) VI-0 500 12.442 12.430(19 ) 16.426 11.047(19 ) VIII-0 3500 23.013 11.723(15 ) 7.153 12.076(15 ) 14-21 -15.363 12.145(16 ) -9.358 16.899(19 ) -16.189 12.214(19 ) -2.540# 12.565(15 ) 0-21 12.206 10.412(16 ) 21.084 18.932(19 ) 12.679 19.667(19 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant differences at p < 0.05 b y Jonckheere-Terpstra trend test. 27.627# 14.343(15 ) 63 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 10 MEAN DAILY FOOD CONSUMPTION (grams/day) OF Pi MALE RATS DURING PREMATING Group: Dose (mg/kg/day): Test Day 1-0 0 III-O 75 V-0 500 VI1-0 3500 1- 8 8-15 15-22 22-29 29-36 36-43 43-50 50-57 57-64 25.805 1.886(19 ) 25.884 2.121(19 ) 27.689 2.147(19 ) 27.774 2.407(19 ) 28.821 2.681(19 ) 28.216 3.281(19 ) 27.889 2.658(19 ) 28.368 2.947(19 ) 28.689 2.680(18 ) 26.805 2.599(20 ) 27.610 3.160(20 ) 28.550 3.107(20 ) 29.280 3.300(20 ) 30.605 3.936(20 ) 30.360 3.254(20 ) 29.330 3.305(20 ) 29.550 3.548(20 ) 30.325 3.750(20 ) 25.060 2.164(20 ) 25.370 2.669(20 ) 26.420 2.798(20 ) 26.870 3.402(20 ) 28.190 3.360(20 ) 27.745 3.445(20 ) 26.335 4.439(20 ) 26.580 3.495(20 ) 27.510 3.227(20 ) 25.175 3.420(20 ) 23.080# 3.871(20 ) 25.685# 4.209(20 ) 25.935# 4.137(20 ) 26.575# 3.790(20 ) 26.563# 3.298(19 ) 24.900# 3.470(19 ) 26.489# 3.482(19 ) 27.895 5.070(19 ) 64-71a 27.695 2.956(19 ) 29.625 3.238(20 ) 27.045 3.225(20 ) 26.622 4.494(18 ) l-71a 27.794 2.218(18 ) D a t a s u m m a r i z e d a s :' M e a n S t a n d a r d D e v i a t i o n (n) 29.215 3.124(20 ) 26.720 2.966(20 ) 25.894# 3.154(18 ) # Statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test, a Day 71 = last weigh day of premating period. 64 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 11 MEAN DAILY FOOD EFFICIENCY (grams weight gain/grams food consumed) OF P, MALE RATS DURING PREMATING Group : Dose (mg/kg/day): Test Day 1-0 0 III-O 75 V-0 500 VII-0 3500 1- 8 8-15 15-22 22-29 29-36 36-43 43-50 50-57 57-64 64-71a l-71a Data summarized as: 0.265 0.031(19 ) 0.242 0.040(19 ) 0.208 0.029(19 ) 0.157 0.027(19 ) 0.127 0.029(19 ) 0.099 0.034(19 ) 0.124 0.025(19 ) 0.073 0.026(19 ) 0.080 0.018(18 ) 0.053 0.020(19 ) 0.141 0.012(18 ) Mean S t a n d a r d D e v i a t i o n (n) 0.231 0.039(20 ) 0.228 0.032(20 ) 0.183 0.030(20 ) 0.165 0.021(20 } 0.130 0.028(20 ) 0.102 0.029(20 ) 0.106 0.020(20 ) 0.078 O'.026 (20 ) 0.080 0.023(20 ) 0.060 0.033(20 ) 0.134 0.016(20 ) 0.229 0.034(20 ) 0.236 0.029(20 ) 0.182 0.031(20 ) 0.155 0.039(20 ) 0.136 0.032(20 ) 0.103 0.042(20 ) 0.069* 0.107(20 ) 0.077 0.043(20 ) 0.067 0.028(20 ) 0.075 0.027(20 ) 0.133 0.014(20 ) 0.163* 0.072(20 ) 0.199* 0.060 (20 ) 0.153* 0.067(20 0.134 0.049(20 ) 0.086* 0.061(20 ) 0.074 0.053 (19 ) 0.035* 0.090(19 ) 0.085 0.042(19 ) 0.061 0.062(19 ) 0.022 0.104(18 ) 0.103* 0.018(18 ) Statistically significant differences at p < 0.05 by One-way Analysis of Variance and Dunnett's tests, a Day 71 = last weigh day of premating period. 65 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 12 MEAN DAILY FOOD CONSUMPTION (grams) OF Pi FEMALE RATS DURING PREMATING Group: Dose (mg/kg/day): Test Day II-O 0 IV-0 75 VI-0 500 VIII-0 3500 1- 8 8-15 15-22 22-29 29-36 36-43 43-50 50-57 57-64 16.945 1.750(20 ) 17.245 1.893(20 ) 18.140 1.542(20 ) 18.440 1.770(20 ) 19.575 2.382(20 ) 18.455 1.911(20 ) 17.290 1.751(20 ) 17.720 1.553(20 ) 17.715 1.531(20 ) 17.705 1.424(20 ) 18.470 2.081(20 ) 18.805 1.596(20 ) 19.110 1.751(20 ) 19.790 1.920(20 ) 18.660 1.377(20 ) 17.930 1.383(20 ) 18.450 1.210(20 ) 18.935 1.982(20 ) 17.230 2.193(20 ) 17.070 2.122(20 ) 18.440 1.858(20 ) 18.990 1.974(20 ) 19.930 1.911(20 ) 17.965 1.867(20 ) 18.035 1.878(20 ) 17.410 2.981(20 ) 17.910 1.594(20 ) 15.805# 1.984(20 ) 16.365 2.502(20 ) 16.790 3.408(20 ) 18.560 2.098(20 ) 18.725 1.972 (20 ) 18.510 2.722(20 ) 17.325 1.599(20 ) 17.975 1.226(20 ) 17.015 1.949 (20 ) 64-71a 17.660 1.509(20 ) l_7ia Data summarized a s : 17.915 1.485(20 ) Mean S t a n d a r d D e v i a t i o n (n) 17.840 1.221(20 ) 18.570 1.156(20 } 17.565 2.125(20 ) 18.055 1.675(20 ) 17.655 2.049(20 ) 17.485 1.097(20 ) # Statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test, a Day 71 = last w e i g h d a y of p r e m a t i n g period. Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 13 MEAN FOOD EFFICIENCY (grams weight gain/grams food consumed) OF Pi FEMALE RATS DURING PREMATING Group: Dose (mg/kg/day): Test Day 1- 8 8-15 15-22 22-29 29-36 36-43 43-50 50-57 57-64 II-O 0 0.099 0.065(20 ) 0.126 0.066(20 ) 0.113 0.053(20 ) 0.061 0.055(20 ) 0.046 0.68(20 ) 0.047 0.056(20 ) 0.075 0.045(20 ) 0.031 0.0.52(20 ) 0.015 0.055(20 ) IV-0 75 0.122 0.054(20 ) 0.138 0.033(20 ) 0.105 0.045(20 ) 0.070 0.047(20 ) 0.057 0.044(20 ) 0.050 0.041(20 ) 0.053 0.028(20 ) 0.041 0.048(20 ) 0.054 0.048(20 ) VI-0 500 0.101 0.051(20 ) 0.116 0.060(20 ) 0.125 0.056(20 ) 0.057 0.042(20 ) 0.039 0.048(20 ) 0.026 0.054(20 ) 0.083 0.054(20 ) 0.049 0.047(20 ) 0.033 0.047(20 ) VIII-0 3500 0.052 0.104(20 ) 0.178 0.120(20 ) 0.100 0.048(20 ) 0.073 0.055(20 ) 0.043 0.091(20 ) 0.002 0.082(20 ) 0.078 0.088(20) 0.051 0.041(20) 0.018 0.050(20 ) 64-71a 0.021 0.052(20 ) 0.010 0.070(20 ) 0.026 0.049(20 ) 0.037 0.072(20 ) 1- 71a Data summarized a s : 0.064 0.012(20 ) Mean S t a n d a r d D e v i a t i o n (n) 0.071 0.008(20 ) 0.066 0.012(20 ) 0.063 0.012(20 ) There were no statistically significant differences at p < 0.05 by One-way Analysis of Variance and Dunnett's tests. t a Day 71 = last weigh day of premating period. 67 in TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 14 MEAN DAILY FOOD CONSUMPTION (grams) OF Pi FEMALE RATS DURING GESTATION Group : Dose (mg/kg/day): Gestation Day 0- 7 II-O 0 23.389 2.041(18 ) IV-0 75 27.319 2.739(16 ) VI-0 500 22.812 2.453(17 ) VIII-0 3500 20.992# 2.094(13 ) 7-14 24.872 2.219(18 ) 23.550 2.696(16 ) 23.894 2.677(17 ) 22.754# 2.219(13 ) 14-21 25.300 1.742(18 ) 24.618 3.590(17 ) 25.113 2.704(16 ) 24.769 2.412(13 ) 0-21 Data summarized as : 24.511 1.820(18 ) Mean S t a n d a r d D e v i a t i o n (n) 23.863 2.608(16 ) 23.937 2.339(16 ) 22.838 2.073(13 ) # Statistically significant differences at p < 0.05 b y Jonckheere-Terpstra trend test. 68 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 15 MEAN FOOD EFFICIENCY (grams weight gain/grams food consumed) OF Pi FEMALE RATS DURING GESTATION Group : Dose (mg/kg/day): Gestation Day 0- 7 7-14 14-21 0-21 II-O 0 0.212 0.034(18 ) 0.176 0.034(18 ) 0.421 0.085(18 ) 0.272 0.035(18 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) IV-0 75 0.189 0.026(16 ) 0.165 0.039(16 ) 0.393 0.127(17 ) 0.252 0.060(16 ) VI-0 500 0.190 0.038(17 ) 0.163 0.027(17 ) 0.439 0.068(16 ) 0.270 0.033(16 ) VIII-0 3500 0.192 0.039(13 ) 0.168 0.021(13 ) 0.457 0.094(13 ) 0.280 0.032(13 ) TheDuniett's0 testsiStiCallY significanfc differences at p < 0.05 b y One-way Analysis of Variance and 69 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 16 SUMMARY OF CLINICAL OBSERVATIONS IN Pj MALE RATS Number of Rats with Observation GROUP: DOSE (mg/kg/day): N: 1-0 0 19 III-O 75 20 V-0 500 20 VII-0 3500 20 OBSERVATIONS Alopecia Discharge Penis Irregular Respiration Lung Noise Salivation Sore Stained Mouth Stained Nose Stained Perineum 3444 0001 0001 0 0 0 2# 0 0 0 5# 0001 0001 0 0 0 2# 0 0 0 3# # Statistically significant trend by Cochran--Armitage trend test; p < 0.05. 70 Company Sanitized. Does not contain TSCA CBI H-25231 : One-Generation Reproduction Study in Rats DuPont-9763 TABLE 17 SUMMARY OF CLINICAL OBSERVATIONS IN Pi FEMALE RATS DURING PREMATING AND COHABITATION Number of Rats with Observation GROUP : DOSE (mg/kg/day): N: II-O 0 20 IV-0 75 20 VI-0 500 20 VIII-0 3500 20 OBSERVATIONS Alopecia Hunched Over Salivation Stained Perineum 3212 0001 0 0 0 3# 0001 # Statistically significant trend by Cochran -Armitage trend test; p < 0.05. 71 Company Sanitized. Does not contain TSCA CBS H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 18 SUMMARY OF CLINICAL OBSERVATIONS IN Pi FEMALE RATS DURING GESTATION Number of Rats with Observation GROUP : DOSE (mg/kg/day): N: II-O 0 20 IV-0 75 17 VI-0 500 17 VIII3500 18 OBSERVATIONS Alopecia Sore Tail 61 6 2 00 0 1 Note: This table includes clinical observations from animals w i t h evidence of copulation observed. There were no statistically significant trends by Cochran-Armitage trend test; p < 0.05. Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 19 SUMMARY OF CLINICAL OBSERVATIONS IN P, FEMALE RATS DURING LACTATION GROUP: DOSE (mg/kg/day): N: Number II-O 0 18 of Rats IV-0 75 19 with Given Sign VI-0 VIII- 500 3500 19 15 OBSERVATIONS Alopecia Total No. of Rats with Hasses Site: 1 M a s s C h e s t (2.0 cm) 5453 0001 000 1 There were no statistically significant trends by Cochran-Armitage trend test; p < 0.05. /"" V 73 Company Sanitized. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 20 SUMMARY OF SPERM PARAMETERS IN Pi MALE RATS Group: Dose (mg/kg/day): 1-0 0 III-O 75 V-0 500 VII-0 3500 MOTILITY Percent Motile Standard Deviation 93.368 3 . 890 (1 9 ) a 93.059 2 , 3 3 1 (17)) 92.389 7 . 5 9 4 (18) 92.588 4 . 1 2 4 (17)) MORPHOLOGY Percent Normal Standard Deviation 99.053 0 . 685 (19) 99.105 0.636 (19) 98.316# 1 . 030 (19) 98.294# 1.251 (17) EPIDIDYMAL SPERM (Millions) Per Cauda 305.558 Standard Deviation 2 7 . 5 3 9 (19) 291.165 7 0.283 (20) Per gram Cauda Standard Deviation 1059.553 1098.255 1 3 2 . 2 3 1 (19) 3 1 3 . 7 4 8 (20) 287.716 6 9 . 5 1 2 (19) 1118.147 3 3 8 . 4 7 2 (19) 286.956 4 6 . 4 6 8 (18) 1166.294 2 0 6 . 0 52 (18) TESTICULAR SPERMATIDS (Millions) Per Testis 174.405 Standard Deviation 1 9 . 8 1 9 (19) Per gram Testis Standard Deviation 122.753 1 9 . 1 4 4 (19) a Number in group is in p a r e n t h e s e s . 167.720 4 2 . 0 2 3 (20) 111.755 2 7 . 2 5 0 (20) 170.511 2 5 . 1 2 3 (19) 116.626 1 4 . 5 2 4 (19) 169.578 2 2 .033 (18) 118.094 1 7 .337 (18) # Statistically significant trend by Jonckheere-Terpstra test; p < 0.05. 74 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 21 MEAN ESTROUS CYCLE PARAMETERS AND PRECOITAL INTERVAL IN Pi FEMALE RATS Percent Percent Percent of Days of Days of Days Mean Cycle Dose in in in Length Group (mg/kg/day) N Estrus Diestrus Proestrus (d a y s ) Mean Precoital Interval (days) II-O 0 20 22 64 14 4 . 3 (0.5)a 2.9(1.1) IV-0 75 20 24 64 11 4.2 (0.3 ) 3.2(1.8)* VI-0 500 20 22 64 13 4.2(0.3) 3.2 (1.8) jb VIII-0 3500 20 25 64 10 a Standard d e v i a t i o n is presented in p a r e n t h e s e s . b N=19. 4.5(1.3) 4.0(3.6) There were no statistically significant trends in estrous cycle length or p r e c o i t a l i n t e r v a l b y J o n c k h e e r e - T e r p s t r a tes t (p < 0.05). Company Sanitized. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 22 SUMMARY OF REPRODUCTIVE INDICES: Pi GENERATION MATERNAL GROUP: DOSE (mg/kg/day): II-O 0 M A T I N G I N DEX <%) (No. c o p u l a t e d / c o h o u s e d ) 100 (20/20) F E R T I L I T Y I N D E X (%) (No. p r e g n a n t / c o p u l a t e d ) 90 (18/20) G E S T A T I O N L E N G T H (days) (No. in group) 22.3 (18) IV-0 75 95 (19/20) 100 (19/19) 22.5 (17)a VI-0 500 95 (19/20) 100 (19/19) 22.2 (17)3 VIII-0 3500 100 (20/20) 75 (15/20) 22.3 (13)3 NUMBER OF IMPLANTATION SITES per pregnant female S t a n d a r d D e v i a t i o n (No. in group) 13.3 11.8 13.3 13.9 3.09(18) 4.38(19) 2.13(19) 1.83(15) IMPLANTATION EFFICIENCY (%)* Standard Deviation(No. in group) 96.9 97.0 93.6 93.0* 5.16(18) 6.64(19) 8.34(19) 6.69(15) a Gestation length could not be calculated for 2 females that were pregnant for which no evidence of copulation was observed. b Number of pup s born/n u m b e r of implantation sites X 100. There were no statistically significant trends in mating or fertility indices b y Cochra n - A r m i t a g e test; p < 0.05. There were no statistically significant differences from control in gestation length or number of implantation sites by Jonckheere-Terpstra test; p < 0.05. * Statistically significant difference from control in implantation efficiency b y Jonckheere-Terpstra test; p < 0.05. /""""N 76 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 23 MEAN PUP NUMBERS AND SURVIVAL: Fi GENERATION MATERNAL GROUP: DOSE (mg/kg/day): N: II-O 0 18 IV-0 75 19 VI-0 500 19 VIII-0 3500 15 Born Born Alive Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 MEAN NUMBER OF PUPS/LITTER 12.9 12.8 12.7 7.8 7.8 7.8 7.8 11.4 11.3 11.3 7.3 7.3 7.3 7.3 12.4 12.3 12.3 8.0 8.0 8.0 8.0 13.0 12.5 12.4 7.9 7.9 7.9 7.9 Born Born Alive Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 MEAN NUMBER OF MALE PUPS/LITTER 6.8 6.6 6.2 6.0 6.7 6.6 6.2 5.9 6.7 6.5 6.2 5.9 4.0 3.9 3.9 3.9 4.0 3.9 3.9 3.9 4.0 3.9 3.9 3.9 4.0 3.9 3.9 3.9 Born Born Alive Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 MEAN NUMBER OF FEMALE PUPS/LITTER 6.1 5.0a 6.1 5.0a 6.0 5.0a 3.8 3.6a 3.8 3.6a 3.8 3.6a 3.8 3.6a 6.1 6.1 6.1 4.1 4.1 4.1 4.1 7.0 6.6 6.5 4.1 4.0 4.0 4.0 Sex Ratio (males) SURVIVAL (%) 0.53 0.59 0.50 0.46 Gestation Index* Mean % Born Alive 0-4 Day Viability 100.0 99.1 99.5 100.0 99.7 99.7 100.0 99.6 99.5 100.0 96.4 .98.8 Lactation Indexc 100.0 100.0 100.0 99.2 Litter Survival^ 100.0 100.0 100.0 100.0 a N = 18. b Percent litters delivered having at least one live pup. c Mean percent survival from Day 4 Postculling to Day 21. d Percent litters born with at least one pup alive on Day 21. There were no statistically significant trends in number of pups, sex ratio, mean percent born alive, 0-4 day viability, or lactation index by Jonckheere-Terpstra test; p < 0.05. There were no statistically significant trends in gestation index and litter survival by Cochran-Armitage test; p < 0.05. Statistics were performed on combined pups per litter only. Male and female data are presented for information only. 77 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 24 MEAN PUP WEIGHTS: Fi GENERATION MATERNAL GROUP: DOSE (mg/kg/day): N: II-O 0 18 IV-0 75 19 VI-0 500 19 Day 0 Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 6.9 (0.5)a 11.1 (1.1) 11.0 (1.2) 17.4 (1.5) 36.9 (2.2) 58.8 (3.4) MEA N PUP WEIGHTS (grams) 7.1 (0.8) 6.8 (0.6) 11.6 (1.6)* 11.5 (1.7) 11.6 (1.6)* 11.4 (1.7) 17.9 (1.9)b 18.1 (2.2) 35.3 (3.5)* 35.7 (3.3) 58.4 (5.6)* 57.2 (5.8) MEA N M A L E PUP WEIGHTS (grams) VIII-0 3500 15 6.3 (0.5)* 10.1 (1.3)* 10.1 (1.4)* 15.0 (2.5)* 28.4 (3.2)* 44.6 (6.9)* Day 0 Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 7.1 (0.4)c 11.3 (1.1) 11.3 (1.2) 17.9 (1.5) 37.7 (2.1 60.4 (3.0) 7.2 (0.8)c 11.9 (1.7)* 11.9 (1.7)* 18.2 (2.0)* 35.9 (3.8)* 60.0 (5.7)* 6.9 (0.6) 11.6 (1.7) 11.5 (1.7) 18.3 (2.3) 36.1 (3.3) 58.3 (6.0) 6.5 (0.5) 10.3 (1.4) 10.2 (1.5) 15.2 (2.7) 28.7 (3.5) 45.2 (7.5) MEAN FEMALE PUP WEIGHTS (grams) Day 0 6.6 (0.4)c 6.8 (0.8)d Day 4 Preculling 10.7 (1.1) 11.1 (1.4)C Day 4 Postculling 10.7 (1.1) 11.1 (1.4)c Day 7 16.9 (1.4) 17.2 (1.5) Day 14 36.0 (2.1) 34.3 (3.1)c Day 21 57.0 (2.8) 55.9 (4.7) c a Standard deviation is reported in parentheses. b N = 18. c N = 17. d N = 16. 6.7 (0.6) 11.3 (1.7) 11.3 (1.7) 17.9 (2.3) 35.3 (3.3) 56.2 (5.6) 6.2 (0.5) 9.9 (1.3) 10.0 (1.3) 14.8 (2.3) 28.2 (2.9) 43.9 (6.5) * Statistically significant trend by linear contrast of least square means; p < 0.05. Note: Statistical analyses were conducted on the combined pup weights. Male and female data are presented for information only. 78 Company Sanitized. Does not contain TSCA CBJ H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 25 SUMMARY GF PUP CLINICAL OBSERVATIONS: Fi GENERATION MATERNAL GROUP: II-O DOSE (mg/kg/day): 0 IV-0 75 VI-0 500 VIII-0 3500 OBSERVATIONS Discharge Right Rear Leg(s) Small Whole Body Sore Subcutaneous Hemorrhage Right Rear Paw Missing 0 0 0 1 (1) 0 0 0 1 (1) 0 0 0 1 (1) 0 0 0 1 (1) 0 0 0 1 (1) TOTAL NUMBER OF SIGNS NUMBER OF LITTERS AFFECTED TOTAL NUMBER OF LITTERS 000 000 18 19 19 a Numbers outside the parentheses are the number of pups affected; the numbers in parentheses are the number of litters affected. 4 2 15 There were no statistically significant trends by Cochran-Armitage test; p < 0.05. Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats TABLE 26 MEAN BODY WEIGHTS (grams) OF F, MALE RATS Group: Dose (mg/kg/day): Test Day3 1 1-1 0 59.528 4.388(18 ) III-l 75 60.653 5.361(19 ) V-l 500 58.568 6.792(19 ) 8 102.144 104.568 99.274 7.927(18 ) 9.728(19 ) 10.356(19 ) 15 163.583 164.237 157.589 12.794(18 ) 13.475(19 ) 17.092(19 ) 22 227.311 227.589 219.937 18.988(18 ) 15.994(19 ) 22.982(19 ) 29 290.800 288.821 280.805 27.093(18 ) 19.655(19 ) 26.033(19 ) 36 357.761 351.395 340.242 35.355(18 ) 20.563(19 ) 27.868(19 ) a Test Day 1 = Postnatal D ay 21 Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # S t a t i s t i c a l l y s i g n i f i c a n t t r e n d s b y J o n c k h e e r e - T e r p s t r a test (p < 0.05). VII-1 3500 45.493# 6.613(15 ) 77.673# 15.459(15 ) 131.320# 21.991(15 ) 191.580# 26.782(15 ) 249.587# 30.792(15 ) 310.753# 36.626(15 ) DuPont-9763 80 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 27 MEAN BODY WEIGHTS GAINS (grams) OF Fi MALE RATS Group: Dose (mg/kg/day): Test Day3 1- 8 1-1 0 42.617 5.165(18 ) III-l 75 43.916 5.443(19 ) V-l 500 40.705 6.299(19 ) 8-15 61.439 5.936(18 ) 59.668 5.371(19 ) 58.316 8.263(19 ) 15-22 63.728 7.552(18 ) 63.353 4.622(19 ) 62.347 7.757(19 ) 22-29 63.489 9.149(18 ) 61.232 6.416(19 ) 60.868 6.133(19 ) 29-36 66.961 9.890(18 ) 62.574 6.790(19 ) 59.437# 6.183(19 ) 1-36 298.233 31.900(18 ) a Test Day 1 = Postnatal Day 21 290.742 16.712(19 ) 281.674 25.514(19 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # S t a t i s t i c a l l y s i g n i f i c a n t t r e n d s b y J o n c k h e e r e - T e r p s t r a te s t (p < 0.05). VTT-1 3500 32.180# 11.494(15 ) 53.647# 8.256(15 ) 60.260 6.039(15 ) 58.007# 5.824(15 ) 61.167# 7.837(15 ) 265.260# 31.823(15 ) 81 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats TABLE 28 MEAN BODY WEIGHTS (grams) OF F, FEMALE RATS Group: Dose (mg/kg/day): Test Daya 1 II-l 0 56.144 4.173(18 ) IV-1 75 55.278 5.510(18 ) VI-1 500 55.732 5.874(19 ) 8 93.661 92.517 90.416 8.359(18 ) 9.708(18 ) 9.718(19 ) 15 139.256 136.717 136.216 10.383(18 ) 12.549(18 ) 11.174(19 ) 22 174.733 171.433 172.453 16.426(18 ) 13.078(18 ) 11.987(19 ) 29 199.917 193.094 198.626 17.403(18 ) 15.963(18 ) 15.353(19 ) 36 226.972 21.451(18 ) a Test Day 1 = Postnatal Day 21 217.950 19.548(18 ) 226.068 17.731(19 ) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # S t a t i s t i c a l l y s i g n i f i c a n t t r e n d s b y J o n c k h e e r e - T e r p s t r a te s t (p < 0.05). VIII-1 3500 44.593# 5.740(15 ) 76.693# 12.012(14 ) 119.514# 16.069(14 ) 156.321# 15.933(14 ) 183.486 16.387(14 ) 212.507 18.594(14 ) DuPont-9763 82 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats TABLE 29 ' MEAN BODY WEIGHTS GAINS (grams) OF F, FEMALE RATS Group: Dose (mg/kg/day): Test Day3 1- 8 II-l 0 IV-1 75 VI-1 500 37.517 5.437(18 ) 37.239 5.004(18 ) 34.684 6.474(19 ) 8-15 45.594 6.136(18 ) 44.200 6.501(18 ) 45.800 4.359(19 ) 15-22 35.478 9.288(18 ) 34.717 4.758(18 ) 36.237 6.683(19 ) 22-29 25.183 6.349(18 ) 21.661 8.574(18 ) 26.174 6.923(19 ) 29-36 27.056 7.717(18 ) 24.856 7.054(18 ) 27.442 5.171(19 ) 1-36 170.828 20.951(18 ) a Test Day 1 = Postnatal Day 21 162.672 18.432(18 ) 170.337 16.088(19 ) Data summarized a s : Mean S t a n d a r d D e v i a t i o n (n) # S t a t i s t i c a l l y s i g n i f i c a n t t r e n d s b y J o n c k h e e r e - T e r p s t r a te s t (p < 0.05). VIII-1 3500 32.443# 7.285(14 ) 42.821 5.108(14 ) 36.807 4.457(14 ) 27.164 5.717(14 ) 29.021 4.440(14 ) 168.257 15.018(14 ) DuPont-9763 83 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats T A B L E 30 MEAN DAILY FOOD CONSUMPTION (grams) OF Fj MALE RATS Group : Dose (mg/kg/day): Test Daya 1- 8 1-1 0 12.322 1.303(18 ) III-l 75 13.389 2.070(19 ) V-l 500 12.626 2.279(19 ) 8-15 19.622 1.711(18 ) 19.584 1.996(19 ) 19.111 1.957(19 ) 15-22 25.028 2.520(18 ) 25.174 1.912(19 ) 23.761 4.547(18 ) 22-29 27.383 2.981(18 ) 27.442 1.886(19 ) 27.400 1.958(18 ) 29-36 30.872 3.872(18 ) ' 30.474 1.913(19 ) 30.068 2.031(19 ) 1-36 23.044 2.288(18 ) a Test Day 1 = Postnatal Day 21 23.200 1.493(19 ) 22.744 1.483(18 ) Data summarized a s : Mean S t a n d a r d D e v i a t i o n (n) # S t a t i s t i c a l l y s i g n i f i c a n t t r e n d s b y J o n c k h e e r e - T e r p s t r a tes t (p < 0.05) VII-1 3500 10.020# 1.911(15 ) 16.553# 2.166(15 > 22.733# 2.802(15 ) 26.073 2.328(15 ) 29.180 2.233(15 ) 20.920# 2.096(15 ) DuPont-9763 84 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 31 MEAN DAILY FOOD EFFICIENCY (grams weight gain/grams food consumed) OF Fi MALE RATS Group: Dose (mg/kg/day): Test Day3 1- 8 1-1 0 0.494 0.033(18 ) 111-1 75 0.475 0.026(19 ) V-l 500 0.464 0.055(19 ) VII-1 3500 0.435 0.161(15 ) 8-15 0.448 0.025(18 ) 0.436 0.026(19 ) 0.435 0.044(19 ) 0.464 0.042(15 ) 15-22 0.364 0.023(18 ) 0.360 0.025(19 ) 0.399 0.222(19 ) 0.381 0.029(15 ) 22-29 0.331 0.024(18 ) 0.319 0.024(19 ) 0.318 0.020(18 ) 0.319 0.026(15 ) 29-37 0.310 0.017(18 ) 0.294 0.028(19 ) 0.283* 0.025(19 ) 0.299 0.027(15 ) 1-36 0.370 0.009(18 ) a Test Day 1 = Postnatal Day 21 0.358 0.015(19 ) 0.360 0.020(18 ) 0.362 0.019(15 ) Data summarized a s : Mean S t a n d a r d D e v i a t i o n (n) * Statistically significant difference from control at p < 0.05 by One-way Analysis of Variance and Dunnett's tests. 85 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats TABLE 32 MEAN DAILY FOOD CONSUMPTION (grams) OF Fi FEMALE RATS Group: Dose (mg/kg/day): Test Day3 1- 8 II-l 0 11.394 1.301(18 ) IV-1 75 11.667 1.209(18 ) VI-1 500 11.100 1.379(19 ) VIII-1 3500 10.293 1.666(14 ) 8-15 16.828 1.356(18 ) 17.150 1.996(18 ) 16.853 1.440(19 ) 15.521 1.763(14 ) 15-22 19.472 2.422(18 ) 19.550 1.908(18 ) 19.479 2.066(19 ) 18.421 1.878(14 ) 22-29 19.717 1.782(18 ) 19.378 3.024(18 ) 20.289 1.635(19 ) 19.707 2.129(14 ) 29-36 21.089 21.078 20.932 21.229 > 2.596(18 ) 5.463(18 ) 1.627(19 ) 2.024(14 ) 1-36 17.706 1.531(18 ) a Test Day 1 = Postnatal Day 21 17.772 1.905(18 ) 17.726 1.281(19 ) 17.029 1.721(14 ) Data summarized a s : Mean S t a n d a r d D e v i a t i o n (n) T h e r e w e r e n o s t a t i s t i c a l l y s i g n i f i c a n t t r e n d s b y J o n c k h e e r e - T e r p s t r a test (p < 0.05) . DuPont-9763 86 Company Sanitized. Does not contain TSCA CBI H-25231; One-Generation Reproduction Study in Rats DuPont-9763 TABLE 33 MEAN FOOD EFFICIENCY (grams weight gain/grams food consumed) OF Fi FEMALE RATS Group : Dose (mg/kg/day): Test Day3 1- 8 IX-1 0 0.470 0.038(18 ) IV-1 75 0.455 0.033(18 ) VI-1 500 0.444 0.050(19 ) VIII-1 3500 0.446 0.060(14 ) 8-15 0.387 0.039(18 ) 0.369 0.039(18 ) 0.389 0.037(19 } 0.395 0.025(14 ) 15-22 0.257 0.043(18 ) 0.255 0.035(18 ) 0.269 0.061(19 ) 0.288 0.042(14 ) 22-29 0.182 0.044(18 ) 0.160 0.054(18 ) 0.183 0.042(18 ) 0.197 0.040(14 ) 29-37 0.183 0.045(18 ) 0.173 0.046(18 ) 0.187 0.031(19 ) 0.195 0.025(14 ) 1-36 a Test Day 1 = Postnatal D a y 21 0.275 0.019(18 ) 0.262 0.021(18 ) 0.275 0.022(19 ) 0.283 0.013(14 ) Data summarized a s : Mean Standard Deviation ( n ) There were no statistically significant differences at p < 0.05 by One-way Analysis of Variance and Dunnett's tests. 87 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 34 SUMMARY OF CLINICAL OBSERVATIONS IN F, MALE RATS GROUP: DOSE (mg/kg/day): N: Number 1-1 0 18 of Rats III-l 75 19 with Given V-l 500 19 Sign VII-1 3500 15 OBSERVATION Alopecia Hunched Over Preputial Separation Stained Underbody Weak Complete 0020 0001 18 19 19 15 0010 00 01 There were no statistically significant trends by Cochran-Armitage test; p < 0.05. 88 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 35 SUMMARY OF CLINICAL OBSERVATIONS IN F* FEMALE RATS GROUP : DOSE (mg/kg/day): N: Number II-l 0 18 of Rats IV-1 75 18 with Given Sign V I -1 VIII-1 500 3500 19 14 OBSERVATION Alopecia Hunched Over S w o l l e n Left F r o n t P a w (s ) S w o l l e n Left F r o n t T o e (s ) Vaginal Patency Complete Weak 101 0 0001 1000 100 0 18 18 19 14 0001 There were no statistically significant trends by Cochran-Armitage test; p < 0.05. 89 ' " "Pa", Saf,:fe' d- D ow not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 36 SUMMARY OF DEVELOPMENTAL LANDMARKS IN F, RATS PREPUTIAL SEPARATION - Fj. MALE RATS OBSERVATIONS AGE (Days)a GROUP : DOSE (mg/kg/day): N: H 1 Number 0 18 of Rats III-l 75 19 with Given V-l 500 19 Sign VII-1 3500 15 42.778 1.833 41.947 1.224 43.632 2.891 45.333* 2.795 VAGINAL PATENCY - Fx FEMALE RATS OBSERVATIONS AGE (Days)3 Data summarized as: GROUP : DOSE (mg/kg/day): N: Number II-1 0 18 of Rats IV-1 75 18 with Given Sign VI-1 VIII-1 500 3500 19 14 31.722 1.227 Mean S t a n d a r d D e v i a t i o n (n) 32.722 3.392 33.316 2.626 33.786c 3.068 a Age was c alculated as follows using data p r e s e n t e d in A p p e n d i x BB: Test day + 2 0 days = Age (days). b Not significant by analysis of covariance (covariates: body weight on the day of achievement and body weight on postnatal day 35). c Not significant by analysis of covariance (covariates: body weight on the day of achievement and body weight on postnatal day 28). 90 C o m p a s mtfwd. Do** not contain TSCA CBJ H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 37 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR P, MALE RATS Group I 0 mg/kg/day Group IH Group V Group VH 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day RBC (x106/^L) DAY 74 HGB (g/dL) DAY 74 HCT (%) DAY 74 MCV (fl) DAY 74 MCH (pg) DAY 74 MCHC (g/dL) DAY 74 RDW (%) DAY 74 ARET (xlOVjiiL) DAY 74 PLT (xlOVjtiL) DAY 74 WBC (xlOVjtiL) DAY 74 ANEU (xl03//iL) DAY 74 ALYM (xl03/fiL) DAY 74 8.35 0.27(10) 15.8 0.5(10) 46.3 1.5(10) 55.4 1.5(10) 19.0 0.5(10) 34.2 0.3(10) 12.8 0.5(10) 204.2 25.2(10) 1251 178(10) 14.65 3.30(10) 2.07 0.76(10) 11.99 2.97(10) 8.04* 0.28(10) 15.3 0.7(10) 45.3 2.0(10) 56.3 1.4(10) 19.1 0.5(10) 33.9 0.5(10) 12.5 0.8(10) 194.2 30.2(10) 1266 145(10) 14.20 3.56(10) 1.68 0.62(10) 12.01 2.89(10) 8.04* 0.26(10) 15.2* 0.5(10) 45.1 1.7(10) 56.1 1.5(10) 18.9 0.4(10) 33.7 0.4(10) 12.9 0.7(10) 181.0 20.9(10) 1224 86(9) 15.66 3.58(10) 1.76 0.68(10) 13.37 3.50(10) 7.97* 0.18(10) 14.9* 0.6(10) 44.1* 1.5(10) 55.4 1.9(10) 18.7 0.7(10) 33.8 0.5(10) 14.0* 1.3(10) 188.2 47.7(10) 1253 132(10) 16.39 3.03(10) 2.28 0.70(10) 13.51 2.92(10) 91 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 37 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR Pi MALE RATS Group I 0 mg/kg/day Group HI Group V Group VH 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day AMON (xl03/jtiL) DAY 74 AEOS (xl03/jtiL) DAY 74 ABAS (xl03/jttL) DAY 74 ALUC (xl03//iL) DAY 74 0.28 0.13(10) 0.14 0.06(10) 0.09 0.06(10) 0.07 0.02(10) 0.24 0.11(10) 0.13 0.05(10) 0.08 0.04(10) 0.06 0.02(10) 0.22 0.09(10) 0.15 0.09(10) 0.09 0.03(10) 0.08 0.03(10) 0.27 0.07(10) 0.14 0.06(10) 0.10 0.04(10) 0.09 0.04(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. 92 Company Sanitized. Does not contain TSCACB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 38 SUMMARY OF HEMATOLOGY VALUES FOR P, FEMALE RATS TEST/ PERIOD Group II 0 mg/kg/day Group IV Group VI Group VUI 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day RBC (xl06/jtiL) DAY 75 HGB (g/dL) DAY 75 HCT (%) DAY 75 MCV (fl) DAY 75 MCH(pg) DAY 75 MCHC (g/dL) DAY 75 RDW (%) DAY 75 ARET (x l0 3/ju.L) DAY 75 PLT (xl03//xL) DAY 75 WBC (x l0 3//xL) DAY 75 ANEU (xl03//iL) DAY 75 A LY M (xl03//rL) DAY 75 8.05 0.32(10) 16.0 0.6(10) 45.4 1.8(10) 56.4 1.6(10) 19.9 0.6(10) 35.2 0.4(10) 11.1 0.4(10) 161.9 29.5(10) 1174 183(8) 9.66 1.74(10) 0.97 0.36(10) 8.29 1.44(10) 8.02 0.25(10) 16.0 0.6(10) 45.3 1.6(10) 56.5 1.3(10) 19.9 0.3(10) 35.2 0.8(10) 11.0 0.3(10) 167.3 37.7(10) 1136 100(8) 11.88 1.56(10) 0.85 0.46(10) 10.59* 1.53(10) 8.12 0.44(10) 16.0 0.6(10) 45.9 2.1(10) 56.6 1.8(10) 19.7 0.8(10) 34.9 0.6(10) 11.1 0.3(10) 174.3 28.5(10) 1140 186(10) 11.64 2.57(10) 1.77 1.71(10) 9.33 1.77(10) 7.87 0.25(10) 15.5 0.7(10) 44.2 1.6(10) 56.2 1.2(10) 19.7 0.6(10) 35.0 0.5(10) 11.5 0.4(10) 166.6 31.7(10) 1109 168(10) 12.63* 2.48(10) 1.45 0.35(10) 10.59* 2.23(10) 93 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 38 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR Pi FEMALE RATS TEST/ PERIOD Group n 0 mg/kg/day Group IV Group VI Group Vm 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day AMON (xl03//xL) DAY 75 AEOS (xl03//xL) DAY 75 ABAS (xl03/pL) DAY 75 ALUC (xl03//iL) DAY 75 0.15 0.05(10) 0.13 0.04(10) 0.06 0.04(10) 0.06 0.02(10) 0.18 0.06(10) 0.12 0.03(10) 0.08 0.03(10) 0.07 0.02(10) 0.25 0.15(10) 0.18 0.08(10) 0.07 0.02(10) 0.05 0.02(10) 0.25 0.13(10) 0.19* 0.06(10) 0.08 0.04(10) 0.06 0.03(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. 94 Company Sanitized. Does not contain TSCA GS| H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 39 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR Pi MALE RATS TEST/ PERIOD Group I 0 mg/kg/day Group El Group V Group VE 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day AST (U/L) DAY 74 ALT (U/L) DAY 74 SDH (U/L) DAY 74 PFLU (/zg/mL) DAY 116 79 10(10) 31 4(10) 10.9 4.3(10) 0.1 0.0(10) 85 15(10) 39@ 7(10) 14.6 6.1(10) 0.1 0.0(10) 81 19(10) 39 13(10) 14.8 5.5(10) 0.2@ 0.0(10) 80 12(10) 40 @ 6(10) 12.6 4.1(10) 0.4@ 0.1(10) Data arranged as: Mean Standard deviation (Number of values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. 95 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 40 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR Pi FEMALE RATS TEST/ Group II PERIOD_____________ 0 mg/kg/day Group IV Group VI Group VIII 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day AST (U/L) DAY 75 ALT (U/L) DAY 75 SDH (U/L) DAY 75 91 16(10) 36 10(10) 13.2 2.3(10) 83 17(10) 40 14(10) 14.5 3.1(10) 79 11(10) 35 6(10) 15.3 3.4(10) 102 45(10) 49 31(10) 19.3 14.7(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) There were no statistically significant differences from control at p < 0.05. # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra trend test. * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test._________________ 96 Company Sanitized. Does not contain TSCA COP H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 41 SUMMARY OF URINALYSIS VALUES FOR P, MALE RATS TEST/ Group I PERIOD_____________ 0 mg/kg/day Group in Group V Group VH 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day UFLU(Mg) DAY 116 12.1 4.1(10) 53.9 9.3(10) 176.1 38.5(10) 512.4 109.5(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. 97 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Pate DuPont-9763 T A B L E 42 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - Pj ADULTS MEA N FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) Group: Dose(mg/kg/day): 1-0 III-O V-0 0 75 500 FINAL BODY WEIGHT LIVER 593.1 64.5(19) 17.630 3.591(19) 596.9 86.3 (20) 19.410 4.390(20) 553.7 72.6(19) 20.327 4.448(19) KIDNEYS 3.898 0.441(18) 4.145 0.432(20) 4.233 0.514(19) THYROID 0.026 0.005(18) 0.026 0.007(20) 0.023 0.006(19) TESTES 3.637 0.286(19) 3.624 0.658(20) 3.685 0.247(19) EPIDIDYMIDES 1.549 0.332(19) 1.463 0.205(20) 1.509 0.104(19) SEMINAL VESICLES 2.661 0.429(19) 2.834 0.359(20) 2.589 0.370(19) PROSTATE 0.924 0.204(19) 0.902 0.212(20) 0.857 0.149 (19) BRAIN Data summarized a s : 2.216 0.107(19) Mean S t a n d a r d D e v i a t i o n (n) 2.180 0.122(20) 2.185 0.116(19) S t a t i s t i c a l M e t h o d s : T r e n d test (J o n c k h e e r e - T e r p s t r a ) . There were no statistically significant differences from control at p < 0.05. VII-0 3500 472.2*# 76.4(18) 23.687# 5.684(18) 4.323*# 0.483(18) 0.023 0.007(18) 3.592 0.353(18) 1.400# 0.114(18) 2.380# 0.412(18) 0.757# 0.197(18) 2.117*# 0.120(18) 98 Company Sanitized. Does not contain TSCA CBi ) H-25231: One-Generation Reproduction Study in Rats ) DuPont-9763 TABLE 42 (Continued) MEAN-FINAL BODY AND ORGAN WEIGHTS FROM M A T E RATS - P , ADULTS ORGAN WEIGHT RELATIVE TO FINAL BODY WEIGHT (arams) Group: Dose(mg/kg/day): LIVER 1-0 0 2.9540 0.3648(19) III-O 75 3.2329# 0.4081(20) V-0 500 3.6486*# 0.5031(19) KIDNEYS THYROID 0.6561 0.0509(18) 0.0043 0.0007(18) 0.6998# 0.0576(20) 0.0044 0.0012(20) 0.7678*# 0.0595(19) 0.0042 0.0011(19) TESTES 0.6186 0.0683(19) 0.6234 0 . 1812 (20) 0.6761 0.0988(19) EPIDIDYMIDES 0.2611 0.0573(19) 0.2489 0.0448(20) 0.2770 0.0398(19) SEMINAL VESICLES PROSTATE BRAIN 0.4500 0.0652(19) 0.1557 0.0278(19) 0.3765 0.0312(19) 0.4816 0.0738(20) 0.1536 0.0387(20) 0.3713 0.0485(20) 0.4731 0.0772(19) 0.1571 0.0335(19) 0.3997 0.0463(19) VII-0 3500 4.9725*# 0.5732(18) 0.9261*# 0.1005(18) 0.0049 0.0014(18) 0.7761# 0.1299(18) 0.3017# 0.0416(18) 0.5122# 0.0987(18) 0.1594 0.0245(18) 0.4581*# 0.0692(18) 99 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 42 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - P, ADULTS ORGAN WEIGHT RELATIVE TO BRAIN (grams) Group: Dosage (mg/kg/day): 1-0 0 III-O 75 V-0 500 VII-0 3500 LIVER 793.3325 141.7064(19) 890.7778 196.2618(20) 927.0919# 180.8646(19) 1 1 2 4 . 4 7 9 8 *# 289.9338(18 KIDNEYS 175.5338 15. 1 4 6 1 (18) 190.1026*# 16.4535(20) 193.5102*# 18.4794(19) 204.3939*# 21.6806(18) THYROID TESTES . 1.1454 0.1973(18) 164.3347 13.4837(19) 1.2010 0.3296(20) 167.3295 36.0624(20) 1.0685 0.2909(19) 168.9197 11.8053(19) 1.1000 0.3379(18) 169.9031 16.3726(18) EPIDIDYMIDES 69.8012 14.9033(19) 67.2511 9.3190(20) 69.2578 5.8373(19) 66.2537(3# 5.6720(18) SEMINAL VESICLES 119.7666 16.1151(19) 129.8044 12.6595(20) 118.5087 15.6399(19) 113.0597 22.4383(18) PROSTATE 41.6833 8.5895(19) 41.4429 9.7835(20) 39.2501 6.6367(19) 35.7325(3# 9.0891(18) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) S t a t i s t i c a l Meth o d s : T r e n d test (J o n c k h e e r e - T e r p s t r a ) . # Significant difference from control at p < 0.05 using Trend test (Jonckheere-Terpstra). * Significant difference from control at p < 0.05 (Parametric comparison to control (D u n n e t t /T a m h a n e -D u n n e t t ) @ Significant difference from control at p < 0.05 by Dunn's nonparametric comparison to control. 100 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 43 MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Pi ADULTS Group: Dose(mg/kg/day): MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS fi II-O IV-0 0 75 (grams) VI-0 500 FINAL BODY WEIGHT 326.8 27.9(18) 332.5 18.7(20) 325.8 24.2(19) LIVER 14.920 2.172(20) 15.110 2.141(20) 15.746 2.053(20) KIDNEYS 2.454 0.278(20) 2.608 0.365(20) 2.666 0.431(20) THYROID 0.024 0.006(19) 0.025 0.006(20) 0.024 0.006(19) UTERUS 0.553 0.152(20) 0.514 0.137(20) 0.564 0.122(20) OVARIES 1.145 0.045(20) 0.161 0.036(20) 0.144 0.033(20) BRAIN 1.929 0.125(20) 2.017 0.125(20) 1.976 0.119(20) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) Stati s t i c a l M e t h o d s : T r e n d test (J o n c k h e e r e - T e r p s t r a ) . There were no statistically significant differences from control at p < 0.05. VIII-0 3500 319.4 27.1(20) 16.678*# 2.292(20) 2.651# 0.256(20) 0.023 0.007(20) 0.583 0.245(20) 0.133 0.036(20) 1.937 0.112(20) 101 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats ) DuPont-9763 TABLE 43 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Pj ADULTS Group: Dose(mg/kg/day): LIVER KIDNEYS THYROID UTERUS OVARIES BRAIN ORGAN WEIGHT RELATIVE TO FINAL BODY WEIGHT (grains) II-O 0 IV-0 75 VI-0 500 4.5945 0.4607(18) 4.5350 0.4991(20) 4.8234 0.4319(20) 0.7550 0.0686(18) 0.7830 0.0874(20) 0.8156*# 0.0874(20) 0.0071 0.0019(17) 0.1727 0.0520(18) 0.0431 0.0118(18) 0.0074 0.0018(20) 0.1553 0.0431(20) 0.0485 0.0106(20) 0.0074 0.0020(19) 0.1746 0.0423(20) 0.0444 0.0107(20) 0.5915 0.0342(18) 0.6075 0.0363(20) 0.6083 0.0413(20) VIII-0 3500 5.2045*# 0.3877 (20) 0.8313*# 0.0605(20) 0.0070 0.0020(20) 0.1873 0.0982(20) 0.0413 0.0101(20) 0.6099 0.0536(20) 102 Company Sanitized. Does not contain TSC A C B I ) H-25231: One-Generation Reproduction Study in Rats } DuPont-9763 TABLE 43 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Pi ADULTS ORGAN WEIGHT RELATIVE TO BRAIN (grams) Group: Dose(mg/kg/day): II-O 0 IV-0 75 VI-0 500 VIII-0 3500 LIVER KIDNEYS 771.5954 85.8678(20) 127.1357 10.5966(20) 748.5316 91.1277(20) 129.0075 14.1537(20) 796.6931 90.6247(20) 134.4536 15.4514(20) 861.6516# 114.7512(20) 137.0244# 12.9314(20) THYROID 1.2254 0 . 3202 (19) 1.2338 0.3207(20) 1.2193 0.2762(19) 1.1684 0.3708(20) UTERUS 28.8868 8.6820(20) 25.6838 7.6432(20) 28.5601 5.9830(20) 30.3206 13.5387(20) OVARIES Data summarized as: 7.4390 2.0118(20) Mean S t a n d a r d D e v i a t i o n (n) 7.9550 1.5233(20) 7.2392 1.3982(20) 6.8039 1.6459(20) Statistical Methods: Trend test (Jonckheere-Terpstra). # Significant difference from control at P < 0.05 using Trend test (Jonckheere-Terpstra). * Significant difference from control at P < 0.05 (Parametric comparison to control (D u n n e t t /T a m h a n e - D u n n e t t ) @ Significant difference from control at P < 0.05 by Dunn's nonparametric comparison to control. 