Document Z4d36XbkXJNYMV0zypKjgzkGJ

AR226-3207 DuPont-5991 TRADE SECRET Study Title H-24516 : Developmental Toxicity Study in Rats Laboratory Project ID: DuPont-5991 TEST GUIDELINES : U.S . EPA Health Effects Test Guidelines OPPTS 870.3700 Prenatal Developmental Toxicity Study OECD Guidelines for the Testing of Chemicals Section 4, No . 414 AUTHOR : Susan M . Munley, M .A. STUDY COMPLETED ON : December 12, 2001 PERFORMING LABORATORY : C cmm~~~ - E.I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 7 W3 Com~raw San'?!'ed. i90es rnt a hta'r TSCA Ci?i Page 1 of 165 Company Sanitized . Does not ' f'9( H-24516 : Developmental Toxicity Study in Rats DuPont-5991 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U .S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards except for the item documented below . The item listed does not impact the validity of the study . Test substance characterization and stability analyses were performed at Regional Analytical Services (RAS), a non-GLP laboratory. The test substance analyses performed 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 I Sponsor: E . L du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A . Study Director: 0.^ h . rte, v. . Susan M_ Munley,& A_ Research Scientist Derv -2W 1 Date Applicant I Sponsor : DuPont Representative Date 1 X00 ,SGP1 'Doesiat~~ 2 H-24516 : Developmental Toxicity Study in Rats QUALITY ASSURANCE STATEMENT Haskell Sample Number(s) : 24516 DuPont-5991 Dates of Inspections : Protocol : March 21, 2001 Conduct : March 20-21,2001 ; April 30, 2001 Records, Reports : October 1,3-5,8-12,15, 2001 Dates Findings Reported to : Study Director: October 10,19, 2001 ; December 5, 2001 Management : October 15, 2001 ; November 29,2001 ; December 11, 2001 Reported by: wn " &-k . Vi m i Wonda K . belly Quality Assurance Auditor l2 Dec 2001 Date ~t 1 H-24516 : Developmental Toxicity Study in Rats DuPont-5991 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study . Analytical Evaluations Reported by: Janet C . Maslanka, B .S . Staff Scientist 12-Dec-2001 Date dil Robert M. Parker, Ph .D ., D.A.B.T . Director Developmental, Reproductive, and Neurobehavioral Toxicology Rued by Study Director : Susan M . Munley, M . . Research Scientist Developmental, Reproductive, and Neurobehavioral Toxicology 12-Dec-2001 Date 12-bee-2001 Date 'Doles n~3 Sa~'tiyed.O -4- H-24516 : Developmental Toxicity Study in Rats TABLE OF CONTENTS GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT QUALITY ASSURANCE STATEMENT CERTIFICATION STUDY INFORMATION STUDY PERSONNEL SUMMARY OBJECTIVE MATERIALS AND METHODS A. Test Guidelines B. Test Substance C. Test Species D . Animal Husbandry 1 . Housing 2 . Feed and Water 3 . Identification 4 . Health Monitoring Program E. Quarantine and Pretest Period F. Study Design G. Selection of Dose Levels H. Randomization I. Preparation, Administration, and Analysis of Test Suspensions J. Animal Euthanasia K. Parameters to be Studied 1 . In-life Observations of Females 2 . Postmortem Observations of Females Surviving to Scheduled Euthanasia 3 . Fetuses of Females Surviving to Scheduled Euthanasia L. Control of Bias M. Statistical Analyses RESULTS AND DISCUSSION A. Maternal Findings 1 . Mortality 2 . Body Weights 3 . Body Weight Changes 4 . Food Consumption 5 - ~- azc , ~e F ~ DuPont-5991 Page 2 3 4 7 8 9 10 10 10 10 10 11 11 11 11 11 12 12 12 13 13 14 14 14 14 14 15 15 16 16 16 16 16 16 H-24516 : Developmental Toxicity Study in Rats TABLE OF CONTENTS (Continued) 5 . Clinical Observations 6 . Postmortem Findings B. Fetal Findings 1 . Mortality 2 . Body Weight 3 . Malformations 4 . Variations CONCLUSIONS RECORDS AND SAMPLE STORAGE REFERENCES TABLES TABLE 1 MEAN MATERNAL BODY WEIGHTS TABLE 2 MEAN MATERNAL BODY WEIGHT CHANGES TABLE 3 MEAN MATERNAL FOOD CONSUMPTION TABLE 4 CLINICAL OBSERVATIONS TABLE 5 REPRODUCTIVE OUTCOME TABLE 6 INCIDENCE OF FETAL MALFORMATIONS TABLE 7 INCIDENCE OF FETAL VARIATIONS APPENDICES APPENDIX A INDIVIDUAL BODY WEIGHTS APPENDIX B INDIVIDUAL BODY WEIGHT CHANGES APPENDIX C INDIVIDUAL FOOD CONSUMPTION APPENDIX D INDIVIDUAL CLINICAL OBSERVATIONS APPENDIX E GROSS POSTMORTEM FINDINGS APPENDIX F INDIVIDUAL REPRODUCTIVE DATA APPENDIX G INDIVIDUAL FETAL WEIGHTS AND ALTERATIONS APPENDIX H ANALYTICAL REPORT DuPont-5991 Page 17 17 17 17 17 17 17 19 19 20 21 22 23 24 25 26 27 28 31 32 46 56 66 83 89 94 152 Apes not contain TSCA sanitized . CB1 PomPanv - 6- H-24516 : Developmental Toxicity Study in Rats STUDY INFORMATION Substance Tested : Synonyms/Codes : Haskell Number : 24516 Composition. DuPont-5991 Physical Characteristics : Pale to medium tan waxy solid Sponsor : E . I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S .A . Study Initiated/Completed : March 2, 2001 / (see report cover page) In-Life Initiated/Completed : March 4, 2001 / May 8, 2001 pmpan ar~a+aZed Does co,'taj r' T~rC~ Get tBOt 7- H-24516 : Developmental Toxicity Study in Rats STUDY PERSONNEL Study Director : Management : Primary Technician : Toxicology Report Preparation : Analytical Chemist: Management : Laboratory Veterinarian : Susan M. Munley, M .A. Robe M. Parker, Ph .D ., D.A.B.T. Gregory L. Poindexter Mary . LaRoe Janet '~r . Maslanka, B .S . S. Mark Kennedy, Ph .D. Wanda L. West, D.V.M., A.C.L.A.M. I I DuPont-5991 Doesa16y gay 8 H-24516 : Developmental Toxicity Study in Rats DuPont-5991 SUMMARY The purpose of this study was to evaluate the potential maternal and developmental toxicity of H-24516, administered by gavage to pregnant rats from the time of implantation to the end of gestation . Groups of 22 time-mated female Crl :CD(SD)IGS BR rats were administered suspensions of the test substance in 0 .5% aqueous methylcellulose over days 6-20 of gestation (G) at daily dose levels of 0, 50, 200, or 500 mg/kg/day . During the in-life portion of the study, body weight, food consumption, and clinical observation data were collected . On day 21G, dams were euthanized ; the thoracic and abdominal viscera were examined grossly . The uterus of each pregnant rat was removed and dissected to permit examination of uterine contents . The fetuses were removed, individually identified, weighed, sexed, and examined for external, visceral, head, and skeletal alterations . Under the conditions of this study, minimal evidence of maternal toxicity including reduced body weight and weight gain, and increased perineal fur staining was observed at 500 mg/kg/day . Similarly, minimal evidence of developmental toxicity was evident at 500 mg/kg/day based on increased skeletal variations including retarded skull bone and pelvic bone ossification and wavy ribs . No toxicologically significant or adverse compound-related effects were seen in dams or fetuses at 50 or 200 mg/kg/day . Thus, the no-observed-effect level (NOEL) a for maternal and developmental toxicity was considered 200 mg/kg/day . a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected . Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U .S . EPA"' ) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(13) 9 pot ~; , ;fcaia T =" A CL H-24516 : Developmental Toxicity Study in Rats DuPont-5991 OBJECTIVE The purpose of this study was to evaluate the potential maternal and developmental toxicity of H-24516 in rats . MATERIALS AND METHODS A. Test Guidelines The study design complies with following test guidelines : United States Environmental Protection Agency (EPA), Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines, OPPTS 870 .3700 Prenatal Developmental Toxicity Study (1998) . Organisation for Economic Cooperation and Development . Guidelines for Testing of Chemicals, Section 4 (No . 414). Paris, France (1981) . B. Test Substance The test substance was supplied by the sponsor, the DuPont Chemical Solutions Enterprise (DCSE), E. I. Du Pont de Nemours and Company, Newark, Delaware . It was assigned the Haskell Laboratory Number 24516 . The sponsor was responsible for the characterization and analysis of identity, concentration, and stability of the test substance . Test substance analyses were conducted by Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey . A reserve sample of the test substance was collected and retained by Haskell Laboratory . C. Test Species The Crl :CD (SD)IGS BR rat was selected for this study because it is a preferred species for developmental toxicity testing as recommended by the testing guidelines . The Crl :CD (SD)IGS BR strain was chosen because extensive background information is available from the literature, the supplier, and previous studies with other compounds at Haskell Laboratory . This strain is also considered suitable relative to hardiness and incidence of spontaneous disease . ~otnpanY ._ Does contain TSCA Cal not - 10 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 Eighty-eight nulliparous, time-mated females, were received on March 1 (66 females) and March 2, 2001 (22 females) from Charles River Laboratories, Inc ., Raleigh, North Carolina . Body weights on the day the rats showed positive evidence of copulation, day 0 of gestation (day OG), were supplied by the vendor; day OG body weights ranged from 226 to 260 grams . The rats for this study were 63 days old upon receipt and were at either 1, 2, or 3 days of gestation . D. Animal Husbandry 1 . Housing Animal rooms were maintained at an acceptable temperature of 20-26C (targeted at 23C) and a targeted relative humidity of 50% 10% . Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours) . Animals were housed individually in suspended, wire-mesh, stainless steel cages . Nesting material was not provided because the dams were euthanized prior to parturition . 2. Feed and Water PMI Nutrition International, Inc . Certified Rodent LabDiet 5002 (formerly known as Purina Certified Rodent Chow) was available ad libitum. Water from United Water Delaware was available ad libitum . 3. Identification Each animal was assigned a unique number and identified with an AVID microchip implant by the supplier prior to shipping . Upon receipt, each animal was assigned a unique Haskell animal number . Both the Haskell animal number and the implant number were recorded on each cage card. A master list of unique Haskell animal numbers and corresponding unique implant numbers was maintained with the study records . 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 H-24516 : Developmental Toxicity Study in Rats DuPont-5991 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 . E. Quarantine and Pretest Period Rats were quarantined according to procedures outlined in Haskell Laboratory and then released for the study upon approval of the laboratory animal veterinarian . F. Study Design The experimental design is shown below : Group Dose s (mg/kg/day) Concentration (mg/mL) Time-Mated Females I Ob 0 22 II 50 5 .0 22 111 200 20 .0 22 IV 500 50 .0 22 a Suspensions of H-24516 were administered once daily, by gavage, over days 6-20 of gestation (days 6-20G) at a dosage volume of 10 mL/kg. b Vehicle only (0 .5% aqueous methylcellulose) . G. Selection of Dose Levels The dose levels for the current study were based on a pilot study(1) conducted with H-24516 in the rat. In the pilot study, groups of 8 time-mated female Crl :CD(SD)IGS BR rats were administered the test substance once daily by gavage during days 6-20 of gestation (days 6-20G) at daily dosages of 0, 125, 250, 500, or 1000 mg/kg/day . During the in-life portion of the study, maternal body weights, food consumption, and clinical signs data were collected . On day 21 G, all dams were euthanatized and examined grossly . Gravid and empty uterine weights were recorded to permit calculation of the adjusted maternal final body weight . The uterine contents were examined and described ; fetuses were weighed, sexed, and examined for any external alterations . Maternal toxicity evident as reduced maternal body weights, weight gains, and food consumption occurred in rats administered dosages of > 250 mg/kg/day . Overall weight values during the no~ co~a~~TgCACB~ as -12- ompany SanAW. H-24516 : Developmental Toxicity Study in Rats DuPont-5991 dosing period (days 6-21G, adjusted for the products of conception) were 5 .7%, 9 .3%, and 14 .2% lower than the control group value for females dosed with 250, 500, or 1000 mg/kg/day, respectively. Overall weight gain values during the dosing period (days 6-21 G, adjusted for the products of conception) were 21 .0%, 35 .4%, or 66% lower than the control value for females dosed with 250, 500, or 1000 mg/kg/day, respectively. Overall mean maternal food consumption values during dosing (days 6-21G) were 7.3%, 6 .5%, and 13 .8% lower than the control value for females dosed with 250, 500, or 1000 mg/kg/day, respectively. One female dosed with 1000 mg/kg/day was sacrificed in extremis on day 13G due to persistent weight loss and not eating. There were no grossly observable postmortem findings in this animal, and she was not pregnant. It cannot be determined from these data whether the death of this animal is compoundrelated or whether it is incidental . Significantly increased incidences of clinical observations occurred in females dosed with 1000 mg/kg/day that included stained and/or wet fur on the perineum, and discharge on the neck . There were no compound-related gross postmortem findings, no effects on number of litters produced, no effects on fetal resorptions, no effects on nidations, no effects on corpora lutea . With regard to fetal findings, compound-related toxicity at this exposure level was limited to a significant reduction in mean fetal weight 9 .8% and 9 .0% for 500, and 1000 mg/kg/day groups . There was no increase in any compound-related fetal external malformations or variations observed. Based on these findings, the dose levels listed above were selected for the current study . H. Randomization Dams were assigned to lots according to their gestation day. Then, they were ranked within their respective lots on the basis of day OG body weights and assigned to control and experimental groups by random sampling from the ranked list . The distribution resulted in mean body weights for all groups that were not statistically different (p > 0 .05) . I. Preparation, Administration, and Analysis of Test Suspensions Suspensions of the test substance in the vehicle (0 .5% aqueous methylcellulose) were prepared 2 or 3 times per week, and stored refrigerated until used . The method of mixing the test material with the vehicle was documented in the study records . The dosing suspensions were administered by gavage because the oral route is the route that is recommended by regulatory agencies for this type of study . The volume administered (10 mL/kg) was based on the most recent body weight . Samples of each test suspension were taken three times during the study, near the beginning, middle, and end of the dosing period . Analyses of the first sampling addressed homogeneity, concentration, and stability . For the second and third samplings, analyses addressed concentration. Samples were submitted, shortly after preparation to the Analytical Chemistry Group at Haskell Laboratory. The methods and results of these analyses are presented in Appendix H . -13- ~ . a ., i H-24516 : Developmental Toxicity Study in Rats J. Animal Euthanasia DuPont-5991 Females were euthanized by carbon dioxide inhalation. Fetuses were decapitated before proceeding with visceral examinations ; those to be viscerally examined without decapitation were injected with sodium pentobarbital . All other fetuses also were injected with sodium pentobarbital before fixation . K. Parameters to be Studied 1 . In-life Observations of Females Body weights were recorded at least twice prior to dosing to provide data for quarantine release, and on days 6-21 G . Food consumption was measured on days 4, 6, 8, 10, 12, 14, 16, 18, 20, and 21 G. Clinical signs were recorded at least twice prior to dosing to provide data for quarantine release ; signs were recorded once daily on days 4, 5, and 21G and twice daily on days 6-20G . 2. Postmortem Observations of Females Surviving to Scheduled Euthanasia The abdominal and thoracic viscera were examined grossly immediately after euthanasia on day 21 G. The intact and the empty uterus of each dam having at least one viable fetus was weighed to permit calculation of maternal body weight adjusted to exclude the products of conception . The corpora lutea count for each ovary of females with viable fetuses was recorded . For each female with visible implantation sites, the types of implants (live and dead fetuses, and resorptions) and their relative positions were recorded . The uterus of each apparently "nonpregnant" female was stained with ammonium sulfide (2) to detect very early resorptions. 3 . Fetuses of Females Surviving to Scheduled Euthanasia For each fetus, the following parameters were recorded : identification number, intrauterine location, sex, and body weight . The external alterations detected for each live fetus were also recorded . For each litter, the first live fetus and every other live fetus thereafter were examined for visceral alterations .