103 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 44 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MATE RATS - Fj ADULTS M E A N F I N A L B O D Y A N D A B S O L U T E O R G A N W E I G H T S (grains) Group: Dose(mg/kg/day): 1-1 III-l V-l 0 75 500 FINAL BODY WEIGHT 383.7 43.5(18) 382.1 22.7(19) 368.1 31.3(19) LIVER 17.431 3.195(18) 17.206 1.590(19) 16.234 2.026(19) KIDNEYS 3.356 0.355(18) 3.343 0.274(19) 3.283 0.307(19) THYROID 0.022 0.003(18) 0.023 0.006(19) 0.022 0.004(19) TESTES 3.140 0.285(18) 3.211 0.244(19) 3.079 0.259(19) EPIDIDYMIDES * 0.768 0.098(18) 0.780 0.103(19) 0.736 0.112(19) SEMINAL VESICLES 1.286 0.270(18) 1.378 0.213(19) 1.304 0.246(19) PROSTATE* 0.476 0.102 (18) 0.474 0.129(19) 0.440 0.107(19) BRAIN < 1.990 0.118(18) 2.027 0.112(19) 1.979 0.093 (19) VII-1 3500 340.3*# 35.9(15) 15.641# 1.701(15) 3.116# 0.347(15) 0.021 0.003(14) 2.848*# 0.386(15) 0.659*# 0.116(15) 1.229 0.258(15) 0.386@# 0.108(14) 1.913 0.121(15) 104 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 44 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - F t ADULTS ORGAN W E I G H T RELATIVE TO FINAL BODY WEIGHT (grams) Group: Dosage(mg/kg/day): 1-1 0 III-l 75 V-l 500 LIVER 4.513 0.394(18) 4.501 0.303(19) 4.413 0.416(19) KIDNEYS 0.878 0.071(18) 0.877 0.076(19) 0.894 0.073(19) THYORID 0.006 0.001(18) 0.006 0.002 (19) 0.006 0.001(19) TESTES 0.828 0.108(18) 0.843 0.086(19) 0.840 0.077(19) EPIDIDYMIDES 0.202 0.030(18) 0.205 0.029(19) 0.200 0.027(19) SEMINAL VESICLES 0.337 0.073(18) 0.361 0.052(19) 0.353 0.056(19) PROSTATE* 0.124 0.023(18) 0.124 0.032(19) 0.119 0.026(19) BRAIN 0.524 0.062(18) 0.532 0.048(19) 0.540 0.041(19) VII-1 3500 4.611 0.398(15) 0.918 0.071(15) 0.006 0.001(14) 0.839 0.090(15) 0.194 0.028(15) 0.364 0.077(15) 0.113 0.028(14) 0.566# 0.044(15) 105 Company Sanitized. Does not contain TSCA CBI ) ) H-25231: One-Generation Reproduction Study in Rats____________________________________________________________________________ ) DuPont-9763 TABLE 44 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - F, ADULTS Group: Dosage (mg/kg/day): LIVER KIDNEYS THYROID TESTES EPIDIDYMIDES SEMINAL VESICLES ORGAN WEIGHT RELATIVE TO B RAIN (grams) 1-1 ' 0 III-l 75 V-l 500 877.435 164.736(18) 852.112 98.697(19) 819.154 8 3.370 (19) 168.825 16.790(18) 165.283 14.528(19) 165.848 12.951(19) 1.091 0.161(18) 1.157 0.303(19) 1.128 0.211(19) 157.948 12.537(18) 158.611 10.872(19) 155.731 13.511(19) 38.549 4.131(18) 38.426 4.038(19) 37.123 5.029(19) 64.500 12.144(18) 67.842 8.443(19) 65.856 12.253 (19) VII-1 3500 816.892 64.904(15) 162.724 13.176(15) 1.108 0.194(14) 148.782 17.054(15) 34.321*# 4.778(15) 64.117 11.855(15) PROSTATES 23.854 4.499(18) 23.315 5.965(19) 22.175 5.055(19) 20.0220# 4.959(14) Data summarized as : Mean S t a n d a r d D e v i a t i o n (n) a Prostate weight from animal 660638 was removed from calculation due to weighing error. Statistical Methods: Trend test (Jonckheere-Terpstra). # Significant difference from control at p < 0.05 using Trend test (Jonckheere-Terpstra) . k S i g n i f i c a n t d i f f e r e n c e f r o m c o n t r o l at p < 0.05 (Parametric c o m p a r i s o n to c o n t r o l (D u n n e 1 1 /T a m h a n e - D u n n e 1 1 ) @ Significant difference from control at p < 0.05 by Dunn's nonparametric comparison to control. 106 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 45 MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - F! ADULTS ME A N FINAL BODY AMD ABSOLUTE O RGAN WEIGHTS (grams) Group: Dosage(mg/kg/day): FINAL BODY WEIGHT LIVER KIDNEYS THYROID UTERUS OVARIES BRAIN II-l 0 237.5 22.9(18) 10.186 1.710(18) 2.148 0.215(18) 0.020 0.004(18) 0.490 0.123(18) 0.247 0.436(18) 1.825 0.112(18) IV-1 75 227.9 22.0(18) 9.761 1.501(18) 2.068 0.204(18) 0.018 0.006(18) 0.509 0.174(18) 0.120 0.017(18) 1.838 0.097(18) VI-1 500 238.7 20.3 (19) 10.677 1.468(19) 2.206 0.227(19) 0.019 0.006 (19) 0.521 0.177(19) 0.149 0.034(19) 1.876 0.109(19) VIII-1 3500 225.5 18.4(14) 10.206 1.014(14) 2.080 0.261(14) 0.018 0.003(14) 0.477 0.142(14) 0.136 0.027(14) 1.762 0.110(14) 107 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 45 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Fj ADULTS ORGAN WEIGHT RELATIVE TO FINAL BODY WEIGHT (grains) Group: Dosage(mg/kg/day): II-l 0 IV-1 75 VI-1 500 LIVER 4.271 0.391(18) 4.274 0.403(18) 4.464 0.387(19) KIDNEYS THYROID UTERUS OVARIES BRAIN 0.906 0.056(18) 0.008 0.002(18) 0.208 0.058(18) 0.102 0.174(18) 0.774 0.074(18) 0.911 0.076(18) 0.008 0.003(18) 0.225 0.078(18) 0.053 0.008(18) 0.813 0.076(18) 0.926 0.080(19) 0.008 0.002(19) 0.220 0.079(19) 0.063 0.014(19) 0.789 0.056(19) VIII-1 3500 4.528# 0.271(14) 0.923 0.093(14) 0.008 0.001(14) 0.211 0.059(14) 0.060 0.011(14) 0.784 0.051(14) 108 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 45 (Continued) t MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Fj ADULTS ORGAN WEIGHT RELATIVE TO B R A I N (grams) Group: Dosage(mg/kg/day): II-l 0 IV-1 75 VI-1 500 VIII-1 3500 LIVER 559.636 97.677(18) 531.860 84.213(18) 568.963 72.115(19) 578.696 36.327(14) KIDNEYS 117.892 1 1.783 (18) 112.617 10.458(18) 117.612 10.588(19) 117.819 10.601(14) THYROID 1.097 0.217 (18) 0.994 0.350(18) 1.013 0.297(19) 1.051 0.174(14) UTERUS 26.805 6.398(18) 27.787 9.727(18) 27.897 9.899(19) 27.158 8.184(14) OVARIES Data summarized a s : 13.571 23.946(18) Mean S t a n d a r d D e v i a t i o n (n) 6.521 0.797(18) 7.897 1.600(19) S t a t i s t i c a l M e t h o d s : T r e n d test (J o n c k h e e r e - T e r p s t r a ) . # Significant difference from control at p < 0.05 using Trend test (Jonckheere-Terpstra). 7.736 1.520(14) 109 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats SITE/LESION: LIVER DILATATION DISCOLORATION ESOPHAGUS PERFORATION RUPTURE LUNGS DISCOLORATION KIDNEYS MASS DILATATION EPIDIDYMIDES SMALL TESTES SMALL SOFT SKIN ULCER/EROSION STAIN WET TABLE 46 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - Pi ADULTS GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: 1-0 0 25 0 0 0 0 0 1 0 0 0 0 1 0 0 III-O 75 26 0 0 0 0 0 0 1 1 1 0 0 0 0 V-0 500 25 1 0 0 1 0 0 0 0 0 0 0 0 0 VII-0 3500 25 0 1 1 0 1 0 0 0 0 1 0 2 1 NOTE: INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. DuPont-9763 110 Company Sanitized. Does not contain TSCA CBI )) H-25231: One-Generation Reproduction Study in Rats________________________ SITE/LESION: KIDNEYS CYST DILATATION VAGINA FLUID SKIN ALOPECIA DISCOLORATION T A B L E 47 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Pi ADULTS GROUP DESIGNATION: ' DOSE (m g/kg/day): NUMBER IN GROUP: II-O ,0 25 0 1 1 0 1 IV -0 75 25 0 1 0 0 0 V I-0 500 25 0 0 0 0 0 V III-0 3500 25 1 1 0 2 0 NOTE: INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. DuPont-9763 111 f&mpany Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats SITE/LESION: LIVER DISCOLORATION URINARY BLADDER THICK CALCULUS KIDNEYS DILATATION DISCOLORATION THYMUS DISCOLORATION TABLE 48 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - Fi ADULTS GROUP DESIGNATION: DOSE (m g/kg/day): NUMBER IN GROUP: 1-1 0 18 1 0 0 3 0 0 III-l 75 19 0 0 0 1 0 0 V -l 500 19 0 1 1 4 1 0 V I I -1 3500 15 0 0 0 5 0 1 NOTE: INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. DuPont-9763 112 Company Sanitized. Does not contain TSCA CBi ) H-25231: One-Generation Reproduction Study in Rats___________ ) SITE/LESION: URINARY BLADDER CALCULUS KIDNEYS DILATATION DEFORMITY TABLE 49 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - F! ADULTS GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: II-l 0 18 0 2 0 IV -1 75 18 0 0 0 V I-1 500 19 1 3 1 V III-1 3500 15 0 3 0 NOTE: INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. DuPont-9763 113 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats SITE/LESION: WHOLE BODY SMALL TABLE 50 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - F! WEANLINGS GROUP DESIGNATION: DOSE (m g/kg/day): NUMBER IN GROUP: 1-1 0 54 III-l 75 55 V -l 500 56 V II-1 3500 43 0004 NOTE: INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. DuPont-9763 114 Company Sanitized. Does not contain TSCA CBI )) H-25231: One-Generation Reproduction Study in Rats_______________________ SITE/LESION: URINARY BLADDER CALCULUS KIDNEYS DILATATION LONG BONE MISSING WHOLE BODY SMALL TABLE 51 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Fi WEANLINGS GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: II-l 0 50 IV -1 75 47 V I -1 500 58 V III-1 3500 45 0 001 0 100 0001 0001 NOTE: INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. DuPont-9763 115 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats TABLE 52 SITE/LESION: STOMACH NO MILK SPOT LUNGS NOT EXPANDED INCIDENCES OF GROSS OBSERVATIONS IN GENERATION Fj MALE PUPS DAM GROUP DESIGNATION: DO$E (m g/kg/day): NUMBER PUPS/LITTERS: II-O 0 v. i / i IV -0 75 1/1 V I-0 500 0/0 V III-0 3500 1/1 1 ( 1) (1 1) 0 ( 0) 1 ( 1) 1 ( 1) 1 ( 1) 0 ( 0) 1 ( 1) TOTAL LITTERS AFFECTED TOTAL PUPS AFFECTED 1101 1 1 01 For each group: The count o f pups o n ly in c lu d e s those which underwent p a th o lo g ic a l exam ination. The count o f l i t t e r s o n ly in c lu d e s those in which pups underwent p a th o lo g ic a l exam ination. For each s it e / le s io n : Numbers o u tsid e the parentheses are the number o f pups a ffe c te d . Numbers in parentheses are the number o f l i t t e r s a ffe c te d . DuPont-9763 116 Company Sanitized. Does not contain TSCACBf H-25231: One-Generation Reproduction Study in Rats TABLE 53 SITE/LESION: STOMACH NO MILK SPOT LUNGS NOT EXPANDED INCIDENCES OF GROSS OBSERVATIONS IN GENERATION F}FEMALE PUPS DAM GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER PUPS/LITTERS: II-O 0 1/1 IV -0 75 0/0 V I-0 500 0/0 V III-0 3500 6/4 1 ( 1) 0 ( 0) 0 ( 0) 4 ( 2) 1 ( 1) 0 ( 0) 0 ( 0) 3 ( 1) TOTAL LITTERS AFFECTED TOTAL PUPS AFFECTED 1 0 02 10 04 For each group: The count o f pups o n ly in c lu d e s those which underwent p a th o lo g ic a l exam ination. The count o f l i t t e r s o n ly in c lu d e s those in w hich pups underwent p a th o lo g ic a l exam ination. For each s it e / le s io n : Numbers o u tsid e the parentheses a re the number o f pups a ffe c te d . Numbers in parentheses are the number o f l i t t e r s a ffe c te d . DuPont-9763 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 54 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS - P! ADULTS TISSUE/LESION LESION GRADES (P ,1 ,2 ,3 ,4 ) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: 1-0 0 20 III-O 75 20 V-0 500 20 V II-0 3500 20 LIVER FATTY CHANGE, MEDIAN CLEFT HYPERTROPHY, HEPATOCYTE, fENTRILOBULAR INFLAMMATION, SUBACUTE/CHRONIC NECROSIS, HEPATOCYTES, CENTRILOBULAR KIDNEYS *B: NEPHROBLASTOMA INFARCT NEPHROPATHY, CHRONIC PROGRESSIVE PYELONEPHRITIS, UNILATERAL THYROID GLAND ALTERATION, COLLOID HYPERTROPHY, FOLLICULAR CELL INFLAMMATION, SUBACUTE/CHRONIC TESTES DEGENERATION/ATROPHY, UNILATERAL SEMINIFEROUS TUBULES, EPIDIDYMIDES OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL SEMINAL VESICLES WITH COA PROSTATE GLAND INFLAMMATION, SUBACUTE/CHRONIC 11 1 - ( - , - , 1 , - , -) 11 - ( ,1, , , ) ( - , 1 , - , - , -) 10 - 9(, , , , ) (-,9,-,-,-) - 12 2 10 (- , 1 , 1 , - , - ) ( ,1 , , , ) ( , n, , , ) 9( !-,9, " 11 - 10 ( , ,1, , ) i~ f - f 0 r - . 10 ( j (- , 9 , 1 , - , - ) 1 (- , - , - , 1 , - ) 12 1 (1, - 4 <-,4,-,-,,-) - 10 2 (-,2,-,-,-) " 11 8( - 8, 10 1 (- ,1 , 9 (- , 9 , - , - , - ) 1 (- ,1, 11 9 - ( - , 7 , 2 , - ,-) 1 (-,1,-,- 10 10 2 (-,5,1,4,-) (, , , , ) (-,2,-,-,-) 12 11 11 1[ - , 1, 4 , 3, 3) l 1t - , 0 , 1 , - , - ) 10 10 (- , - , 3 , 2 , 5 ) 9(, , , , ) (- , 8 , 1 , - , - ) 1 !- , 1 , - , - , - ) 2116 " 1 (-,-,-,-,1) 1 (- , - , - , - , 1 ) 2115 1 (-,-,-,-,1) " - 2 115 2115 - - - 1 (- , 1 , - , - , - ) 118 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 50 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS - Pi ADULTS TISSUE/LESION LESION GRADES (P, 1, 2, 3, 4) GROUP DESIGNATION: DOSE (mg/kg/day) : NUMBER IN GROUP: 1-0 0 20 III-O 75 20 V-0 500 20 V I I -0 3500 20 OTHER ESOPHAGUS: INFLAMMATION/NECROSIS ESOPHAGUS: NO ABNORMALITY DETECTED LUNG: CONGESTION SKIN: INFLAMMATION/ULCER PITUITARY GLAND 1 1 (-, 0 0 _ - 0 1 1 (1,- 0 2 1 (-,-,-,1,-) 1 <1, 0 TOTAL ANIMALS WITH PRIMARY TUMORS TOTAL ANIMALS WITH BENIGN TUMORS TOTAL ANIMALS WITH MALIGNANT TUMORS 10 00 10 00 00 00 NOTES: THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN EACH GRADE WAS OBSERVED. DOUBLE DIGIT NUMBERS ARE EXPRESSED VERTICALLY, FOR EXAMPLE: { ,1 , ,1,1) MEANS NO LESIONS ( - , 0 ,6 ,1 ,5 ) WERE GRADED "PRESENT", 10 LESIONS WERE "MINIMAL" , 6 LESIONS WERE "MILD", 11 LESIONS WERE "MODERATE", AND 15 LESIONS WERE "SEVERE".' TUMOR CODES: *B = BENIGN Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 55 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - Pi ADULTS TISSUE/LESION LESION GRADES (P, 1, 2, 3, 4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: ii- 0 0 20 IV -0 75 20 V I-0 500 20 V III-0 1 3500 20 LIVER INFLAMMATION, SUBACUTE/CHRONIC KIDNEYS . CYST HYDRONEPHROSIS, BILATERAL HYDRONEPHROSIS, UNILATERAL INFARCT NEPHROPATHY, CHRONIC PROGRESSIVE PYELONEPHRITIS, BILATERAL' THYROID GLAND ALTERATION, COLLOID HYPERTROPHY, FOLLICULAR CELL OVARIES WITH OVIDUCTS UTERUS AND CERVIX DILATATION, GLAND/LUMEN VAGINA OTHER SKIN: NO ABNORMALITIES DETECTED PITUITARY GLAND 10 0 0 10 2 - - 1 (-, 1 , - , - , - ) 11 1 1 1 10 5 (-,4,1,-,-) - 1 1 (-,-,1,-,-) - - 0 - - 11 1 (-, 1 , - , - , - ) 1 (-, - , 1 , - , - ) 1 (-,, 1 , - , - , - ) 1 (-,, 1 , - , - , - ) 10 4 (-,4,-,-,-;1 - 10 3 5 19 (-,, , , ,-;1 5 (-, 1 10 10 8 (-., 4 , 1 , 5 , - ) (- , 8 , - , - , - ) 2115 2115 1 (-,-,1,-,-) - - 1 (- ,1, 2115 10 01 1 - - 1 (1 000 TOTAL ANIMALS WITH PRIMARY TUMORS TOTAL ANIMALS WITH BENIGN TUMORS TOTAL ANIMALS WITH MALIGNANT TUMORS 0000 0000 0000 120 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 51 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - Pi ADULTS TISSUE/LESION LESION GRADES <P,1, 2, 3, 4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: II-O 0 20 .f IV -0 75 20 VI-0 500 20 V III-0 3500 20 NOTES: THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN EACH GRADE WAS OBSERVED. FOR EXAMPLE: ( - , 1 , 2 , - , - ) MEANS NO LESIONS WERE GRADED "PRESENT" (NON-GRADED LESIONS), 1 LESION WAS GRADED "MINIMAL" , 2 LESIONS WERE GRADED "MILD", NO LESIONS WERE GRADED "MODERATE" AND NO LESIONS WERE GRADED "SEVERE". 121 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 56 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS - Fj ADULTS TISSUE/LESION LESION GRADES (P,1,2,3,4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: 1-1 0 18 III-l 75 19 V -l 500 19 V II- 1 3500 15 LIVER INFLAMMATION, SUBACUTE/CHRONIC NECROSIS, FOCAL KIDNEYS CYST HYDRONEPHROSIS, BILATERAL HYDRONEPHROSIS, UNILATERAL HYPERPLASIA, TRANSITIONAL CELL INFARCT NEPHROPATHY, CHRONIC PROGRESSIVE PYELONEPHRITIS, BILATERAL PYELONEPHRITIS, UNILATERAL THYROID GLAND ALTERATION, COLLOID HYPERTROPHY, FOLLICULAR CELL TESTES EPIDIDYMIDES SEMINAL VESICLES WITH COA PROSTATE GLAND OTHER THYMUS: NO ABNORMALITY DETECTED URINARY BLADDER: INFLAMMATION/HYPERPLASIA 18 9 r 1[ , , , , ) [- , 9 ) 0 - - 0 15 - 10 ( , 1, , , ) (- , 0 , 1 (- , 1, 18 - 1 (-,-,1,-,-) 2 (-,1,1,-,-) - 1 (-,1, 11 ( ,1 , ,,) (-,1, - - 1 - 1 (-,-,1,-,-) - - i < , , , , ;1 (-,1, 1 - - 5 " 3 (-,.2, -, 1, - ) 1 (-,.1, 4 ( ,, , , , ) (-,, 4 , - , - , - ) 2 r1, - , 1, -) 1 (-.,1, 15 2I 2, - , - , - ) 1 (: - , i , - , - , - ) 5 (; - , 4 , i , - , - i 10 ![ , i , i[-, 0, ,,) 17 1 (-,1, ~ 0 19 3 (-,3, 0 19 1 (-., 1 , - , - , - ) ) 6 (- , 6 , - , - , - ) 15 2 7 (-,2,-,-,-) (-,7,-,-,-) 00 0000 0 00 0 0 000 0 01 1 -_ - 1 ( l, - - 1 (- 122 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 52 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS - Fi ADULTS TISSUE/LESION LESION GRADES (P,1,2,3,4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: 1-1 0 18 III-l 75 19 V -l 500 19 V II-1 3500 15 PITUITARY GLAND 0 000 TOTAL ANIMALS WITH PRIMARY TUMORS TOTAL ANIMALS WITH BENIGN TUMORS TOTAL ANIMALS WITH MALIGNANT TUMORS 0 000 0000 0000 NOTES: THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN EACH GRADE WAS OBSERVED. DOUBLE DIGIT NUMBERS ARE EXPRESSED VERTICALLY, FOR EXAMPLE: ( ,1 , ,1,1) MEANS NO LESIONS (-,0 ,6 ,1 ,5 ) WERE GRADED "PRESENT", 10 LESIONS WERE "MINIMAL", 6 LESIONS WERE "MILD", 11 LESIONS WERE "MODERATE", AND 15 LESIONS WERE "SEVERE". TUMOR CODES: *B = BENIGN 123 Company Sanltizod. Does no. oontaln TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 57 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - Fi ADULTS TISSUE/LESION LESION GRADES (P,1,2,3,4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: II-l 0 18 IV -1 75 18 V I-1 500 19 V III-1 3500 15 o| ! oi LIVER KIDNEYS HYDRONEPHROSIS, BILATERAL HYDRONEPHROSIS, UNILATERAL HYPERPLASIA, TRANSITIONAL CELL NEPHROPATHY, CHRONIC PROGRESSIVE PYELONEPHRITIS, UNILATERAL THYROID GLAND HYPERTROPHY, FOLLICULAR CELL OVARIES WITH OVIDUCTS UTERUS AND CERVIX VAGINA OTHER URINARY BLADDER: HYPERPLASIA, TRANSITIONAL CELL URINARY BLADDER: INFLAMMATION, SUBACUTE/CHRONIC PITUITARY GLAND 0 2 1 (-,-,1,-,-) 1 i-,-,-,1,-) - 18 " 0 0 0 0 - 0 0 - 0 - 0 0 0 0 - 0 0 4 3 (-,1,2,-,-) 1 (-,1, 2 (-,2,-,-,-) 1 (-,-,-,1,-) 3 i (-,-,i,-,-; 2 (-,2,-,-,-: 2 (-,2,-,-,-' " 19 - 0 14 1 (-,1,-,-,- 0 00 00 1 1 (-,-,-,1,-) 1 (-,-,1,-,-) 0 - 00 TOTAL ANIMALS WITH PRIMARY TUMORS TOTAL ANIMALS WITH BENIGN TUMORS TOTAL ANIMALS WITH MALIGNANT TUMORS 00 00 0000 00 00 124 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 53 (Continued) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - Fj ADULTS TISSUE/LESION LESION GRADES (P, 1, 2, 3, 4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: II-l 0 18 IV -1 75 18 VI-1 500 19 V III-1 3500 15 NOTES: THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN EACH GRADE WAS OBSERVED. FOR EXAMPLE: ( - , 1 , 2 , - , - ) MEANS NO LESIONS WERE GRADED "PRESENT" (NON-GRADED LESIONS), 1 LESION WAS GRADED "MINIMAL", 2 LESIONS WERE GRADED "MILD", NO LESIONS WERE GRADED "MODERATE" AND NO LESIONS WERE GRADED "SEVERE". Company Sanitized. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 TABLE 58 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS - Fi WEANLINGS TISSUE/LESION LESION GRADES (P,1,2,3,4) GROUP DESIGNATION: DOSE (mg/kg/day): NUMBER IN GROUP: II-l 0 50 IV -1 75 47 VI-1 500 58 V III-1 3500 45 LIVER KIDNEYS HYDRONEPHROSIS, UNILATERAL THYROID GLAND OVARIES WITH OVIDUCTS UTERUS AND CERVIX VAGINA OTHER LONG BONE: FRACTURE/CALLUS LONG BONE: INFLAMMATION, SUBACUTE/CHRONIC URINARY BLADDER: HYPERPLASIA, TRANSITIONAL CELL URINARY BLADDER: INFLAMMATION, SUBACUTE/CHRONIC PITUITARY GLAND 0 0 - 0 0 0 0 0 - 0 0 1 1 (-,-,-,-,1) 0 0 0 0 0 - 0 0 0 - 0 0 0 0 0 - 0 0 0 - 0 0 0 0 2 1 (1,-, 1 1 1 (-,-, 0 TOTAL ANIMALS WITH PRIMARY TUMORS TOTAL ANIMALS WITH BENIGN TUMORS TOTAL ANIMALS WITH MALIGNANT TUMORS 0 00 0 0 00 0 0 00 0 NOTES : THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN EACH GRADE WAS OBSERVED. FOR EXAMPLE: ( - , 1 , 2 , - , - ) MEANS NO LESIONS WERE GRADED "PRESENT" (NON-GRADED LESIONS), 1 LESION WAS GRADED "MINIMAL", 2 LESIONS WERE GRADED "MILD", NO LESIONS WERE GRADED "MODERATE" AND NO LESIONS WERE GRADED "SEVERE". 126 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDICES 127 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX A ANALYTICAL DATA 128 Company Sanitized. Does not contain i SCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Table I. Concentration Verification and Stability of H-25231 in Dosing Solutions Preparation Day Sample Type Test Day 2 Concentration Verification(B) Control ms/mL H-25231 (A) Nominal Measured 0.0 n d (c ) Percent Nominal -- Stability Test Day 9 Concentration Verification(B) Control 15-1 15-1/1 15-1/2 Mean(D): 15-2 MeanOE): 100-1 100-2 M ean(E); 700-1 700-2/1 700-2/2 M ean(P): Mean(E): 15 100 700 8.62 9.36 8.18 8.72 12.8 10.8 2.9 C.V. 27% 91.6 97.2 94.4 4 .0 C.V. 4% 715 698 638 668 691 3 3 C.V. 5% 10.8(D) 87.7 759(F) 0.0 ND(C) 57.4 62.4 54.5 (58.1) 85.3 (72.0) 91.6 97.2 (94.4) 102.1 99.6 91.2 (95.4) (98.8) 72.0 87.7 108.4 -- 15-1 12.6 84.0 15-1/1 15-1/2 12.8 12.7 85.3 84.7 M ean(P): 15-2/1 15-2/2 12.7 16.0 15.2 (84.7) 106.7 101.3 M ean(F): 15.6 (104.0) M ean(): 14.2 2 .0 C.V. 14% (94.7) Stability 5-Hour Room Temperature 15 16.5 110.0 (A) Dosing solution concentration mg H-25231/mL, based on 5 mL dose volume. H-25231 is approximately] (B) Duplicate samples per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixi (C) Denotes not detected. (D) Mean result for all analyses on original sample. (E) Mean result for analyses on duplicate samples. (F) Mean result for duplicate reanalyzes of original sample. Original analysis not reported due to aliquot error. 129 Company Sanitized. Does not contain T8CA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 /"N Table n. Concentration Verification of H-25231 in Dosing Solutions Preparation Day mg/mL H-25231(A) Percent Sample Type Nominal Measured Nominal Test Day 46 Concentration Verification(B) Control 0.0 ND(C) -- 15-1 15-2 Mean: 15.1 16.6 15.9 LI C.V. 7% 100.7 110.7 (106.0) 100-1 100-2 Mean: 112 113 113 0.7 C.V. 1% 112.0 113.0 (113.0) Test Day 114 Concentration Verification(B) Control 700-1 700-2 Mean: 0.0 749 666(D) 708 59 C.V. 8% ND(C) 107.0 95.1 (101.1) -- 15-1 15-2 Mean: 16.5 12.9(D) 14.7 2.5 C.V. 17% 110.0 86.2 (98.0) 100-1 100-2 Mean: 107 120 114 9.1 C.V. 8% 107.0 120.0 (114.0) 700-1 700-2 Mean: 765 681 723 59 C.V. 8% 109.3 97.3 (103.3) (A) Dosing solution concentrgfjpn mg H-25231/mL hased on 5 mL dose volume. H-25231 is a p p r o x im a te l^ p B H I H B B M liA (B) Duplicate samples per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (C) Denotes not detected. (D) Mean result for duplicate reanalyzes of original sample. Original analysis not reported due to aliquot error. C o m p a n y S a n it iz e d . D o e s not contain T SC A CBI H-25231: One-Generation Reproduction Study in Rats Figure 1 Representative Analytical Calibration Curves DuPont-9763 Figure la: Calibration curve (LC/MS - C6-C6/bis) showing linear fit (line) to replicate peak area measurements (squares) for calibration solutions of H-25231 diluted over a concentration range of 0.24 to 0.74 ppm (0.00024 to 0.00074 mg/mL). Figure lb: Calibration curve (LC/MS - C6-C8 bis) showing linear fit (line) to replicate peak area measurements (squares) for calibration solutions of H-25231 diluted over a concentration range of 0.24 to 0.74 ppm (0.00024 to 0.00074 mg/mL). 131 Com pany Sanitised. Does nol contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats Figure 1 (continued) Representative Analytical Calibration Curve DuPont-9763 Figure lc: Calibration curve (LC/MS - C8-C8 bis) showing non-linear fit (line) to replicate peak area measurements (squares) for calibration solutions of H-25231 diluted over a concentration range of 0.24 to 0.74 ppm (0.00024 to 0.00074 mg/mL). Figure Id: Calibration curve (LC/MS - C10-C8 bis) showing non-linear fit (line) to replicate peak area measurements (squares) for calibration solutions of H-25231 diluted over a concentration range of 0.24 to 0.74 ppm (0.00024 to 0.00074 mg/mL). not contain 1SCACBI 132 Company Sanitized. Does H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Figure 2 Representative HPLC/MS Chromatography Chromatograms 0.0 mg/ml 5/2 050902vc3 Sm (Mn, 2x3) User: V C 0 9 -M a y -2 0 0 2 11:06:58 SIR of 4 Channels ES- Figure 2a: Representative HPLC/MS chromatograms of 0.00 mg/mL dosing solution of H-25231. 133 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Figure 2 (continued) Representative HPLC/MS Chromatography Chromatograms 050202vc37 Smooth(IVfri,2x3) 100- %- 789 6.78 1339.12 SIR of 4 channels,ES789.08 9.265e+003 0-t T "f"r-T""|" I" ",1 "j 'I | r |" r r" i " T 050202vc37 Smooth(Mn,2x3) 100-i % T '~'-fTT 889 7.36 1777.20 i'"'f.V 'l ..i..r-fn.r*i.I.. min SIR of 4 channels,ES889.06 1.223e+004 0- ..I.... ...f T f T T j i ......................r i -- 050202vc37 Smooth(Mn,2x3) 100- %- i.if "' i ...I................................................................................................... r ... m i n SIR of 4 channels,ES989 989.06 7.82 5.871 e+003 901.95 r T i.|..i.r.T ..ilii I .j .............. j ., 050202vc37 Smooth(Mn,2x3) 100-1 * ! In [ ! %- 0 -1 1iVi,p..|.ii| j I n"I "T"|..I..I "I "I........... r.r".p r -r'.r -T"*| i 2.00 4.00 9.54 i i 'v"|'"i..i..1` r p i ' i 1" I "I. I I I m in SIR of 4 channels,ES- 1089 8.23 1089.04 3.177e+003 494.60 ..vi'r T " T "ip"i..| i ^ l -..... 6.00 8.00 9.56 "T m in Figure 2b: -Representative HPLC/MS chromatograms of 0.50 ppm (0.0005 mg/mL) analytical reference solution of H-25231. 134 Company Sanitized, Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 Figure 2 (continued) Representative HPLC/MS Chromatography Chromatograms 050202vc42 Smooth(Mn,2x3) 10CH %- 0.01 / v S _ ... 0- I I I . . . . . . . . . 050202vc42 Smooth(Mn,2x3) 100-1 %- 789 6.78 1739.45 SIR of 4 channels ,ES789.08 1.116e+004 'T.p T T T T f 'T 9.10 r,ir ili 111')..v t "T"'1..11""I" r - v min SIR of 4 channels ,ES- 889 _ 7.36 I 889.06 1,300e+004 1984.45 T 050202vc42 Smooth(Mn,2x3) TT T _ nr . min SIR of4 channels,ES- Figure 2c: Representative HPLC/MS chromatograms of 100 mg/mL dosing solution diluted to nominal concentration of 0.50 ppm (0.0005 mg/mL) of H-25231. The measured concentration of the representative solution is 112 mg/mL. 135 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIXB INDIVIDUAL BODY WEIGHTS OF Pi MALE RATS 136 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats INDIVIDUAL BODY WEIGHTS OF Pi MALE RATS EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period Abbreviations AK = Accidentally Killed RD = Found dead SD = Sacrificed by design SE = Sacrificed in extremis', data excluded from group means. (Group 1-0, Animal No. 657409) = No Data DuPont-9763 137 Company Sanitized. Does not contain TSC A C B i H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 I N D I V I D U A L B O D Y W E I G H T S (grams) OF Px M A L E R A T S GROUP: 1-0 DOSE: 0 MG/KG/DAY 1 8 15 22 29 36 43 279.5 288.6 3 02.5 271.3 274.3 282.1 280.9 268.0 275.9 283.9 299.4 262.0 274.4 287.7 295.4 273.9 288.4 279.2 295.3 266.0 333.8 335.8 361.0 329.0 322.2 321.2 321.1 313.4 326.4 328.1 337.2 294.7 319.0 346.4 351.5 319.0 349.6 323.0 345.1 314.7 374.7 384.5 403.7 387.9 362.2 353.0 348.2 356.7 370.3 364.6 374.7 332.3 366.4 397.8 410.1 380.0 392.8 363.5 390.5 359.4 421.1 424.9 438.9 443.2 403.7 400.0 382.3 395.6 402.2 407.8 410.6 367.9 404.1 452.6 454.6 416.2 435.5 389.3 433.9 401.5 453.2 465.9 465.7 472.1 431.0 424.3 396.0 423.3 438.9 435.6 445.6 401.3 437.3 492.5 485.5 447.2 468.6 418.9 481.4 429.3 470.1 488.8 485.3 508.9 458.3 452.8 414.6 455.5 460.0 462.9 471.5 424.6 449.8 529.1 513.2 483.2 496.9 446.5 501.2 448.3 495.3 502.7 495.5 529.2 487.7 474.5 436.9 480.8 479.6 479.1 490.3 442.9 448.9 553.1 535.4 513.0 516.6 464.3 525.7 469.3 138 Company Sanitized. Does noi contain TSCA O B H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 I N D I V I D U A L B O D Y W E I G H T S (grams) O F Pi M A L E R A T S GROUP: 1-0 DOSE: 0 MG/KG/DAY 50 57 64 71 78 85 92 520.1 532.6 532.3 559.9 512.4 497.4 448.3 511.9 502.4 492.6 516.0 468.5 465.9 582.9 562.6 540.1 542.6 482.5 535.4 489.7 530.3 554.9 551.2 581.5 524.9 504.9 458.4 532.9 515.4 511.6 520.5 484.0 474.4 611.7 581.5 557.8 554.8 490.5 531.6 502.2 545.5 573.9 568.8 598.1 545.7 525.5 467.9 549.7 536.4 527.2 537.1 494.0 487.7 628.7 599.6 581.9 576.1 502.1 SE (DAY 510.3 548.6 581.7 576.2 602.7 557.0 537.5 473.9 560.3 542.7 539.0 549.8 504.7 501.2 651.1 609.0 592.8 592.8 511.6 60) 518.5 536.8 564.0 561.5 598.0 530.8 517.2 466.8 546.0 532.9 530.0 545.4 498.6 503.3 655.2 607.2 594.6 597.9 503.6 513.8 548.8 592.3 594.5 610.9 549.1 542.2 479.2 568.4 550.6 538.3 565.0 517.3 497.6 671.1 617.4 621.1 608.5 521.5 526.6 563.4 603.1 609.9 627.5 568.0 551.2 475.7 584.9 557.4 547.1 586.3 533.7 508.6 695.4 637.9 643.0 619.6 533.7 540.8 139 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DAYS ON TEST: ANIMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 INDIVIDUAL BODY WEIGHTS (grams) OF Pa MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY 99 106 113 574.2 620.5 619.2 642.0 582.8 572.2 486.5 600.0 578.2 566.2 588.0 537.8 517.2 709.6 651.6 661.5 637.8 536.0 591.3 634.6 612.1 655.9 597.9 576.3 495.4 601.8 579.7 567.2 592.7 549.1 . 519.0 727.9 659.8 671.5 646.7 530.7 . 599.6 640.8 633.4 665.7 609.9 584.3 500.5 613.6 585.9 579.3 606.1 549.5 520.0 749.1 664.6 682.7 663.3 534.9 SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 117) SD (DAY 117) SD (DAY 117) 547.9 553.3 550.1 SD (DAY 117) DuPont-9763 140 Company Sanitized. Does not contain TSCA C B I H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 657596 INDIVIDUAL BODY WEIGHTS (grams) OF Px MALE RATS GROUP: III-O DOSE: 75 MG/KG/DAY 1 8 15 22 29 36 43 280.9 288.4 271.9 274.5 284.4 296.6 263.2 280.1 285.7 317.4 263.9 282.9 282.0 299.9 273.5 290.7 295.5 302.2 261.5 247.8 322.0 329.9 306.8 310.5 322.5 335.9 295.0 327.1 334.5 375.0 297.9 331.6 327.6 362.0 333.0 331.1 356.6 353.1 294.7 271.5 360.1 359.6 344.7 356.6 358.5 380.7 333.7 366.3 390.1 441.5 343.2 379.0 368.6 416.6 378.9 384.5 409.6 406.4 327.4 299.3 394.3 391.0 378.6 394.6 390.3 413.8 359.1 408.5 432.0 498.7 376.7 409.0 395.9 472.8 421.5 426.4 454.4 449.7 351.5 325.0 418.8 425.3 409.0 427.0 421.0 448.5 388.9 440.0 463.6 539.6 407.4 445.2 438.6 512.7 460.8 471.5 502.1 483.2 371.4 350.5 441.1 439.2 439.0 457.7 450.0 481.2 406.0 473.2 488.2 577.6 433.0 479.5 466.6 542.9 496.1 508.1 538.9 509.5 392.4 365.7 455.0 459.6 450.2 481.9 466.1 514.5 424.4 496.6 518.1 621.1 453.6 501.6 481.8 561.1 524.9 532.1 567.9 534.5 406.7 375.1 141 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 657596 I N D I V I D U A L B O D Y W E I G H T S (grains) O P P x M A L E R A T S GROUP: III-O DOSE: 75 MG/KG/DAY 50 57 64 71 78 85 92 477.8 475.9 470.3 506.0 478.3 528.7 446.6 516.9 540.0 655.6 481.0 521.7 501.4 586.2 544.1 553.4 600.2 558.2 429.2 391.5 487.2 489.8 480.5 522.0 484.1 548.9 465.2 535.0 558.8 683.7 487.7 541.9 520.2 614.5 557.0 572.0 629.6 577.9 438.4 400.0 502.1 505.0 488.2 535.6 510.2 571.5 473.0 559.1 569.8 705.0 502.0 556.4 541.7 637.2 579.4 592.1 653.4 598.5 449.3 409.3 514.9 521.6 496.1 554.7 510.6 585.3 496.1 570.6 591.9 721.5 511.0 562.1 542.4 649.7 599.6 607.8 673.5 615.1 459.0 409.1 504.9 519.9 490.7 545.3 509.4 584.8 464.5 560.1 561.2 704.4 509.1 562.8 545.0 643.0 605.9 602.4 674.5 609.6 459.7 406.0 515.2 535.6 497.3 551.0 530.3 591.7 485.3 581.0 572.8 722.3 524.4 582.8 553.2 651.8 612.1 607.2 671.2 619.0 475.3 413.2 526.6 550.0 502.5 562.5 542.4 600.1 502.6 596.2 589.6 743.2 540.7 591.8 570.0 662.8 617.9 611.7 691.8 635.4 475.9 418.6 142 Company Sanitized. Does not contain IS C A CBI H-25231: One-Generation Reproduction Study in Rats DAYS ON TEST: ANIMAL NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 657596 INDIVIDUAL BODY WEIGHTS (grams) OF Pi MALE RATS GROUP: III-O DOSE: 75 MG/KG/DAY 99 106 113 536.1 571.1 516.1 581.0 538.5 616.7 512.5 610.7 601.0 763.3 552.0 605.8 586.4 686.0 623.3 625.6 725.3 662.4 491.1 427.7 546.4 574.8 527.2 594.7 538.7 627.7 516.7 625.2 593.6 787.1 559.4 619.2 593.5 688.8 637.3 652.3 741.7 675.8 505.9 434.7 552.6 586.9 530.2 603.0 557.3 631.7 529.6 636.5 594.1 795.6 559.9 619.6 609.2 710.3 649.5 649.5 750.8 676.3 514.7 445.6 SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 117) SD (DAY 117) SD (DAY 117) SD (DAY 117) SD (DAY 117) DuPont-9763 /" " 'N 143 Company Sanitized. Does not contain TSCA CBf H-25231 : One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 I N D I V I D U A L B O D Y W E I G H T S (grains) O F Pi M A L E R A T S GROUP : V-0 DOSE: 500 MG/KG/DAY 1 8 15 22 29 36 43 288.8 249.2 288.3 280.6 297.8 256.2 276.1 274.8 284.0 258.6 290.5 288.8 291.3 269.7 268.3 293.8 324.9 2 64.6 275.6 280.0 330.6 278.3 337.0 327.4 347.3 289.2 310.8 313.8 336.7 303.3 339.2 338.2 328.7 317.5 295.5 323.5 372.1 300.1 309.7 311.6 363.9 308.3 385.4 373.2 389.5 322.4 347.6 347.6 378.4 354.9 384.9 390.9 372.2 362.4 327.0 376.8 433.6 341.4 342.5 351.5 406.9 330.6 414.5 416.2 423.2 347.0 369.9 381.5 420.3 389.6 431.6 428.4 400.4 399.2 345.8 408.9 481.8 382.8 368.2 390.1 435.4 348.5 449.2 444.3 461.3 366.6 401.4 415.9 463.2 418.7 469.3 469.7 421.1 430.4 364.8 435.2 527.7 420.3 377.0 411.7 467.7 359.7 479.3 489.9 491.1 384.6 432.3 442.2 478.7 443.0 503.6 494.2 447.6 461.6 382.3 462.4 569.4 441.3 401.9 441.4 483.5 355.6 508.3 510.6 512.3 399.5 451.3 467.7 488.2 462.7 533.7 518.5 480.9 482.9 397.7 488.8 594.2 463.5 421.9 461.2 144 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 I N D I V I D U A L B O D Y W E I G H T S (grams) O F Pi M A L E RATS GROUP: V-0 DOSE: 500 MG/KG/DAY 50 57 64 71 78 85 92 503.4 371.4 521.5 546.1 530.6 413.3 469.1 491.5 503.0 483.9 551.8 534.3 446.7 488.3 415.2 498.5 617.2 483.2 433.9 478.0 510.2 376.3 533.4 579.2 543.4 423.2 484.9 510.8 511.0 486.8 575.1 544.5 479.3 510.9 428.0 516.0 630.9 491.3 447.8 485.7 522.9 395.4 538.4 601.8 551.2 427.9 499.6 518.5 524.7 502.3 591.4 558.1 501.5 526.4 432.9 531.5 646.5 506.5 459.7 491.4 534.7 399.4 555.6 600.5 561.7 443.4 514.2 535.1 543.0 515.4 612.7 566.1 516.0 543.9 445.3 552.3 663.2 524.2 476.4 509.0 520.9 386.1 529.6 591.7 549.3 427.1 513.7 528.8 527.2 497.0 616.6 552.6 527.8 539.5 447.7 550.6 659.2 516.3 473.3 460.1 535.7 395.8 559.2 614.5 547.7 435.1 522.5 542.0 542.5 510.8 618.8 570.2 536.8 550.2 456.4 556.7 667.2 531.8 476.4 486.7 539.5 404.6 569.2 615.9 566.0 440.1 533.1 547.8 548.0 516.3 636.6 566.5 546.0 564.5 466.0 558.5 679.5 532.7 A K (DAY 497.8 86) 145 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DAYS ON TEST: ANIMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 INDIVIDUAL BODY WEIGHTS (grams) OF Px MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY 99 106 113 538.8 413.5 580.7 629.2 580.6 443.4 540.7 554.3 558.9 526.2 640.2 575.2 555.9 574.3 471.1 566.6 699.6 538.1 510.9 545.7 410.3 586.3 645.9 578.3 454.0 548.7 563.0 570.5 541.7 642.4 586.2 574.0 572.6 481.1 566.0 710.4 553.8 524.6 553.6 415.5 585.7 671.2 572.7 458.7 557.9 568.3 572.4 543.1 653.0 599.4 581.0 584.4 488.5 570.8 729.1 554.2 SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 117) SD (DAY 117) SD (DAY 117) 530.9 SD (DAY 117) DuPont-9763 146 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: .ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 INDIVIDUAL BODY WEIGHTS (grams) OF Px MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY 1 8 15 22 29 36 43 267..4 265,.2 286,.3 297 ,.6 255,.1 271,.3 290,.9 299,.8 270..5 261..0 288,.8 301,.0 279..0 275..7 287 ,.8 293..2 274..8 281..8 287.,8 284.,0 271 .4 280 .4 283 .8 318 .4 287 .0 293..7 322..9 341..4 314..7 286..6 330,.0 347..7 326..6 289..4 318..8 338..9 295..0 328..9 313 .2 326..7 316 .0 309 .3 324 .1 344 .3 315 .2 302 .0 372..1 366..1 336..0 305,.1 355..2 391..8 369..2 334,.6 362 .6 389..0 333 ,.5 383..7 334..0 354..8 360.6 335.0 324.2 370.6 337.4 322.9 408.2 397.0 365.7 322.7 350.8 436.9 408.2 364.6 388.4 438.0 355.1 413.0 383.6 385.3 377.5. 352.7 365.6 388.2 349.3 337.7 439.9 401.7 389.1 338.9 383.7 473.6 441.5 389.5 418.1 474.3 376.2 444.5 421.6 398.2 393.8 372.5 406.0 418.5 373.2 350.7 452.0 430.1 409.7 356.1 388.5 478.6 469.9 381.8 422.2 500.3 383.7 449.4 431.4 418.8 424.2 369.4 433.8 438.2 377.0 352.0 468.4 452.4 424.5 349.4 400.1 A K (DAY 488.7 401.3 435.1 523.5 394.5 466.0 457.1 428.6 42) 147 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 INDIVIDUAL BODY WEIGHTS (grams) OF Pi MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY 50 57 64 71 78 85 92 453.9 384.4 424.0 463.1 383.9 351.7 485.9 478.5 418.9 371.9 419.5 - 513.8 397.4 430.6 497.3 404.4 462.5 436.9 431.7 475.5 393.1 444.5 485.1 396.2 362.2 500.9 493.4 410.8 391.1 437.3 - 533.9 411.2 450.4 525.0 423.6 477.4 456.6 445.7 478.2 390.0 460.0 503.0 383.6 368.9 507.1 516.4 439.5 396.5 451.7 - 540.6 414.9 466.4 565.7 449.4 497.7 490.5 452.6 494.7 396.0 480.9 511.5 397.9 374.5 507.3 530.0 440.0 409.6 453.6 - 551.2 412.8 480.5 590.0 FD (DAY 454.1 484.5 460.3 477.8 359.8 437.8 492.4 388.8 315.0 503.1 515.1 438.6 403.3 451.0 543.3 409.7 464.8 590.2 66) 460.2 484.9 472.9 492.0 391.1 458.8 470.3 416.6 337.6 500.4 520.9 424.8 402.7 439.2 559.0 429.5 453.0 606.1 481.0 473.6 487.0 495.6 391.9 442.8 482.0 426.6 366.4 512.4 531.1 440.3 399.8 461.5 573.6 419.6 472.8 627.5 494.3 488.8 437.0 148 Sanitized. Does not contain TSCA CBI Company H-25231: One-Generation Reproduction Study in Rats DAYS ON TEST: A N I M A L NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 INDIVIDUAL BODY WEIGHTS (grams) OF Px MALE RATS GROUP : VII-0 DOSE: 3500 MG/KG/DAY 99 106 113 505.1 408.8 436.7 504.1 419.2 379.7 524.7 520.5 448.1 406.7 448.7 - 568.0 427.4 482.9 638.6 - 501.1 503.9 480.3 526.4 399.8 465.7 490.0 421.8 375.5 523.7 495.9 434.4 422.4 451.7 - 590.9 426.2 451.4 660.5 - 492.1 506.3 494.2 511.2 412.5 461.3 497.6 430.0 383.2 533.3 497.2 442.7 428.6 471.7 - 604.8 428.6 475.4 667.7 - 492.3 533.4 509.3 SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 114) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 115) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 116) SD (DAY 117) SD (DAY 117) SD (DAY 117) SD (DAY 117) DuPont-9763 149 Company Sanitized. Does not contain TSCA CBf 31-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX C INDIVIDUAL BODY WEIGHT GAINS OF Pi MALE RATS /* 150 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS OF Pi MALE RATS EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period Abbreviations AK = Accidentally Killed FD = Found dead SD = Sacrificed by design SE = Sacrificed in extremis; data excluded from group means. (Group 1-0, Animal No. 657409) = No Data 151 Company Sanitized. Does not contain TSCA CBf H-2523: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: A N IMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pi H A L E RATS GROUP: I--0 DOSE: 0 MG/KG/DAY 1-8 8-15 15-22 22-29 29-36 36-43 43-50 54.3 47.2 58.5 57.7 47.9 39.1 40.2 45.4 50.5 44.2 37.8 32.7 44.6 58.7 56.1 45.1 61.2 43.8 49.8 48.7 40.9 48.7 42.7 58.9 40.0 31.8 27.1 43.3 43.9 36.5 37.5 37.6 47.4 51.4 58.6 61.0 43.2 40.5 45.4 44.7 46.4 40.4 35.2 55.3 41.5 47.0 34.1 38.9 31.9 43.2 35.9 35.6 37.7 54.8 44.5 36.2 42.7 25.8 43.4 42.1 32.1 41.0 26.8 28.9 27.3 24.3 13.7 27.7 36.7 27.8 35.0 33.4 33.2 39.9 30.9 31.0 33.1 29.6 47.5 27.8 16.9 22.9 19.6 36.8 27.3 28.5 18.6 32.2 21.1 27.3 25.9 23.3 12.5 36.6 27.7 36.0 28.3 27.6 19.8 19.0 25.2 13.9 10.2 20.3 29.4 21.7 22.3 25.3 19.6 16.2 18.8 18.3 -0.9 24.0 22.2 29.8 19.7 17.8 24.5 21.0 24.8 29.9 36.8 30.7 24.7 22.9 11.4 31.1 22.8 13.5 25.7 25.6 17.0 29.8 27.2 27.1 26.0 18.2 9.7 20.4 152 Company Sanitized. Does not contain TSCA C M H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pi M A L E R A T S GROUP : 1-0 DOSE : 0 MG/KG/DAY 50-57 57-64 64-71 71-78 78-85 85-92 92-99 10.2 22.3 18.9 21.6 12.5 7.5 10.1 21.0 13.0 19.0 4.5 15.5 8.5 28.8 18.9 17.7 12.2 8.0 -3.8 12.5 15.2 3.1 19.0 7.8 17.6 7.4 16.6 4.6 20.8 11.3 20.6 12.0 9.5 6.0 16.8 10.6 21.0 6.3 15.6 11.8 16.6 12.7 10.0 10.7 13.3 13.5 17.0 22.4 18.1 9.4 24.1 10.9 21.3 16.7 11.6 9.5 SE (DAY 60) - 8.1 8.2 -11.8 -17.7 -14.7 -4.7 -26.2 -20.3 -7.1 -14.3 -9.8 -9.0 -4.4 -6.1 2.1 4.1 -1.8 1.8 5.1 -8.0 -4.7 12.0 28.3 33.0 12.9 18.3 25.0 12.4 22.4 17.7 8.3 19.6 18.7 -5.7 15.9 10.2 26.5 10.6 17.9 " 12.8 14.6 10.8 15.4 16.6 18.9 9.0 -3.5 16.5 6.8 8.8 21.3 16.4 11.0 24.3 20.5 21.9 11.1 12.2 14.2 10.8 17.4 9.3 14.5 14.8 21.0 10.8 15.1 20.8 19.1 1.7 4.1 8.6 14.2 13.7 18.5 18.2 2.3 " 7.1 153 Company Sanitized. Does not contain TSCA CBt H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 INDIVIDUAL BODY WEIGHT GAINS (grams) OF Pa MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY 99-106 106-113 1-71 1-113 17.1 14.1 -7.1 13.9 15.1 4.1 8.9 1.8 1.5 1.0 4.7 11.3 1.8 18.3 8.2 10.0 8.9 -5.3 5.4 8.3 6.2 21.3 9.8 12.0 8.0 5.1 11.8 6.2 12.1 13.4 0.4 1.0 21.2 4.8 11.2 16.6 4.2 -3.2 269.1 293.1 273.7 331.4 282.7 255.4 193.0 292.3 266.8 255.1 250.4 242.7 226.8 363.4 313.6 318.9 304.4 232.4 252.5 320.1 352.2 330.9 394.4 335.6 302.2 219.6 345.6 310.0 295.4 306.7 287.5 245.6 461.4 369.2 408.8 374.9 255.7 284.1 154 Company Sanitized. Does not contain TSCA C M /S*"!-,, H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIM A L NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 657596 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pi M A L E R A T S GROUP: III-O DOSE: 75 MG/KG/DAY 1-8 8-15 15-22 22-29 29-36 36-43 43-50 41.1 41.5 34.9 36.0 38.1 39.3 31.8 47.0 48.8 57.6 34.0 48.7 45.6 62.1 59.5 40.4 61.1 50.9 33.2 23.7 38.1 29.7 37.9 46.1 36.0 44.8 38.7 39.2 55.6 66.5 45.3 47.4 41.0 54.6 45.9 53.4 53.0 53.3 32.7 27.8 34.2 31.4 33.9 38.0 31.8 33.1 25.4 42.2 41.9 57.2 33.5 30.0 27.3 56.2 42.6 41.9 44.8 43.3 24.1 25.7 24.5 34.3 30.4 32.4 30.7 34.7 29.8 31.5 31.6 40.9 30.7 36.2 42.7 39.9 39.3 45.1 47.7 33.5 19.9 25.5 22.3 13.9 30.0 30.7 29.0 32.7 17.1 33.2 24.6 38.0 25.6 34.3 28.0 30.2 35.3 36.6 36.8 26.3 21.0 15.2 13.9 20.4 11.2 24.2 16.1 33.3 18.4 23.4 29.9 43.5 20.6 22.1 15.2 18.2 28.8 24.0 29.0 25.0 14.3 9.4 22.8 16.3 20.1 24.1 12.2 14.2 22.2 20.3 21.9 34.5 27.4 20.1 19.6 25.1 19.2 21.3 32.3 23.7 22.5 16.4 155 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 657596 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pi M A L E RATS GROUP: III-O DOSE: 75 MG/ K G / D A Y 50-57 57-64 64-71 71-78 78-85 85-92 92-99 9.4 13.9 10.2 16.0 5.8 20.2 18.6 18.1 18.8 28.1 6.7 20.2 18.8 28.3 12.9 18.6 29.4 19.7 9.2 8.5 14.9 15.2 7.7 13.6 26.1 22.6 7.8 24.1 11.0 21.3 14.3 14.5 21.5 22.7 22.4 20.1 23.8 20.6 10.9 9.3 12.8 16.6 7.9 19.1 0.4 13.8 23.1 11.5 22.1 16.5 9.0 5.7 0.7 12.5 20.2 15.7 20.1 16.6 9.7 -0.2 -10.0 -1.7 -5.4 -9.4 -1.2 -0.5 -31.6 -10.5 -30.7 -17.1 -1.9 0.7 2.6 -6.7 6.3 -5.4 1.0 -5.5 0.7 -3.1 10.3 15.7 6.6 5.7 20.9 6.9 20.8 20.9 11.6 17.9 15.3 20.0 8.2 8.8 6.2 4.8 -3.3 9.4 15.6 7.2 11.4 14.4 5.2 11.5 12.1 8.4 17.3 15.2 16.8 20.9 16.3 9.0 16.8 11.0 5.8 4.5 20.6 16.4 0.6 5.4 9.5 21.1 13.6 18.5 -3.9 16.6 9.9 14.5 11.4 20.1 11.3 14.0 16.4 23.2 5.4 13.9 33.5 27.0 15.2 9.1 156 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 657596 INDIVIDUAL BODY WEIGHT GAINS (grams) OF P x MALE RATS GROUP: III-O DOSE: 75 MG/KG/DAY 99-106 106-113 1-71 1-113 10.3 3.7 11.1 13.7 0.2 11.0 4.2 14.5 -7.4 23.8 7.4 13.4 7.1 2.8 14.0 26.7 16.4 13.4 14.8 7.0 6.2 12.1 3.0 8.3 18.6 4.0 12.9 11.3 0.5 8.5 0.5 0.4 15.7 21.5 12.2 -2.8 9.1 0.5 8.8 10.9 234.0 233.2 224.2 280.2 226.2 288.7 232.9 290.5 306.2 404.1 247.1 279.2 260.4 349.8 326.1 317.1 378.0 312.9 197.5 161.3 271.7 298.5 258.3 328.5 272.9 335.1 266.4 356.4 308.4 478.2 296.0 336.7 327.2 410.4 376.0 358.8 455.3 374.1 253.2 197.8 157 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: A N IMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pi M A L E R A T S GROUP: V-0 DOSE: 500 MG/KG/DAY 1-8 8-15 15-22 22-29 29-36 36-43 43-50 41.8 29.1 48.7 46.8 49.5 33.0 34.7 39.0 52.7 44.7 48.7 49.4 37.4 47.8 27.2 29.7 47.2 35.5 34.1 31.6 33.3 30.0 48.4 45.8 42.2 33.2 36.8 33.8 41.7 51.6 45.7 52.7 43.5 44.9 31.5 53.3 61.5 41.3 32.8 39.9 43.0 22.3 29.1 43.0 33.7 24.6 22.3 33.9 41.9 34.7 46.7 37.5 28.2 36.8 18.8 32.1 48.2 41.4 25.7 38.6 28.5 17.9 34.7 28.1 . 38.1 19.6 31.5 34.4 42.9 29.1 37.7 41.3 20.7 31.2 19.0 26.3 45.9 37.5 8.8 21.6 32.3 11.2 30.1 45.6 29.8 18.0 30.9 26.3 15.5 24.3 34.3 24.5 26.5 31.2 17.5 27.2 41.7 21.0 24.9 29.7 15.8 -4.1 29.0 20.7 21.2 14.9 19.0 25.5 9.5 19.7 30.1 24.3 33.3 21.3 15.4 26.4 24.8 22.2 20.0 19.8 19.9 15.8 13.2 35.5 18.3 13.8 17.8 23.8 14.8 21.2 18.1 15.8 -34.2 5.4 17.5 9.7 23.0 19.7 12.0 16.8 158 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 INDIVIDUAL BODY WEIGHT GAINS (grams) OF Pi MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY 50-57 57-64 64-71 71-78 78-85 85-92 92-99 6.8 4.9 11.9 33.1 12.8 9.9 15.8 19.3 8.0 2.9 23.3 10.2 32.6 22.6 12.8 17.5 13.7 8.1 13.9 7.7 12.7 19.1 5.0 22.6 7.8 4.7 14.7 7.7 13.7 15.5 16.3 13.6 22.2 15.5 4.9 15.5 15.6 15.2 11.9 5.7 11.8 4.0 17.2 -1.3 10.5 15.5 14.6 16.6 18.3 13.1 21.3 8.0 14.5 17.5 12.4 20.8 16.7 17.7 16.7 17.6 -13.8 -13.3 -26.0 -8.8 -12.4 -16.3 -0.5 -6.3 -15.8 -18.4 3.9 -13.5 11.8 -4.4 2.4 -1.7 -4.0 -7.9 -3.1 -48.9 14.8 9.7 29.6 22.8 -1.6 8.0 8.8 13.2 15.3 13.8 2.2 17.6 9.0 10.7 8.7 6.1 8.0 15.5 3.1 26.6 3.8 -0.7 8.8 8.9 10.0 11.5 1.4 13.3 18.3 14.6 5.0 3.3 10.6 7.6 5.8 6.5 5.5 10.9 5.5 9.9 17.8 3.6 -3.7 8.7 9.2 9.9 14.3 9.8 9.6 5.1 1.8 8.1 12.3 20.1 0.9 5.4 AK (DAY 86) - 11.1 13.1 159 Company Sanitized. Does not contain TSCA CBi /* * * % H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 INDIVIDUAL BODY WEIGHT GAINS (grams) OF Px MALE RATS GROUP : V-0 DOSE: 500 MG/KG/DAY 99-106 106-113 1-71 1-113 6.9 -3.2 5.6 16.7 -2.3 10.6 8.0 8.7 11.6 15.5 2.2 11.0 18.1 -1.7 10.0 -0.6 10.8 15.7 - 13.7 7.9 5.2 -0.6 25.3 -5.6 4.7 9.2 5.3 1.9 1.4 10.6 13.2 7.0 11.8 7.4 4.8 18.7 0.4 6.3 245.9 150.2 267.3 319.9 263.9 187.2 238.1 260.3 259.0 256.8 322.2 277.3 224.7 274.2 177.0 258.5 338.3 259.6 200.8 229.0 264.8 166.3 297.4 390.6 274.9 202.5 281.8 293.5 288.4 284.5 362.5 310.6 289.7 314.7 220.2 277.0 404.2 289.6 250.9 160 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: .ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 INDIVIDUAL BODY WEIGHT GAINS (grams) OF Px M A L E RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY 1-8 8-15 15-22 22-29 29-36 36-43 43-50 4.0 15.2 -2.5 20.8 31.9 22.4 32.0 41.6 44.2 25.6 41.2 46.7 47.6 13.7 31.0 45.7 20.2 47.1 25.4 42.7 44.6 28.9 40.3 25.9 28.2 8.3 49.2 24.7 21.3 18.5 25.2 44.1 42.6 45.2 43.8 50.1 38.5 54.8 20.8 28.1 44.6 25.7 0.1 26.3 22.2 20.9 36.1 30.9 29.7 17.6 -4.4 45.1 39.0 30.0 25.8 49.0 21.6 29.3 49.6 30.5 16.9 17.7 41.4 17.6 11.9 14.8 31.7 4.7 23.4 16.2 32.9 36.7 33.3 24.9 29.7 36.3 21.1 31.5 38.0 12.9 16.3 19.8 40.4 30.3 23.9 13.0 12.1 28.4 20.6 17.2 4.8 5.0 28.4 -7.7 4.1 26.0 7.5 4.9 9.8 20.6 30.4 29.7 -3.1 15.0 27.8 -9.8 19.7 24.9 3.8 6.9 1.3 -0.3 16.4 17.5 22.3 26.1 14.8 -5.6 -6.7 22.5 11.6 19.4 A K (DAY 42) - 18.8 25.1 19.5 -3.9 12.9 -4.5 23.2 -26.2 10.8 9.9 16.6 -3.5 25.7 -20.2 9.8 3.1 161 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O P Pi M A L E RATS GROUP : VII-0 DOSE: 3500 MG/KG/DAY 50-57 57-64 64-71 71-78 78-85 85-92 92-99 21.6 8.7 20.5 22.0 12.3 10.5 15.0 14.9 -8.1 19.2 17.8 - 20.1 13.8 19.8 27.7 19.2 14.9 19.7 14.0 2.7 -3.1 15.5 17.9 -12.6 6.7 6.2 23.0 28.7 5.4 14.4 6.7 3.7 16.0 40.7 25.8 20.3 33.9 6.9 16.5 6.0 20.9 8.5 14.3 5.6 0.2 13.6 0.5 13.1 1.9 " 10.6 -2.1 14.1 24.3 FD (DAY -43.6 -6.0 7.7 -16.9 -36.2 -43.1 -19.1 -9.1 -59.5 -4.2 -14.9 -1.4 -6.3 -2.6 -7.9 -3.1 -15.7 0.2 66) - 6.1 0.4 12.6 14.2 31.3 21.0 -22.1 27.8 22.6 -2.7 5.8 -13.8 -0.6 -11.8 15.7 19.8 -11.8 15.9 20.8 -11.3 14.1 3.6 0.8 -16.0 11.7 10.0 28.8 12.0 10.2 15.5 -2.9 22.3 14.6 -9.9 19.8 21.4 13.3 15.2 -50.0 9.5 16.9 -6.1 22.1 -7.4 13.3 12.3 -10.6 7.8 6.9 -12.8 -5.6 7.8 10.1 11.1 6.8 15.1 43.3 162 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 DAYS ON TEST: ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) OF Pj. M A L E R A T S GROUP: VII-0 DOSE: 3500 MG/KG/DAY 99-106 106-113 1-71 1-113 21.3 -9.0 29.0 -14.1 2.6 -4.2 -1.0 -24.6 -13.7 15.7 3.0 22.9 -1.2 -31.5 21.9 -9.0 2.4 13.9 -15.2 12.7 -4.4 7.6 8.2 7.7 9.6 1.3 8.3 6.2 20.0 13.9 2.4 24.0 7.2 0.2 27.1 15.1 227.3 130.8 194.6 213.9 142.8 103.2 216.4 230.2 169.5 148.6 164.8 272.2 137.1 192.7 296.8 172.3 196.7 176.3 243.8 147.3 175.0 200.0 174.9 111.9 242.4 197.4 172.2 167.6 182.9 325.8 152.9 187.6 374.5 210.5 245.6 225.3 163 Company Sanitized. Does not contain TSCACBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX D INDIVIDUAL BODY WEIGHTS OF Pi FEMALE RATS DURING PREMATING 164 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS OF Pi FEMALE RATS DURING PREMATING EXPLANATORY NOTES Notes Test Days 1-75 Test Days 76-90 Premating period Cohabitation period 165 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L B O D Y W E I G H T S (grams) OF Px F E M A L E R A T S D U R I N G P R E M A T I N G GROUP: II-O DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 1 8 15 22 29 36 43 159.1 207.0 182.8 195.7 196.6 184.4 193.8 183.7 194.6 210.7 186.2 180.1 197.8 204.8 178.6 194.9 195.3 197.3 182.5 187.0 179.7 234.2 196.4 197.8 200.3 197.5 208.0 192.6 217.7 221.5 192.1 179.5 218.2 206.9 190.3 224.7 211.9 214.1 187.3 188.9 180.0 267.7 220.0 224.4 213.5 211.1 212.0 198.3 239.2 228.6 206.6 186.2 234.7 238.5 208.1 234.5 233.6 230.3 196.6 206.1 197.3 259.0 237.5 238.3 227.0 221.6 238.5 220.6 250.8 245.6 217.6 202.1 251.7 249.0 224.3 255.3 250.3 240.1 212.8 218.8 197.9 272.5 237.7 242.4 231.9 220.2 247.8 238.5 253.9 258.3 229.8 209.2 254.0 266.8 222.4 262.8 268.4 257.1 229.7 21-8.1 209.0 312.0 246.2 234.8 227.2 233.9 256.0 235.8 272.4 265.7 232.0 213.7 268.1 273.7 222.0 271.3 268.7 273.9 232.0 212.5 207.4 301.8 253.8 244.2 242.9 238.6 256.9 236.4 282.4 271.6 234.4 219.1 291.4 278.4 239.1 274.3 268.6 278.0 234.5 225.8 166 Sanitized. Does not contain TSCA CBt Company H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L B O D Y W E I G H T S (grams) O F Px F E M A L E R A T S D U R I N G P R E M A T I N G GROUP: II-O DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL N O . 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 50 57 64 71 219.0 298.2 263.9 252.4 255.2 250.0 266.5 253.3 287.1 288.9 242.9 233.8 302.7 288.9 244.8 280.1 286.8 280.2 244.7 225.7 224.5 285.2 271.7 254.7 250.3 250.8 272.9 252.0 290.0 292.2 246.1 242.4 296.5 306.1 250.7 290.5 295.6 287.7 253.7 230.6 228.7 310.3 280.0 253.6 247.4 256.3 270.9 260.8 285.9 297.4 241.7 248.0 295.9 301.8 247.4 295.8 289.3 294.7 252.4 228.9 231.4 312.3 280.8 259.4 252.2 257.0 276.0 251.2 300.2 293.7 256.7 241.7 298.1 314.3 247.0 294.8 287.0 296.1 260.9 229.1 167 Company Sanitized. Does not contain TSCA CM H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS (grams) OF Px FEMALE RATS DURING PREMATING GROUP : IV-0 DOSE : 75 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 1 8 15 22 29 36 43 186.2 176.4 192.4 197.1 198.4 185.6 189.4 199.2 208.0 185.1 194.0 191.0 193.5 178.9 197.6 198.3 201.4 185.5 185.9 198.6 207.4 182.8 203.0 205.1 214.7 197.3 216.6 215.0 235.5 201.7 201.1 204.1 224.7 184.8 220.1 208.0 210.5 200.0 202.0 214.4 225.9 199.7 217.6 225.2 231.1 218.7 225.1 232.9 244.8 222.0 222.4 216.8 241.6 207.0 236.9 229.7 227.6 220.9 220.8 234.8 233.5 214.3 229.5 246.3 240.0 232.6 246.1 237.7 259.8 228.8 236.5 225.6 258.2 217.8 246.3 234.6 252.3 236.2 251.8 256.7 235.9 224.2 249.5 262.7 238.6 241.2 250.9 247.1 277.3 237.0 240.0 228.4 280.6 230.4 258.5 251.6 265.5 237.6 254.2 263.0 251.2 228.9 253.2 265.2 246.3 247.7 246.2 250.8 281.4 255.5 255.1 241.2 289.3 233.0 262.9 261.4 267.1 256.4 268.0 272.7 251.0 233.7 258.1 282.1 253.9 261.0 263.0 253.9 292.5 254.9 253.1 250.9 298.0 241.6 273.3 264.0 265.4 262.2 273.3 280.5 168 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS (grams) OF Pj. FEMALE RATS DURING PREMATING GROUP: IV-0 DOSE: 75 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 50 57 64 71 255.0 240.0 270.0 293.5 258.1 266.0 273.7 254.3 295.6 264.1 257.6 255.0 299.8 246.6 281.4 271.6 280.5 273.2 280.6 285.3 255.1 247.0 277.9 312.7 258.9 278.7 279.8 263.9 305.9 266.4 263.3 256.7 308.5 243.9 295.6 271.8 289.8 276.7 271.5 285.5 268.6 253.3 279.8 325.3 270.6 277.1 276.1 272.5 321.8 273.8 263.4 266.8 318.4 256.3 291.3 283.0 291.0 286.1 293.3 290.5 272.8 247.2 280.7 303.1 276.7 285.6 279.9 270.7 306.5 282.1 271.6 279.3 317.6 256.0 304.6 284.6 286.0 284.5 298.8 297.0 169 Company Sanitized. Does not contain f SCA CBf ]H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS (grams) OF Pi FEMALE RATS DURING PREMATING GROUP : VI-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 1 8 15 22 29 36 43 196.3 193.1 192.3 211.8 183.0 206.2 168.4 210.1 168.3 189.0 196.3 203.8 173.2 185.1 193.4 214.3 184.3 195.3 198.6 202.0 205.0 207.7 199.1 213.3 191.7 211.5 191.2 232.4 182.4 200.4 204.0 215.3 181.1 197.0 205.7 236.2 189.7 209.4 231.0 211.1 219.8 226.1 214.2 238.5 209.0 215.3 195.5 254.6 189.0 225.4 209.8 227.3 192.9 213.4 206.9 257.4 216.8 220.5 253.7 214.4 233.9 243.0 227.5 263.0 228.3 231.1 211.9 267.4 195.3 241.2 223.0 253.7 204.7 215.6 239.4 263.3 230.0 232.8 282.9 239.8 236.1 255.6 241.5 269.0 229.3 229.0 224.0 269.5 206.9 247.8 235.8 256.4 207.0 224.1 242.1 277.4 239.4 245.7 305.2 244.0 244.5 254.1 246.9 275.4 244.7 235.0 228.7 269.8 215.3 256.8 238.9 263.1 220.1 233.5 249.4 280.2 245.9 251.4 285.3 250.5 245.4 263.4 253.4 277.2 245.5 236.8 223.0 273.8 212.4 253.6 239.5 272.8 227.3 241.8 245.9 288.2 256.9 252.7 310.6 242.9 170 Sanitized. Does not contain iSCA CM Company H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L B O D Y W E I G H T S (grams) O F Pi F E M A L E R A T S D U R I N G P R E M A T I N G GROUP: VI-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 50 57 64 71 256.7 277.6 252.9 292.8 264.0 249.8 234.9 300.5 211.5 260.9 250.1 280.1 239.7 241.0 262.7 293.8 269.9 256.9 318.3 259.5 258.9 282.6 272.3 299.0 258.1 256.8 242.8 316.7 218.5 267.1 254.3 288.7 237.0 242.7 265.8 300.4 270.9 259.6 336.5 265.8 257.3 286.0 277.2 297.4 269.6 264.4 248.7 327.4 227.8 276.5 258.7 291.3 255.0 245.5 269.0 301.0 267.7 261.8 326.7 266.2 265.0 295.7 280.8 314.4 265.9 265.8 245.5 341.7 226.2 277.6 255.5 295.4 255.5 255.0 268.2 304.1 279.9 269.2 320.8 263.4 171 Company Sanitized. Does not contain TSCA CM H-25231: One-Generation Reproduction Study in Rats DuPont-9763 IN DIVIDUAL BODY WEIG H T S (grams) OF Px FEMALE RATS DU R I N G P R E MATING GROUP: VIII-0 DOSE : 3500 MG/KG/DAY DAYS ON TEST: A N I M A L NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 1 8 15 22 29 36 43 187.2 185.9 196.7 179.8 180.7 185.8 204.7 184.1 194.2 198.9 210.7 177.3 191.1 193.2 200.9 178.2 188.5 204.9 204.0 181.5 187.9 214.5 197.6 184.0 200.8 176.7 213.7 198.2 227.9 199.4 227.2 188.4 195.0 179.4 212.0 190.1 182.7 215.4 203.1 169.7 204.9 232.8 221.8 208.2 216.7 191.3 234.7 202.1 231.9 214.5 244.7 190.4 216.7 212.7 244.0 201.9 216.9 231.8 231.0 201.1 223.1 247.7 233.1 210.7 222.9 215.0 247.3 210.4 240.9 229.2 250.5 203.8 228.8 221.7 247.4 209.2 235.4 245.8 246.2 206.6 237.0 262.6 244.2 231.0 240.9 227.0 266.5 221.1 233.6 240.9 257.3 214.1 240.3 224.3 256.9 209.0 245.3 252.4 244.1 220.5 264.9 245.9 225.9 245.1 245.2 221.2 267.8 230.0 253.6 254.7 257.2 228.7 245.8 238.1 267.2 212.1 240.4 257.1 264.0 222.5 242.4 274.3 227.0 246.6 242.6 213.7 271.6 228.7 257.7 255.2 270.3 222.0 248.4 231.7 263.8 216.1 247.2 266.2 253.3 222.7 172 