(3) Retarded renal development was classified using the scheme of Woo and Hoar .(4) In addition, all live fetuses with malformations visible at external examination were examined for soft tissue alterations ; decapitation of these fetuses was at the discretion of the study director or a designee . After fixation in Bouin's fixative, the heads of decapitated fetuses were examined and alterations were recorded. Examinations were based on the method of Barrow and Taylor .(5) After alcohol fixation, the alizarin-stained skeletons were examined and skeletal alterations were recorded for all live fetuses, excluding the fetal heads fixed in Bouin's fixative . ComPa~y Sanitized VoeS not contatn'tSCA CB` - 14 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 L. Control of Bias In addition to random assignment to groups, all females were coded before scheduled euthanasia and remained coded during the collection of postmortem and fetal data . M. Statistical Analyses Sequential trend testing (6) was applied to the data for each parameter as tabulated below . 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 . For litter parameters, the proportion of affected fetuses per litter or the litter mean was used as the experimental unit for statistical evaluation .(7 The level of significance selected wasp < 0 .05 . Where the data were tied and the standard large sample version of Jonckheere's test was not applicable, exact p values were calculated using permutation methodology .(8) Parameter Maternal weight Maternal weight changes Maternal food consumption Live fetuses Dead fetuses Resorptions Implantations Incidence of fetal alterations Incidence of pregnancy Clinical observations Maternal mortality Females with total resorptions Early deliveries Fetal weight (Covariates : litter size, sex ratio) Sex ratio (Covariate : litter size) Trend Test Linear contrast of means(9) Jonckheere's test(' 0) Cochran-Armitage test(9) Linear contrast of least square means" porpany S,am tided . tic:='S ROk ~` - 15 - PR1 ~ H-24516 : Developmental Toxicity Study in Rats DuPont-5991 RESULTS AND DISCUSSION A. Maternal Findings 1 . Mortality There was no compound-related mortality at any level tested ; all rats on study survived to scheduled sacrifice . 2. Body Weights (Table 1, Appendix A) There was a minimal, compound-related reduction in mean maternal body weight at 500 mg/kg/day. Mean final body weight was 96% of the control and was statistically significant . There were no compound-related effects on mean maternal weight at 50 or 200 mg/kg/day . 3 . Body Weight Changes (Table 2, Appendix B) There were compound-related reductions in mean maternal body weight gain at 200 and 500 mg/kg/day. At 200 mg/kg/day, overall weight gain was 91 1/o/79% of control using the absolute/adjusted final weight to calculate gain over days 6-21G . At 500 mg/kg/day, overall weight gain was 85%/63% of control using the absolute/adjusted final weight to calculate gain over days 6-21 G . These overall reductions in body weight gain were statistically significant and considered the result of compound-related, statistically significant reductions in mean weight gain over days 6-8, 8-10, and 18-20G . While the effects on body weight gain at both 200 and 500 mg/kg/day were considered compound-related, the effect seen at 200 mg/kg/day was not considered adverse as the magnitude of the change was small and it had no adverse impact on mean body weight at this level. There were no compound-related effects on maternal body weight changes at 50 mg/kg/day. 4. Food Consumption (Table 3, Appendix C) There were minimal, compound-related reductions in mean maternal food consumption at 50, 200, and 500 mg/kg/day. At 50 mg/kg/day, mean food consumption was significantly reduced over days 6-8G . This reduction was not considered adverse because it had no adverse impact on either overall mean food consumption or on body weight parameters . At 200 and 500 mg/kg/day, overall food consumption was 94 and 95% of control, respectively, when averaged over days 6-21 G . These reductions in overall food consumption, which were not statistically significant, were considered the result of compound-related, statistically significant reductions in mean food consumption over days 6-8, 8-10, and 10-12G . Despite the statistical significance, these food consumption reductions at 200 and 500 mg/kg/day were not considered adverse because the reductions were transient and had no adverse impact on overall food consumption . _- -16- n d. Does ~ompanY'$e nta; n TSCACS' H-24516 : Developmental Toxicity Study in Rats DuPont-5991 5 . Clinical Observations (Table 4, Appendix D) Significant compound-related clinical observations were seen at 500 mg/kg/day and were limited to fur staining in the perineal area that was reported for 9/22 animals at this level . There were no compound-related clinical observations at 50 mg/kg/day . 6 . Postmortem Findings (Appendix E) There were no compound-related gross postmortem findings at any level tested . B. Fetal Findings 1 . Mortality (Table 5, Appendix F) There was no compound-related embryofetal mortality evident as increased resorptions and/or dead fetuses at any level tested . 2. Body Weight (Table 5, Appendices F and G) There was a slight (97% of control) reduction in mean fetal weight at 200 and 500 mg/kg/day ; at 500 mg/kg/day, the value was significantly different (p=0 .04) whereas at 200 mg/kg/day, it was not significantly different (p=0.07) . While these reductions were considered compound-related, they were not considered adverse based on the minimal magnitude of the reduction . Mean fetal weight at 50 mg/kg/day was equivalent to the control group value . 3 . Malformations (Table 6, Appendix G) There were no compound-related fetal malformations at any level tested . 4. Variations (Table 7, Appendix G) Statistically significant increases in fetal skeletal variations were observed at 200 and 500 mg/kg/day. At 200 mg/kg/day, there was a significant increase in retarded skull bone ossification . This increase was not considered compound-related; rather, the incidence of this finding at 200 mg/kg/day (26 fetuses from 14 litters) appeared increased due to a relatively low value for the concurrent control group (7 fetuses from 7 litters) . Recent historical control group values for retarded skull bone ossification are presented below for perspective : -17- 13 i 1'ot ' i H-24516 : Developmental Toxicity Study in Rats DuPont-5991 Year Study Conducted Reference No. Affected Fetuses No. Affected Litters 1997 1998-01367 19 10 1998 1998-01382 24 11 1998 DuPont-1165 11 8 1998 DuPont-1559 37 13 1999 1998-01500 18 8 1999 DuPont-2287 19 12 1999 DuPont-1454 21 10 1999 DuPont-3378 36 14 2000 DuPont-4177 47 14 2000 DuPont-4341 6 6 2001 DuPont-5676 58 19 At 500 mg/kg/day, there were significant increases in the following fetal skeletal variations : retarded skull bone ossification, retarded pelvic ossification, and wavy ribs . These observations were all considered compound-related . anttlzed 0O Comply S t~~ rR% not cost&~~ H-24516 : Developmental Toxicity Study in Rats DuPont-5991 CONCLUSIONS Under the conditions of this study, minimal evidence of maternal toxicity including reduced body weight and weight gain, and increased perineal fur staining was observed at 500 mg/kg/day . Similarly, minimal evidence of developmental toxicity was evident at 500 mg/kg/day based on increased skeletal variations including retarded skull bone and pelvic bone ossification and wavy ribs. No toxicologically significant or adverse compound-related effects were seen in dams or fetuses at 50 or 200 mg/kg/day . Thus, the no-observed-effect level (NOEL) a for maternal and developmental toxicity was considered 200 mg/kg/day . RECORDS AND SAMPLE STORAGE Laboratory-specific or site-specific raw data such as personnel files and equipment records will be retained at 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 . Characterization data will be stored at Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey . a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected . Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U .S . EPA(12) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union . (13) -19- not conta:n'rSC 4CB1 Cot"r anySanit z.edDoes H-24516 : Developmental Toxicity Study in Rats DuPont-5991 REFERENCES 1 . DuPont Haskell Laboratory Report- 2 . Salewski, E . (1964). Farbemethode zum makroskopischen Nachweis von Implantationstellen am Uterus der Ratte . Archiv . Path. Exp . Pharmakol. 247 :367. 3. Staples, R.E. (1974). Detection of Visceral Alterations in Mammalian Fetuses . Teratology, 9(3) :A37-A38 . 4. Woo, D .C. and Hoar, R .M . (1972). Apparent Hydronephrosis as a Normal Aspect of Renal Development in Late Gestation of Rats : The Effect of Methyl Salicylate . Teratology, 6 :191196 . 5. Barrow, M .V. and Taylor, W .J. (1969). A Rapid Method for Detecting Malformations in Rat Fetuses . J . Morph., 127(3) :291-306. 6. Selwyn, M .R. (1995). The Use of Trend Tests to Determine a No-Observable-Effect Level in Animal Safety Studies . Journal of the American College of Toxicology 14(2) :158-168. 7 . Haseman, J .K. and Hogan, M .D . (1975). Selection of the Experimental Unit in Teratology Studies . Teratology, 12 :165-171 . 8. Patefield, W . (1982). Exact Tests for Trends in Ordered Contingency Tables . Applied Statistics 31 :32-43 . 9. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th ed . The Iowa State University Press, Iowa, pp . 246-248, 349-352 . 10 . Jonckheere, A .R. (1954). A Distribution-Free K-Sample Test Against Ordered Alternatives . Biometrika 41 :133-145. 11 . Dempster, A.P., Selwyn, M.R., Patel, C .M., and Roth, A.J. (1984). Statistical and Computational Aspects of Mixed Model Analysis . The Journal of the Royal Statistical Society, Series C (Applied Statistics), 33(2) :203-214. 12 . 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 ., 20460 . EPA-540/9-85-020, June 1985 . 13 . Risk Assessment of Notified New Substances Technical Guidance Document (X11283/94-EN), Chapter I, Sections 2 .24 and 2 .25. -20- Company Sanitized . Does not contain TSCA CBI H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLES company Sarilize? Ums W cOwlin '+ "k Got -21- H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 1 MEAN MATERNAL BODY WEIGHTS (GRAMS) Group : I Days Dose (mg/kg/day) : 0 Of Gestation n: 22 II III IV 50 200 500 22 22 22 0 240 .6 (8 .40) a 241 .9 (9 .56) 242 .7 (9 .12) 242 .2 (8 .99) 4b 243 .3 (20 .24) 252 .3 (12 .89) 250 .9 (19 .39) 253 .2 (7 .46) 6 260 .1 (13 .13) 264 .5 (12 .16) 264 .3 (18 .07) 266 .3 (9 .12) 7 265 .8 (14 .03) 264 .3 (14 .51) 265 .2 (15 .61) 264 .4 (9 .22) 8 270 .2 (14 .92) 270 .2 (16 .00) 268 .3 (19 .66) 269 .0 (11 .55) 9 275 .0 (16 .97) 275 .7 (13 .98) 272 .9 (17 .31) 272 .0 (11 .57) 10 281 .6 (19 .01) 281 .0 (13 .44) 274 .8 (20 .20) 275 .2 (11 .75) 11 289 .7 (18 .36) 288 .7 (14 .38) 283 .5 (18 .33) 284 .3 (12 .01) 12 296 .7 (18 .54) 296 .0 (15 .22) 291 .0 (18 .26) 290 .0 (12 .89) 13 302 .9 (17 .28) 302 .0 (16 .33) 296 .5 (17 .71) 298 .1 (13 .34) 14 310 .7 (17 .98) 307 .8 (15 .80) 304 .1 (17 .42) 304 .7 (14 .09) 15 318 .8 (19 .58) 316 .0 (16 .91) 312 .9 (18 .46) 311 .8 (15 .11) 16 329 .1 (19 .22) 326 .7 (16 .70) 322 .4 (18 .95) 326 .4 (14 .98) 17 342 .5 (20 .67) 341 .3 (18 .97) 337 .2 (20 .95) 339 .8 (17 .54) 18 359 .8 (20 .64) 358 .6 (19 .22) 354 .0 (21 .44) 357 .2 (17 .65) 19 374 .9 (23 .64) 373 .1 (20 .57) 367 .9 (22 .91) 369 .7 (20 .51) 20 393 .4 (24 .74) 391 .4 (22 .83) 383 .5 (22 .88) 383 .1 (24 .38) 21 416 .8 (27 .86) 415 .9 (23 .54) 407 .5 (28 .74) 399 .4 (28 .51)* 21c 319 .0 (19 .75) 315 .3 (17 .44) 310 .9 (21 .05) 303 .4 (18 .99)* a Standard deviation is presented in parentheses . b Day 4 : Group I - N = 16 ; Group II - N = 17 ; Group III - N = 16 ; Group IV - N = 17 . c Body weight calculated using the final body weight minus the weight of the products of conception . * Significant trend (linear contrast of means) ; p < 0 .05 . H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 2 MEAN MATERNAL BODY WEIGHT CHANGES (GRAMS) Group : I Days Dose (mg/kg/day) : 0 Of Gestation n: 22 II III IV 50 200 500 22 22 22 0-4a 4-6a 6-8 8-10 10-12 12-14 14-16 16-18 18-20 20-21 6-21 2 .6 (17 .68) b 15 .3 (11 .33) 10 .2 (7 .79) 11 .4 (5 .82) 15 .1 (4 .69) 14 .0 (6 .42) 18 .4 (4 .50) 30 .7 (4 .77) 33 .6 (5 .68) 23 .4 (4 .86) 156 .7 (22 .42) 10 .2 (11 .03) 13 .4 (10 .61) 5 .7 (10 .35) 10 .8 (8 .31) 15 .0 (4 .79) 11 .8 (4 .95) 18 .9 (3 .81) 31 .9 (5 .25) 32 .9 (5 .12) 24 .5 (6 .78) 151 .4 (15 .78) 7 .9 (17 .39) 13 .4 (6 .76) 4 .0 (8 .52)* 6 .5 (9 .60)* 16 .2 (5 .51) 13 .0 (7 .27) 18 .4 (3 .96) 31 .6 (6 .14) 29 .6 (6 .03)* 24 .0 (7 .44) 143 .2 (21 .08)* 11 .2 (10 .88) 12 .9 (9 .10) 2 .7 (6 .79)* 6 .2 (5 .27)* 14 .9 (5 .62) 14 .7 (5 .74) 21 .7 (7 .26) 30 .8 (6 .62) 25 .8 (15 .00)* 16 .4 (17 .83) 133 .1 (27 .54)* 6-21C 58 .9 (14 .88) 50 .8 (12 .39) 46 .6 (15 .74)* 37 .1 (18 .48)* `C a Day 4 : Group I - N = 16 ; Group II - N = 17 ; Group III - N = 16 ; Group IV - N = 17 . CO) b standard deviation is presented in parentheses . ra c Body weight calculated using the final body weight minus the weight of the products of conception . * Significant trend (linear contrast of means) ; p < 0 .05 . 06 v 0 N 0 n 0 a .r. O1 n nC3 - 23 - H-24516 : Developmental Toxicity Study in Rats TABLE 3 MEAN MATERNAL FOOD CONSUMPTION (GRAMS/DAY) Group : I Days Dose (mg/kg/day) : 0 Of Gestation n: 22 II III IV 50 200 500 22 22 22 4-6 22 .7 (5 .99) a 23 .6 (5 .01) 23 .6 (4 .89) 23 .1 (2 .16) 6-8 24 .6 (4 .21) 20 .6 (5 .01)* 20 .3 (4 .84)* 20 .6 (2 .94)* 8-10 25 .3 (4 .13) 23 .5 (2 .42) 20 .8 (4 .32)* 20 .8 (3 .20)* 10-12 27 .6 (3 .99) 26 .4 (3 .12) 24 .5 (2 .85)* 24 .8 (2 .83)* 12-14 27 .9 (2 .87)b 26 .5 (3 .18) 26 .1 (2 .12) 26 .1 (2 .89) 14-16 28 .4 (3 .44) 26 .9 (3 .89) 26 .9 (2 .65) 27 .8 (3 .84) 16-18 30 .4 (3 .09) 29 .1 (3 .50) 28 .3 (3 .05) 30 .2 (3 .43) 18-20 28 .6 (3 .95) 28 .1 (3 .40) 27 .2 (2 .85) 27 .6 (4 .81) 20-21 27 .1 (4 .68) 26 .6 (3 .94) 25 .5 (4 .28) 24 .8 (9 .93) 4-21 26 .1 (4 .12) 25 .6 (2 .73) 24 .8 (2 .18) 25 .1 (1 .75) 6-21 26 .6 (4 .71) 25 .9 (2 .67) 24 .9 (2 .13) 25 .4 (1 .91) O a Standard deviation is presented in parentheses . "3p b N=21 Ds * Significant trend (linear contrast of means) ; p < 0 .05 . N DuPont-5991 0 0 a m - 24 - H-24516 : Developmental Toxicity Study in Rats TABLE 4 CLINICAL OBSERVATIONS GROUP : I II DAY OF DOSE (mg/kg/day) : 0 50 GESTATION OBSERVATION : NO . EXAMINED : 22 22 4- 5 ALOPECIA 1 1 6-21 ALOPECIA DEHYDRATED SORE STAINED BOTH SHOULDER STAIN PERINEUM STAIN PERIORAL TEETH MISSING WET PERINEUM 6 11 0 1 1 0 0 1 0 0 0 0 1 0 0 0 * Significant trend (Cochran-Armitage test) ; p < 0 .05 . III IV 200 500 22 22 0 0 11 10 0 0 1 0 0 0 1 9* 0 1 1 0 0 1 DuPont-5991 N i=r C3 0 - 25 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 5 REPRODUCTIVE OUTCOME Group : I Dose (mg/kg/day) : 0 II III IV 50 200 500 No . Mated 22 No . Pregnant 22 No . Deaths 0 No . With Total Resorptions 0 No . Litters 22 22 22 22 22 22 22 0 0 0 0 0 0 22 22 22 Means Per Litter Mean Corpora Lutea a 16 .7 (1 .93) b 16 .6 (2 .32) 16 .6 (3 .02) 15 .8 (1 .77) Implantations 14 .2 (1 .31) 14 .8 (1 .82) 14 .2 (2 .29) 14 .4 (1 .81) Resorptions : Total Early Late 0 .4 (0 .58) 0 .4 (0 .58) 0 0 .4 (0 .59) 0 .3 (0 .57) 0 .1 (0 .29) 0 .2 (0 .39) 0 .2 (0 .39) 0 0 .4 (0 .91) 0 .4 (0 .91) 0 Dead Fetuses 0 0 0 0 Live Fetusesc : Total Males Females 13 .9 (1 .49) 6 .3 (2 .29) 7 .6 (1 .94) 14 .4 (1 .71) 6 .5 (2 .22) 8 .0 (2 .24) 14 .0 (2 .44) 6 .9 (2 .31) 7 .1 (2 .29) 14 .0 (2 .24) 6 .5 (1 .79) 7 .5 (1 .71) Mean Fetal Weight : Total 5 .53 (0 .30) 5 .52 (0 .26) 5 .36 (0 .20) 5 .38 (0 .44)* Sex Ratiod 0 .45 (0 .14) 0 .45 (0 .14) 0 .49 (0 .15) 0 .46 (0 .09) a Statistical analyses are not conducted on mean corpora lutea data ; these data are presented for information only . b Standard deviation is reported in parentheses . c Statistical analyses are only conducted on the mean total number of live fetuses per litter . The mean number of males and females are presented for information only . d Number male fetuses/total number fetuses per litter . * Significant trend ; p < 0 .05 . - 26 - Comp any 'n ~SGA eel cQnk s . t~~Pd Doug nOt a H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 6 INCIDENCE OF FETAL MALFORMATIONS Group : I Dose (mg/kg/day) : 0 II III 50 200 EXTERNAL No . Examineda Umbilical hernia Micrognathia No . Affected 305 (22) 317 (22) 1 (1) 1 (1) 2 (2) 309 (22) IV 500 307 (22) VISCERAL No . Examined No . Affected 160 (22) 165 (22) 159 (22) 158 (22) HEAD No . Examined Brain - Distended Ventricles No . Affected 160 (22) 164 (22) 1 (1) 1 (1) 159 (22) 1 (1) 1 (1) 158 (22) SKELETAL No Examined Rib - Fused Micrognathia Vertebra Fused Hemi No . Affected 302 (22) 316 (22) 1 (1) 1 (1) 306 (22) 303 (22) 1 (1) 1 (1) 2 (2) TOTAL NUMBER AFFECTED 0 (0) 4 (4) 1 (1) 0 (0) a Number examined and affected, including the number affected with the listed malformations are expressed as Fetuses (Litters) . b For ease of reading, zeros have been replaced with dashes for the listed malformations . No significant trends were detected . Note : Statistical analyses are only conducted on the individual endpoints . The overall total and totals by exam type are presented for information only . - 27 - lk rqA Tar anP~ ~~~ ~^,,}m ~ Vnmt"1 Sa~'i'~ed 4,ornpa1 - satf tlLLY. t contain T .CA C81 H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 7 INCIDENCE OF FETAL VARIATIONS Group : I Dose (mg/kg/day) : 0 II III IV 50 200 500 DEVELOPMENTAL VARIATIONS EXTERNAL No . Examineda No . Affected 305 (22) 317 (22) 309 (22) 307 (22) VISCERAL No . Examined No . Affected 160 (22) 164 (22) 159 (22) 158 (22) HEAD No . Examined No . Affected 160 (22) 164 (22) 159 (22) 158 (22) SKELETAL No . Examined Rib - Rudimentary Cervical Rib - Supernumerary Scapula - Misshapen Sternebra - Fused No . Affected TOTAL WITH DEVELOPMENTAL VARIATIONS 302 (22) 1 (1) 16 (5) 17 (6) 17 (6) 316 (22) 1 (1) 6 (6) 1 (1) 8 (8) 8 (8) 306 (22) 1 (1) 25 (7) 1 (1) 26 (7) 26 (7) 303 (22) 1 (1) 16 (6) 17 (6) 17 (6) Company Sanitized . Does not contain TSCA C81 - 28 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group : I Dose (mg/kg/day) : 0 II III IV 50 200 500 VARIATIONS DUE TO RETARDED DEVELOPMENT EXTERNAL No . Examined No . Affected 305 (22) 317 (22) 309 (22) 307 (22) VISCERAL No . Examined Heart &/or Greater Vessels Patent Ductus Arteriosis Kidney, Papillae Small Papilla - Size 1 Small Papilla - Size 2 Papilla - Size 3 No . Affected 160 (22) 165 (22) 159 (22) 158 (22) 2 (2) 12 (12) 16 (12 ) 28 (18) 2 (2) 11 (8) 11 (10) 26 (16) 1 (1) 2 (2) 9 (6) 12 (8) 2 (2) 12 (11) 14 (12) HEAD No . Examined No . Affected 160 (22) 164 (22) 159 (22) 158 (22) SKELETAL No . Examined Femur - Retarded Ossification Pelvis - Retarded Ossification Rib - Wavy Skull - Retarded Ossification Sternebra - Retarded Ossification Vertebra - Retarded Ossification No . Affected 302 (22) 1 (1) 7 (7) 1 (1) 110 (21) 116 (21) 316 (22) 1 (1) 10 (8) 2 (2) 146 (21) 149 (21) 306 (22) 1 (1) 1 (1) 1 (1) 26 (14) 4 (3) 124 (21) 136 (22) 303 (22) 6 (3) 10 (4)* 65 (18)* 5 (2) 69 (19) 125 (21) - 29 - ccnt~"i" TgCA Chi Sanitized . Does rO{ pomPany H-24516 : Developmental Toxicity Study in Rats DuPont-5991 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group : I Dose (mg/kg/day) : 0 II III IV 50 200 500 TOTAL WITH VARIATIONS DUE TO RETARDED DEVELOPMENT 136 (22) 166 (22) 145 (22) 135 (21) TOTAL NUMBER FETUSES WITH VARIATIONS 145 (22) 169 (22) 160 (22) 147 (21) a Number examined and affected, including the number affected with the listed variations, are expressed as Fetuses (Litters) . b For ease of reading, zeros have been replaced with dashes for the listed variations . * Significant trend (Jonckheere's test) ; p < 0 .05 Note : Statistical analyses are only conducted on the individual endpoints . The overall total and totals by exam are presented for information only . . Does not contain TSCA CBt CoInPany Sanitized - 30 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 APPENDICES Sanitize ~ 3t to tairc TSCA C61 - 31 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 APPENDIX A Individual Body Weights Company Sanitized . Does not contain TSCA C81 - 32 - H-24516 : Developmental Toxicity Study in Rats Individual Body Weights DuPont-5991 Explanatory Notes Footnotes a Day 0G body weights are provided by the vendor ; the vendor-supplied body weight data are only recorded to 3 significant figures and are reported in this appendix accordingly b Maternal body weight minus the weight of the products of conception . Abbreviations --- = No Data - 33 - 3 ( ~t2 3s++$3 a ~~ A CIBi H-24516 : Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 0a 646224 247 646225 230 646226 260 646230 252 646236 230 646241 245 646251 246 646252 235 646256 250 646257 244 646261 235 646265 234 646272 235 646276 243 646278 235 646282 252 646284 242 646288 236 646290 226 646292 236 646294 240 646308 240 INDIVIDUAL BODY WEIGHTS (grams) 4 255 .6 237 .3 271 .6 241 .0 252 .1 259 .9 259 .9 246 .5 258 .6 246 .9 228 .8 --- --260 .7 227 .4 195 .4 243 .2 208 .6 DAYS OF GESTATION 6 7 8 261 .9 249 .2 291 .2 265 .0 268 .7 271 .4 267 .6 255 .2 257 .4 259 .0 261 .0 250 .6 263 .8 276 .8 260 .4 274 .3 258 .2 264 .9 240 .3 238 .8 252 .4 233 .7 275 .7 254 .0 294 .7 273 .2 267 .9 282 .3 272 .7 265 .3 269 .4 264 .0 266 .4 254 .9 266 .7 272 .2 265 .6 275 .9 268 .4 275 .2 243 .7 225 .7 261 .4 251 .9 279 .7 258 .1 297 .7 285 .4 275 .2 290 .4 275 .5 266 .5 278 .8 264 .9 269 .2 257 .5 271 .3 274 .7 268 .4 282 .8 270 .9 280 .4 247 .2 228 .8 263 .1 258 .8 9 288 .7 262 .6 305 .4 289 .5 283 .4 296 .4 276 .9 270 .3 281 .8 268 .6 276 .9 261 .7 276 .7 287 .5 272 .4 288 .2 274 .3 286 .1 249 .2 226 .8 264 .3 261 .6 DuPont-5991 10 298 .0 268 .0 313 .0 293 .0 291 .3 305 .8 289 .5 284 .7 286 .2 272 .5 282 .2 267 .6 281 .9 294 .1 280 .0 292 .9 280 .1 294 .4 252 .5 222 .8 267 .9 276 .9 Company Sanitized . Does not contain TSCA C181 - 34 - H-24516 : Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 11 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 301 .1 278 .8 324 .4 301 .5 299 .6 312 .5 294 .1 292 .4 301 .4 281 .0 286 .4 273 .4 286 .2 299 .7 288 .2 302 .3 285 .9 303 .8 263 .5 235 .5 274 .2 287 .6 INDIVIDUAL BODY WEIGHTS (grams) 12 309 .1 282 .7 326 .0 307 .6 305 .4 319 .1 295 .0 297 .5 302 .0 283 .9 293 .9 280 .7 305 .9 315 .1 298 .4 313 .4 303 .0 308 .5 265 .9 245 .5 277 .3 291 .7 DAYS OF GESTATION 13 14 15 313 .9 285 .4 337 .9 313 .4 309 .0 320 .5 303 .7 305 .9 318 .6 294 .3 303 .6 284 .5 304 .0 314 .5 302 .2 314 .6 301 .1 318 .6 273 .9 261 .0 283 .9 299 .5 327 .0 295 .2 350 .4 323 .2 321 .4 332 .0 310 .6 312 .6 316 .9 297 .2 304 .6 289 .6 307 .7 321 .8 308 .2 320 .9 306 .7 329 .9 280 .2 273 .9 291 .8 313 .4 330 .5 302 .1 361 .8 327 .9 323 .2 348 .9 315 .9 316 .0 325 .2 302 .2 309 .0 299 .8 313 .0 341 .1 319 .3 333 .3 319 .1 333 .5 285 .6 279 .8 300 .1 326 .5 16 340 .5 313 .9 376 .0 338 .4 334 .0 352 .5 326 .8 329 .2 340 .3 313 .7 315 .2 302 .5 327 .0 347 .6 334 .0 340 .0 329 .2 345 .8 299 .9 296 .2 305 .6 332 .7 DuPont-5991 17 357 .3 326 .6 394 .3 352 .0 349 .6 365 .6 331 .8 343 .9 348 .1 322 .9 324 .2 314 .9 326 .9 359 .9 343 .4 360 .6 347 .9 364 .3 318 .2 311 .9 319 .3 350 .8 - 35 - H-24516 : Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 18 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 373 .9 340 .3 409 .7 368 .7 362 .0 384 .1 354 .0 358 .5 368 .8 340 .4 339 .1 334 .9 347 .5 381 .2 360 .4 376 .2 360 .0 382 .8 331 .2 334 .1 335 .4 373 .2 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 19 20 21 386 .1 350 .5 424 .1 388 .9 378 .3 405 .1 365 .7 379 .4 381 .3 354 .1 348 .4 344 .0 364 .1 403 .8 377 .4 393 .9 380 .2 402 .3 342 .4 345 .0 343 .4 388 .9 405 .3 372 .2 448 .0 402 .9 394 .2 429 .5 385 .0 401 .7 398 .8 368 .3 365 .3 361 .2 385 .5 417 .7 389 .5 413 .2 397 .1 420 .0 358 .6 365 .8 360 .8 414 .5 432 .6 395 .0 471 .4 419 .2 418 .5 459 .1 404 .4 430 .8 427 .8 391 .5 382 .2 383 .5 409 .0 444 .8 417 .2 440 .7 420 .8 443 .1 369 .3 387 .1 378 .6 442 .4 21b 335 .6 301 .4 353 .0 321 .0 321 .0 342 .8 307 .8 325 .7 339 .4 306 .6 305 .8 302 .8 312 .5 342 .5 328 .9 327 .4 325 .1 331 .3 276 .5 283 .2 296 .3 330 .5 DuPont-5991 Company Sanitized . Does not contain TSCA CSI - 36 - H-24516 : Developmental Toxicity Study in Rats GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 0a INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 4 6 7 8 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 252 267 .3 285 .6 285 .5 286 .5 230 237 .6 257 .1 258 .8 266 .4 255 263 .2 282 .3 284 .9 285 .3 246 260 .6 272 .6 278 .5 273 .5 251 256 .5 264 .1 265 .7 267 .2 235 250 .9 252 .4 247 .2 259 .3 253 266 .7 279 .5 268 .1 283 .0 233 218 .6 252 .1 253 .0 262 .3 239 259 .3 272 .9 278 .1 288 .6 245 258 .9 272 .6 272 .0 283 .4 257 238 .3 277 .1 274 .9 289 .2 248 --- 270 .6 275 .2 278 .6 232 253 .1 253 .8 261 .2 233 247 .8 249 .3 252 .1 258 256 .7 227 .0 220 .1 235 --- 273 .9 276 .5 278 .4 230 243 .0 244 .2 249 .5 254 .5 230 246 .5 253 .3 257 .0 263 .8 243 251 .7 256 .5 259 .6 266 .8 233 248 .1 264 .7 269 .4 280 .8 238 254 .2 254 .7 255 .9 263 .1 245 267 .7 274 .9 275 .7 280 .8 9 296 .4 272 .7 295 .9 287 .0 271 .7 263 .4 296 .5 261 .3 285 .6 288 .7 291 .3 277 .9 262 .5 262 .0 248 .3 282 .4 256 .8 267 .1 267 .7 279 .8 266 .9 283 .7 DuPont-5991 10 301 .2 277 .6 298 .6 287 .4 272 .1 266 .2 293 .0 268 .3 296 .7 292 .9 298 .6 282 .8 270 .5 260 .2 264 .5 293 .6 261 .4 272 .1 268 .6 288 .6 277 .7 288 .8 lcpTnp f r .a.~~ TSCCA 0131 itized . l o S got con H-24516 : Developmental Toxicity Study in Rats GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 11 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 12 13 14 15 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 312 .8 284 .2 307 .6 294 .8 280 .2 268 .5 307 .4 274 .3 305 .1 299 .2 300 .6 289 .6 276 .6 271 .4 273 .4 301 .2 268 .0 277 .0 276 .3 298 .7 284 .5 299 .3 320 .7 292 .3 308 .1 302 .2 282 .3 277 .7 320 .1 283 .6 315 .0 308 .8 314 .9 296 .7 283 .9 279 .6 289 .4 305 .1 269 .5 282 .9 278 .6 306 .7 290 .8 303 .4 327 .8 302 .2 318 .1 309 .8 286 .3 286 .7 323 .8 294 .8 321 .7 320 .6 320 .7 298 .5 295 .9 273 .7 292 .3 311 .2 270 .8 290 .9 286 .3 310 .0 294 .7 307 .6 335 .4 313 .3 327 .1 320 .3 295 .1 287 .0 323 .3 296 .6 327 .8 321 .6 321 .2 302 .1 301 .8 285 .5 299 .2 318 .0 276 .5 297 .3 290 .0 313 .1 307 .5 311 .5 340 .5 328 .1 330 .6 325 .4 295 .9 292 .2 337 .8 302 .7 336 .2 330 .5 335 .7 315 .5 306 .1 293 .3 309 .0 330 .1 286 .7 310 .0 294 .6 325 .1 310 .5 315 .0 16 353 .9 335 .3 339 .9 334 .6 306 .0 306 .4 348 .5 316 .5 346 .0 344 .8 344 .1 322 .1 322 .0 304 .2 315 .1 337 .2 296 .8 320 .1 304 .2 336 .6 321 .5 331 .3 DuPont-5991 17 368 .9 355 .3 359 .3 357 .0 321 .8 310 .7 361 .4 330 .3 361 .9 361 .1 360 .1 337 .0 332 .7 310 .6 330 .0 349 .9 305 .4 333 .8 324 .2 351 .4 338 .9 347 .1 Sanit9zed . 0099 not Cpntasn TSCA CE Company - 38 - H-24516 : Developmental Toxicity Study in Rats GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 18 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 19 20 21 21b 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 390 .5 377 .8 368 .2 371 .7 338 .1 324 .0 379 .8 347 .9 376 .4 375 .4 377 .7 352 .9 352 .5 329 .4 350 .8 371 .8 321 .4 356 .2 341 .6 369 .4 355 .9 359 .4 402 .3 391 .6 382 .9 385 .7 348 .8 338 .7 394 .4 357 .1 395 .5 392 .5 397 .1 367 .6 373 .0 350 .0 369 .4 388 .7 328 .4 364 .9 349 .6 380 .1 374 .4 375 .8 423 .2 411 .1 406 .5 406 .9 362 .8 357 .0 421 .0 377 .2 411 .6 413 .1 418 .3 380 .2 387 .1 361 .0 384 .7 410 .0 345 .4 380 .6 368 .0 404 .0 392 .1 389 .9 447 .1 438 .5 437 .3 435 .2 385 .2 379 .0 450 .2 404 .4 432 .5 430 .8 443 .6 404 .3 393 .1 396 .1 408 .8 432 .7 364 .5 417 .4 399 .3 424 .3 407 .5 418 .4 348 .5 340 .8 333 .3 331 .0 296 .3 295 .8 332 .0 314 .1 319 .4 319 .9 336 .2 307 .9 295 .5 301 .8 303 .5 310 .4 284 .8 326 .6 292 .7 316 .1 304 .8 325 .4 DuPont-5991 - 39 - r,$ ,n~~dt.,atlR 95 ~, - H-24516 : Developmental Toxicity Study in Rats GROUP III : 200 MG/KG/DAY ANIMAL NUMBER 0a INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 4 6 7 8 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 252 252 .8 264 .3 263 .8 272 .8 257 273 .6 291 .4 292 .0 301 .2 236 248 .4 259 .4 239 .5 228 .3 251 252 .8 268 .0 270 .0 270 .3 246 255 .3 265 .5 269 .5 272 .3 239 246 .2 260 .2 260 .8 266 .1 243 257 .9 269 .2 261 .7 266 .1 260 242 .8 278 .8 284 .8 285 .5 234 249 .9 264 .1 261 .3 270 .1 241 260 .9 271 .5 278 .6 275 .6 250 256 .3 272 .2 270 .8 279 .5 255 --- 278 .0 275 .9 280 .5 230 248 .4 242 .9 251 .4 245 265 .8 270 .1 274 .9 244 263 .9 264 .6 273 .8 242 268 .9 268 .5 272 .5 236 --- 261 .3 269 .5 272 .1 230 255 .6 262 .7 266 .0 267 .9 230 186 .7 195 .5 221 .0 205 .4 249 276 .8 285 .8 283 .6 287 .7 231 250 .1 257 .9 255 .7 262 .8 238 247 .7 262 .2 263 .8 266 .7 9 268 .6 307 .4 249 .6 278 .0 281 .9 269 .1 263 .0 294 .9 267 .9 275 .7 282 .4 289 .4 254 .5 275 .8 275 .6 274 .6 276 .1 276 .9 235 .4 299 .7 263 .5 243 .8 DuPont-5991 10 270 .6 306 .7 260 .5 282 .5 266 .4 273 .9 271 .9 295 .7 270 .1 280 .2 286 .9 292 .0 265 .1 279 .2 282 .8 278 .8 281 .6 275 .5 209 .9 304 .7 264 .0 246 .6 . Does not contain TSCA ( :RI Company sanitized H-24516 : Developmental Toxicity Study in Rats GROUP III : 200 MG/KG/DAY ANIMAL NUMBER 11 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 12 13 14 15 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 276 .0 315 .9 261 .1 290 .3 275 .0 277 .2 281 .7 305 .6 275 .9 289 .0 298 .4 300 .3 267 .8 287 .8 289 .0 284 .6 288 .1 289 .2 244 .3 316 .3 274 .6 249 .4 288 .0 319 .7 273 .3 298 .8 287 .8 283 .3 292 .5 315 .2 278 .8 295 .9 302 .9 310 .3 277 .1 298 .3 300 .3 295 .1 298 .5 293 .1 244 .7 315 .0 276 .7 257 .6 291 .0 327 .7 279 .9 303 .5 301 .0 288 .8 301 .4 323 .7 287 .6 306 .3 317 .2 303 .8 279 .4 302 .4 299 .7 295 .0 293 .8 296 .1 250 .9 319 .9 281 .4 272 .9 302 .6 337 .8 288 .7 312 .7 315 .8 298 .6 305 .8 329 .6 290 .2 309 .7 319 .6 320 .2 289 .7 306 .3 302 .4 301 .3 292 .8 303 .7 265 .3 330 .0 283 .3 283 .6 304 .7 347 .3 292 .7 311 .2 320 .8 305 .1 311 .7 336 .1 301 .2 319 .9 326 .1 333 .4 297 .3 321 .1 311 .0 312 .1 310 .4 320 .9 273 .1 346 .5 290 .4 291 .8 16 314 .5 358 .7 301 .2 328 .6 335 .4 311 .7 325 .9 351 .4 313 .9 333 .5 336 .6 339 .1 310 .4 329 .9 317 .5 322 .5 312 .5 321 .2 282 .4 349 .5 293 .0 304 .1 DuPont-5991 17 335 .9 376 .0 316 .4 344 .4 346 .7 327 .3 336 .1 366 .8 325 .0 345 .1 351 .5 352 .4 319 .6 344 .1 339 .1 336 .8 324 .2 337 .8 289 .7 375 .0 303 .3 325 .0 Does 'not contalr, ,,,,Pang -anttized . - 41 - H-24516 : Developmental Toxicity Study in Rats GROUP III : 200 MG/KG/DAY ANIMAL NUMBER 18 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 19 20 21 21b 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 349 .2 394 .8 333 .9 360 .0 359 .5 344 .7 353 .3 389 .5 349 .4 360 .0 368 .1 368 .4 336 .1 352 .1 350 .1 357 .2 336 .1 354 .7 316 .5 398 .3 316 .0 339 .9 360 .9 411 .0 346 .3 373 .0 371 .0 355 .3 367 .3 407 .7 367 .7 377 .4 386 .3 382 .5 354 .8 371 .5 368 .0 370 .6 350 .3 365 .7 325 .5 407 .8 322 .4 351 .6 381 .0 425 .2 358 .6 393 .2 383 .2 367 .2 381 .8 426 .9 387 .9 387 .2 402 .5 397 .4 375 .4 393 .2 377 .9 388 .7 365 .1 373 .4 343 .9 420 .3 338 .5 369 .6 403 .6 460 .9 371 .3 414 .8 416 .3 389 .0 394 .9 460 .2 407 .0 407 .1 438 .7 424 .1 403 .0 423 .2 403 .8 410 .9 389 .8 397 .2 363 .8 449 .3 345 .3 391 .1 318 .7 358 .2 289 .7 314 .8 304 .3 311 .1 306 .9 355 .4 288 .4 314 .9 338 .3 330 .3 296 .8 304 .3 306 .6 300 .4 310 .0 302 .3 279 .8 331 .5 291 .8 285 .5 DuPont-5991 . Does not contain TSCA CB1 Company Sanitized H-24516 : Developmental Toxicity Study in Rats GROUP IV : 500 MG/KG/DAY ANIMAL NUMBER 0a INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 4 6 7 8 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 245 255 .5 273 .0 264 .8 277 .6 257 262 .4 280 .9 272 .0 286 .5 253 246 .6 269 .9 270 .6 280 .1 248 260 .8 273 .3 264 .9 278 .8 239 258 .8 271 .1 263 .0 275 .2 250 251 .1 261 .5 263 .1 261 .7 239 257 .5 257 .6 272 .2 276 .4 243 260 .7 275 .4 270 .5 266 .3 255 241 .3 279 .9 282 .5 285 .4 226 248 .4 261 .1 264 .9 268 .0 243 253 .7 271 .8 264 .0 262 .8 229 255 .2 254 .5 257 .3 236 266 .4 264 .5 260 .0 250 277 .8 276 .3 280 .5 250 271 .5 272 .3 280 .5 250 264 .2 263 .8 277 .2 236 252 .4 255 .7 252 .0 252 .2 233 253 .5 263 .1 261 .7 260 .4 240 242 .4 255 .0 246 .5 254 .6 231 260 .2 267 .4 268 .2 268 .9 246 259 .9 261 .2 260 .8 262 .2 230 238 .6 245 .9 243 .2 244 .9 9 280 .0 293 .3 288 .0 278 .7 274 .7 263 .4 281 .4 274 .1 282 .2 269 .3 261 .0 263 .8 267 .9 284 .9 276 .9 275 .3 256 .5 266 .6 254 .4 277 .1 268 .9 245 .8 DuPont-5991 10 275 .6 290 .6 283 .4 285 .6 272 .7 264 .9 288 .3 272 .6 289 .4 273 .1 255 .5 273 .1 268 .6 292 .4 287 .4 284 .0 259 .7 271 .3 261 .1 279 .0 273 .5 251 .5 ComPa - 43 - n ot conla r, A . H-24516 : Developmental Toxicity Study in Rats GROUP IV : 500 MG/KG/DAY ANIMAL NUMBER 11 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 12 13 14 15 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 286 .1 300 .1 289 .1 297 .0 283 .1 271 .0 292 .5 275 .7 301 .4 280 .2 260 .4 284 .0 283 .2 293 .9 298 .1 296 .7 265 .1 286 .0 277 .4 290 .4 281 .8 262 .1 285 .9 310 .4 293 .4 302 .6 288 .2 273 .8 301 .7 281 .9 297 .6 290 .4 275 .9 280 .7 295 .8 309 .0 312 .7 301 .8 275 .4 288 .8 280 .0 289 .0 280 .3 265 .2 291 .5 316 .2 308 .1 313 .8 302 .4 282 .5 310 .1 292 .4 313 .9 298 .6 288 .2 288 .9 297 .5 310 .0 316 .2 310 .4 281 .3 287 .9 296 .5 297 .2 288 .6 265 .7 298 .0 322 .9 317 .5 328 .8 306 .2 280 .5 313 .9 295 .1 317 .1 304 .7 296 .7 294 .1 298 .4 317 .1 325 .9 316 .3 289 .0 300 .2 303 .6 304 .4 298 .1 275 .3 299 .4 325 .4 329 .6 332 .9 318 .2 285 .2 310 .4 304 .7 328 .6 313 .9 306 .2 300 .6 308 .9 330 .5 338 .1 317 .4 295 .0 308 .5 313 .0 313 .6 296 .6 282 .8 16 312 .8 336 .9 335 .4 347 .7 333 .9 298 .7 314 .1 319 .1 342 .8 330 .5 329 .4 315 .4 319 .4 341 .5 351 .7 338 .0 312 .7 323 .7 337 .7 330 .9 310 .0 298 .6 DuPont-5991 17 330 .6 351 .6 356 .5 361 .1 351 .1 302 .4 333 .0 331 .6 360 .8 346 .0 346 .2 310 .2 339 .3 338 .9 364 .4 354 .8 324 .0 348 .5 349 .2 342 .4 324 .8 308 .3 1 sa"10zed- Does not contain TSCA CB CompanY - 44 - H-24516 : Developmental Toxicity Study in Rats GROUP IV : 500 MG/KG/DAY ANIMAL NUMBER 18 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION 19 20 21 21b 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 341 .3 364 .8 370 .6 383 .8 361 .1 315 .8 349 .9 350 .4 381 .6 359 .2 365 .2 351 .4 359 .3 361 .0 377 .1 369 .1 337 .7 367 .9 369 .5 362 .6 335 .7 323 .7 344 .4 380 .9 386 .6 395 .0 372 .9 321 .3 367 .4 366 .4 391 .2 367 .5 388 .8 371 .0 363 .8 379 .3 395 .8 383 .5 346 .3 374 .6 389 .1 371 .3 343 .4 333 .7 362 .4 401 .4 407 .1 416 .2 382 .1 336 .4 376 .8 376 .3 411 .8 322 .6 401 .9 388 .0 378 .9 393 .4 399 .0 398 .8 363 .4 396 .1 403 .2 393 .2 365 .6 352 .7 377 .1 428 .6 432 .4 441 .4 390 .4 357 .4 397 .0 400 .8 430 .6 353 .6 421 .1 414 .4 396 .0 363 .3 358 .3 421 .2 376 .2 423 .0 426 .4 426 .0 384 .6 367 .5 303 .8 327 .4 330 .4 340 .2 282 .9 301 .4 297 .5 307 .6 313 .9 276 .1 309 .0 303 .0 297 .3 276 .2 272 .6 326 .4 280 .0 309 .4 305 .2 324 .5 303 .3 286 .9 DuPont-5991 'C paMt - 45 - Contairl 0 09-S to' H-24516 : Developmental Toxicity Study in Rats DuPont-5991 APPENDIX B Individual Body Weight Changes Company 1?nee not rn^+~+~~ T~~`A r:R' 'Company Sanitized. Does not contain TSCA CS) - 46 - H-24516 : Developmental Toxicity Study in Rats Individual Body Weight Changes Explanatory Notes Footnotes a Maternal body weight minus the weight of the products of conception . Abbreviations --- = No Data DuPont-5991 t - 47 - H-24516 : Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 0-4 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 8 .6 7 .3 11 .6 -11 .0 22 .1 14 .9 13 .9 11 .5 8 .6 2 .9 -6 .2 24 .7 1 .4 -40 .6 3 .2 -31 .4 INDIVIDUAL BODY WEIGHT CHANGES (grams) DAYS OF GESTATION 4-6 6-8 8-10 6 .3 11 .9 19 .6 24 .0 16 .6 11 .5 7 .7 8 .7 -1 .2 12 .1 32 .2 4 .2 12 .9 43 .4 9 .2 25 .1 17 .8 8 .9 6 .5 20 .4 6 .5 19 .0 7 .9 11 .3 21 .4 5 .9 8 .2 6 .9 7 .5 -2 .1 8 .0 8 .5 12 .7 15 .5 6 .9 10 .0 10 .7 25 .1 18 .3 9 .9 15 .3 7 .6 16 .1 15 .4 14 .0 18 .2 7 .4 7 .6 13 .0 10 .1 10 .6 19 .4 11 .6 10 .1 9 .2 14 .0 5 .3 -6 .0 4 .8 18 .1 10-12 11 .1 14 .7 13 .0 14 .6 14 .1 13 .3 5 .5 12 .8 15 .8 11 .4 11 .7 13 .1 24 .0 21 .0 18 .4 20 .5 22 .9 14 .1 13 .4 22 .7 9 .4 14 .8 12-14 17 .9 12 .5 24 .4 15 .6 16 .0 12 .9 15 .6 15 .1 14 .9 13 .3 10 .7 8 .9 1 .8 6 .7 9 .8 7 .5 3 .7 21 .4 14 .3 28 .4 14 .5 21 .7 DuPont-5991 14-16 13 .5 18 .7 25 .6 15 .2 12 .6 20 .5 16 .2 16 .6 23 .4 16 .5 10 .6 12 .9 19 .3 25 .8 25 .8 19 .1 22 .5 15 .9 19 .7 22 .3 13 .8 19 .3 - 48 - f:~~~pl^'rRrA 081 COm"A^ -_ . Does Clot cps~tain'5SCA G~1 ?CoMri Drs 'Sanitized H-24516 : Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 16-18 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 33 .4 26 .4 33 .7 30 .3 28 .0 31 .6 27 .2 29 .3 28 .5 26 .7 23 .9 32 .4 20 .5 33 .6 26 .4 36 .2 30 .8 37 .0 31 .3 37 .9 29 .8 40 .5 INDIVIDUAL BODY WEIGHT CHANGES (grams) DAYS OF GESTATION 18-20 20-21 6-21 31 .4 31 .9 38 .3 34 .2 32 .2 45 .4 31 .0 43 .2 30 .0 27 .9 26 .2 26 .3 38 .0 36 .5 29 .1 37 .0 37 .1 37 .2 27 .4 31 .7 25 .4 41 .3 27 .3 22 .8 23 .4 16 .3 24 .3 29 .6 19 .4 29 .1 29 .0 23 .2 16 .9 22 .3 23 .5 27 .1 27 .7 27 .5 23 .7 23 .1 10 .7 21 .3 17 .8 27 .9 170 .7 145 .8 180 .2 154 .2 149 .8 187 .7 136 .8 175 .6 170 .4 132 .5 121 .2 132 .9 145 .2 168 .0 156 .8 166 .4 162 .6 178 .2 129 .0 148 .3 126 .2 208 .7 6-21a 73 .7 52 .2 61 .8 56 .1 52 .3 71 .4 40 .2 70 .5 82 .0 47 .6 44 .8 52 .2 48 .7 65 .7 68 .5 53 .1 66 .9 66 .4 36 .2 44 .4 43 .9 96 .8 DuPont-5991 Does not contain TSCA CB% S. anitized !ComPoy - 49 - H-24516 : Developmental Toxicity Study in Rats GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 0-4 INDIVIDUAL BODY WEIGHT CHANGES (grams) DAYS OF GESTATION 4-6 6-8 8-10 10-12 12-14 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 15 .3 7 .6 8 .2 14 .6 5 .5 15 .9 13 .7 -14 .4 20 .3 13 .9 -18 .7 --13 .0 16 .5 8 .7 15 .1 16 .2 22 .7 18 .3 19 .5 19 .1 12 .0 7 .6 1 .5 12 .8 33 .5 13 .6 13 .7 38 .8 --1 .2 6 .8 4 .8 16 .6 0 .5 7 .2 0 .9 9 .3 3 .0 0 .9 3 .1 6 .9 3 .5 10 .2 15 .7 10 .8 12 .1 8 .0 8 .1 4 .3 -36 .6 4 .5 10 .3 10 .5 10 .3 16 .1 8 .4 5 .9 14 .7 11 .2 13 .3 13 .9 4 .9 6 .9 10 .0 6 .0 8 .1 9 .5 9 .4 4 .2 9 .3 8 .1 44 .4 15 .2 6 .9 8 .3 1 .8 7 .8 14 .6 8 .0 19 .5 14 .7 9 .5 14 .8 10 .2 11 .5 27 .1 15 .3 18 .3 15 .9 16 .3 13 .9 13 .4 19 .4 24 .9 11 .5 8 .1 10 .8 10 .0 18 .1 13 .1 14 .6 14 .7 21 .0 19 .0 18 .1 12 .8 9 .3 3 .2 13 .0 12 .8 12 .8 6 .3 5 .4 17 .9 5 .9 9 .8 12 .9 7 .0 14 .4 11 .4 6 .4 16 .7 8 .1 DuPont-5991 14-16 18 .5 22 .0 12 .8 14 .3 10 .9 19 .4 25 .2 19 .9 18 .2 23 .2 22 .9 20 .0 20 .2 18 .7 15 .9 19 .2 20 .3 22 .8 14 .2 23 .5 14 .0 19 .8 - 50 - '''`t (,Ei 4~='in ," SC'A H-24516 : Developmental Toxicity Study in Rats GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 16-18 INDIVIDUAL BODY WEIGHT CHANGES (grams) DAYS OF GESTATION 18-20 20-21 6-21 6-21a 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 36 .6 42 .5 28 .3 37 .1 32 .1 17 .6 31 .3 31 .4 30 .4 30 .6 33 .6 30 .8 30 .5 25 .2 35 .7 34 .6 24 .6 36 .1 37 .4 32 .8 34 .4 28 .1 32 .7 33 .3 38 .3 35 .2 24 .7 33 .0 41 .2 29 .3 35 .2 37 .7 40 .6 27 .3 34 .6 31 .6 33 .9 38 .2 24 .0 24 .4 26 .4 34 .6 36 .2 30 .5 23 .9 27 .4 30 .8 28 .3 22 .4 22 .0 29 .2 27 .2 20 .9 17 .7 25 .3 24 .1 6 .0 35 .1 24 .1 22 .7 19 .1 36 .8 31 .3 20 .3 15 .4 28 .5 161 .5 181 .4 155 .0 162 .6 121 .1 126 .6 170 .7 152 .3 159 .6 158 .2 166 .5 133 .7 140 .0 148 .3 152 .1 158 .8 120 .3 164 .1 142 .8 159 .6 152 .8 143 .5 62 .9 83 .7 51 .0 58 .4 32 .2 43 .4 52 .5 62 .0 46 .5 47 .3 59 .1 37 .3 42 .4 54 .0 46 .8 36 .5 40 .6 73 .3 36 .2 51 .4 50 .1 50 .5 DuPont-5991 c omps nY Sanitized . 00 nt H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP III : 200 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 0-4 4-6 6-8 8-10 10-12 12-14 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 0 .8 16 .6 12 .4 1 .8 9 .3 7 .2 14 .9 17 .2 15 .9 19 .9 6 .3 25 .6 -43 .3 27 .8 19 .1 9 .7 11 .5 17 .8 11 .0 15 .2 10 .2 14 .0 11 .3 36 .0 14 .2 10 .6 15 .9 7 .1 8 .8 9 .0 7 .8 14 .5 8 .5 9 .8 31 .1 2 .3 6 .8 5 .9 3 .1 6 .7 6 .0 4 .1 7 .3 2 .5 3 .0 9 .1 9 .9 3 .6 10 .8 5 .2 9 .9 1 .9 4 .9 4 .5 -2 .2 5 .5 32 .2 12 .2 -5 .9 7 .8 5 .8 10 .2 0 .0 4 .6 7 .4 11 .5 13 .7 4 .3 9 .0 6 .3 9 .5 7 .6 4 .5 17 .0 1 .2 -20 .1 17 .4 13 .0 12 .8 16 .3 21 .4 9 .4 20 .6 19 .5 8 .7 15 .7 16 .0 18 .3 12 .0 19 .1 17 .5 16 .3 16 .9 17 .6 34 .8 10 .3 12 .7 11 .0 14 .6 18 .1 15 .4 13 .9 28 .0 15 .3 13 .3 14 .4 11 .4 13 .8 16 .7 9 .9 12 .6 8 .0 2 .1 6 .2 -5 .7 10 .6 20 .6 15 .0 6 .6 26 .0 DuPont-5991 14-16 11 .9 20 .9 12 .5 15 .9 19 .6 13 .1 20 .1 21 .8 23 .7 23 .8 17 .0 18 .9 20 .7 23 .6 15 .1 21 .2 19 .7 17 .5 17 .1 19 .5 9 .7 20 .5 - 52 - TSCA CS 1 . does 01 t0nla'n antfigz`'d H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP III : 200 MG/KG/DAY ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-20 20-21 6-21 6-21a 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 34 .7 36 .1 32 .7 31 .4 24 .1 33 .0 27 .4 38 .1 35 .5 26 .5 31 .5 29 .3 25 .7 22 .2 32 .6 34 .7 23 .6 33 .5 34 .1 48 .8 23 .0 35 .8 31 .8 30 .4 24 .7 33 .2 23 .7 22 .5 28 .5 37 .4 38 .5 27 .2 34 .4 29 .0 39 .3 41 .1 27 .8 31 .5 29 .0 18 .7 27 .4 22 .0 22 .5 29 .7 22 .6 35 .7 12 .7 21 .6 33 .1 21 .8 13 .1 33 .3 19 .1 19 .9 36 .2 26 .7 27 .6 30 .0 25 .9 22 .2 24 .7 23 .8 19 .9 29 .0 6 .8 21 .5 139 .3 169 .5 111 .9 146 .8 150 .8 128 .8 125 .7 181 .4 142 .9 135 .6 166 .5 146 .1 154 .6 157 .4 139 .9 142 .0 128 .5 134 .5 168 .3 163 .5 87 .4 128 .9 54 .4 66 .8 30 .3 46 .8 38 .8 50 .9 37 .7 76 .6 24 .3 43 .4 66 .1 52 .3 48 .4 38 .5 42 .7 31 .5 48 .7 39 .6 84 .3 45 .7 33 .9 23 .3 DuPont-5991 Compon San;t ;7gd s ~~, A '.c . nfof ran}A1 Arc eo% -53- H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP IV : 500 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 0-4 4-6 6-8 8-10 10-12 12-14 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 10 .5 5 .4 -6 .4 12 .8 19 .8 1 .1 18 .5 17 .7 -13 .7 22 .4 10 .7 --- --16 .4 20 .5 2 .4 29 .2 13 .9 8 .6 17 .5 18 .5 23 .3 12 .5 12 .3 10 .4 0 .1 14 .7 38 .6 12 .7 18 .1 --- --3 .3 9 .6 12 .6 7 .2 1 .3 7 .3 4 .6 5 .6 10 .2 5 .5 4 .1 0 .2 18 .8 -9 .1 5 .5 6 .9 -9 .0 2 .1 -6 .4 2 .7 9 .0 13 .0 -3 .5 -2 .7 -0 .4 1 .5 1 .0 -1 .0 -2 .0 4 .1 3 .3 6 .8 -2 .5 3 .2 11 .9 6 .3 4 .0 5 .1 -7 .3 15 .8 8 .6 11 .9 6 .9 6 .8 7 .5 10 .9 6 .5 10 .1 11 .3 6 .6 10 .3 19 .8 10 .0 17 .0 15 .5 8 .9 13 .4 9 .3 8 .2 17 .3 20 .4 7 .6 27 .2 16 .6 25 .3 17 .8 15 .7 17 .5 18 .9 10 .0 6 .8 13 .7 12 .1 12 .5 24 .1 26 .2 18 .0 6 .7 12 .2 13 .2 19 .5 14 .3 20 .8 13 .4 2 .6 8 .1 13 .2 14 .5 13 .6 11 .4 23 .6 15 .4 17 .8 10 .1 DuPont-5991 14-16 14 .8 14 .0 17 .9 18 .9 27 .7 18 .2 0 .2 24 .0 25 .7 25 .8 32 .7 21 .3 21 .0 24 .4 25 .8 21 .7 23 .7 23 .5 34 .1 26 .5 11 .9 23 .3 - 54 - H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP IV : 500 MG/KG/DAY ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-20 20-21 6-21 6-21a 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 28 .5 27 .9 35 .2 36 .1 27 .2 17 .1 35 .8 31 .3 38 .8 28 .7 35 .8 36 .0 39 .9 19 .5 25 .4 31 .1 25 .0 44 .2 31 .8 31 .7 25 .7 25 .1 21 .1 36 .6 36 .5 32 .4 21 .0 20 .6 26 .9 25 .9 30 .2 -36 .6 36 .7 36 .6 19 .6 32 .4 21 .9 29 .7 25 .7 28 .2 33 .7 30 .6 29 .9 29 .0 14 .7 27 .2 25 .3 25 .2 8 .3 21 .0 20 .2 24 .5 18 .8 31 .0 19 .2 26 .4 17 .1 -30 .1 -40 .7 22 .4 12 .8 26 .9 23 .2 32 .8 19 .0 14 .8 104 .1 147 .7 162 .5 168 .1 119 .3 95 .9 139 .4 125 .4 150 .7 92 .5 149 .3 159 .2 129 .6 85 .5 86 .8 157 .0 120 .5 159 .9 171 .4 158 .6 123 .4 121 .6 30 .8 46 .5 60 .5 66 .9 11 .8 39 .9 39 .9 32 .2 34 .0 15 .0 37 .2 47 .8 30 .9 -1 .6 1 .1 62 .1 24 .3 46 .3 50 .2 57 .1 42 .1 41 .0 DuPont-5991 . Does floe conjoin TSCA CSe Company Sanitized - 55 - H-24516 : Developmental Toxicity Study in Rats DuPont-5991 APPENDIX C Individual Food Consumption Parry San'` zed' 00 nv contain SCA CB , - 56 - H-24516 : Developmental Toxicity Study in Rats Individual Food Consumption Explanatory Notes Abbreviations --- = No Data DuPont-5991 . Does not contain TSCA CB% Company Sanitized H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 14-16 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 20 .1 23 .2 23 .2 15 .1 27 .7 24 .0 22 .0 40 .4 8 .4 23 .3 26 .6 20 .3 23 .5 26 .8 23 .2 23 .7 24 .2 26 .0 19 .5 23 .7 21 .5 13 .9 36 .1 24 .4 27 .6 28 .0 22 .9 28 .0 21 .8 24 .7 24 .1 21 .0 22 .2 19 .9 23 .8 26 .7 22 .6 23 .3 27 .7 28 .3 20 .8 14 .6 24 .4 27 .3 29 .7 22 .6 28 .2 25 .3 24 .5 29 .3 23 .5 28 .0 27 .0 21 .4 23 .9 23 .2 24 .9 30 .2 24 .3 25 .7 28 .7 31 .0 20 .3 12 .4 23 .9 28 .3 30 .9 27 .4 32 .5 30 .9 28 .1 31 .2 24 .1 28 .9 30 .9 24 .4 25 .2 22 .1 29 .3 31 .4 26 .4 26 .3 31 .6 29 .2 20 .8 18 .6 23 .7 32 .4 29 .7 25 .3 33 .5 30 .6 28 .0 31 .0 23 .8 28 .9 29 .8 24 .7 24 .4 24 .8 27 .4 26 .6 29 .1 27 .6 31 .9 22 .9 29 .5 25 .8 31 .1 29 .0 30 .3 34 .7 29 .5 27 .9 34 .1 23 .3 26 .0 29 .7 25 .6 23 .8 23 .9 29 .9 32 .5 29 .3 25 .8 31 .4 31 .1 23 .2 26 .3 26 .4 31 .6 DuPont-5991 16-18 31 .6 29 .7 35 .9 29 .6 28 .7 34 .0 26 .8 31 .6 33 .2 26 .1 25 .4 26 .9 28 .9 34 .5 29 .7 30 .4 33 .5 35 .2 25 .8 30 .6 30 .0 31 .3 Company Sanitized , DO ;-'S t1oa Corlakln T . H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 18-20 DAYS OF GESTATION 20-21 4-21 6-21 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 31 .6 28 .7 30 .7 29 .2 29 .8 34 .3 25 .9 29 .9 32 .0 27 .9 23 .8 26 .9 31 .1 36 .3 28 .3 31 .6 30 .5 30 .6 22 .6 22 .4 24 .2 21 .1 31 .1 25 .5 32 .0 24 .4 26 .7 32 .9 22 .9 28 .6 30 .8 22 .9 19 .9 24 .5 26 .9 26 .9 32 .6 32 .5 34 .2 28 .6 17 .8 24 .8 19 .9 30 .3 29 .9 26 .4 30 .8 27 .1 27 .2 30 .9 23 .8 29 .7 27 .1 24 .2 24 .1 23 .6 27 .3 12 .3 26 .7 27 .3 29 .7 30 .3 21 .7 22 .4 24 .7 27 .3 31 .2 26 .8 31 .9 28 .7 27 .1 31 .8 24 .1 28 .3 29 .6 24 .4 23 .8 24 .0 27 .8 10 .4 27 .1 27 .8 30 .4 30 .9 22 .0 22 .2 25 .1 29 .1 H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 4-6 6-8 DAYS OF GESTATION 8-10 10-12 12-14 14-16 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 26 .5 26 .1 25 .0 23 .6 20 .3 20 .6 22 .4 24 .6 29 .6 21 .4 25 .1 22 .0 24 .0 18 .4 12 .6 26 .9 21 .5 23 .6 20 .9 21 .9 39 .9 22 .1 22 .3 23 .9 19 .9 20 .2 17 .9 17 .3 15 .6 22 .9 27 .0 23 .1 23 .9 20 .4 23 .8 17 .1 2 .1 23 .6 19 .9 24 .1 20 .9 24 .0 23 .4 20 .8 25 .1 22 .8 21 .9 22 .3 20 .7 20 .9 23 .8 24 .4 28 .6 24 .7 23 .0 21 .4 24 .4 19 .1 24 .4 27 .4 21 .2 24 .3 21 .1 24 .0 28 .0 22 .9 29 .9 29 .0 24 .5 25 .8 22 .9 24 .9 28 .7 27 .5 33 .6 29 .4 28 .3 23 .0 25 .0 23 .2 31 .8 26 .4 21 .7 25 .8 22 .3 25 .4 26 .6 24 .6 29 .1 31 .3 25 .7 26 .9 22 .0 25 .6 26 .1 29 .7 31 .3 30 .1 27 .6 24 .2 27 .6 22 .2 30 .9 28 .7 20 .7 25 .2 23 .3 24 .3 27 .4 23 .0 30 .7 34 .7 25 .7 28 .6 17 .1 23 .3 28 .5 31 .9 30 .3 29 .9 27 .3 27 .0 27 .2 21 .8 27 .6 28 .6 22 .9 29 .7 22 .2 24 .6 26 .4 26 .1 DuPont-5991 16-18 33 .8 37 .8 27 .9 30 .4 23 .1 25 .0 28 .1 30 .9 32 .8 32 .5 31 .2 28 .8 28 .8 23 .2 28 .8 28 .0 24 .8 28 .6 27 .9 28 .8 32 .3 27 .6 ;Company Sanitized . Does not contain TSCA rte , -60- H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP II : 50 MG/KG/DAY ANIMAL NUMBER 18-20 DAYS OF GESTATION 20-21 4-21 6-21 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 30 .4 33 .4 27 .3 29 .0 23 .0 25 .8 30 .3 31 .8 31 .1 32 .0 32 .4 26 .4 30 .1 23 .4 28 .6 29 .4 22 .6 25 .0 23 .5 26 .2 31 .8 25 .6 27 .4 31 .6 30 .4 30 .2 22 .5 21 .9 26 .7 30 .1 28 .7 23 .1 27 .0 25 .2 19 .2 28 .3 23 .0 30 .7 19 .3 31 .2 28 .7 25 .8 22 .7 31 .2 28 .4 30 .0 25 .1 26 .1 20 .9 22 .8 25 .5 28 .1 30 .4 27 .6 27 .3 24 .2 25 .9 21 .5 23 .3 27 .6 21 .8 26 .1 23 .1 24 .9 29 .1 24 .5 28 .7 30 .5 25 .1 26 .4 21 .0 23 .1 25 .9 28 .6 30 .5 28 .5 27 .6 24 .5 26 .2 21 .9 24 .8 27 .7 21 .8 26 .4 23 .4 25 .3 27 .6 24 .8 DuPont-5991 CAI . Does not contain T$GA Sanitized pimpany - 61 - H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP III : 200 MG/KG/DAY ANIMAL NUMBER 4-6 6-8 DAYS OF GESTATION 8-10 10-12 12-14 14-16 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 20 .8 26 .4 21 .0 22 .4 23 .3 19 .9 20 .4 27 .4 22 .3 26 .1 26 .6 23 .1 21 .1 22 .9 22 .2 36 .0 30 .1 24 .9 10 .1 22 .1 20 .9 28 .6 17 .8 23 .4 1 .3 19 .3 21 .9 19 .9 17 .8 24 .7 20 .1 21 .4 21 .6 21 .0 19 .2 24 .0 20 .6 20 .4 25 .5 22 .7 17 .5 20 .7 20 .6 25 .5 16 .7 23 .3 19 .3 21 .4 15 .6 18 .3 18 .1 25 .7 18 .5 21 .3 25 .0 23 .1 21 .8 22 .6 22 .9 23 .9 25 .3 24 .1 15 .1 26 .7 20 .1 8 .3 23 .8 25 .3 21 .7 24 .8 22 .7 22 .7 25 .1 29 .1 21 .6 26 .4 29 .1 26 .6 22 .9 25 .9 25 .6 26 .1 24 .8 26 .1 25 .3 26 .2 22 .4 15 .7 25 .3 26 .6 27 .2 25 .8 28 .1 23 .7 26 .1 29 .2 23 .9 28 .3 31 .3 27 .9 23 .7 26 .8 24 .8 27 .9 24 .9 25 .4 24 .9 25 .1 22 .6 23 .8 27 .4 30 .4 26 .2 26 .0 27 .6 25 .5 24 .7 29 .0 22 .2 27 .7 28 .1 29 .6 26 .2 25 .9 25 .2 29 .3 23 .3 26 .7 33 .9 27 .3 22 .6 27 .4 DuPont-5991 16-18 29 .2 31 .9 26 .3 28 .4 27 .6 29 .4 25 .1 31 .9 24 .4 27 .9 30 .7 32 .3 25 .5 24 .7 28 .4 29 .6 26 .8 31 .9 21 .5 33 .8 26 .9 28 .4 - 62 - H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP III : 200 MG/KG/DAY ANIMAL NUMBER 18-20 DAYS OF GESTATION 20-21 4-21 6-21 646222 646228 646232 646234 646237 646238 646243 646248 646254 646258 646259 646266 646268 646269 646271 646273 646285 646299 646302 646303 646305 646307 29 .1 29 .8 25 .1 28 .3 20 .7 27 .8 26 .5 31 .3 27 .1 29 .4 32 .4 31 .0 26 .3 27 .7 27 .5 28 .6 26 .2 22 .4 26 .7 26 .3 23 .0 25 .7 27 .2 32 .7 20 .4 24 .1 25 .9 24 .7 17 .2 35 .3 24 .8 21 .7 32 .3 28 .2 25 .3 26 .5 23 .4 24 .0 27 .8 24 .5 24 .5 27 .7 18 .6 25 .1 24 .0 27 .5 21 .0 24 .5 23 .6 23 .5 22 .6 28 .9 22 .7 25 .8 28 .3 26 .9 23 .5 25 .1 24 .6 27 .5 26 .0 25 .5 22 .0 26 .1 22 .2 23 .1 24 .4 27 .6 21 .0 24 .8 23 .6 24 .0 22 .9 29 .1 22 .7 25 .8 28 .6 27 .4 23 .8 25 .4 24 .9 26 .4 25 .4 25 .5 23 .6 26 .7 22 .3 22 .3 DuPont-5991 co ntain 'TSCA C81 . Does not 'Company Sanitized - 63 - H-24516 : Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP IV : 500 MG/KG/DAY ANIMAL NUMBER 4-6 6-8 DAYS OF GESTATION 8-10 10-12 12-14 14-16 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 23 .4 24 .3 20 .1 24 .3 26 .8 20 .7 18 .4 24 .8 24 .9 25 .5 24 .8 22 .0 24 .0 24 .7 24 .3 20 .0 21 .6 24 .8 22 .2 22 .3 20 .8 24 .6 19 .8 21 .4 23 .8 20 .6 21 .3 16 .8 25 .0 17 .1 27 .3 22 .2 16 .8 19 .2 17 .7 22 .8 21 .8 21 .1 16 .3 22 .4 16 .4 22 .7 19 .8 20 .7 18 .7 22 .7 22 .1 21 .8 20 .9 15 .6 24 .8 16 .9 22 .9 23 .9 11 .8 23 .9 19 .4 24 .9 21 .3 21 .4 18 .1 22 .0 18 .1 23 .3 20 .8 21 .4 20 .8 26 .8 24 .3 27 .3 25 .6 19 .2 26 .8 20 .0 28 .4 28 .0 19 .6 25 .3 26 .0 26 .7 28 .4 24 .7 26 .1 26 .2 24 .4 25 .3 21 .6 24 .6 21 .4 25 .9 27 .4 32 .1 25 .8 22 .1 27 .9 23 .2 29 .3 30 .9 27 .3 23 .5 26 .4 28 .1 30 .3 25 .5 24 .6 23 .8 26 .6 25 .4 22 .6 24 .2 26 .2 27 .3 30 .5 30 .6 30 .3 22 .6 18 .1 25 .9 30 .3 32 .7 34 .9 25 .6 27 .2 29 .7 32 .3 25 .0 25 .9 28 .1 29 .5 28 .9 21 .9 27 .1 DuPont-5991 16-18 27 .3 27 .2 32 .8 34 .7 29 .0 24 .6 29 .2 28 .4 32 .8 35 .4 35 .6 28 .3 32 .3 24 .0 31 .8 28 .0 27 .6 34 .1 33 .8 31 .5 27 .0 28 .7 Prili`0Tly y .3rt t V J -64- H-24516: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER 18- 20 DAYS OF GESTATI ON 20- 21 4- 21 6-:21 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 25 .1 27 .7 31 .9 32 .4 24 .4 22 .9 28 .2 25 .1 27 .8 16 .1 31 .8 29 .6 26 .2 30 .1 30 .9 26 .0 28 .1 22 .7 34 .1 22 .4 38 .8 25 .3 24 .5 28 .6 31 .0 31 .4 19 .3 26 .0 25 .4 24 .2 24 .5 50 .6 25 .0 30 .8 18 .1 0 .7 1 .6 24 .1 24 .1 29 .7 24 .7 31 .8 24 .4 24 .6 22 .9 25 .6 26 .9 28 .2 25 .1 20 .9 24 .8 22 .8 27 .7 28 .2 25 .3 25 .0 24 .5 24 .9 26 .1 24 .0 23 .6 25 .7 25 .6 25 .6 24 .2 24 .6 22 .9 25 .8 27 .8 28 .7 24 .9 20 .9 25 .7 22 .5 28 .1 28 .6 25 .4 25 .4 24 .6 24 .9 26 .3 24 .5 23 .8 25 .9 26 .0 26 .1 24 .6 24 .6 DuPont-5991 Company Sanffi.ed. Doea not con*- ^ -l -65- H-24516: Developmental Toxicity Study in Rats______________________________DuPont-5991 APPENDIX D Individual Clinical Observations --'sa.