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS (grams) OF Pi FEMALE RATS DURING PREMATING GROUP: VIII-0 DOSE: 3500 MG/KG/DAY DAYS ON TEST: A N I M A L NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 50 57 64 71 248.8 283.8 258.8 225.1 254.1 229.2 277.7 235.5 293.2 267.6 274.1 225.5 261.3 245.3 275.8 223.8 247.2 270.6 260.3 235.2 256.9 289.5 261.6 238.6 258.6 241.5 284.9 245.3 288.4 277.0 280.3 235.8 265.2 240.6 282.9 230.1 257.4 270.5 273.2 240.9 250.4 283.8 271.3 242.7 268.9 235.2 290.4 246.0 285.9 279.7 276.1 244.8 266.7 251.9 281.7 237.8 259.6 273.6 281.1 244.8 269.5 289.3 279.7 242.8 279.4 244.3 290.6 229.4 297.7 292.8 276.6 245.5 278.4 258.1 288.9 240.1 263.9 283.7 287.6 239.2 173 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX E INDIVIDUAL BODY WEIGHT GAINS OF Pi FEMALE RATS DURING PREMATING 174 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS OF P, FEMALE RATS DURING PREMATING EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period 175 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BO D Y WEIGHT GAINS (grams) OF Px FEMALE RATS DURING PREMATING GROUP: II-O DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 1-8 8-15 15-22 22-29 29-36 36-43 43-50 20.6 27.2 13.6 2.1 3.7 13.1 14.2 8.9 23.1 10.8 5.9 -0.6 20.4 2.1 11.7 29.8 16.6 16.8 4.8 1.9 0.3 33.5 23.6 26.6 13.2 13.6 4.0 5.7 21.5 7.1 14.5 6.7 16.5 31.6 17.8 9.8 21.7 16.2 9.3 17.2 17.3 -8.7 17.5 13.9 13.5 10.5 26.5 22.3 11.6 17.0 11.0 15.9 17.0 10.5 16.2 20.8 16.7 9.8 16.2 12.7 0.6 13.5 0.2 4.1 4.9 -1.4 9.3 17.9 3.1 12.7 12.2 7.1 2.3 17.8 -1.9 7.5 18.1 17.0 16.9 -0.7 11.1 39.5 8.5 -7.6 -4.7 13.7 8.2 -2.7 18.5 7.4 2.2 4.5 14.1 6.9 -0.4 8.5 0.3 16.8 2.3 -5.6 -1.6 -10.2 7.6 9.4 15.7 4.7 0.9 0.6 10.0 5.9 2.4 5.4 23.3 4.7 17.1 3.0 - 0.1 4.1 2.5 13.3 11.6 -3.6 10.1 8.2 12.3 11.4 9.6 16.9 4.7 17.3 8.5 14.7 11.3 10.5 5.7 5.8 18.2 2.2 10.2 -0.1 176 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OF FEMALE RATS DURING PREMATING GROUP: II-O DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 50-57 57-64 64-71 1-71 5.5 -13.0 7.8 2.3 -4.9 0.8 6.4 -1.3 2.9 3.3 3.2 8.6 -6.2 17.2 5.9 10.4 8.8 7.5 9.0 4.9 4.2 25.1 8.3 -1.1 -2.9 5.5 -2.0 8.8 -4.1 5.2 -4.4 5.6 -0.6 -4.3 -3.3 5.3 -6.3 7.0 -1.3 -1.7 2.7 2.0 0.8 5.8 4.8 0.7 5.1 -9.6 14.3 -3.7 15.0 -6.3 2.2 12.5 -0.4 - 1.0 -2.3 1.4 8.5 0.2 72.3 105.3 98.0 63.7 55.6 72.6 82.2 67.5 105.6 83.0 70.5 61.6 100.3 109.5 68.4 99.9 91.7 98.8 78.4 42.1 177 Company S a n d e d . Do not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OF Pi FEMALE RATS DURING PREMATING GROUP: IV-0 DOSE: 75 MG/KG/DAY DAYS ON TEST: ,A N I M A L NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 1-8 8-15 15-22 22-29 29-36 36-43 43-50 21.2 6.4 10.6 8.0 16.3 11.7 27.2 15.8 27.5 16.6 7.1 13.1 31.2 5.9 22.5 9.7 9.1 14.5 16.1 15.8 18.5 16.9 14.6 20.1 16.4 21.4 8.5 17.9 9.3 20.3 21.3 12.7 16.9 22.2 16.8 21.7 17.1 20.9 18.8 20.4 7.6 14.6 11.9 21.1 8.9 13.9 21.0 4.8 15.0 6.8 14.1 8.8 16.6 10.8 9.4 4.9 24.7 15.3 31.0 21.9 2.4 9.9 20.0 16.4 -1.4 8.6 4.8 9.4 17.5 8.2 3.5 2.8 22.4 12.6 12.2 17.0 13.2 1.4 2.4 6.3 15.3 4.7 3.7 2.5 7.7 6.5 -4.7 3.7 4.1 18.5 15.1 12.8 8.7 2.6 4.4 9.8 1.6 18.8 13.8 9.7 -0.2 4.8 4.9 16.9 7.6 13.3 16.8 3.1 11.1 -0.6 -2.0 9.7 8.7 8.6 10.4 2.6 -1.7 5.8 5.3 7.8 4.0 6.3 11.9 11.4 4.2 5.0 10.7 0.4 3.1 9.2 4.5 4.1 1.8 5.0 8.1 7.6 15.1 11.0 7.3 4.8 178 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pj. F E M A L E R A T S D U R I N G P R E M A T I N G GROUP: IV-0 DOSE : 75 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 50-57 57-64 64-71 1-71 0.1 7.0 7.9 19.2 0.8 12.7 6.1 9.6 10.3 2.3 5.7 1.7 8.7 -2.7 14.2 0.2 9.3 3.5 -9.1 0.2 13.5 6.3 1.9 12.6 11.7 -1.6 -3.7 8.6 15.9 7.4 0.1 10.1 9.9 12.4 -4.3 11.2 1.2 9.4 21.8 5.0 4.2 -6.1 0.9 -22.2 6.1 8.5 3.8 -1.8 -15.3 8.3 8.2 12.5 -0.8 -0.3 13.3 1.6 -5.0 -1.6 5.5 6.5 86.6 70.8 88.3 106.0 78.3 100.0 90.5 71.5 98.5 97.0 77.6 88.3 124.1 77.1 107.0 86.3 84.6 99.0 112.9 98.4 179 Company Sanitized. Does not contain TSCA CBI /-"N H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OF P1 FEMALE RATS DURINGPREMATING GROUP: VI-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 6575 60 1-8 8-15 15-22 22-29 29-36 36-43 43-50 8.7 14.6 6.8 1.5 8.7 5.3 22.8 22.3 14.1 11.4 7.7 11.5 7.9 11.9 12.3 21.9 5.4 14.1 32.4 9.1 14.8 18.4 15.1 25.2 17.3 3.8 4.3 22.2 6.6 25.0 5.8 12.0 11.8 16.4 1.2 21.2 27.1 11.1 22.7 3.3 14.1 16.9 13.3 24.5 19.3 15.8 16.4 12.8 6.3 15.8 13.2 26.4 11.8 2.2 32.5 5.9 13.2 12.3 29.2 25.4 2.2 12.6 14.0 6.0 1.0 -2.1 12.1 2.1 11.6 6.6 12.8 2.7 2.3 8.5 2.7 14.1 9.4 12.9 22.3 4.2 8.4 -1.5 5.4 6.4 15.4 6.0 4.7 0.3 8.4 9.0 3.1 6.7 13.1 9.4 7.3 2.8 6.5 5.7 -19.9 6.5 0.9 9.3 6.5 1.8 0.8 1.8 -5.7 4.0 -2.9 -3.2 0.6 9.7 7.2 8.3 -3.5 8.0 11.0 1.3 25.3 -7.6 11.3 14.2 -0.5 15.6 18.5 13.0 11.9 26.7 -0.9 7.3 10.6 7.3 12.4 - 0.8 16.8 5.6 13.0 4.2 7.7 16.6 180 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OP Pi FEMALE RATS DURING PREMATING GROUP: VI-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 50-57 57-64 64-71 1-71 2.2 5.0 19.4 6.2 -5.9 7.0 7.9 16.2 7.0 6.2 4.2 8.6 -2.7 1.7 3.1 6.6 1.0 2.7 18.2 6.3 -1.6 3.4 4.9 -1.6 11.5 7.6 5.9 10.7 9.3 9.4 4.4 2.6 18.0 2.8 3.2 0.6 -3.2 2.2 -9.8 0.4 7.7 9.7 3.6 17.0 -3.7 1.4 -3.2 14.3 -1.6 1.1 -3.2 4.1 0.5 9.5 -0.8 3.1 12.2 7.4 -5.9 -2.8 68.7 102.6 88.5 102.6 82.9 59.6 77.1 131.6 57.9 88.6 59.2 91.6 82.3 69.9 74.8 89.8 95.6 73.9 122.2 61.4 181 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L B O D Y W E I G H T G A I N S (grams) O F Pj. F E M A L E R A T S D U R I N G P R E M A T I N G GROUP: VIII-0 DOSE: 3500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 1-8 8-15 15-22 22-29 29-36 36-43 43-50 0.7 28.6 0.9 4.2 20.1 -9.1 9.0 14.1 33.7 0.5 16.5 11.1 3.9 -13.8 11.1 11.9 -5.8 10.5 -0.9 - 11.8 17.0 18.3 24.2 24.2 15.9 14.6 21.0 3.9 4.0 15.1 17.5 2.0 21.7 33.3 32.0 11.8 34.2 16.4 27.9 31.4 18.2 14.9 11.3 2.5 6.2 23.7 12.6 8.3 9.0 14.7 5.8 13.4 12.1 9.0 3.4 7.3 18.5 14.0 15.2 5.5 13.9 14.9 11.1 20.3 18.0 12.0 19.2 10.7 -7.3 11.7 6.8 10.3 11.5 2.6 9.5 -0.2 9.9 6.6 -2.1 13.9 27.9 -16.7 -18.3 14.1 4.3 -5.8 1.3 8.9 20.0 13.8 - 0.1 14.6 5.5 13.8 10.3 3.1 -4.9 4.7 19.9 2.0 -22.5 28.4 1.1 1.5 -2.6 -7.5 3.8 -1.3 4.1 0.5 13.1 -6.7 2.6 -6.4 -3.4 4.0 6.8 9.1 -10.7 0.2 6.4 9.5 31.8 -21.5 11.5 15.5 6.1 6.8 35.5 12.4 3.8 3.5 12.9 13.6 12.0 7.7 0.0 4.4 7.0 12.5 182 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OF Pi FEMALE RATS DURING PREMATING GROUP: VIII-0 DOSE: 3500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 50-57 57-64 64-71 1-71 8.1 5.7 2.8 13.5 4.5 12.3 7.2 9.8 -4.8 9.4 6.2 10.3 3.9 -4.7 7.1 6.3 10.2 -0.1 12.9 5.7 -6.5 -5.7 9.7 4.1 10.3 -6.3 5.5 0.7 -2.5 2.7 -4.2 9.0 1.5 11.3 -1.2 7.7 2.2 3.1 7.9 3.9 19.1 5.5 8.4 0.1 10.5 9.1 0.2 -16.6 11.8 13.1 0.5 0.7 11.7 6.2 7.2 2.3 4.3 10.1 6.5 -5.6 82.3 103.4 83.0 63.0 98.7 58.5 85.9 45.3 103.5 93.9 65.9 68.2 87.3 64.9 88.0 61.9 75.4 78.8 83.6 57.7 183 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX F INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pi FEMALE RATS DURING GESTATION 184 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pi FEMALE RATS DURING GESTATION EXPLANATORY NOTES Abbreviations NP = No litter delivered; data excluded from statistical analysis. = No Data 185 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Px FEMALE RATS DURING GESTATION GROUP: II-0 DOSE: 0 MG/KG/DAY GESTATION DAYS: ANIMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 (NP) (NP) GESTATION DAYS: A N I M A L NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 (NP) (NP) 0 7 14 21 M E A N BODY WEIGHT (grams) 223.1 303.1 268.3 264.8 260.1 254.7 278.6 269.0 288.7 297.8 258.2 245.0 303.4 312.3 248.4 291.1 294.1 297.2 267.6 236.7 259.6 351.1 301.5 300.1 282.3 273.7 314.7 302.4 316.2 339.0 293.0 284.4 334.5 345.7 290.6 331.0 330.3 328.3 271.8 260.1 288.2 395.8 338.1 336.3 315.8 277.3 346.8 331.4 336.0 367.2 323.4 318.0 359.7 380.7 319.5 347.6 355.0 368.5 274.0 289.2 316.8 490.4 406.7 426.5 382.2 270.3 436.2 408.5 413.2 446.2 405.2 405.3 401.8 458.2 398.6 416.3 438.6 456.7 257.9 358.4 0-7 7-14 14-21 0-21 MEAN BODY WEIGHT GAINS (grams) 36.5 48.0 33 .2 35.3 22.2 19.0 36.1 33.4 27.5 41.2 34.8 39.4 31.1 33.4 42.2 39.9 36.2 31.1 4.2 23.4 28.6 44.7 36.6 36.2 33.5 3.6 32.1 29.0 19.8 28.2 30.4 33.6 25.2 35.0 28.9 16.6 24.7 40.2 2.2 29.1 28.6 94.6 68.6 90.2 66.4 -7.0 89.4 77.1 77.2 79.0 81.8 87.3 42.1 77.5 79.1 68.7 83.6 88.2 -16.1 69.2 93.7 187.3 138.4 161.7 122.1 15.6 157.6 139.5 124.5 148.4 147.0 160(3 98.4 145.9 150.2 125.2 144.5 159.5 -9.7 121.7 186 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pj. FEMALE RATS DURING GESTATION GROUP: IV-0 DOSE: 75 MG/KG/DAY GESTATION DAYS: ANIMAL NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 (NP) 657529s 657530s 657531 657532 657533 657534 657535 0 7 14 21 M E A N BODY W E I G H T (grams) 266.9 250.3 287.7 267.2 289.5 282.0 277.1 319.4 268.0 271.1 270.4 316.8 - - 295.1 293.0 269.5 301.5 287.1 309.8 283.3 309.9 294.8 310.5 313.3 298.9 352.6 297.1 300.5 303.7 345.5 - 328.6 327.1 297.1 334.0 319.5 345.0 312.2 337.2 329.1 337.5 340.2 311.3 391.5 333.3 323.6 339.8 363.5 - 354.8 346.3 322.5 356.6 346.3 427.7 409.0 403.8 " 399.0 415.0 403.3 336.7 489.1 399.3 353.3 449.3 451.3 - 413.2 389.1 398.1 393.1 431.7 GESTATION DAYS: A N I M A L NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 (NP) 657529s 657530s 657531 657532 657533 657534 657535 0-7 7-14 14-21 0-21 M E A N B O D Y W E I G H T G A I N S (g r a m s ) 42.9 33.0 22.2 27.6 21.0 31.3 21.8 33.2 29.1 29.4 33.3 28.7 - 33.5 34.1 27.6 32.5 32.4 35.2 28.9 27.3 34.3 27.0 26.9 12.4 38.9 36.2 23.1 3 6-. 1 18.0 - 26.2 19.2 25.4 22.6 26.8 82.7 96.8 66.6 69.9 77.5 63.1 25.4 97.6 66.0 29.7 109.5 87.8 - 58.4 42.8 75.6 36.5 85.4 160.8 158.7 116.1 131.8 125.5 121.3 59.6 169.7 131.3 82.2 178.9 134.5 - 118.1 96.1 128.6 91.6 144.6 a Evidence of copulation was not observed; therefore, no gestation data were collected. 187 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L B O D Y W E I G H T S A N D B O D Y W E I G H T G A I N S O F P x :F E M A L E R A T S DURING GESTATION GROUP: V I -0 DOSE: 500 MG/KG/DAY GESTATION DAYS: ANIMAL NO . 0 7 14 21 M E A N BODY W EIGHT (grams) 6575413 657542 657543 657544 657545 657546 657547 657548 657549 657550* 657551* 657552 657553 657554 657555 657556 6 5 7 5 5 7 (NP) 657558 657559 657560 GESTATION DAYS: ANIMAL NO . 6575413 657542 657543 657544 657545 657546 657547 657548 657549 657550* 657551* . 657552 657553 657554 657555 657556 6 5 7 5 5 7 (NP) 657558 657559 657560 270.6 295.1 270.0 309.4 265.9 268.9 237.2 346.0 229.1 - - 293.4 255.1 251.8 272.9 312.4 - 266.1 336.5 276.5 0-7 294.7 317.8 302.0 343.4 303.2 291.1 275.5 363.5 265.9 - - 320.1 289.7 282.7 310.3 343.8 282.8 376.8 311.0 7-14 321.8 345.2 321.1 374.9 333.6 328.4 297.1 385.7 293.5 - 339.9 322.6 310.0 340.3 374.0 " 305.3 401.8 342.4 14-21 - 422.2 407.9 444.9 418.6 413.9 362.3 447.8 368.3 - 432.4 403.4 365.7 412.9 473.7 376.8 460.6 434.1 0-21 MEAN BODY WEIGHT GAINS (grams) 24.1 22.7 32.0 34.0 37.3 22.2 38.3 17.5 36.8 - - 26.7 34.6 30.9 37.4 31.4 - 16.7 40.3 34.5 27.1 27.4 19.1 31.5 30.4 37.3 21.6 22.2 27.6 - - 19.8 32.9 27.3 30.0 30.2 - 22.5 25.0 31.4 - 77.0 86.8 70.0 85.0 85.5 65.2 62.1 74.8 - - 92.5 80.8 55.7 72.6 99.7 71.5 58.8 91.7 _ 127.1 137.9 135.5 152.7 145.0 125.1 101.8 139.2 - 139.0 148.3 113.9 140.0 161.3 110.7 124.1 157.6 , a Animal delivered prior to collection of Gestation Day 21 data. jb Evidence of copulation was not observed; therefore, no gestation data were collected. 188 Company Sanitized. Does not contain SCA CBt H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pi FEMALE RATS DURING GESTATION GROUP: V I I I -0 DOSE: 3500 MG/KG/DAY GESTATION DAYS: ANIMAL NO. 657566a 6 5 7 5 6 7 (NP) 657568 6 5 7 5 6 9 (NP) 657570 6575713 657572 657573 657574 6 5 7 5 7 5 (NP) 657576 657577 6 5 7 5 7 8 (NP) 657579 657580 657581 6 5 7 5 8 2 (NP) 657583 657584 657585 0 7 14 21 MEAN BODY WEIGHT (grams) _ 327.6 275.8 250.0 281.7 289.3 252.2 293.9 301.3 281.9 252.8 271.6 257.6 298.2 247.7 268.8 283.5 285.5 236.5 _ 338.9 308.8 280.0 298.4 315.7 285.2 328.3 316.7 316.9 276.5 274.7 288.6 320.5 272.4 294.4 311.3 310.5 267.8 340.6 331.5 279.9 323.3 337.7 312.3 356.4 314.9 356.8 303.8 279.6 315.6 341.9 304.0 270.1 338.7 334.3 292.4 325.9 416.5 259.6 422.6 420.7 364.6 434.5 325.5 450.9 376.7 279.5 359.6 434.5 386.6 280.8 409.7 419.2 382.1 GESTATION DAYS: ANIMAL NO. 0-7 7-14 14-21 *' MEAN BODY WEIGHT GAINS 0-21 (g r a m s ) 657566a 657567 657568 657569 657570 (NP) (NP) 6575713 657572 657573 657574 657575 657576 657577 657578 (NP) (NP) 657579 657580 657581 657582 (NP) 657583 657584 657585 _ 11.3 33.0 30.0 16.7 - 26.4 33.0 34.4 15.4 35.0 23.7 3.1 31.0 22.3 24.7 25.6 27.8 25.0 31.3 - 1.7 22.7 - 0.1 24.9 22.0 27.1 28.1 -1.8 39.9 27.3 4.9 27.0 21.4 31.6 -24.3 27.4 23.8 24.6 - -14.7 85.0 -20.3 99.3 83.0 52.3 78.1 10.6 94.1 72.9 - 0.1 44.0 92.6 82.6 10.7 71.0 84.9 89.7 -1.7 140.7 9.6 140.9 131.4 112.4 140.6 24.2 169.0 123.9 7.9 102.0 136.3 138.9 12.0 126.2 133.7 145.6 a Evidence of copulation was not observed; therefore, no gestation data were collected. 189 Company Sanitized. Does not contain TSCA CBS H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX G INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pi FEMALE RATS DURING LACTATION 190 C o m p a n y Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF P, FEMALE RATS DURING LACTATION EXPLANATORY NOTES Note Test days for animal fates are determined from the initiation of test substance administration. Abbreviations No Data Not pregnant Sacrificed by design 191 Company Sanitized. Does not contain TSCA C B I H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Px FEMALE RATS \ DURING LACTATION GROUP: II-0 DOSE: 0 MG/KG/DAY LACTATION DAYS: A N I M A L NO. 0 7 14 21 M EAN BODY WEIGHT (grams) 657491s 657492 657493s 657494 657495 6 5 7 4 9 6 (NP) 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 6 5 7 5 0 9 (NP) 657510 LACTATION DAYS: IMAL NO. 278.7 362.1 333.6 304.9 298.8 - 309.3 300.3 311.1 351.9 300.1 300.3 328.6 359.4 318.8 346.3 323.9 343.9 262.7 286.6 373.7 321.3 333.1 320.7 - 335.2 301.6 336.7 364.6 300.8 287.7 341.7 385.1 316.8 351.6 341.6 332.6 - 294.7 301.4 394.5 344.9 348.0 330.6 - 348.0 322.4 340.2 364.0 318.9 312.1 358.0 376.1 339.3 367.6 353.8 372.7 - 317.3 - S D (DAY 121) 381.6 S D (DAY 121) - S D (DAY 121) 317.1 S D (DAY 123) 315.6 SD (DAY 123) - SD (DAY 124) 326.1 S D (DAY 124) 301.6 S D (DAY 123) 332.5 S D (DAY 122) 356.0 S D (DAY 122) 336.7 S D (DAY 123) 310.1 S D (DAY 120) 330.6 S D (DAY 122) 352.6 SD (DAY 122) 324.0 SD (DAY 123) 357.9 SD (DAY 123) 334.6 SD (DAY 122) 354.0 SD (DAY 121) - SD (DAY 124) 286.7 SD (DAY 126) 0-7 7-14 14-21 0-21 M E A N B O D Y W E I G H T G A I N S (g r a m s ) 657491s 657492 657493s 657494 657495 6 5 7 4 9 6 (NP) 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 6 5 7 5 0 9 (NP) 7.9 11.6 -12.3 28.2 21.9 - 25.9 1.3 25.6 12.7 0.7 -12.6 13.1 25.7 -2.0 5.3 17.7 -11.3 - 14.8 20.8 23.6 14.9 9.9 - 12.8 20.8 3.5 -0.6 18.1 24.4 16.3 -9.0 22.5 16.0 12.2 40.1 - -12.9 - -30.9 -15.0 - -21.9 -20.8 -7.7 -8.0 17.8 -2.0 -27.4 -23.5 -15.3 -9.7 -19.2 -18.7 - SD (DAY 121) 19.5 SD (DAY 121) - SD 12.2 SD 16.8 SD - SD 16.8 SD 1.3 SD 21.4- SD 4.1 SD 36.6 SD 9.8 SD 2.0 SD -6.8 SD 5.2 SD 11.6 SD 10.7 SD 10.1 SD - SD (DAY 121) (DAY 123) (DAY 123) (DAY 124) (DAY 124) (DAY 123) (DAY 122) (DAY 122) (DAY 123) (DAY 120) (DAY 122) (DAY 122) (DAY 123) (DAY 123) (DAY 122) (DAY 121) (DAY 124) a Lactation day 21 body weight inadvertently not recorded. 192 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats 657510 32.0 22.6 -30.6 DuPont-9763 24.0 SD (DAY 126) 193 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Px FEMALE RATS DURING LACTATION GROUP: IV-0 DOSE: 75 M G / K G / D A Y __________________ LACTATION DAYS: 0 7 14 21 A N I M A L NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 (NP) LACTATION DAYS: A N I M A L NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 (NP) MEAN BODY WEIGHT (grams) 318.3 290.6 310.4 288.4 333.5 331.8 290.9 290.4 293.6 304.3 322.7 345.8 280.0 309.7 329.6 321.8 289.2 340.9 325.4 315.2 298.2 326.7 _ 325.2 331.8 344.3 312.6 379.6 330.7 330.9 339.9 348.3 305.0 327.3 358.3 343.1 303.5 343.3 332.8 338.2 321.4 340.1 - 330.0 336.8 312.4 316.9 389.2 353.0 341.4 351.5 336.1 317.7 347.3 368.6 354.6 328.6 355.1 356.8 328.7 SD (DAY 120) 300.0 SD (DAY 123) 322.6 SD (DAY 122) - SD (DAY 124) 323.4 SD (DAY 121) 330.5 SD (DAY 123) 348.4 SD (DAY 123) 323.4 SD (DAY 123) 368.9 SD (DAY 125) 321.8 SD (DAY 121) 341.1 SD (DAY 122) 333.0 SD (DAY 120) 351.6 SD (DAY 121) 302.7 SD (DAY 122) 355.3 SD (DAY 123) 341.4 SD (DAY 127) 343.3 SD (DAY 123) 296.1 SD (DAY 121) 343.4 SD (DAY 125) 342.3 SD (DAY 123) 0-7 7-14 '14-21 0-21 M E A N B O D Y W E I G H T G A I N S (g r a m s ) -3.1 7.6 16.3 _ 36.8 -1.7 12.5 21.7 89.2 37.1 26.6 17.2 2.5 25.0 17.6 28.7 21.3 14.3 2.4 7.4 23.0 23.2 13.4 _ 4.8 5.0 -31.9 4.3 9.6 22.3 10.5 11.6 -12.2 12.7 20.0 10.3 11.5 25.1 11.8 24.0 -9.5 -21.4 -17.5 - -6.6 -6.3 36.0 6.5 -20.3 -31.2 -0.3 -18.5 15.5 -15.0 8.0 -27.2 -11.3 -32.5 -11.7 -14.5 10.4 SD (DAY 120) 9.4 SD (DAY 123) 12.2 SD (DAY 122) - SD (DAY 124) 35.0 SD (DAY 121) -3.0 SD (DAY 123) 16.6 SD (DAY 123) 32.5 SD (DAY 123) 78.5 SD (DAY 125) 28.2 SD (DAY 121) 36.8 SD (DAY 122) 10.3 SD (DAY 120) 5.8 SD (DAY 121) 22.7 SD (DAY 122) 45.6 SD (DAY 123) 11.8 SD (DAY 127) 21.5 SD (DAY 123) 6.9 SD (DAY 121) 2.5 SD (DAY 125) 16.9 SD (DAY 123) 194 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pi FEMALE RATS DURING LACTATION GROUP: VI-0 DOSE: 500 MG/KG/DAY_______________ LACTATION DAYS: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 (NP) LACTATION DAYS: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 (NP) 0 7 14 21 MEAN BODY WEIGHT (grams) 305.4 322.8 298.6 349.2 301.5 306.6 282.2 380.7 274.1 307.2 284.8 309.7 314.8 274.8 306.1 355.8 -- 304.9 376.9 319.9 304.0 316.7 319.5 370.8 322.6 304.7 283.6 378.9 288.8 341.1 314.0 331.3 322.6 304.7 326.0 369.5 _ 302.8 384.3 326.5 317.9 343.8 331.3 353.5 345.5 331.6 305.5 379.2 308.1 349.4 330.4 347.5 331.3 323.8 350.6 385.9 - 331.9 404.9 352.4 319.0 SD 327.2 SD 312.8 SD 308.0 SD 328.7 SD 326.1 SD 291.7 SD 359.1 SD 301.7 SD 310.9 SD 316.1 SD 351.6 SD 317.4 SD 306.6 SD 329.1 SD 378.6 SD - SD 314.4 SD 374.3 SD 343.6 SD (DAY 122) (DAY 122) (DAY 121) (DAY 123) (DAY 120) (DAY 122) (DAY 123) (DAY 128) (DAY 121) (DAY 125) (DAY 122) (DAY 124) (DAY 123) (DAY 121) (DAY 123) (DAY 121) (DAY 124) (DAY 121) (DAY 130) (DAY 122) 0-7 7-14 14-21 0-21 MEAN BODY WEIGHT GAINS (grams ) -1.4 -6.1 20.9 21.6 21.1 -1.9 1.4 -1.8 14.7 33.9 29.2 21.6 7.8 29.9 19.9 13.7 _ -2.1 7.4 6.6 13.9 27.1 11.8 -17.3 22.9 26.9 21.9 0.3 19.3 8.3 16.4 16.2 8.7 19.1 24.6 16.4 - 29.1 20.6 25.9 1.1 -16.6 -18.5 -45.5 -16.8 -5.5 -13.8 -20.1 -6.4 -38'. 