--'S'Rtwi^--d'"- Doestiol^31^3^01 .*rfM"aW - -66- H-24516: Developmental Toxicity Study in Rats______________________________DuPont-5991 Individual Clinical Observations Explanatory Notes Footnotes a The first observation recorded each day is indicated by "a"; the second by "b". Observations were made twice daily on days 6-20G. If no signs were observed during the study examinations, the "b" entries are omitted from the printout. Company Sanitized, Does not contain TSCA CBI -67- H-24516: Developmental Toxicity Study in Rats GROUP I: ANIMAL NUMBER: 0 MG/KG/DAY OBSERVATION 646224 ALOPECIA LEFT FRONT PAW ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 03/19/01 646225 SACRIFICED BY DESIGN 03/19/01 646226 SACRIFICED BY DESIGN 03/19/01 646230 SACRIFICED BY DESIGN 03/19/01 646236 SACRIFICED BY DESIGN 03/19/01 646241 ALOPECIA RIGHT FRONT LEG ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 03/19/01 646251 SACRIFICED BY DESIGN 03/20/01 646252 SACRIFICED BY DESIGN 03/20/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, a i i i i t i i i i t i i 1- / 141 i i i i i --} i t i i i t i i i i i ,J-J,-L~t, , , , , , a b a b c- ,,,,I ,I ,,,,I ,,,,I ,,,,I ,,,,I ,,,,t ,,,,I ,,,,t , ,,,I ,,, , ,,,I , ,,,I , , , , t ,15,16,17,18,19,20 ,15,16,17,18,19,20 ,15,16,17,18,19,20 ,15,16,17,18,19,20 I I I I t t a * '* i t i i i i i i i i i i t t i i i i I , , , , , , , , , , , a- ^ 111111111 I I I t I I I I I t , , , , , , , , , , , ,11,1,1,1,1,1,1,1, a: , , , , ,15, ,17,18.19,20 D; i i i i i i /-L7,18/ly/<&U 3-! i i i i i i i i t i i i i i /-Lb/ / , / 3; i i i i i i i i i t i i t /J.-3/.LOj, / / / 3-1 i i i i i i i i f i i i i i i i f i f i i i i i i i i i i i i i i i i i i i 9-1 i i i i i i i i i t i i i t i i i i f -68- H-24516: Developmental Toxicity Study in Rats GROUP I: ANIMAL NUMBER: 0 MG/KG/DAY OBSERVATION 646256 SACRIFICED BY DESIGN 03/20/01 646257 SACRIFICED BY DESIGN 03/20/01 646261 SACRIFICED BY DESIGN 03/20/01 646265 SACRIFICED BY DESIGN 3/21/01 646272 ALOPECIA LEFT HIND QUARTERS SACRIFICED BY DESIGN 3/21/01 646276 SACRIFICED BY DESIGN 3/21/01 646278 SACRIFICED BY DESIGN 3/21/01 646282 ALOPECIA BOTH FRONT PAW SORE NOSE SACRIFICED BY DESIGN 3/21/01 646284 SACRIFICED BY DESIGN 3/21/01 646288 SACRIFICED BY DESIGN 3/22/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 a: ,,,,,,,,, , , , , , , , , , , a: , , , , , , , , , , ,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,, a: , , ,13,14,15,16,17,18,19,20 b: , , ,13,14,15,16,17,18.19,20 ,,,,,,,,,,,,,,,,,,,,,,,,,,, a: , , , , , , , , , , a: , , , , , , , , , , ,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,, a: , , , , , ,16,17,18,19,20 b: , , , , , ,16,17,18.19,20 ,,,,,,,,, a: , , , , , , , , , ,20 ,,,,,,,,,,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,,,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,, a; , , , , , , , , , , -^- H-24516: Developmental Toxicity Study in Rats GROUP I: ANIMAL NUMBER: 0 MG/KG/DAY OBSERVATION 646290 SACRIFICED BY DESIGN 03/22/01 646292 TOP TEETH MISSING ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 03/22/01 646294 SACRIFICED BY DESIGN 03/22/01 646308 ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 03/22/01 INDIVIDUAL CLINICAL OBSERVATIONSS DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,2 a: i i i i i i i i t a: i i i i i i ,9,10,11,12,13,14,15, , b: 8,9,10,11,12,13,14, , , a: , , , , , ,14,15,16, iiiiiii b: , , , , , ,14,15,16, iiiiiii a: / / / / / / / / / a: , , , ,5, ,7,8,9,10,11,12, b: a: .70- H-24516: Developmental Toxicity Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS^ GROUP II: 50 MG/KG/DAY ANIMAL OBSERVATION DAYS OP GESTATION ON WHICH SIGN WAS OBSERVED NUMBER: 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 ;======ss^:^^s;KS==^==:s:=:a:siss==:=;=K:=:==;s:=^:=:=:a=;===:====:a=====:=^:=s;a:==;a==s 646227 ALOPECIA RIGHT HIND QUARTERS SACRIFICED BY DESIGN 03/19/01 646229 SACRIFICED BY DESIGN 03/19/01 646231 SACRIFICED BY DESIGN 03/19/01 646235 SACRIFICED BY DESIGN 03/19/01 646242 SACRIFICED BY DESIGN 03/19/01 646245 SACRIFICED BY DESIGN 03/20/01 646246 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/20/01 646249 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 03/20/01 a: 10,11, , ,14,15, , , , , b: ,10,11, , ,14,15, ,,,,,,,,, a: , , , , , , , , , , ,,,.,,,,,,,,,,,,,,,,,,,,,,, ,,,,, a: , , , , , , , , , , a: , , , , , , , , , - ,,,,,,,,, a: ,,,,,,,,,,,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,, a: , , , ,14,15,16,17,18,19,20 b: , , , ,14, ,16,17,18,19,20 ,,,,,,,,, a: , , , , , ,16,17,18,19,20 ,,,,,,,,, b: , , , , ,15,16,17,18,19,20 ,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,,,,, ,, ,, ,. a: , , , , , , , ,9,10,11,12,13,14,15,16,17,18,19,20 b: ,9,10,11,12,13,14,15,16,17,18,19,20 a: , , , , , , , , ,19,20 ,,,,,,, b: . , , , , , , , ,19,20 ,,,,,,,,,,,,,,,,,,,,,,,,,,, a: , , , , , , , , , , -71 H-24516: Developmental Toxicity Study in Rats GROUP II: ANIMAL NUMBER: 50 MG/KG/DAY OBSERVATION 646250 SACRIFICED BY DESIGN 03/20/01 646253 ALOPECIA RIGHT FRONT PAW STAIN BOTH SHOULDER YELLOW STAIN BOTH SHOULDER BROWN SACRIFICED BY DESIGN 03/20/01 646264 ALOPECIA ABDOM-INAL SACRIFICED BY DESIGN 03/20/01 646267 SACRIFICED BY DESIGN 3/21/01 646274 ALOPECIA RIGHT FRONT PAW SACRIFICED BY DESIGN 3/21/01 646279 SACRIFICED BY DESIGN 3/21/01 646280 DEHYDRATED SACRIFICED BY DESIGN 3/21/01 INDIVIDUAL CLINICAL OBSERVATIONS'^ DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 ======:==S==========;S ==s====^=====:s===s==s=:=;=:= ,///// //////;/////////// l i l I l f l i l l f / l l l i l l l i l l i f l i i .18, ,18, ,19, ,19, ,20 ,20 , a: b: 3-1 / / / / / / / / / , , , ,5,6,7, ,9,10,11, , , , , ,6,7, , ,10,11, / ; ,,/ ,,/ ,,/ ,,/ ,,/ ,,/,,/ ,20 ,20 / / / / / / , , 3-! u^ 9-^ iti iii iii fii fii ifi iti iiiiit i i f i i i i i i i i i i t i i i i f i i f i i I /19/20/ ;xy/^u i I f a: 9-S 9.^ IiiIiIiIiIiiI^IIiIi i f i I i I i f i T i I i f i I i I i I -72- H-24516: Developmental Toxicity Study in Rats GROUP II: ANIMAL NUMBER: 50 MG/KG/DAY OBSERVATION 646286 ALOPECIA LEFT FRONT PAW ALOPECIA LEFT FRONT LEG SACRIFICED BY DESIGN 3/21/01 646291 SACRIFICED BY DESIGN 03/22/01 646296 SACRIFICED BY DESIGN 03/22/01 646297 ALOPECIA BOTH FRONT LEG ALOPECIA ABDOMINAL ALOPECIA BASE TAIL SACRIFICED BY DESIGN 03/22/01 646298 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 03/22/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 a: , , ,13,14,15,16,17,18,19,20 b: , ,12,13,14,15,16,17,18,19,20 ,,,,,,,,, a: , , ,13,14,15,16,17,18,19,20 ,,,,,,,,, b: , , ,13,14,15,16,17,18,19,20 .,,,,,,,, ^ : i i i i t i i i i i ,i,i,i,i,ii,i,i,i, ^: 111111111 i i i i i i i i i i 111111111 -la . l l i i l l l i l t a , ,12,13,14,15,16,17,18,19,20 b , ,12,13,14,15,16,17,18,19,20 ,,,,,,,,.,,,,,,,,, /18,19, /.Lo/.L;?,20 a, / / / / / i i 20 b i i i i i i i i i i i t i i i i ///////// 9, i i i i i i i /18/X9,20 b /18/19/20 i/i/i/i/ii/i,i/i///,///// a a: ,9,10,11,12,13,14,15,16,17,18,19,20 b: ,9,10,11,12,13,14,15,16,17,18,19,20 ,,,,,,, a: ,10,11,12,13,14,15,16,17,18,19,20 ,.,,,,,,,,,,',,,,,,,,,,, b: ,10,11,12,13,14,15,16,17,18,19,20 -73- H-24516: Developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL NUMBER: OBSERVATION ==:s=i=s==:s=35=:s:=3=3===========s==a===;====a=s=s===s====as=a 646300 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT FRONT LEG ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 03/22/01 646306 ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/22/01 INDIVIDUAL CLINICAL OBSERVATIONS" DAYS OP GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, ====:=:=z=^:===as=:=:==^=:= ,12,13,14,15,16,17.18,19,20 ,12,13,14,15,16,17,18,19,20 11111 / -L-3 f , ,16,17,18,19,20 , ,16,17,18,19,20 a: ,15, a: a: -74- H-24516: Developmental Toxicity Study in Rats GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 646222 SACRIFICED BY DESIGN 03/19/01 646228 ALOPECIA LEFT FRONT PAW ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/19/01 646232 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 03/19/01 646234 SACRIFICED BY DESIGN 03/19/01 646237 SACRIFICED BY DESIGN 03/19/01 646238 ALOPECIA RIGHT SIDE SACRIFICED BY DESIGN 03/19/01 646243 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/20/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 ==;=s===a==s=s======; a: a: ,18,19, b: ,18,19, a: ,20 b: ,20 a: , ,14,15,16,17,18,19,20 ,14,15,16,17,18,19,20 ,16,17,18,19,20 , , ,16,17,18,19,20 , , , , ,18,19,20 ,18,19,20 / / t i i i i a: a: a: ,15,16,17,18,19,20 b: ,15,16,17,18,19,20 a: , , , , , , a: ,14,15,16,17,18,19,20 b: ,14,15,16,17,18,19,20 a: / , / , / / / -75- H-24516: Developmental Toxicity Study in Rats GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION =;===S=:====S=:==:=;==S===S=======i===S===;=:====S=;==:===== 646248 SACRIFICED BY DESIGN 03/20/01 646254 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/20/01 646258 SORE MOUTH SACRIFICED BY DESIGN 03/20/01 646259 SACRIFICED BY DESIGN 03/20/01 646266 ALOPECIA ABDOMINAL ALOPECIA RIGHT HIND QUARTERS ALOPECIA RIGHT SIDE ALOPECIA BOTH PROMT PAW SACRIFICED BY DESIGN 3/21/01 646268 SACRIFICED BY DESIGN 3/21/01 646269 ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 3/21/01 INDIVIDUAL CLINICAL OBSERVATIONS'3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 s==ss=s====assss===a=a:s a: b: a- ^ I,,,,.1 ,,I ,,I ,,I ,,I ,,I ,,I,,I , , I , , I , , I , , I ,15,16,17,18,19,20 ,15,16,17,18,19,20 t I I t I f acl t 1 1 1 1 1 1 i i i i i i t i i i i i '5w0 b: 9- ^ ,ii,i/i/i/i/i/i/i/ / i / i / i / i / t / i / i / i / i /20 i / / / / a ,11,12,13,14,15,16,17,18,19, b ,11,12,13,14,15,16,17,18,19, ,,,,,,,,, a ,11,12,13,14,15,16,17,18,19,20 ,,,,,,,,, b ,11,12,13,14,15,16,17,18,19,20 ,,,,,,,,, a. , / , / / , , , , i f i i , , ,.,,,,,,,, 16,,1177/,1188,/1199,/2200 b , , , / / / , , 3- i i i i i i i f i ,20 ////,/, /"" b i i i i i i i i i iiIliiliitiiiiliiliiliiliil Q- I I I I I I t I t I a: b: a: ,,,,,,,,,,,,,,,,,,,,,,,,,,, , , , , , , ,13,14,15,16,17,18,19,20 ,13,14,15,16,17,18,19,20 , , , , , , , , 76- H-24516: Developmental Toxicity Study in Rats GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 646271 ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 3/21/01 646273 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 3/21/01 646285 SACRIFICED BY DESIGN 3/21/01 646299 ALOPECIA BOTH FRONT PAW STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 03/22/01 646302 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW ALOPECIA LEFT FRONT LEG SACRIFICED BY DESIGN 03/22/01 646303 SACRIFICED BY DESIGN 03/22/01 646305 SACRIFICED BY DESIGN 03/22/01 INDIVIDUAL CLINICAL OBSERVATIONS^ DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 ,17,18,19,20 / / ,17,18,19,20 / / , , , , , , , a: ,2200 ba:: /"' / / / I f I I I I t a: / / / , i a: a: a: ,14, ,16,17,18,19,20 ,14, ,16,17,18,19,20 ,15,16,17,18,19,20 ,15,16,17,18,19,20 ,15, a: -77- H-24516: Developmental Toxicity Study in Rats____________ _______ ______ INDIVIDUAL CLINICAL OBSERVATIONS8 GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION DAYS OP GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 646307 TOP TEETH MISSING SACRIFICED BY DESIGN 03/22/01 a: b: a: ,,, ,,, ,,, ,,, ,,, ,,,,,, 9,1 ,, ,,9,1 0 0 , , , 11,12,13,14, 11,12,13,14, , , , , 1 5 , ,, , ,, , ,, , ,, , ,, , -78. m^ .. H-24516: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 646221 STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 03/19/01 646223 STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 03/19/01 646233 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/19/01 646239 SACRIFICED BY DESIGN 03/19/01 646240 ALOPECIA BOTH FRONT PAW STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 03/19/01 646244 SACRIFICED BY DESIGN 03/20/01 646247 SACRIFICED BY DESIGN 03/20/01 646255 SACRIFICED BY DESIGN 03/20/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 ,,,,,,,,, a: , , , , , , ,17, , , a: ', ', ', ', ', ', ', ', , , , , , , , . , , , , ,19,20 a: ,19,20 b: , , , , , , , , , , , , , , , , ,,,,.,,,, a: ,,,,,,,,,,,,,,,, , , , , , , , , , , , , , a: , , , , , , , ,9,10,11,12,13,14,15,16,17,18,19,20 b: ,9,10,11,12,13,14,15,16,17,18,19,20 a: ,,,,,,,,,,,,,,,,,,,,,.,,,, a: , , , , , , , , , , ,,,,,,,,, ,15, a: ,15, b: , , , , , , , , , , , , ,,,,,,,,, a: , , , , , , , , , , ,,,,,,,,,,,,,,,,,,,,,,,,,,, ,,,,, a: , , , , , , , , , , ,,,,,,,,,,,,,,,,,,, a: ,,,,,,,,, a: ,,,,,,,,, a: , , , , , , , , , , , , , , , , , , , , -79- H-24516: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 646260 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/20/01 646262 ALOPECIA BOTH FRONT PAW STAIN PERINEUM YELLOW WET PERINEUM SACRIFICED BY DESIGN 03/20/01 646263 SACRIFICED BY DESIGN 03/20/01 646270 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 3/21/01 646275 STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 3/21/01 646277 STAIN PERINEUM YELLOW STAIN PERIORAL RED SACRIFICED BY DESIGN 3/21/01 INDIVIDUAL CLINICAL OBSERVATIONS^ DAYS OP GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, S===s=s=;==2S===== a: , ,8,9,10,11,12,13,14,15,16,17,18,19,20, b: ,7, ,9,10,11,12,13,14,15,16,17,18,19,20, a: , , ,9,10,11,12,13,14,15,16,17,18,19,20, b: , ,8,9,10,11,12,13,14,15,16,17,18,19,20, a: a , ,12,13,14,15,16,17,18,19,20, b , ,12,13,14,15,16,17,18,19,20, ,,,,,,,,, a i i i i /15, , , ,19,20, ,1,1,11,1,1,1,1,1, i t i i i i i t t i t i i i i i i i i-- -- '" 2 o, a i i t i t i i i i i t t i t i i i i / b i i i i i t i i i i i i i i i i i i /"Of 11111 i i i i i i i i i i ,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, ,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, a: i i i i i i t i i t i r t t I t I t ,20, a: 111111111 i i i i i i i i i i a: ,11,12, , ,15, , , ,19,20, b: ,11,12,13, ,15, , , ,19,20, ,,,,,,,,,,,,,,,,,, 111111111 0-1 tlltlllll a- ! t t I I I I I I I I I I I I I I I I I I .80- w .. H-24516: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 646281 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT LEG STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 3/21/01 646283 SACRIFICED BY DESIGN 3/21/01 646287 ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT PAW STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 03/22/01 646289 ALOPECIA RIGHT SHOULDER STAIN PERINEUM YELLOW SACRIFICED BY DESIGN 03/22/01 646293 ALOPECIA LEFT FRONT PAW SACRIFICED BY DESIGN 03/22/01 INDIVIDUAL CLINICAL OBSERVATIONS^ DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 ===s===ss=s=== a .8, ,13,14,15,16,17,18,19,20 b ,8, ,13,14,15,16,17,18,19,20 ,,,,,,,,,,,, ,,, a i 1.1. {A-^, i f i f , i f i tiff/fill,,, i i i i i i i i i i 1.1. i i.^ i i i , i i , , /ii/i/i/ii/f/i/i/////,/ a , , , / / / / / / / , / / , , ,17,18/19,20 b /16/17,18,19/20 a i i i i i i i i ,-Ly, ;19/ b i i i i i i i i i f i i i i i i i a i i i i i i i i t i i i i i i i i i i iiiiiiiii a t t f i i i i i i t D i i i i i i i i t f f t i /Ib,/-LD/j-//j-o/xy/ a. , , , , / , , , , , , / / / , , / , 111111111 D i i i i i f i.u / L f f 1.0 f j-y f a i i t i i i i i i t i i f t i i i i i a 1,11111111 i i i i i i i i i i a: ,9,10,11,12,13,14,15,16,17,18, , b: ,9,10,11,12,13,14,15,16,17,18, , ,,,,,,,,,,,,,, 111111111 i i i i i i i i i ba:: //2200 i i i i i i i i i iiiiiiiii a; i i t i i i i i i i i i i i i t i i i a: b: a: ,i,,,i ,,i ,,i ,,i ,,i ,,i ,,i,,t , , i , , i , , i , , i , , i , , i , , i ,18,19,20 ,18,19,20 i i i -81- H-24516: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 646295 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 03/22/01 646301 SACRIFICED BY DESIGN 03/22/01 646304 SACRIFICED BY DESIGN 03/22/01 INDIVIDUAL CLINICAL OBSERVATIONS'^ DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 5 ========= S: = 3.: / / / / / / / ; / / / / / / /lb/17/18,19/ b: i i i i i 111111111 /16/17/18/19/ a: , , , , , , , , , , ,,,,,,i-i/i,i a: i i i i i i i i i i -82- H-24516: Developmental Toxicity Study in Rats______________________________DuPont-5991 APPENDIX E Gross Postmortem Findings ,,-------- .83- H-24516: Developmental Toxicity Study in Rats Gross Postmortem Findings ' Explanatory Notes Abbreviations NAD = No Abnormalities Detected DuPont-5991 - .-^^iwt^181"1180^^ H-24516: Developmental Toxicity Study in Rats DuPont-5991 GROSS POSTMORTEM FINDINGS Group I: 0 mg/kg/day Animal Number Dam Code Structurefs) Findingfs) 646224 7 646225 21 646226 12 646230 11 646236 20 646241 2 646251 40 646252 43 646256 31 646257 34 646261 23 646265 48 646272 46 646276 51 646278 52 646282 50 646284 56 646288 72 646290 69 646292 84 646294 82 646308 87 Perineum NAD NAD NAD NAD NAD Mass 2 x 1.5 cm NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD CompanySani^ed.Doesnotoo^^SCA- 85- H-24516: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS Group n: 50 mg/kg/day Animal Number 646227 646229 646231 646235 646242 646245 646246 646249 646250 646253 646264 646267 646274 646279 646280 646286 646291 646296 646297 646298 646300 646306 Dam Code 4 17 13 5 6 28 25 33 24 27 26 63 54 58 62 55 83 86 81 78 85 80 Structurefs) DuPont-5991 FindineCs) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD - <^f.^"T?ce^oicor.talnTSC .^-'f.f-S.RS"'1' "a^11"- .86- H-24516: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-5991 Group ffl: 200mg/kg/day Animal Number Dam Code 646222 19 646228 15 646232 22 646234 3 646237 9 646238 10 646243 44 646248 41 646254 42 646258 36 646259 30 646266 57 646268 53 646269 47 646271 49 646273 61 646285 45 646299 70 646302 67 646303 88 646305 68 646307 76 Stmcture(s') Findingfs) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD ^pany^^.B------c.^^.O., .87- H-24516: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS Group IV: 500 mg/kg/day Animal Number Dam Code StructureCs) 646221 1 646223 8 646233 16 646239 18 646240 14 644244 37 646247 38 646255 32 646260 39 646262 35 646263 29 646270 64 646275 59 646277 65 646281 60 646283 66 646287 71 646289 73 646293 77 646295 74 646301 75 646304 79 DuPont-5991 FindingCs) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD ^SamntSWA' -Doe^ contain T^ .88- H-24516: Developmental Toxicity Study in Rats ________________DuPont-5991 APPENDIX F Individual Reproductive Data Company Sanifeed. Does Tioi co^" TtwAWI .89- H-24516: Developmental Toxicity Study in Rats GROUP I: ANIMAL NUMBER 0 MG/KG;''DAY CORPORA LUTEA NIDATIONS e 0 3 "0 d < (0 575,3 N" 0 p. 0 % <9 (0 3 a " 0 3 3" 5" -1 fl > :"> 646224 646225 646226 646230 646236 646241 646251 646252 646256 646257 646261 646265 646272 646276 646278 646282 646284 646288 646290 646292 646294 646308 17 14 15 14 18 17 23 15 15 13 17 16 19 14 16 15 13 13 16 14 16 12 18 12 15 13 17 . 15 15 13 17 15 18 13 17 15 16 14 17 15 16 15 17 16 IND'IVIDUAL EREPRODUCTIVE DATA R ESORPTION S TOTAL EARLY LATE 1 1 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 2 2 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 1 1 0 DEAD FETUSES LIVE FETUSE S TOTAL FEMALE MALE MEAN WEIGH 0 13 6 7 5 0 13 9 4 5 0 17 7 10 5 0 15 9 6 5 0 13 8 5 5 0 16 7 9 5 0 14 11 3 5 0 15 5 10 5 0 12 6 6 5 0 12 5 7 5 0 11 8 3 5 0 12 6 6 5 0 13 8 5 5 0 15 6 9 5 0 13 11 2 5 0 15 11 4 5 0 13 7 6 5 0 15 8 7 5 0 14 6 8 5 0 15 8 7 5 0 14 5 9 4 0 15 10 5 5 -90- H-24516: Developmental Toxicity Study in Rats GROUP II : 50 MG/ICG/DAY ANIMAL NUMBER CORPORA LUTEA NIDATIONS 646227 17 16 646229 16 14 646231 20 18 646235 17 14 646242 14 14 646245 14 12 646246 17 16 646249 12 12 646250 20 18 646253 16 15 646264 17 15 646267 17 16 646274 17 14 646279 18 15 646280 16 15 Ftps' 646286 17 17 i ^ j. to, 646291 14 11 s '. .s"^ S3 646296 15 13 S 646297 16 16 f< 646298 17 16 a;f.t 646300 16 15 3 646306 23 14 ^R i ffi p 0 e> (a , "3' i b ' (.fl^ n 0 3 R5". -4 K> 0 > 0 VS ass^ IND'IVIDUAL EREPRODUCTIVE DATA R ESORPTION S TOTAL EARLY LATE 1 1 0 0 0 0 2 2 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 1 1 0 0 0 0 0 0 0 1 0 1 DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN WEIGH 0 15 12 3 5 0 14 11 3 5 0 16 12 4 5 0 14 9 5 5 0 13 6 7 5 0 12 8 4 5 0 16 8 8 5 0 12 6 6 5 0 17 10 7 5 0 15 7 8 5 0 15 10 5 5 0 15 7 8 5 0 14 5 9 5 0 15 7 8 5 0 15 9 6 5 0 17 7 10 5 0 10 6 4 6 0 13 5 8 5 0 15 5 10 5 0 16 7 9 5 0 15 11 4 5 0 13 7 6 5 -91 H-24516: Developmental Toxicity Study in Rats GROUP II I: 200 M(3/KG/DAY ANIMAL NUMBER CORPORA LUTEA NIDATIONS 646222 13 12 646228 14 14 646232 19 12 646234 17 15 646237 21 17 646238 12 11 646243 20 14 646248 16 15 646254 19 18 646258 17 14 646259 22 14 646266 18 15 646268 18 15 646269 21 18 646271 15 13 646273 16 15 646285 14 12 ff 646299 15 15 0 1 646302 646303 12 17 12 17 646305 12 9 < 646307 17 16 u> . ?? (0 p"0. 0 (0 0) 3 2. 0 0 3. SU 3' -1 W 0 > 0 at INEIIVIDUAL RREPRODUCTIVE DATA R ESORPTIONS TOTAL EARLY LATE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 1 1 0 0 0 0 0 0 0 1 1 0 0 0 0 DEAD FETUSES LIVE FETUSI2S TOTAL FEMALE MALE MEAN WEIGH 0 12 6 6 5 0 14 8 6 5 0 12 7 5 5 0 15 10 5 5 0 17 9 8 5 0 11 3 8 5 0 14 7 7 5 0 15 5 10 5 0 18 10 8 5 0 14 8 6 5 0 14 8 6 5 0 14 8 6 5 0 15 3 12 5 0 18 10 8 5 0 13 7 6 5 0 15 8 7 5 0 11 5 6 5 0 14 5 9 5 0 12 11 1 5 0 17 9 8 5 0 8 4 4 4 0 16 6 10 5 -92- H-24516: Developmental Toxicity Study in Rats Ifil 'ss] 9sSs S .3l (rf. EB 3tw. R" sr,i S. 0 tS =5, 0 ".vi r 0 3' t"#! S ^ ^ .'j 3 GROUP IV: 500 MG,/KG/DAY ANIMAL NUMBER CORPORA LUTEA NIDATIONS 646221 646223 646233 646239 646240 646244 646247 646255 646260 646262 646263 646270 646275 646277 646281 646283 646287 646289 646293 646295 646301 646304 13 11 16 14 16 15 16 15 18 15 15 12 18 15 16 13 19 18 15 14 17 17 15 15 16 15 15 . 15 15 15 14 12 14 14 18 16 19 17 15 14 14 12 13 12 INCIIVIDUAL REPRODUCTIVE DATA R .ESORPTIOM S TOTAL EARLY LATE 1 1 0 0 0 0 0 0 0 1 1 0 0 0 0 4 4 0 0 0 0 0 0 0 0 0 0 1 1 0 1 1 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0. 0 0 0 DEAD FETUSES LIVE PETUSE'S TOTAL FEMALE MALE MEAN WEIGH 0 10 6 4 5 0 14 8 6 5 0 15 10 5 5 0 14 6 8 5 0 15 9 6 5 0 8 5 3 5 0 15 7 8 5 0 13 5 8 5 0 18 10 8 5 0 13 6 7 4 0 16 7 9 5 0 15 9 6 5 0 14 7 7 5 0 15 7 8 4 0 15 11 4 4 0 12 7 5 6 0 14 8 6 5 0 16 6 10 5 0 17 10 7 5 0 14 6 8 5 0 12 7 5 5 0 12 7 5 5 -93. H-24516: Developmental Toxicity Study in Rats _________________________DuPont-5991 APPENDIX G Individual Fetal Weights and Alterations -94- company Sanitized Does not contain TSCA OR! H-24516: Developmental Toxicity Study in Hats______________________________DuPont-5991 Individual Fetal Weights and Alterations Explanatory Notes a No skeletal evaluation was done for these fetuses; due to technical error, the fetal skeletons marked with this footnote were disarticulated. For ease of recording, many of the findings have been abbreviated or coded, as listed below: ar bil cen It lu NAD rt th = arch(es) = bilateral = centrum or centra = left = lumbar = No Abnormalities Detected = right = thoracic = No Data * Subcutaneous hemorrhage that was not present in utero. Renal papillary sizes refer to papillary development using the scheme of Woo and Hoar.^ Alterations are classed as: N = Notes DV = Developmental Variations VR = Variation due to Retarded Development M = Malformations Numbers are used to: Indicate renal papillary size Identify specific stemebra Refer to skeletal position for ribs or vertebra Specify skull bones according to the following key: 1. Interparietal 2. Parietal 3. Frontal 4. Nasal 5. Premaxilla 6. Maxilla 7. Zygoma 8. Squamosal 9. Tympanic annulus 10. Basioccipital 11. Exoccipital 12. Supreoccipital 13. Hyoid ^ ^ ' r-S.-g-^--r.tit'^w-ii*^0'3'3 -ssc^01'" -95 H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]DIVIDUAL FETAL W]EIGHTS (grams) AND ALTERATIONIS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS HO. FETUS WT . STRUCTURE FIND ING(S) CLASSIFICATION 646224 1 2 3 4 5 6 7 8 9 10 11 12 13 646225 1 2 3 4 5 6 7 8 5.60 5.60 5.83 5.74 5.90 5.43 5.79 5.96 5.61 5.31 5.63 5.59 6.12 Vertebra Vertebra Sternebra Vertebra Kidney Vertebra Vertebra Vertebra Vertebra Vertebra 6.01 5.69 5.76 5.94 5.77 5.64 6.21 5.48 Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll,12) VR Retarded Ossification (cen thll,12) VR Retarded Ossification (4) VR Retarded Ossification (cen thl2) VR Papilla - Size 3 (rt) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen th8,ll) VR NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl3) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thll-12) VR noic^ Cowp9"^ San^-O^5 .96- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FET1US W r. STRUCTURE FINDING(S) CLAS!3IFICATION 646225 (Ccmt.) 9 5 .34 10 5 .79 11 5 .70 12 4 .74 13 5 .94 Vertebra Vertebra Kidney Vertebra 646226 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 5 .63 5 .33 5 .54 5 .66 5 .43 4 .68 5 .67 5 .45 5 .25 5 .55 6 .10 5 .87 5 .70 5 .73 5 .62 5 .98 5 .85 Vertebra Rib Kidney Vertebra Vertebra Vertebra Rib Rib Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thil) VR NAD Small Papilla - Size 2 (bilateral) VR Retarded Ossification (cen thl0,ll) VR NAD NAD NAD Retarded Ossification (cen thil) VR NAD Supernumerary (site thl4 bil) DV Small Papilla - Size 2 (bil) VR Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (cen thl0,l2) VR NAD Retarded Ossification (cen thl2) VR NAD Supernumerary (site thl4 It) DV Supernumerary (site thl4 It) DV NAD 646230 1 5 .61 NAD ^oinpany-- S.n-- lyti^TW.BSon^al"ea"188" -97- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AMD ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646230 (Cont.) 2 5.36 5.15 5.28 5.15 6 5.43 7 5.31 8 4.96 9 5.14 10 5.26 11 5.94 12 5.01 13 5.25 14 4.90 15 5.48 Vertebra Vertebra Kidney Vertebra Kidney Vertebra Retarded Ossification (cen fch8,10-12) VR MAD NAD Retarded Ossification (cen thIO) VR NAD NAD NAD NAD NAD Papilla - Size 3 (left) VR Retarded Ossification (cen thIO) VR NAD NAD Papilla - Size 3 (bilateral) VR Retarded Ossification (cen thIO) VR 646236 1 2 3 4 5 6 10 11 12 13 5.88 6.20 5.97 5.83 5.67 5.57 5.81 6.25 5.31 6.15 6.36 6.34 5.83 Vertebra Vertebra Kidney Rib Kidney NAD NAD NAD NAD NAD Retarded Ossification (cen thil) - VR Retarded Ossification (cen th9) VR NAD Papilla - Size 3 (bil) VR Rudimentary Cervical (7 rt) DV NAD NAD NAD Papilla - Size 3 (bil) VR ^ ^ G e l i .d.OO611' W^88"'illWd. -98- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AMD ALTERATIONS GROUP I: 0 MG/KG/DAY DAM MO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646236 (Cont.) Vertebra 646241 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5 .53 5 .39 5 .35 5 .78 5 .85 5 .63 6 .25 6 .24 5 .54 5 .53 5 .70 5 .76 5 .75 5 .42 5 .19 6 .02 Rib Vertebra Vertebra Rib Vertebra Vertebra Vertebra Vertebra Vertebra 646251 1 2 3 4 5 6 5 .12 5 .51 5 .61 5 .98 5 .49 5 .21 5.80 Subcutis Vertebra Retarded Ossification (cen thil) VR Supernumerary (thl4 site bil) DV Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thIO) VR Supernumerary (thl4 site It) DV Retarded Ossification (cen thlO-12) VR NAD NAD Retarded Ossification (cen fchll-12) VR NAD NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR NAD NAD Hemorrhage (back*) N NAD NAD Retarded Ossification (cen thl2) VR NAD .gniaio .arf**0085' -99- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY ./ DAM NO FETUS NO. FETUS WT STRUCTURE FIND ING (S) CLASSIFICATION 646251 8 9 10 11 12 13 14 (Cont.) 5.18 5.25 5.26 5.59 5.99 5.81 5.32 Skull Vertebra 646252 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 646256 1 5.15 5.33 5.59 4.90 5.62 5.86 4.92 5.05 5.70 5.67 5.24 4.41 4.76 5.48 5.19 Vertebra Kidney Vertebra Vertebra Vertebra Skull Vertebra 5.85 Vertebra 5.73 5.79 Kidney Retarded Ossification (6 bil) VR NAD NAD NAD NAD NAD Retarded Ossification (cen thl3) VR NAD NAD NAD Retarded Ossification (cen thl25 VR Papilla - Size 3 (rt) VR NAD NAD Retarded Ossification (cen thl2-13) VR NAD Retarded Ossification (cen ttill) VR Retarded Ossification (cen thil) VR Retarded Ossification (2 bil) VR NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thil,12,13) VR Retarded Ossification (cen thl2,13) VR Small Papilla - Size 2 (bil) VR NAD Bd.W^ontalnTSCAC. 100- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IMDIVIDUAL FETAL WlSIGHTS (grams) AND ALTERAT:EONS GROUP 3:: 0 MG/KG/DA-y DAM NO. / FETUS NO. FETUS WT STRUCTURE FINDING(S) CLASSIFICATION 646256 (Cont.) 5 6.00 6 5.79 7 5.61 8 6.20 9 5.74 10 5.01 11 5.77 12 5.72 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 646257 1 2 3 4 5 .6 7 8 9 10 11 12 5.61 5.94 6.12 6.02 5.43 6.44 5.03 5.46 5.42 5.52 5.20 5.90 Kidney Vertebra Vertebra Vertebra Vertebra Kidney Vertebra 646261 1 5.56 Retarded Ossification (cen thll,12) VR Retarded Ossification (cen fchll) VR Retarded Ossification (cen thl0,ll,12,13) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl3) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl2,13) VR Retarded Ossification (cen thl0,13) VR NAD NAD Papilla - Size 3 (bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thil-12) VR Small Papilla - Size 2 (left) VR Retarded Ossification (cen thil) VR NAD ^iflNny88^263' 101 H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM MO./ FETUS WO. FETUS WT STRUCTURE FIND ING (S) CLASSIFICATION 646261 2 3 4 (Cont.) 5.94 5.74 5.78 5 5.12 6 6.09 7 5.81 8 5.36 9 5.30 10 5.61 11 5.60 646265 1 2 5.62 5.18 3 4.67 4 5.28 5 5.19 6 4.85 7 5.08 8 5.22 9 5.13 10 5.42 11 4.82 12 5.11 Vertebra Skull Vertebra Kidney Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Vertebra 646272 1 5.66 Rib MAD NAD Retarded Ossification (cen thll-13) VR NAD Retarded Ossification (6bil) VR NAD Retarded Ossification (cen thl2) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen thl2) VR NAD NAD Retarded Ossification (cen thIO) Small Papilla - Size 2 (bilateral) NAD Retarded Ossification (cen thil) Retarded Ossification (cen thll-13) NAD Retarded Ossification (cen thl2) NAD NAD MAD Retarded Ossification (cen thil) VR VR VR VR VR VR Supernumerary (thl4 site bil) DV ,^.BoeBo,conWnTSCACB> Saniti; C-owpany 102- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT STRUCTURE FINDING(S) CLASSIFICATION 646272 (Cent.) 2 5.07 3 6.14 4 5.20 5 5.51 6 5.60 7 5.67 8 5.94 9 5.97 10 5.92 11 6.06 12 6.06 13 646276 1 2 3 4 5 6 7 8 9 10 6.63 5.54 5.47 5.18 5.36 4.41 5.47 5.54 5.46 4.50 5.64 Vertebra Vertebra Vertebra Rib Vertebra Rib Vertebra Kidney Rib Rib Kidney Rib Vertebra Kidney Vertebra Vertebra Rib Rib Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thl3) VR Retarded Ossification (cen fchIO) VR NAD Supernumerary (thl4 site rt) DV Retarded Ossification (cen thil) VR NAD Supernumerary (thl4 site It) DV Retarded Ossification (cen thl2) VR Papilla - Size 3 (It) VR Supernumerary (thl4 site rfc short It) DV Supernumerary (thl4 site It) DV Papilla - Size 3 (bil) VR Supernumerary (thl4 site bil) DV Retarded Ossification (cen thil) VR Small Papilla - Size 2 (bil) VR NAD NAD NAD NAD Retarded Ossification (cen thll,lul) VR Retarded Ossification (cen thil) VR Supernumerary (th site 14rt) DV NAD NAD Supernumerary (th site 14bil) DV Uoasho"? contain TSCA <';&'< iloSipany'S'anilized. 103- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WBIGHTS (grams) AND ALTERATIONS GROUP X: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646276 (Cont.) 11 12 13 14 15 646278 1 2 3 4 5.42 5.38 5.16 5.28 5.54 6.31 5.70 5.34 5.70 5.38 5.28 5.40 10 11 12 13 646282 1 5.56 5.53 5.81 5.22 5.06 5.45 5.71 6.27 5.98 5.43 6.12 6.25 5.64 Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Kidney Vertebra Kidney Retarded Ossification (cen thl2) VR NAD NAD NAD NAD NAD HAD NAD NAD Retarded Ossification (cen thll-12) VR NAD NAD Papilla - Size 3 (bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thll-12) VR NAD Retarded Ossification (cen thl2) VR NAD NAD Papilla - Size 3 (bil) VR Retarded Ossification (cen thil) VR NAD NAD NAD Small Papilla - Size 2 (left) VR NAD NAD C^pWSanlto-. D.""