5 -14.3 4.1 -13.9 -17.2 -21.5 -7.3 - -17.5 -30.6 -8.8 13.6 SD (DAY 122) 4.4 SD (DAY 122) 14.2 SD (DAY 121) -41.2 SD (DAY 123) 27.2 SD (DAY 120) 19.5 SD (DAY 122) 9.5 SD (DAY 123) -21.6 SD (DAY 128) 27.6 SD (DAY 121) 3.7 SD (DAY 125) 31.3 SD (DAY 122) 41.9 SD (DAY 124) 2.6 SD (DAY 123) 31.8 SD (DAY 121) 23.0 SD (DAY 123) 22.8 SD (DAY 121) - SD (DAY 124) 9.5 SD (DAY 121) -2.6 SD (DAY 130) 23.7 SD (DAY 122) 195 Company Sanitized. Does not contain TSCA CBf /***% . H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Px FEMALE: RATS DURING LACTATION GROUP : VIII-0 DOSE: 3500 MG/KG/DAY LACTATION DAYS 0 7 14 21 A N I M A L NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 (NP) (NP) (NP) (NP) (NP) M E A N BODY W E I G H T (grams) 287.6 - 319.2 - 302.9 266.5 318.0 296.0 335.3 - 341.8 283.8 - 268.7 326.2 285.7 316.0 313.9 262.6 306.8 - 341.4 - 325.7 298.8 348.5 309.7 341.0 - 370.3 318.6 - 309.5 322.0 309.6 336.4 333.8 297.3 314.8 - 366.6 - 338.8 315.5 343.1 307.8 328.8 357.4 333.8 - 336.5 333.7 312.4 336.1 344.6 306.8 321.6 S D (DAY 122) - S D (DAY 124) 337.6 SD (DAY 120) - SD (DAY 124) 325.7 SD (DAY 122) 290.0 SD (DAY 123) 343.4 SD (DAY 121) 313.9 SD (DAY 122) 340.3 SD (DAY 123) - SD (DAY 124) 360.9 SD (DAY 121) 333.4 SD (DAY 122) - SD (DAY 124) 326.1 SD (DAY 121) 340.3 SD (DAY 122) 301.9 SD (DAY 123) - SD (DAY 124) 347.7 SD (DAY 121) 349.0 SD (DAY 125) 306.8 SD (DAY 123) LACTATION DAYS: ANIM A L NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 (NP) (NP) (NP) (NP) (NP) 0-7 7-14 14-21 0-21 MEAN BODY W E I G H T GAINS (grams) 19.2 - 22.2 - 22.8 32.3 30.5 13.7 5.7 - 28.5 34.8 - 40.8 -4.2 23.9 - 20.4 19.9 34.7 8.0 25.2 13.1 16.7 -5.4 -1.9 -12.2 - -12.9 15.2 - 27.0 11.7 2.8 - -0.3 10.8 9.5 6.8 - -29.0 - -13.1 -25.5 0.3 6.1 11.5 - 3.5 -0.4 - -10.4 6.6 -10.5 - 11.6 4.4 0.0 34.0 SD (DAY 122) - SD (DAY 124) 18.4 SD (DAY 120) - SD (DAY 124) 22.8 SD (DAY 122) 23.5 SD (DAY 123) 25.4 SD (DAY 121) 17.9 SD (DAY 122) 5.0 SD (DAY 123) - SD (DAY 124) 19.1 SD (DAY 121) 49.6 SD (DAY 122) - SD (DAY 124) 57.4 SD (DAY 121) 14.1 SD (DAY 122) 16.2 SD (DAY 123) - SD (DAY 124) 31.7 SD (DAY 121) 35.1 SD (DAY 125) 44.2 SD (DAY 123) 196 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX H INDIVIDUAL FOOD CONSUMPTION OF Pi MALE RATS 197 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION OF Pi MALE RATS EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period Abbreviations AK = Accidentally Killed SE = Sacrificed in extremis; data excluded from group means. (Group 1-0, Animal No. 657409) - = No Data 198 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 /" N '`'"'N I N D I V I D U A L F O O D C O N S U M P T I O N ( g r ams/day) O F Pj. M A L E R A T S GROUP: 1-0 DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 1-8 8-15 15-22 22-29 29-36 36-43 43-50 27..0 26..0 28,.1 27..5 24..4 23..8 24..7 24..3 26..2 25..4 25..2 22,.4 23 .7 30..3 26..9 26..1 27..6 26..6 27 .6 24..1 26 .8 26 .8 28 .3 28 .0 23 .7 25 .1 23 .1 26 .2 25 .2 23 .4 23 .9 22 .7 24 .6 30 .1 29 .1 26 .0 26 .3 27 .8 27 .6 24 .7 28. 4 29. 2 28. 9 31. 1 26. 8 25. 8 24. 9 27. 4 26. 2 26. 0 25. 3 25. 6 26. 0 32. 7 29. 7 28. 7 28. 9 25. 7 30. 4 28. 8 28,.7 29 .2 27 .9 32 .2 26..8 24,.9 23,.5 28..0 27..3 26..1 26..0 25..4 27..7 33 .2 30..3 27..8 29..4 25..8 31..6 27..5 30 .8 28 .6 29 .0 33 .4 27 .4 26..2 24..6 28.,9 28..9 27 ,.6 27..3 25,.6 29..4 34..4 32..3 30..1 30..8 26..4 31..7 25..9 29,.3 27 .6 29 .4 31 .3 27,.3 26..5 36.,5 29.,0 27.,0 25..4 25..3 26,.5 21..3 32..9 29..4 30..7 28,.7 26..1 31.,6 25..9 27..7 28 .8 31,.2 32..0 27..2 26..3 23..6 29..4 27..4 24..1 26,.1 25..5 25..7 32..7 30..8 30..8 28..3 25..9 29..4 26..4 199 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Pi MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY DAYS ON TEST: AN I M A L NO. 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 657407 657408 657409 657410 50-57 57-64 64-71 1-71 28..5 29..4 31..1 31..9 27..0 25..5 24..4 30..9 28,.2 24..9 26..2 26..3 24..5 33..6 30,.8 31,.9 31,.4 25,.0 26,.4 27 ,.5 29.5 29.9 30.8 30.8 28.1 _a 24.0 29.6 29.0 26.4 26.6 26.3 25.2 34.3 30.7 31.4 30.7 25.1 SE (DAY 60) 28.0 27,.8 27,.3 29,.6 28,.1 27,.9 26,.1 22,.5 29,.2 27 ,.9 24,.1 25,.6 25..7 24..9 33..9 29..9 32..2 32..1 24..9 26,.5 28 .5 28 .3 29 .5 30 .6 26 .7 _<3. 25 .2 28 .3 27 .3 25 .4 25 .8 25 .2 25 .3 32 .8 30 .0 29 .6 29 .4 25 .9 26 .5 a No d a t a d ue to w e i g h i n g e r r o r on T est D a y 64. 200 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px MALE RATS GROUP: III-O DOSE: 75 MG/KG/DAY DAYS ON TEST: ANI M A L NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 1-8 8-15 15-22 22-29 29-:36 3 6 - 43 43- 50 27.9 28.6 24.5 24.2 26.5 29.5 24.1 26.6 28.1 31.0 24.6 25.9 26.5 29.9 28.7 26.7 30.9 27.3 23.1 27.1 25.2 25.5 25.4 27.0 28.7 25.5 29.6 30.8 33.5 25.1 26.8 27.0 30.5 28.1 29.1 32.7 30.8 22.0 27.7 26.1 26.4 26.5 27.3 29.4 26.5 31.1 31.2 35.4 26.8 28.3 27.5 32.5 29.3 27.9 33.1 31.1 24.1 27.3 28.1 26.6 27.5 27.3 28.7 27.6 30.5 30.2 35.4 27.2 28.8 30.7 33.2 31.9 32.2 34.3 31.8 22.7 28 .2 26 .1 22 .9 29 .9 29 .4 31 .5 29 .8 32 .6 32 .0 38 .1 32 .3 31 .9 30 .2 35 .8 33 .2 32 .6 35 .6 31 .0 25 .3 26 .8 28 .4 26 .8 29 .8 28 .4 30 .9 28 .1 31 .6 32 .8 39 .0 27 .5 29 .3 29 .8 32 .5 32 .0 33 .2 34 .5 32 .3 24 .7 27 .8 28 .0 25 .8 29 .5 26 .2 29 .4 26 .2 31 .0 32 .2 36 .3 27 .7 28 .6 29 .0 33 .0 28 .6 31 .3 35 .1 31 .8 26 .2 201 Company Sanitized. Does not contain TSCA CB! H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Pi MALE RATS GROUP: III-0 DOSE: 75 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 657429 657430 657431 657432 657433 657435 50-57 57-64 64-71 1-71 27. 0 28. 2 25.. 6 29. 1 26. 1 30. 2 27. 5 30. 6 30. 7 38. 1 27 .4 29. 5 30. 3 33 .1 30. 5 32 .4 35. 8 30. 4 24. 6 29,.0 30,.4 26,.1 30,.8 29,.0 31,.0 28,.4 32 ,.0 29,.8 37,.8 27,.4 29,.6 33..0 33 ,.3 30,.9 31,.4 37 ,.5 32,.5 24,.0 28 .4 30 .7 25 .6 29 .2 28 .1 30 .8 29 .0 31 .1 29 .4 36 .3 26 .6 29 .0 30 .5 32 .7 31 .3 31 .2 34 .8 30 .6 25 .0 27,.7 28 .0 25 .6 28,.2 27 .5 30,.0 27,.3 30,.7 30,.7 36,.1 27..3 28..8 29..5 32,.6 30,.5 30,.8 34,,4 31,,0 24..2 202 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Pi MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: A N I M A L NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 1-8 8-15 15-22 22-29 29-36 36-43 43-50 26.6 22.0 26.2 25.6 25.7 21.1 23.4 23.8 27.5 26.2 26.4 26.9 24.7 25.9 24.3 24.7 30.5 22.2 23.7 23.8 25,.5 20,.3 27,.2 27,.2 25,.5 21..6 23..1 22..8 27..7 26..6 26..0 28..4 23 .7 26..1 23 .6 26..1 32 .1 24..7 22 .8 26..4 27 .5 21 .4 26 .8 28 .9 26 .0 21 .7 23 .4 24 .6 28 .6 27 .4 28 .8 28 .8 24 .2 27 .8 23 .9 26 .9 32 .6 27 .5 23 .5 * 28 .1 27,.9 21..7 28,.5 29,.3 26,.5 21..5 25,.0 24,.9 30,.1 28,.1 29,.5 29,.4 24,.9 27,.5 25,.1 27..9 34,.3 28,.2 19,.4 27 ,.7 . 28,.7 21,.2 29..6 32,.1 27..8 24,.2 26,.7 26..7 29..8 28..0 32..4 28..7 26,.1 29..6 25..3 29..3 36..7 28..6 23 .9 28..4 28,.2 18,.5 30,.4 33,.0 28,.0 24,.2 26,.7 26,.4 27,.7 28,.1 31,.0 28,.7 26,.9 29,.4 24,.8 27,.3 35,.0 28,.3 24..2 28,.1 27.2 21.1 33.2 32.9 25.8 22.7 25.1 25.9 27.0 27.7 28.7 28.0 13.2 26.3 24.5 26.9 33.1 26.8 23.6 27.0 203 Company Sanitized. Does not contain TSCA C8I H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px MALE RATS GROUP : V-0 DOSE: 500 MG, DAYS ON TEST: ANIMAL NO. 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 657453 657454 657455 657456 657457 657458 657459 657460 50-57 57-64 64-71 1-71 27.0 20.0 27.2 35.3 26.3 22.7 25.7 26.5 26.1 26.5 31.1 26.7 23.4 27.2 24.3 26.5 32.6 26.7 21.9 27.9 27.1 22.0 27.6 32.5 27.0 22.6 25.8 27.0 27.1 28.5 31.5 28.2 26.7 29.7 23.0 28.4 35.6 27.7 25.3 26.9 26.9 20.5 28.7 30.6 25.3 21.6 24.2 26.0 28.3 27.8 31.5 27.3 26.3 28.2 24.2 29.0 34.0 28.0 23.9 28.6 27.3 20.9 28.5 30.8 26.4 22.4 24.9 25.4 28.0 27.5 29.7 28.1 24.0 27.8 24.3 27.3 33.7 26.9 23.2 27.3 204 _ _ _ Mu H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L F O O D C O N S U M P T I O N { g r a m s / d a y ) O F Pj. M A L E R A T S GROUP : VII-0 DOSE:: 3500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 1-8 8-15 15-22 22-29 29-36 36-43 43-50 20.5 20.6 22.0 24.2 23.6 21.8 25.3 27.2 28.0 21.2 26.4 27.6 27.8 20.9 22.8 29.4 25.9 32.5 27.0 28.8 22.0 19.1 20.7 23.4 25.8 17.7 27.2 22.8 21.6 18.5 20.9 28.4 27.7 24.2 25.4 30.6 24.7 31.2 22.3 27.4 24.8 21.1 20.1 24.3 25.7 19.9 27.3 29.6 25.0 18.8 21.4 32.3 28.7 23.4 24.4 32.6 24.7 29.1 31.3 29.2 21.7 24.7 23.8 25.5 21.5 21.2 27.8 22.4 25.3 19.3 24.1 34.2 29.5 25.0 24.4 33.0 24.6 29.7 31.8 29.2 27.5 24.1 27.6 27.6 25.7 23.2 27.8 26.2 25.7 20.8 23.9 32.5 29.9 20.9 22.8 33.2 22.9 27.2 34.1 27.9 26.8 23.7 28.4 26.6 24.5 22.2 29.4 28.0 26.1 20.0 24.0 A K (DAY 42) 27.0 25.2 24.2 33.4 24.6 30.9 30.9 28.8 26.6 21.9 23.1 27.9 21.5 19.6 27.0 29.9 23.1 20.7 26.4 32.2 20.8 21.7 26.2 23.8 26.9 25.3 28.5 205 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 657480 657481 657482 657483 657484 657485 50-57 57-64 64-71 1-71 29.0 24.2 28.0 30.4 23.9 23.5 27.3 29.2 20.4 21.9 26.0 32.6 23.4 25.1 25.0 25.0 26.5 33.6 28.3 26.7 21.5 29.3 29.9 18.4 22.8 27.3 32.3 27.5 23.1 29.6 29.2 23.8 27.1 38.3 27.1 30.8 38.6 26.7 26.7 22.0 28.8 29.6 25.0 22.6 26.4 31.1 25.1 23.1 26.6 32.3 21.1 25.5 35.0 F D (DAY 66) 17.2 29.9 31.2 25.2 22.3 25.2 26.9 23.6 21.4 27.3 27.9 24.8 20.7 24.9 29.7 22.9 24.3 31.7 28.2 30.5 28.6 206 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX I INDIVIDUAL FOOD CONSUMPTION OF Pi FEMALE RATS DURING PREMATING 207 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION OF P! FEMALE RATS DURING PREMATING EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period Abbreviation - = No Data 208 Company Sanitized. Does not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Pi FEMALE RATS DURING PREMATING GROUP: II-0 DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 1-8 8-15 15-22 22-29 29-36 36-43 43-50 16..0 19..1 16..0 16..6 16..4 17..8 17..8 16..4 19..0 17..3 15..5 14..7 19..4 15..6 14..7 20..8 17..9 17..9 15..7 14..3 16..2 22,.4 17..5 17 ,.4 17..0 16..0 16,.1 15..7 19..3 17,.8 15..3 14..0 18..1 17 .8 15..9 18..7 19..9 17..3 17,.3 15..2 17..0 18,.2 18..4 18..7 17 .6 16,.8 19..0 19..0 19,.2 20..1 16..2 15..4 18..5 17 .9 16,.6 20..2 21,.0 19,.2 18,.4 15..4 18 .6 18 .7 18 .2 19 .1 17 .9 17 .0 20 .3 18 .3 18 .9 18 .6 16 .0 15 .6 18 .9 18 .0 15 .5 22 .0 20 .7 21 .3 18 .7 16 .5 16 .8 25..2 18,.7 19..1 17..6 18..9 20,.3 18..4 22 ,.1 21..7 17,.1 16..0 21,.6 20..2 17..9 21..8 20..6 21..7 19..9 15..9 16. 8 22. 8 18. 4 19. 2 19. 1 19. 1 18. 5 17. 6 20. 4 19. 6 15. 7 15. 8 21. 1 18. 9 15. 6 19. 5 18. 8 18. 9 17. 8 15. 5 17.1 15.8 17.6 17.9 17.3 17.2 17.1 18.7 18.1 19.2 15.5 15.3 21.4 16.6 15.6 17.8 19.5 18.0 16.8 13.3 209 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px FEMALE RATS DURING PREMATING GROUP: II-O DOSE: 0 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 50-57 57-64 64-71 1-71 16.8 17.9 18.6 17.4 16.1 17.7 18.4 17.4 18.9 17.9 15.6 17.1 17.5 19.3 16.1 18.9 19.5 21.5 17.3 14.5 16.2 19.9 18.2 17.4 19.5 17.9 18.8 17.9 17.5 18.6 15.3 16.6 18.7 18.5 15.3 19.0 18.3 19.7 16.4 14.6 16.8 17.9 18.3 17.8 17.5 18.0 19.1 19.0 18.4 19.2 15.9 15.4 19.7 18.8 15.2 17.8 18.7 17.8 18.0 13.9 16.8 19.8 18.0 18.1 17.6 17.6 18.5 17.8 19.2 19.0 15.8 15.6 19.5 18.2 15.8 19.7 19.5 19.3 17.6 14.9 210 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 I N D I V I D U A L F O O D C O N S U M P T I O N (grams/day) O F Pj. F E M A L E R A T S D U R I N G P R E M A T I N G GROUP : IV-0 DOSE: 75 MG/KG/DAY DAYS ON TEST: a n i m a l NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 1-8 8-15 15-22 22-29 29-36 36-43 43-50 19.0 15.4 17.5 17.4 18.9 15.7 17.6 17.2 20.8 16.3 16.6 16.9 18.4 16.4 18.4 18.4 19.6 16.2 17.9 19.5 17.8 17.2 17.4 18.5 17.9 20.6 25.0 17.5 17.1 16.8 18.0 15.8 20.0 16.5 18.0 18.7 20.4 16.9 18.4 20.9 16.9 17.7 18.1 20.3 18.5 17.1 17.7 17.3 18.6 17.8 18.9 18.3 21.3 17.1 18.6 18.2 21.5 18.9 21.7 21.6 19.8 16.4 19.7 21.4 20.2 18.3 16.5 18.0 23.1 19.0 18.2 18.3 21.8 16.7 18.0 18.9 19.4 18.3 20.6 19.6 19.7 21.2 19.1 20.5 18.4 18.2 19.3 15.9 21.7 18.4 18.9 19.0 21.8 18.0 17.5 19.9 20.4 23.5 23.2 21.2 17.2 20.3 18.4 19.9 19.7 17.9 20.0 15.7 19.8 17.6 18.1 17.6 21.4 17.2 17.8 18.2 19.7 17.9 19.7 19.1 17.3 16.4 17.9 20.0 17.3 15.7 18.1 15.7 18.6 17.5 15.9 18.8 19.5 16.4 18.2 18.4 19.7 18.7 20.0 18.5 2 1 1 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px FEMALE RATS DURING PREMATING GROUP: IV-0 DOSE: 75 M G / K G / D A Y DAYS ON TEST: ANIMAL NO. 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 50- 57 57- 64 64-'71 1-71 18 .0 17 .0 18 .7 20 .7 18 .6 17 .8 18 .4 16 .3 20 .2 17 .7 17 .4 17 .5 19 .9 16 .8 18 .6 18 .0 18 .9 19 .4 20 .3 18 .8 19 .9 17 .1 17 .5 23 .5 19 .4 16 .6 18 .3 15 .4 22 .6 18 .2 17 .4 19 .1 20 .6 17 .7 19 .0 20 .4 18 .6 17 .5 20 .9 19 .0 18 .0 16 .6 18 .4 17 .1 18 .7 17 .1 17 .6 15 .1 18 .8 17 .2 17 .3 18 .4 19 .9 16 .2 18 .8 18 .7 18 .5 16 .5 19 .9 18 .0 18.3 17.5 18.3 19.9 18.8 17.5 18.8 16.4 20.1 17.6 17.7 18.0 20.5 16.9 18.3 18.8 19.7 18.4 20.3 19.6 212 Company Sanitized. Does not contain TSCA CBf H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px FEMALE RATS DURING PREMATING GROUP: VI-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 1-8 8-15 15-22 22-29 29-36 36-43 43-50 15.9 17.1 16.0 16.1 15.0 15.8 15.6 17.6 15.6 16.5 16.9 16.0 18.3 18.9 16.0 21.1 17.4 16.8 24.4 17.6 16.8 16.3 16.1 17.2 15.4 16.0 14.3 19.9 13.7 18.1 16.3 15.4 15.4 16.5 15.8 20.5 19.6 18.4 21.9 17.8 19.3 17.3 18.1 20.6 17.0 17.3 16.6 21.1 16.1 18.6 17.7 18.3 16.4 16.3 19.0 21.0 18.4 16.9 22.7 20.1 17.8 18.3 19.4 20.5 17.1 16.8 16.3 19.0 18.5 19.3 19.1 17.3 18.0 21.6 17.3 23.0 20.8 18.2 23.4 18.1 20.4 20.1 20.6 20.2 17.8 18.1 17.0 20.8 18.4 18.7 18.4 16.8 22.3 21.2 19.5 22.5 23.3 18.9 22.8 20.8 18.4 17.4 18.3 18.6 17.0 16.3 15.0 21.1 15.2 15.5 18.0 17.3 18.0 18.6 17.2 20.3 20.2 16.5 21.8 18.6 17.8 17.2 19.2 20.6 16.6 16.8 15.8 20.3 14.7 16.1 18.4 18.1 18.3 16.7 17.2 20.1 18.5 16.3 22.0 20.0 213 Company Samtized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px FEMALE RATS DURING PREMATING GROUP: VI-0 DOSE: 500 MG/KG/DAY DAYS ON TEST: AN I M A L NO. 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 50-57 57-64 64-71 1-71 18.3 17.2 18.7 18.6 15.7 16.6 16.2 21.9 16.3 17.0 17.1 17.4 18.5 16.3 15.3 20.7 17.9 16.5 23.6 8.4 18.3 17.6 19.1 19.0 16.3 16.6 16.3 21.4 16.3 16.9 18.2 17.7 19.2 15.2 16.9 20.0 18.8 16.3 20.1 18.0 18.7 17.1 18.4 20.1 15.7 15.7 15.9 24.0 14.7 16.2 16.4 17.0 15.9 16.6 16.6 19.6 19.0 16.6 19.1 18.0 18.2 17.6 18.4 19.1 16.4 16.6 15.9 20.7 15.9 17.3 17.6 17.1 18.0 17.8 17.1 20.9 19.4 17.1 22.2 17.8 214 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 /*****., I N D I V I D U A L F O O D C O N S U M P T I O N (grams/day) O F Pi F E M A L E R A T S D U R I N G P R E M A T I N G GROUP : VIII-0 DOSE : 3500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 1-8 8-15 15-22 22-29 29-36 36-43 43-50 13.0 18.9 14.0 15.5 16.8 13.3 15.4 16.7 20.0 14.0 19.3 14.5 15.1 14.7 16.1 15.5 15.4 18.0 16.1 13.8 14.7 17.9 16.8 18.2 16.5 12.9 17.0 15.7 18.6 16.6 18.4 14.2 16.2 15.7 17.8 15.7 8.4 18.5 19.5 18.0 16.6 16.5 16.4 17.5 19.2 15.6 17.8 17.7 18.1 17.2 18.1 17.2 17.7 16.8 3.0 17.9 18.3 19.3 19.1 15.8 17.8 20.8 19.7 21.3 16.2 15.8 21.0 15.4 16.4 18.8 17.6 21.2 18.9 17.0 21.8 15.2 20.2 19.2 18.5 18.4 17.0 17.8 19.0 17.9 18.8 13.6 18.9 16.7 18.2 20.3 19.4 21.7 20.2 18.7 18.8 17.4 18.7 21.4 22.5 17.5 15.9 18.5 19.5 17.3 17.4 15.3 17.7 17.3 17.2 16.9 19.1 17.9 22.5 17.1 19.8 28.0 19.2 18.8 17.7 17.1 16.2 17.0 16.3 18.0 16.9 15.3 17.3 16.8 22.7 18.6 17.6 14.9 17.5 17.5 17.4 17.8 16.9 18.7 17.3 15.8 215 Company Sanitized. Does not contain TSCA. CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Px FEMALE RATS DURING PREMATING GROUP: VIII-0 DOSE: 3500 MG/KG/DAY DAYS ON TEST: ANIMAL NO. 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 50-57 57-64 64-71 1-71 15.8 20.0 17.7 19.7 18.9 16.9 17.4 16.4 19.8 18.7 17.8 16.8 18.3 16.2 18.8 17.7 18.0 19.3 18.2 17.1 11..6 15..4 19,.5 17 .4 19 .1 12,.8 16,.4 16..8 17..1 16..9 18..2 17..6 18..3 18 .4 17..0 18..4 17 ,.6 16,.7 . 18..8 16..3 17..6 16..9 18..8 19 .6 18..8 15,.9 16..2 11..9 19..5 19..0 17..2 17..2 18..4 17..8 20..4 18..5 17 ,.3 20..0 18..2 13..9 15..6 18 .0 17 .8 18 .3 17 .9 14..8 17..5 16..1 18..8 17..7 18,.3 17 .3 18..3 17 ,.0 17..1 18..2 17..0 19..0 18..6 16..4 216 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX J INDIVIDUAL FOOD CONSUMPTION OF PxFEMALE RATS DURING GESTATION 217 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION OF P, FEMALE RATS DURING GESTATION EXPLANATORY NOTES Abbreviations NP = No litter delivered; data excluded from statistical analysis. = No Data 218 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) BY Px FEMALE RATS DURING GESTATION GROUP: II-O DOSE: 0 MG/KG/DAY GESTATION DAYS: A N IMAL NO. 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 (NP) (NP) 0-7 7-14 14-21 0-21 21.7 26.9 23.0 25.1 20.7 20.7 26.3 23.9 21.7 26.5 22.8 22.2 24.5 22.8 21.4 22.7 24.5 24.6 17.0 19.7 23.1 30.5 25.7 25.7 24.8 20.2 26.0 25.6 22.3 25.7 24.1 23.0 24.7 26.2 22.8 25.8 25.4 26.4 17.4 19.9 22.0 28.2 24.8 26.5 22.6 15.9 27.9 25.6 23.2 26.2 24.6 25.2 25.5 24.9 26.4 27.3 25.4 26.0 16.8 23.1 22.2 28.5 24.5 25.8 22.7 18.9 26.7 25.0 22.4 26.1 23.8 23.5 24.9 24.6 23.5 25.3 25.1 25.7 17.1 20.9 219 Company Sanitized, Does not contain TSC CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) BY Pi FEMALE RATS DURING GESTATION GROUP: IV-0 DOSE: 75 MG/KG/DAY GESTATION DAYS: A N I M A L NO. 657516 657517 657518 657519 657520 (NP) 657521a 657522 657523 657524 657525 657526 657527 657528 657529* 657530* 657531 657532 657533 657534 657535 0-7 7-14 14-21 0-21 25.6 21.7 21.8 - 23.3 96.9 23.6 20.1 27.6 20.6 21.9 21.9 23.5 - - 29.0 25.9 19.7 25.7 21.2 25.7 21.9 22.8 - 23.7 - 24.5 19.3 29.7 23.3 21.9 24.8 22.8 - - 21.6 25.4 18.7 26.4 24.3 24.9 24.1 22.7 24.8 22.9 26.2 20.8 30.7 23.2 15.1 27.3 24.5 - - 25.6 25.2 23.3 30.9 26.3 25.4 22.6 22.4 23.9 - 24.7 20.1 29.3 22.4 19.6 24.7 23.6 - - 25.4 25.5 20.6 27.7 23.9 a Due to error, food data were not recorded on 7G. Data for 0-7G excluded from the calculations. p Evidence of copulation was not observed; therefore, no gestation data were collected. 