-""""""TM* "" 104- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]DIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 646282 8 9 (Cont.) 6.01 6.10 10 5.24 11 12 13 14 15 646284 1 2 5.93 5.46 6.10 6.48 5.98 5.66 5.59 3 5.61 4 5.14 5 5.45 6 6.14 7 5.69 8 6.48 9 5.44 Vertebra Skull Vertebra Vertebra Vertebra Vertebra Kidney Skull Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Vertebra Kidney Vertebra NAD Retarded Ossification (cen thll,l2) VR Retarded Ossification (2 bil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thIO) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen fchll) VR NAD NAD Papilla - Size 3 (bil) VR Retarded Ossification (6 bil) VR Retarded Ossification (cen thlO-11) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thll-12) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl3) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl3) VR Small Papilla - Size 2 (bil) VR Retarded Ossification (cen thlO-12) VR 105- contain TSCA f.m H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646284 (Ccmt.) 10 5 .87 11 5 .57 12 6 .26 13 5 .94 646288 1 2 3 4 5 .47 5 .84 5 .65 5 .61 5 4 .87 6 5 .33 7 5 .63 8 5 .65 9 5 .73 10 5 .58 11 5 .17 12 5 .42 13 5 .46 14 5 .94 15 5 .85 Vertebra Vertebra Kidney Kidney Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra 646290 1 2 3 5 .41 5 .66 5 .27 Kidney Vertebra Retarded Ossification (cen thll-12) VR NAD Retarded Ossification (cen thll-13) VR NAD Small Papilla - Size 2 (left) VR NAD Papilla - Size 3 (bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thiO) VR Retarded Ossification (cen thl0,ll) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl0,l2) VR NAD Retarded Ossification (cen thl0,12) VR NAD NAD Retarded Ossification (6 It) VR Retarded Ossification (cen thil) VR Small Papilla - Size 2 (bil) VR Retarded Ossification (cen thl2) VR NAD company Sanitized. Does not contain TSCA CBi 106. H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM HO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646290 (Cont.) 4 5.67 5 5 .50 6 4 .91 7 8 9 10 11 12 13 14 646292 1 2 3 4 5 6 7 8 9 10 11 123 13 14 15 646294 1 5 .27 5 .33 4 .81 4 .94 5 .56 5 .14 5 .42 5 .26 5 .15 5 .43 5 .43 5 .56 5 .52 5 .21 5 .05 4 .74 5 .37 5 .37 5 .05 5 .29 5 .13 5 .48 4 .96 4 .89 Vertebra Subcutis Vertebra Vertebra Kidney Rib Rib Kidney Rib Retarded Ossification (cen thl2) VR NAD Hemorrha9e (back*) N Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thil) VR NAD NAD NAD NAD NAD Small Papilla - Size 2 (bil) VR Supernumerary (thl4 site It) DV NAD NAD Supernumerary (thl4 site bil) DV NAD NAD NAD NAD Papilla - Size 3 (bilateral) VR NAD HAD NAD NAD NAD Supernumerary (thl4 site It) DV NAD 107- Sanitised. Does not contain TSCA C3. H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646294 (C(ant.) 2 4 .92 3 4 .02 4 4 .48 5 5 .25 6 4 .61 7 4 .57 8 4 .44 9 4 .82 10 4 .85 11 4 .75 12 4 .79 13 4 .26 14 4 .69 646308 1 23 3 4 5 63 7 8 9 10 11 12 13 14 5 .59 6 .02 6 .49 5 .65 5 .80 5 .96 5 .85 5 .71 5 .37 5 .85 5 .97 5 .92 5 .60 5 .65 Vertebra Vertebra Vertebra Vertebra Vertebra Pelvis Skull Subcutis Vertebra Retarded Ossification (cen thll-12) VR NAD NAD NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (cen thlO-11) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl2) VR Retarded Ossification (pubis bil) VR Retarded Ossification (2 bil) VR NAD NAD NAD NAD Hemorrhage (nose*) N NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thil) VR 108- pompany Sanilize'd. Ooes nol contain TSOA CF H-24516: Developmental Toxicity Study in Rats____________________________DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646308 (Cont.) 15 5.82 Kidney Small Papilla - Size 2 (bit) VR ^cmpai.v -Sanmzaa. XJoe?ftt? w^^ ry.^ v 109- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM HO./ FETUS NO. 50 MG/KG/DAY FETUS WT STRUCTURE FIND ING (S) CLASSIFICATION 646227 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 646229 1 2 3 4 5 6 7 8 9 5.38 5.17 5.23 5.42 5.48 5.03 5.35 3.18 5.36 5.31 5.01 5.33 4.91 5.35 5.40 Vertebra Vertebra Skull Sternebra Vertebra Brain 5.53 5.88 5.67 5.58 5.49 5.78 5.17 4.96 5.40 Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Retarded Ossification (cen thIO) VR NAD NAD HAD NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (3 bil) VR Retarded Ossification (1,4,6) VR NAD Retarded Ossification (cen thil,13) VR NAD NAD NAD NAD Distended (ventricles) M Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thlO-12) VR Retarded Ossification (cen thil) VR NAD Small Papilla - Size 2 (left) VR Retarded Ossification (cen fch7,9-12) VR Retarded Ossification (cen thlO-12) VR Retarded Ossification (cen thil) VR MAD 110- company Sanitized. Does not contain VSCA cr H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP II: DAM HO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING(S) CLASSIFICATION 646229 (Cont.) 10 5.45 11 5.65 12 5.48 14 646231 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 646235 1 2 3 4 5 6 .14 5 .46 5 .79 5 .48 5 .24 5 .77 5 .43 5 .46 4 .68 5 .13 5 .48 4 .95 4 .77 5 .57 . 5 .13 4 .93 5 .26 5 .89 5 .71 5 .26 5 .44 5 .39 Vertebra Skull Vertebra Vertebra Rib Skull Rib Vertebra Vertebra Retarded Ossification (ceil thl2) VR NAD Retarded Ossification (12,6bil) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thlO-11) VR Supernumerary (th site 14 It) DV Retarded Ossification (6bil) VR NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary (th short 13rt) DV NAD Retarded Ossification (cen th9) VR NAD NAD NAD NAD Retarded Ossification (cen th4) VR NAD NAD ^5^^^'^^ eon^" Tscft rr 111- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY PETUS W F. STRUCTURE FINDING(S) CLAS!SIFICATION 646235 6 7 8 9 10 11 (Cor.it.) 5 .81 5 .99 5 .55 5 .95 5 .81 5 .38 12 5 .95 13 5 .62 14 5 .94 Skull' Kidney Vertebra Vertebra Vertebra Vertebra 646242 1 2 3 4 5 6 7 8 5 .93 5 .04 5 .76 5 .35 5 .01 5 .53 4 .79 4 .23 Kidney Vertebra Vertebra Kidney Vertebra Vertebra Scapula Rib Skull Vertebra Kidney Vertebra Retarded Ossification (2 bil) VR Papilla - Size 3 (It) VR NAD HAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil,12) VR Small Papilla - Size 2 (bil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thIO) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR HAD Misshapen (bil) DV Wavy (5-13 bil) VR Retarded Ossification (1,12 bil) VR Retarded Ossification (cen fchl3) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen thil5 VR NAD -112- 'Company Sanitized. Does nol contain TSCA CBI H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM MO./ FETUS MO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646242 (Cont.) 9 5.63 10 5.15 11 5.21 12 5.55 13 646245 1 4.52 5 .00 2 5 .55 3 5 .28 4 5 .46 5 5 .77 6 5 .66 7 5 .51 8 3 .02 9 6 .34 10 5 .04 11 5.43 Vertebra Skull Vertebra Kidney Vertebra Kidney Kidney Vertebra Rib Vertebra Vertebra Skull Sternebra Vertebra Vertebra Rib Vertebra Retarded Ossification (cen thl2) VR NAD NAD Retarded Ossification (1,6 bil) VR Retarded Ossification (cen thl2) VR NAD Small Papilla - Size 2 (lt;size 3rt) VR Retarded Ossification (cen thl2) VR NAD Small Papilla - Size 2 (rt) VR NAD Papilla - Size 3 (It) VR NAD Retarded Ossification (cen thl2) VR Fused (th3-5 It) M Fused (th3-5 arch It) M Hemi (cen fch3,7) M Retarded Ossification (3 bil) VR Retarded Ossification (1,3-4,6) VR Retarded Ossification (cen th9-l0.12) VR Retarded Ossification (cen thiO) VR Supernumerary (fch.14 site rt) DV Retarded Ossification (cen thl2) VR NAD ''Soyny^y ^''.'nR.fee"''. 'Does ffot eor.tair 113- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN1DIVIDUAL FETAL WEIG!ITS (grams) AND ALTERATIO;NS GROUP 3:I: 50 MG/KG/1DAY DAM NO. / FETUS NO. FETUS WT . STRUCTURE FIND ING (S) CLASSIFICATION 646245 (Cent.) 12 5.59 Vertebra 646246 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5.77 5.83 5.72 5.80 5.36 5.66 5.52 5.62 5.23 5.04 5.79 5.60 5.90 5.43 6.06 6.31 Vertebra Vertebra Sternebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Heart &/or Greater Vessels Vertebra Vertebra Vertebra Vertebra Subcutis Vertebra Vertebra Skull Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thlO-12) VR Retarded Ossification (3) VR Retarded Ossification (cen thl0,ll) VR Retarded Ossification (cen tfall) VR Retarded Ossification (cen thil,13) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thlO-13) VR Retarded Ossification (cen thl2) VR Patent Ductus Arteriosis VR Retarded Ossification (cen fchIO) VR Retarded Ossification (cen thlO-13) VR Retarded Ossification (cen fchll,12) VR Retarded Ossification (cen thl2) VR Hemorrhage (chin*) N Retarded Ossification (cen thll-13) VR Retarded Ossification (cen thll-13) VR Retarded Ossification (6 It) VR Cottipany Sanitized. Does not contain TSCA CBS 114- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646246 (Cont.) Vertebra 646249 1 2 3 4 5 6 7 8 9 10 11 12 4.25 6.50 5.80 5.47 5.79 5.73 6.14 6.30 6.39 5.61 5.90 5.47 Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Vertebra 646250 1 2 3 4 5 6 7 8 4.90 5.08 5.16 5.66 5.36 5.43 4.99 5.20 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl2-13) VR Retarded Ossification (cen thl2) VR NAD NAD Retarded Ossification (cen thll-12) VR Papilla - Size 3 (left) VR NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thll-12) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl2) VR HAD NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thll-12) VR ,&nitlz8'd.13!oss notctmlalriTSCACBS 115 H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP II: DAM NO./ FETUS HO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646250 (Cent.) 9 5.34 10 4.99 11 5.42 12 5.79 13 5.34 14 5.24 15 5.13 16 5.65 17 5.08 Vertebra Vertebra Vertebra Rib Vertebra Retarded Ossification (cen thl2) VR Retarded Ossification (cen fchl2) VR NAD NAD NAD Retarded Ossification (cen fchll) VR NAD Supernumerary (site 14rt) DV Retarded Ossification (cen thl2) VR 646253 1 2 3 8 9 10 11 12 13 14 15 5.45 5.71 6.31 6.03 5.94 5.89 5.35 5.40 5.65 5.72 6.22 5.57 5.73 5.82 5.85 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra NAD NAD Retarded Ossification (cen thll,l2) VR NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen fchl2) VR NAD 116- ICompany Sanlfced. Does not contain TSCA CBI H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646264 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 646267 1 2 3 4 5 6 7 8 5 .51 5 .60 5 .96 5 .46 5 .15 5 .27 5 .21 5 .18 5 .16 5 .31 5 .50 5 .62 5 .17 5 .34 5 .53 Vertebra Kidney Vertebra Vertebra Rib Vertebra Kidney Vertebra Vertebra Vertebra 5 .26 5 .11 4 .92 5 .30 4 .64 5 .27 5 .16 5 .01 Vertebra Vertebra Vertebra Skull NAD Retarded Ossification (cen thl2) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen thll,12) VR NAD Retarded Ossification (cen thil) VR Supernumerary (thl3 site rt) DV Retarded Ossification (cen thl2) VR NAD NAD Small Papilla - Size 2 (It) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil-12) VR NAD Retarded Ossification (cen thIO) VR NAD NAD Retarded Ossification (6 bil) VR ^panySanllUed-Doe.tacnonota-in TSCACM 117- "iiii' ^,?iili>llli "IIIUly H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN1D'IVIDUAL FETAL W SIGHTS (grams) AMD ALTERAT IONS /t"jKD-/'UtTUTTr) II: DAM NC'./ FETUS NO. 50 MG/KG/:DIAY FETUS WT STRUCTURE FIND ING (S) CLASSIFICATION 646267 (Cent.) 9 4.71 10 5.29 11 5.50 12 5.29 13 4.86 14 4.91 15 5.37 Kidney Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 646274 1 2 3 4 5 6 ' 7 8 9 10 11 12 13 14 5.55 5.46 5.35 5.33 5.33 5.50 6.06 5.35 5.50 5.05 5.24 6.02 5.13 5.53 Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Small Papilla - Size 1 (left) VR Retarded Ossification (cen thl2-13) VR Retarded Ossification (cen thl0,l2) VR Retarded Ossification (cen thl0,ll) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl0,13) VR NAD Retarded Ossification (cen thil) VR NAD NAD NAD Retarded Ossification .(cen thil) VR NAD NAD Retarded Ossification (cen fchIO) VR NAD NAD Retarded Ossification (cen thl2) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen fchl2) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thl2) VR NAD Ir.C-.o---y^-a-,n;-,. -"'-a^!-1V-106- 'i"v'v TITpompanyS^^ ionif.fion^SCAC^ H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]DIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: ./ DAM NO FETUS N0. 50 MG/KG/:DAY FETUS WT STRUCTURE FINDING(S) CLASSIFICATION 646279 1 5.17 2 5.71 3 5.24 Vertebra 4 5.36 5 5.53 Vertebra NAD NAD Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thl2) VR 6 4.99 7 5.25 8 5.56 9 5.31 Vertebra 10 5.54 11 5.89 NAD NAD HAD Retarded Ossification (cen thil) VR NAD NAD 12 5.38 NAD 13 5.44 Heart ie/or Greater Patent Ductus Arteriosis VR Vessels 14 5.61 NAD 15 5.19 Vertebra Vertebra Retarded Ossification (cen thil,13) VR Retarded Ossification (cen thl2) VR 646280 1 2 3 4 5 6 5.55 5.77 5.83 5.76 5.67 5.53 Kidney Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Small Papilla - Size 2 (rfc) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thll-13) VR Retarded Ossification (cen thl2) VR ^,^^^.-f-'"-- ,,...-- . ,^na!n wi->:""-r"?^> ?"'-^ 119- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646280 (C<snt.) 7 5 .79 8 6 .08 9 5 .61 10 5 .40 11 5 .95 12 4 .99 13 5 .45 14 5 .53 15 5 .19 646286 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 6 .30 5 .91 6 .21 6 .01 5 .70 5 .51 5 .77 6 .08 5 .43 5 .84 5 .58 5 .81 6 .06 5 .75 5 .74 6 .13 5 .24 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Kidney Kidney Rib Retarded Ossification (cen thll-125 VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl3) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thlO-12) VR Retarded Ossification (cen thll-12) VR Papilla - Size 3 (bil) VR NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Papilla - Size 3 (rt) VR NAD Supernumerary (site 14 It) DV Company Sanitized. Does not contain "rwn /* 120- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IM]DIVIDUAL FETAL WlEIGHTS (grams) AMD ALTERATI ONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/:DAY FETUS WT STRUCTURE FIND ING (S) CLASSIFICATION 646291 1 2 3 4 5 6 7 8 9 10 646296 1 2 3 4 5 6 7 6.01 6.09 6.42 6.32 6.21 6.16 6.36 6.34 6.51 6.26 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 5.17 - 5.31 5.67 5.72 5.61 5.39 5.28 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra . NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl2-13) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil-12) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thlO-12) VR NAD Retarded Ossification (cen thl2-13) VR Retarded Ossification (cen thlO-13) VR Retarded Ossification (cen thil) VR ... ..,,^no^^^^cACD( ^ann.. ^.UQ'-3 121- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646296 (0ant.) 8 5.05 9 5.65 10 5.34 11 5.55 12 5.57 13 5.68 Vertebra Kidney Vertebra Vertebra Vertebra Rib Vertebra Retarded Ossification (cen thIO) VR Papilla - Size 3 (bil) VR Retarded Ossification (cen thll-12) VR NAD Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thlO-13) VR Rudimentary Cervical (7 It) DV Retarded Ossification (cen thIO) VR 646297 1 23 3 4 5 6 7 8 9 10 11 12 13 14 15 5.67 5.63 5.80 5.95 5.71 6.25 5.68 5.89 5.73 5.61 5.82 5.75 5.69 4.69 5.71 Kidney Vertebra Vertebra Kidney Abdomen Vertebra Vertebra Vertebra Small Papilla - Size 2 (rt) VR NAD NAD NAD NAD NAD Retarded Ossification (cen fchl2) VR Retarded Ossification (cen thll-12) VR Small Papilla - Size 2 (bil) VR NAD NAD NAD Malformation (umbilical hernia) M Retarded Ossification (cen th9-12) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thll-12) VR ,conia1T8CACB5 -Co^S^^oesn. 122- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646298 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5.29 5.33 5.00 5.65 5.28 5.06 5.71 5.28 5.28 5.19 5.51 5.64 5.10 4.96 5.01 5.60 Kidney Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Vertebra Small Papilla - Size 2 (right) VR NAD Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thio) VR NAD Papilla - Size 3 (bil) VR Retarded Ossification (cen thio-13) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR NAD NAD NAD NAD NAD NAD Retarded Ossification VR 646300 1 2 3 4 5 6 7 8 9 10 11 12 5.70 5.58 5.45 5.58 5.79 5.16 5.03 5.55 5.14 5.47 5.32 5.37 Skull Vertebra NAD Retarded Ossification (2 bil) VR NAD NAD NAD Retarded Ossification (cen thio) VR NAD NAD NAD NAD NAD NAD ..^...xa,"--0'"'"8'"'1'5" 123- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: DAM NO./ FETUS NO. 50 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646300 13 14 (Cont.) 5.37 5.32 15 5.39 646306 1 2 3 10 11 12 13 5.50 6.08 5.54 5.86 5.25 5.51 6.00 5.53 5.69 5.53 5.30 5.27 5.41 Vertebra Chin Skull Kidney Skull Vertebra Vertebra Vertebra Vertebra Vertebra Kidney Kidney NAD Retarded Ossification (cen thll-12) VR Micrognathia M Micrognathia M Small Papilla - Size 2 (It) VR Retarded Ossification (2 bil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thll-13) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil) VR Small Papilla - Size 2 (lt;size 3rt) VR NAD Small Papilla - Size 1 (left) VR NAD NAD 124- 'pompany Sanitized. Ooes not contain TSCA CB1 H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646222 1 2 3 4 5 6 7 8 9 10 11 12 4 .85 5 .06 5 .94 5 .30 5 .05 4 .08 5 .67 6 .30 5 .95 5 .66 5 .83 5 .09 Vertebra Vertebra Skull Vertebra Rib Vertebra Sternebra Vertebra Vertebra Rib Sternebra Vertebra Rib Vertebra Kidney Rib Sternebra Vertebra Retarded Ossification (cen thil, lu2) VR Retarded Ossification (cen thll-13) VR NAD Retarded Ossification (6rt) VR Retarded Ossification (cen thlO-11) VR Supernumerary (thl3 short rt) DV Retarded Ossification (cen thlO-12) VR Retarded Ossification (6) VR Retarded Ossification (cen thlO-13, lul) VR Retarded Ossification (cen thl2) VR Supernumerary (thl3 short rt) DV Fused (1.2) DV Retarded Ossification (cen fchlO-13) VR Rudimentary Cervical (7rt) DV Retarded Ossification (cen thl3) VR NAD Small Papilla - Size 1 (bil) VR Supernumerary (thl3 short It) DV Retarded Ossification (6) VR Retarded Ossification (cen th9-13) VR 646228 1 5.69 5.81 6.13 Vertebra Vertebra Vertebra Retarded Ossification (cen thil,12) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR p.^."^----^0"""1"'"' 125 H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]DIVIDUAL FETAL W]EIGHTS (grams) AND ALTERA":riONS GROUP III: DAM NO./ FETUS NO. 250 MG/KI3/DAY FETUS WT STRUCTURE FINDING (S) CLASSIFICATION 646228 (Cont.) 4 6.10 5 5.84 6 5.69 7 5.86 8 5.17 9 5.93 10 5.93 11 5.92 12 6.06 13 6.11 14 6.30 Vertebra Vertebra Vertebra Vertebra Sternebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra 646232 1 2 3 4 5 6 5.13 5.20 5.26 4.69 5.14 5.35 Skull Vertebra Skull Vertebra Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thl2) VR Retarded Ossification (cen fch5) VR Retarded Ossification (cen thl2) VR Retarded Ossification (5) VR Retarded Ossification (arches eel It) VR Retarded Ossification (cen thil lul) VR NAD Retarded Ossification (cen thil,12) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (8,2 bil) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (2 bil) VR Retarded Ossification (cen thil-12) VR Retarded Ossification (6 bil) VR Retarded Ossification (can thl0,12) VR NAD Sanitized. Dsestiot eohlain TSCA "CBI Company 126- H-24516: Developmental Toxicity Study m Rats^ DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646232 (Cont .) 