220 Sanitized. Does not contain t s c a c b i Company H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) BY Pi FEMALE RATS DURING GESTATION GROUP: V I -0 DOSE: 500 MG/KG/DAY GESTATION DAYS: A N I M A L NO. 657541a 657542 657543 657544 657545 657546 657547 657548 657549 657550* 657551* 657552 657553 657554 657555 657556 6 5 7 5 5 7 (NP) 657558 657559 657560 1 o 7-14 14-21 0-21 22.9 20.8 23.1 24.2 21.5 19.9 23.0 23.5 23.8 - - 21.5 23.4 21.3 22.9 25.3 - 17.4 28.8 24.5 23.9 20.7 23.1 26.1 22.4 24.0 20.8 25.2 22.2 - - 21.1 27.2 22.6 24.3 27.2 19.7 28.9 26.8 - 23.2 27.5 24.3 24.3 24.6 22.3 29.0 23.7 - - 22.5 27.7 21.4 23.9 29.4 22.8 25.5 29.7 - 21.6 24.5 24.9 22.8 22.8 22.0 25.9 23.2 - 21.7 26.1 21.8 23.7 27.3 20.0 27.7 27.0 a Animal delivered prior to collection of Gestation Day 21 data. b Evidence of copulation was not observed; therefore, no gestation data were collected. 221 Company Sanitized. Does not contain TSG CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL FOOD CONSUMPTION (grams/day) BY Pj. FEMALE RATS DURING GESTATION GROUP: VIII-0 DOSE: 3500 MG/KG/DAY GESTATION DAYS : AN I M A L NO. 657566s 6 5 7 5 6 7 (NP) 657568 6 5 7 5 6 9 (NP) 657570 657571s 657572 657573 657574 6 5 7 5 7 5 (NP) 657576 657577 6 5 7 5 7 8 (NP) 657579 657580 657581 6 5 7 5 8 2 (NP) 657583 657584 657585 0-7 7-14 14-21 0-21 _ 20.8 21.3 29.1 19.4 - 20.2 21.3 24.0 19.7 23.7 18.5 17.1 19.7 22.2 23.5 21.0 20.6 21.6 16.9 - 22.2 23.4 18.7 19.8 - 19.5 22.7 25.2 20.8 26.9 21.9 16.6 21.8 24.5 25.3 16.9 22.4 21.4 21.0 - 14.6 27.3 20.5 22.1 22.7 23.4 27.0 20.6 28.2 23.9 16.2 20.9 24.9 27.0 16.1 24.6 27.5 22.5 - 19.2 24.0 22.7 20.4 20.8 22.5 25.4 20.4 26.3 21.4 16.6 20.8 23.9 25.3 18.0 22.5 23.5 20.1 a Evidence of copulation was not observed; therefore, no gestation data were collected. company Sanitized. D oes not contain TSCA CB1 H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX K INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi MALE RATS 223 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi MALE RATS EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period 224 company Sanitized. Does not contain TSCA CB1 /"N, H-25231: One-Generation Reproduction Study in Rats________________________________________ DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657391 657392 657393 657394 657395 657396 657397 657398 657399 657400 657401 657402 657403 657404 657405 657406 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 ALOPECIA BOTH FRONT PAW(S) ALOPECIA LEFT FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 114 ALOPECIA BOTH FRONT L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA LEFT FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED- BY DESIGN TEST DAY 116 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 15 50 85 85 29 78 29 78 85 85 - 8 64 15 71 225 Company Sanitized. Does not contain TSCA CBl H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657407 657408 657409 657410 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 SORE BOTH SHOULDER(S) SORE RIGHT SHOULDER(S) SORE NECK SACRIFICED IN EXTREMIS TEST DAY 60 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 10 36 43 60 43 60 226 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px MALE RATS GROUP: III-O DOSE: 75 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657416 657417 657418 657419 657420 657421 657422 657423 657424 657425 657426 657427 657428 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 115 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 * NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 36 115 36 115 8 115 57 99 t> 227 Company Sanitized. Does not contain TSCA CBi H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px MALE RATS GROUP: III-O DOSE: 75 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657429 657430 657431 657432 657433 657435 657596 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA RIGHT FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT LEG(S) SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 15 99 29 116 106 116 117 117 117 117 228 Sanitized. Does not contain TSCA CBI Company H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pa MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657441 657442 657443 657444 657445 657446 657447 657448 657449 657450 657451 657452 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 ALOPECIA LEFT FRONT PAW(S) ALOPECIA BOTH FRONT PAW(S) ALOPECIA LEFT FRONT L E G {S ) SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA LEFT FRONT PAW(S) ALOPECIA LEFT FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 99 99 106 115 106 115 50 78 50 78 106 115 106 115 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P2 MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657453 657454 657455 657456 657457 657458 657459 657460 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA LEFT FRONT PAW(S) ACCIDENTLY KILLED TEST DAY 86 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 117 8 50 8 50 85 85 29 117 29 117 230 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 /&****. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657466 657467 657468 657469 657470 657471 657472 657473 657474 657475 657476 657477 657478 657479 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 DISCHARGE PENIS RED LUNG NOISE SORE PENIS SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 STAINED PERINEUM YELLOW LUNG NOISE SACRIFICED BY DESIGN TEST DAY 114 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 114 ALOPECIA BOTH FRONT PAW(S) SALIVATION STAINED PERINEUM YELLOW SACRIFICED BY DESIGN TEST DAY 115 ALOPECIA BOTH FRONT L E G (S ) SALIVATION ALOPECIA RIGHT FRONT L E G (S ) ALOPECIA RIGHT FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 115 SALIVATION ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 115 STAINED NOSE RED SACRIFICED BY DESIGN TEST DAY 115 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED ACCIDENTLY KILLED TEST DAY 42 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 116 43 43 48 49 92 92 80 92 80 80 8 16 16 16 78 78 43 78 52 54 85 115 85 115 54 54 92 99 92 99 86 86 Company Samt.zed. Does not contain S C CBS H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi MALE RATS GROUP: V I I -0 DOSE: 3500 MG/KG/DAY .ANIMAL NUMBER OBSERVATION FIRST DAY OBSERVED LAST DAY OBSERVED 657480 657481 657482 657483 657484 657485 ALOPECIA RIGHT FRONT PAW(S) ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 116 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 SALIVATION SALIVATION SALIVATION FOUND DEAD TEST DAY 66 STAINED MOUTH BROWN STAINED NOSE BROWN IRREGULAR RESPIRATION SACRIFICED BY DESIGN TEST DAY 117 SALIVATION SALIVATION SALIVATION SALIVATION STAINED PERINEUM YELLOW SACRIFICED BY DESIGN TEST DAY 117 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 117 22 29 36 92 10 22 31 31 52 52 66 69 66 69 66 66 24 24 32 35 54 54 65 69 85 85 232 Company Sanitized. Does not contain TSC A C B I H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX L INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING PREMATING AND COHABITATION 233 Company Sanitized. D oes not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING PREMATING AND COHABITATION# EXPLANATORY NOTES Notes Test Days 1-75 = Premating period Test Days 76-90 = Cohabitation period 234 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING PREMATING AND COHABITATION GROUP: II-O DOSE: 0 MG/KG/DAY ANIMAL NUMBER OBSERVATION TEST DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S) ALOPECIA RIGHT SIDE(S) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA ABDOMEN NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED 8 71 29 71 57 71 8 57 57 8 8 8' 36 71 71 71 57 36 235 Company Sanitized. D oes not contain T S C A CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING PREMATING AND COHABITATION GROUP: IV-0 DOSE: 75 MG/KG/DAY ANIMAL NUMBER OBSERVATION TEST~DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657516 657517 657518 657519 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 657530 657531 657532 657533 657534 657535 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT P A W {S ) ALOPECIA BOTH FRONT P A W (S ) ALOPECIA BOTH FRONT L E G (S ) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED 88 15 71 22 71 236 Sanitized. D oes noi conialo TSCA CB1 Company H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING PREMATING AND COHABITATION GROUP: VI-0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION TEST DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 657554 657555 657556 657557 657558 657559 657560 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES'DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED 237 Company Sanitized. Does not contain 1 SCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING PREMATING AND COHABITATION ______ GROUP: VIII-0 ANIMAL NUMBER OBSERVATION DOSE: 3500 MG/KG/DAY TEST DAYS FIRST DAY OBSERVED LAST DAY OBSERVED 657566 657567 657568 657569 657570 657571 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 STAINED PERINEUM YELLOW HUNCHED OVER NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED SALIVATION NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED SALIVATION ALOPECIA BOTH FRONT L E G (S ) ALOPECIA LEFT REAR L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA ABDOMEN SALIVATION NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED 60 61 60 61 16 16 51 51 43 71 43 64 57 71 57 71 71 71 9 10 * 238 Company Sanitized. Does not contain TSC CBi 0 -2 5 2 3 1: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX M INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING GESTATION 239 Sanitized. Does not contain TSCA CBI Company i-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING GESTATION EXPLANATORY NOTES Note This Appendix contains data from females with evidence of copulation observed. 240 Company Sanitized. Does not contain TSCA CB1 M-25231: One-Generation Reproduction Study in Rats________________________________________ DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING GESTATION GROUP: II-O DOSE: 0 MG/KG/DAY ANIMAL NUMBER OBSERVATION GESTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657491 657492 657493 657494 657495 657496 657497 657498 657499 657500 657501 657502 657503 657504 657505 657506 657507 657508 657509 657510 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA RIGHT SIDE(S) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA LEFT SIDE(S) ALOPECIA RIGHT SIDE(S) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA RIGHT FRONT L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA LEFT FRONT L E G (S ) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) 00 0 21 0 21 14 14 21 21 00 00 14 21 21 21 0 21 7 21 00 241 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 /""N INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING GESTATION ANIMAL NUMBER GROUP: IV-0 DOSE: 75 MG/KG/DAY OBSERVATION GESTATI0N DAYS FIRST DAY OBSERVED LAST DAY OBSERVED 657516 657517 657518 657520 657521 657522 657523 657524 657525 657526 657527 657528 657531 657532 657533 657534 657535 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA RIGHT FRONT L E G (S ) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED 0 14 0 14 21 21 242 Company Sanitized- Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING GESTATION GROUP: VI-0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION GESTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657541 657542 657543 657544 657545 657546 657547 657548 657549 657552 657553 657554 657555 657556 657558 657559 657560 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA LEFT FRONT LEG(S) ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA LEFT FRONT PAW(S) ALOPECIA LEFT FRONT L E G (S ) NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) NO ABNORMALITIES DETECTED ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) 7 21 0 21 0 21 21 21 21 21 0 14 0 21 0 21 0 21 7 21 7 21 243 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING GESTATION GROUP: VIII-0 DOSE: 3500 MG/KG/DAY ANIMAL NUMBER OBSERVATION GESTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657567 657568 657569 657570 657572 657573 657574 657575 657576 657577 657578 657579 657580 657581 657582 657583 657584 657585 NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED ALOPECIA RIGHT SIDE(S) ALOPECIA RIGHT L E G (S ) ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA ABDOMEN NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED SORE TAIL NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED NO ABNORMALITIES DETECTED 14 21 21 21 0 21 0 21 0 21 0 21 244 Company Sanitized. Does not contain IS C A CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 APPENDIX N INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING LACTATION 245 Company Sanitized. Does not contain TSCA CBI H-25231 : One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING LACTATION EXPLANATORY NOTES Note Test days for animal fates are determined from the initiation of test substance administration. 246 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 ./*****% INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING LACTATION GROUP: II-O DOSE: 0 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657491 657492 657493 657494 657495 657497 657498 657499 657500 657501 657502 657503 657504 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA BOTH FRONT L E G {S ) ALOPECIA RIGHT SIDE(S) ALOPECIA RIGHT FRONT L E G {S ) SACRIFICED BY DESIGN TEST DAY 124 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 ALOPECIA RIGHT SIDE(S) SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 120 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 0 14 0 21 21 21 14 247 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pj. FEMALE RATS DURING LACTATION GROUP: II-0 DOSE: 0 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657505 657506 657507 657508 657510 ALOPECIA BOTH FRONT PAW(S) ALOPECIA RIGHT FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA LEFT FRONT L E G (S ) ALOPECIA BOTH FRONT L E G (S ) ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 126 07 0 21 0 21 00 7 21 21 21 248 Company Sanitized. Does not contain TSCA CBI M-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING LACTATION GROUP: IV-0 DOSE: 75 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657516 657517 657518 657520 657521 657522 657523 657524 657525 657526 657527 657528 657529 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 120 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA RIGHT FRONT L E G {S ) ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 125 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 ALOPECIA RIGHT FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 120 NO ABNORMALITIES DETECTED ' SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 14 21 21 21 0 21 0 21 0 14 - 249 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 /'"'s INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pa FEMALE RATS DURING LACTATION GROUP: IV-0 DOSE: 75 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657530 657531 657532 657533 657534 657535 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 127 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 125 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 14 21 14 21 250 Sanitized. D oes not contain TSCA C B I H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS DURING LACTATION GROUP: VI-0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657541 657542 657543 657544 657545 657546 657547 657548 657549 657550 657551 657552 657553 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 ALOPECIA LEFT FRONT L E G (S ) ALOPECIA RIGHT FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 120 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 128 ALOPECIA LEFT FRONT PAW(S) ALOPECIA LEFT FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 125 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 124 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 00 7 21 0 21 0 21 0 14 0 14 251 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats_________________________________________DuPont-9763 /"N /'"'N INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pa FEMALE RATS DURING LACTATION GROUP: V I -0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657554 657555 657556 657558 657559 657560 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA BOTH FRONT L E G (S ) SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 130 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT LEG(S) SACRIFICED BY DESIGN TEST DAY 122 0 21 0 21 0 21 252 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Pi FEMALE RATS DURING LACTATION GROUP: VIII-0 DOSE: 3500 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657566 657568 657570 657571 657572 657573 657574 657576 657577 657579 657580 657581 657583 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 120 MASS 1 2.0 cm CHEST SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 ALOPECIA BOTH FRONT PAW(S) ALOPECIA BOTH FRONT LEG(S) ALOPECIA ABDOMEN ALOPECIA CHEST SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 121 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 122 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 123 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 121 14 14 0 21 0 21 0 21 14 21 7 21 - 253 Company Sanitized. Does not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats DuPont-9763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Px FEMALE RATS ! DURING LACTATION GROUP: VIII-0 DOSE: 3500 MG/KG/DAY ANIMAL NUMBER OBSERVATION LACTATION DAYS FIRST DAY LAST DAY OBSERVED OBSERVED 657584 657585 NO ABNORMALITIES DETECTED SACRIFICED BY DESIGN TEST DAY 125 ALOPECIA BOTH FRONT PAW(S) SACRIFICED BY DESIGN TEST DAY 123 21 21 /" "N /**"*N, 254 Company Sanitized. Does not contain TSCA CB1