7 5.33 8 5.42 9 5.64 10 5.59 11 5.42 12 5.05 Vertebra Vertebra Vertebra Vertebra 646234 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 646237 1 2 3 4 5 5.23 5.39 4.46 5.22 5.16 5.01 4.94 5.28 4.93 5.26 5.63 5.31 4.84 5.19 5.28 Vertebra Vertebra Vertebra 5.25 5.36 5.07 5.59 5.46 Vertebra Retarded Ossification (cen thll-12) VR MAD MAD Retarded Ossification (cen thll,13) VR Retarded Ossification (cen thlO-11) VR Retarded Ossification (cen fchll-12) VR MAD MAD Retarded Ossification (can thil) VR MAD MAD Retarded Ossification (cen thl2,13) VR Retarded Ossification (cen fchio) VR NAD MAD MAD NAD NAD NAD NAD MAD NAD NAD Retarded Ossification (cen thl2) VR NAD MAD fan,'s,s.fe."^.'-,"^" ^^^{!^ 127- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646237 6 7 8 9 10 11 12 13 14 15 (Con t.) 4 .91 4 .84 5 .45 4 .60 5 .38 5 .46 5 .21 5 .33 4 .74 5 .53 16 5 .06 17 5 .24 646238 1 2 3 4 5 .41 5 .10 5 .56 5 .81 5 5 .94 6 5 .96 7 5 .73 8 5 .05 9 5 .26 10 5 .68 11 5 .24 ' Vertebra Kidney Rib Rib Rib Skull Rib Rib Rib Rib Skull Rib 646243 1 2 3 4 .73 5 .34 5 .61 Vertebra Skull Vertebra NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thil) VR NAD Papilla - Size 3 (bil) VR Supernumerary (thl4 site bil) DV Supernumerary (thl4 site bil) DV NAD Supernumerary (thl4 site bil) DV Retarded Ossification (6bil) VR Supernumerary (thl4 site bil) DV Supernumerary (thl4 site bil) DV NAD Supernumerary (thl4 site bil) DV Supernumerary (thl4 site bil) DV Retarded Ossification (61t) VR Supernumerary (thl4 site rt;short It) DV Retarded Ossification (cen thil) VR Retarded Ossification (2,6 bil) VR Retarded Ossification (cen thil) VR NAD Company S.nn,ze^o>c.n,.^cn, -128- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646243 (C(ant.) 4 5 .71 5 5 .30 6 5 .43 7 5 .54 8 4 .19 9 10 11 12 13 14 646248 1 2 3 4 5 6 7 8 9 10 6 .26 5 .95 4 .60 4 .88 4 .71 4 .59 5 .52 5 .33 5 .95 5 .74- 5 .69 5 .20 5 .68 5 .56 5 .51 5 .61 11 4 .99 12 5 .20 13 6 .16 Vertebra Vertebra Skull Vertebra Skull Vertebra Vertebra Skull Kidney Vertebra Vertebra Skull Vertebra Vertebra Skull Retarded Ossification (cen thil) VR Retarded Ossification (cen thlO-11) VR Retarded Ossification (6 bil) VR Retarded Ossification (cen thlO-11) VR NAD Retarded Ossification (2 bil) VR Retarded Ossification (cen thil-12) VR MAD MAD NAD MAD Retarded Ossification (cen thl2) VR Retarded Ossification (6 bil) VR NAD MAD Papilla - Size 3 (bilateral) VR Retarded Ossification (cen thl0,13) VR NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (6bil) VR Retarded Ossification (cen thl3) VR Retarded Ossification (cen thl2) VR Retarded Ossification (6bil) VR NAD ^^anffi^^^^2""^^^1 129- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT STRUCTURE FINDING(S) CLASSIFICATION 646248 14 15 (Cont.) 5.43 5.20 646254 1 5.20 2 4.37 3 4.43 4 4.69 5 4.38 6 5.82 7 5.53 8 4.99 9 5.32 10 5.04 11 4.73 12 5.82 13 5.62 14 5.61 15 5.43 16 5.16 17 4.87 18 4.95 Vertebra Vertebra Vertebra Skull Vertebra Skull Vertebra Vertebra Skull Vertebra Skull NAD NAD Retarded Ossification (cen thlO-11) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (l,12,6bil) VR Retarded Ossification (cen thl0-ll,lul) VR NAD NAD NAD Retarded Ossification (l,12;2.6-8bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (6bil) VR NAD NAD Retarded Ossification (cen thl2) VR Retarded Ossification (12;6bil) VR 646258 1 4.97 Kidney Papilla - Size 3 (bil) VR ^sr'kra ^i."0'51'0'0 Comp8^ 130- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]0 IVIDUAL FETAL W1SIGHTS (grams) AMD ALTERA'.nous GROUP III: 250 MG/Ri-i /DAY DAM NO./ FETUS NO. ... FETUS WT , .. STRUCTURE . 646258 (Cont.) 2 5.00 Vertebra 3 5.18 Vertebra 4 5.32 Vertebra 5 5.10 Vertebra 6 4.60 Skull Vertebra 7 4.75 Vertebra 8 5.19 Vertebra 9 5.18 Vertebra 10 5.26 Vertebra 11 6,38 12 5.83 Vertebra 13 4.54 14 5.38 Vertebra FIND ING (S) CLASSIFICATION Retarded Ossification (cen thlO-11) VR Retarded Ossification (cen th9-10,12) VR Retarded Ossification (cen fchl2-13) VR Retarded Ossification (cen thl2) VR Retarded Ossification (2 bil) VR Retarded Ossification (cen thil,13) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thll-12) VR NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thll-12) VR 646259 1 2 3 4 5 6 7 8 9 4.84 5.19 4.83 5.59 5.58 5.72 5.53 5.69 6.08 Subcutia Vertebra Vertebra Hemorrhage (back*) N NAD Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thil) VR NAD NAD NAD Sanitized iTol contain TSCA C6i 131- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250'MG/KG/DAY FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646259 10 11 (Cent.) 5.75 5.55 12 5.65 13 5.82 14 5.16 Subcutis Subcutis Vertebra Skull 646266 1 2 4 5 6 7 8 9 10 11 12 13 14 4.56 5.00 5.32 4.97 5.29 6.01 5.61 5.14 5.41 5.29 5.50 4.91 5.04 5.46 Vertebra Vertebra Vertebra Vertebra Subcutis Vertebra 646268 1 2 4.95 5.46 4.70 6.58 4.45 Vertebra Vertebra Hemorrhage (back*) Hemorrhage (back*) Retarded Ossification (cen thl3) VR NAD NAD Retarded Ossification (6bil,7rfc) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thIO) VR NAD Hemorrhage (head*) N Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR NAD NAD ..n^.^.o.c...-"--------- 'Company 132- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT STRUCTURE FIND ING (S) CLASSIFICATION 646268 6 7 8 (Cont.) 5.40 5.64 4.83 9 5.83 10 5.24 11 5.49 12 5.09 13 6.98 14 4.58 15 5.07 Rib Subcutis Rib Kidney Rib Kidney Vertebra Vertebra Vertebra 646269 1 2 3 4 5 6 7 8 9 10 5.97 5.13 5.12 5.24 5.42 5.01 5.35 5.19 5.13 4.71 Rib Vertebra Skull Kidney Rib Vertebra Vertebra Vertebra Rib Vertebra Supernumerary (site thl4 It) DV NAD Hemorrhage (chin*) N Supernumerary (site thl4 bil) DV Papilla - Size 3 (bil) VR Supernumerary (short thl3 It) DV NAD Small Papilla - Size 2 (bil) VR Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification . (cen thl2) VR Retarded Ossification (cen thl2) VR Supernumerary (thl4 site rt) DV Retarded Ossification (cen fchll) VR Retarded Ossification (2 bil) VR Small Papilla - Size 2 (bilateral) VR Supernumerary (thl4 site bil) DV NAD NAD Retarded Ossification (cen thl2-13) VR Retarded Ossification (cen thil-12) VR Retarded Ossification (cen fchl2) VR Supernumerary (thl4 site bil) DV Retarded Ossification (cen thil) VR iip^ganIt^'^sffotcoT^nTSCACBl 133- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN1DIVIDUAL FETAL W;EIGHTS (grams) AMD ALTERATIOMS GROUP III: DAM NO./ FETUS NO. 250 MG/KI3/DAY FETUS WT STRUCTURE FINDIHG(S) CLASSIFICATION 646269 (Cont.) 11 5.36 12 6.06 13 5.87 14 5.35 15 5.22 16 5.34 17 18 646271 1 2 3 4 5 4.81 4.99 5.52 5.67 5.62 5.83 - 5.20 6 5.53 7 5.50 8 5.36 9 5.15 10 5.57 11 5.45 12 5.40 13 5.61 Vertebra Vertebra Vertebra Vertebra Rib Vertebra Rib Vertebra Vertebra Brain Vertebra Kidney Vertebra Vertebra Kidney Vertebra Kidney Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen fchll) VR Retarded Ossification (cen thl2) VR Supernumerary (thl4 site It) DV Retarded Ossification (cen thl3) VR Supernumerary (thl4 site It) DV Retarded Ossification (cen thlO-12) VR Retarded Ossification (cen thll-12) VR NAD Distended (ventricles) M NAD NAD Retarded Ossification (cen thil) VR Papilla - Size 3 (It) VR Retarded Ossification (cen thll-12) VR NAD NAD Retarded Ossification (cen thil) VR Papilla - Size 3 (bil) VR NAD Retarded Ossification (cen thIO) VR NAD Papilla - Size 3 (It) VR TSCAC8S .contain S^"^^008"01 ''CoiW8"^ 134- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT STRUCTURE FINDING(S) CLASSIFICATION 646273 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 646285 1 2 3 4 5 6 7 5.32 5.41 5.11 5.42 5.61 5.27 6.07 5.61 5.45 5.50 5.14 5.45 4.83 5.32 5.56 Vertebra Skull Vertebra Rib Kidney Vertebra Skull Vertebra Kidney Rib Vertebra Rib Rib Skull Vertebra 5.77 5.50 6.11 5.51 5.41 5.54 5.72 Vertebra Skull Vertebra NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (12;6bil) VR Retarded Ossification (cen thlO-11) VR Supernumerary (th site 14bil) DV Papilla - Size 3 (It) VR Retarded Ossification (cen thil) VR Retarded Ossification (6rt) VR Retarded Ossification (cen thil-13) VR Papilla - Size 3 (right) VR Supernumerary (th site 14lt) DV Retarded Ossification (cen thiO) VR Supernumerary (th site 14lt) DV NAD Supernumerary (th site 14rt) DV Retarded Ossification (6bil) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl2) VR Retarded Ossification (6 bil) VR NAD NAD Retarded Ossification (cen thil,12) VR NAD NAD -V^C* ^ '~-$ .ri.Sani^d-.^O-onensesW)^0"15"" 135- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646285 8 9 (Confc.) 5.40 4.78 10 11 646299 1 9 10 11 12 13 14 646302 1 5.40 6.00 5.46 6.07 5.49 5.63 5.38 5.23 5.40 4.94 5.02 5.31 5.31 5.12 5.27 5.64 5.19 Rib Femur Pelvis Rib Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Skull Vertebra Supernumerary (th.14 site rt) DV Retarded Ossification (bil) VR Retarded Ossification (pubis,bil) VR Wavy (7-llbil,-6rt) VR Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thil) VR NAD NAD NAD NAD Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thl2) VR NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (2 bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cent thll-12) VR Retarded Ossification (6 left) VR Retarded Ossification (cen thl2) VR Company s.nn^."-"0'"""""'5"'1"' 136- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646302 (Cont .) 2 5.70 3 5.43 4 5.87 5 5.54 6 5.61 7 5.36 8 5.37 9 5.36 10 11 12 646303 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.67 5.25 5.16 5.52 5.57 3.25 5.60 5.71 6.08 5.75 5.14 5.19 5.17 5.73 5.10 5.48 5.59 5.91 Vertebra Vertebra Rib Sternebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll,13) VR Retarded Ossification (cen fchll) VR NAD Supernumerary (thl4 site It) DV NAD NAD NAD Retarded Ossification (5) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl0,12) VR NAD NAD NAD Retarded Ossification .(cen thil) VR NAD MAD NAD Retarded Ossification (cen thll-12) VR NAD NAD NAD NAD Retarded Ossification (cen thil) VR NAD Retarded Ossification (cen thil) VR Retarded Ossification (cen thIO) VR NAD 137- ^.iww S&mlSzstl. Does not contain TSCA CS, H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: DAM NO./ FETUS NO. 250 MG/KG/DAY FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646303 16 17 (Cont .) 5.36 5.71 646305 1 2 5.28 4.35 3 5.19 4 4.91 5 5.13 6 4.70 7 4.87 8 5.45 Vertebra Vertebra Vertebra Vertebra Vertebra 646307 1 2 3 4 5 6 7 83 9 10 11 12 13 14 15s 163 5.34 5.13 5.19 5.23 5.44 5.32 5.65 5.27 5.21 5.69 5.29 5.02 5.09 4.90 5.39 4.99 Skull Vertebra Vertebra NAD NAD NAD Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thlO-13) VR Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen thIO) VR Retarded Ossification (cen thll-12) VR NAD Retarded Ossification (6 It) VR NAD NAD Retarded Ossification (cen thl2-13) VR NAD NAD NAD NAD NAD Retarded Ossification (cen thIO) VR NAD NAD NAD NAD NAD , ^ = ^ s s ^ ^ -----mSanWrfl-0--09^i i , , ^ ' - ' " ^ " " WW^ ,.,,, -138. ^^ri-f't.^^ft--d'.U^- H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]DIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500 '14G/KG,/DAY DAM NO./ FETUS NO. FET1JS WT . STRUCTURE FINDING (S) CLASS IFICATION 646221 1 2 3 4 5 6 7 8 9 10 646223 1 2 3 4 5 6 5 .03 Vertebra 6 .16 Skull Vertebra 4 .84 Vertebra 5 .34 Skull 5 .78 4 .99 Skull Vertebra 5 .93 4 .86 Vertebra 6 .07 Pelvis Rib Vertebra 5 .61 Pelvis Rib Skull 5 .78 5 .74 5 .61 5 .91 5 .38 5 .56 Skull Vertebra Vertebra Rib Retarded Ossification (cen thil) VR Retarded Ossification (6,7,2 bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (2,6 bil) VR NAD Retarded Ossification (6 bil) VR Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen thl2) VR Retarded Ossification (pubis bil) VR Wavy (10-11 rt) VR Retarded Ossification (cen thl2) VR Retarded Ossification (pubis bil) VR Wavy (9-12 bil;5-8 rt) VR Retarded Ossification (1,2,6 bil) VR NAD Retarded Ossification (1;6 It) VR Retarded Ossification (cen thl3) VR Retarded Ossification (cen thl0,12) VR NAD Supernumerary (thl4 site It) DV NAD ^^'n" ^'.^~ '^SiS----'-'' 139- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646223 7 8 (C(snt.) 5 .55 5 .68 9 5 .71 10 5 .90 11 5 .30 12 5 .75 13 5 .56 14 5 .67 646233 1 2 3 4 5 6 4 .87 5 .20 5 .82 5 .72 4 .79 4 .94 7 5 .29 8 5 .62 9 6 .07 10 5 .24 11 5 .14 12 5 .93 13 5 .93 14 5 .43 15 4 .99 646239 1 2 6 .07 5 .54 3 5 .45 4 6 .18 Vertebra Skull Rib Vertebra Rib Kidney Skull Skull Vertebra NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (1;2,6 bil,-7-8 It) VR Supernumerary (thl4 site It) DV NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) VR NAD NAD NAD NAD Wavy (th8-lllt, 6-9 rt) VR NAD Papilla - Size 3 (bilateral) VR NAD NAD NAD Retarded Ossification (2,6 bil) VR NAD Retarded Ossification (6 bil) VR Retarded Ossification (cen thl0,12) VR .icorfalnTSCAC? w^8"^063'0 140- H-24516. Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP IV: 500'MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646239 (C(ant.) 5 5 .45 6 5 .87 7 5 .51 8 5 .74 9 5 .95 10 5 .19 11 5 .87 12 5 .70 13 5 .53 14 5 .68 Vertebra Vertebra Vertebra Skull Kidney Skull Vertebra Skull Vertebra Retarded Ossification (cen fchIO) VR NAD NAD Retarded Ossification (cen thll-12) VR Retarded Ossification (cen thll-12) VR Retarded Ossification (6 bil) VR Papilla - Size 3 (It) VR Retarded Ossification (2 bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (2,6 bil) VR Retarded Ossification (cen fchll) VR 646240 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 6 .01 5 .50 5 .52 5 .97 5 .12 5 .78 5 .90 5 .89 5 .31 5 .48 5 .57 5 .78 5 .59 5 .82 5 .59 Vertebra Skull Vertebra Vertebra Skull Kidney Retarded Ossification (can thil) VR Retarded Ossification (6 It) VR NAD NAD NAD NAD Retarded Ossification (cen fchll) VR. NAD Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (6 It) VR Papilla - Size 3 (bil) VR NAD NAD SC&CB ^^SSS^^T-^^^00^^ as----- 141- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646244 1 2 3 4 5 6 7 8 646247 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5 .48 5 .42 5 .79 5 .37 5 .68 5 .43 5 .44 5 .73 Vertebra Skull Vertebra 4 .71 4 .98 4 .80 5 .27 5 .05 5 .21 4 .92 4 .89 5 .26 5 .43 4 .86 5 .41 5 .19 5 .35 5 .62 Rib Skull Skull Vertebra Skull Vertebra Skull Skull Vertebra Kidney Vertebra Retarded Ossification (ceil thll-13) VR Retarded Ossification (6 bil) VR Retarded Ossification (cen thl2) VR HAD NAD NAD NAD NAD Supernumerary (th.13 site It) DV NAD NAD NAD NAD Retarded Ossification (2,6 bil) VR NAD Retarded Ossification (7,8 bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (6 bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (6 It) VR NAD Retarded Ossification (8 It) VR Retarded Ossification (cen thl2) VR Papilla - Size 3 (rt) VR Retarded Ossification (cen thl2) VR ^ Saw^ed-O^ cpmp^ .OflW^ ,50^ 142. H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 646255 1 2 3 4 5 6 7 8 9 10 11 12 13 646260 1 2 3 4 5 6 7 8 9 5.45 6.15 7.05 5.47 5.62 5.81 5.81 5.64 5.49 5.87 6.05 5.41 6.57 Skull Vertebra Skull Vertebra Skull Vertebra Vertebra Skull 4.94 5.15 5.08 4.66 5.66 5.47 5.44 4.28 4.85 Skull Skull Rib Skull Rib Vertebra Pelvis Rib Skull Vertebra NAD Retarded Ossification (61t) VR NAD NAD NAD Retarded Ossification (cen thlO-11) VR NAD Retarded Ossification (6bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (6bil) VR Retarded Ossification (cen thil) VR Retarded Ossification (cen thil) VR Retarded Ossification (6bil) VR NAD NAD Retarded Ossification (2 bil) VR NAD Retarded Ossification (6 bil) VR Supernumerary (thl3 site It) DV Retarded Ossification (6,8,2 bill VR Wavy (th7,9-ll rt) VR Retarded Ossification (cen thl2) VR Retarded Ossification (pubis bil) VR Wavy (th9-ll bil,thl-8 rfc) VR Retarded Ossification (6 bil) VR Retarded Ossification (cen thil) VR ^ec 143- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646260 (Cont.) 10 5.01 11 4.99 12 4.86 13 5.35 14 5.18 15 4.55 16 4.94 17 4.52 18 5.48 Vertebra Kidney Pelvis Rib Skull Rib Skull Vertebra Rib Rib Skull 646262 1 4.60 4.64 4.69 4.81 4.51 4.70 5.01 Kidney Pelvis Sternebra Vertebra Skull Skull Sternebra Vertebra Skull Sternebra Retarded Ossification (cen thil) VR Papilla - Size 3 (right) VR Retarded Ossification (pubis bil,ischium bil) VR NAD Wavy (th7-12 rt) VR Retarded Ossification (2,3,6 bil) VR Wavy (th6-ll rt) VR Retarded Ossification (2,6 bil) VR Retarded Ossification (cen thll-13) VR Wavy (th8-12 bil) VR Wavy (thlO-12 bil,th8-9 rt) VR Retarded Ossification (3,6 bil) VR Papilla - Size 3 (It) VR Retarded Ossification (ischium,pubis bil) VR Retarded Ossification (3-4) VR Retarded Ossification (cen thl2,13) VR Retarded Ossification (2,3,7 bil) VR NAD Retarded Ossification (2,3 bil) VR Retarded Ossification (3,4) VR Retarded Ossification (cen thil) VR Retarded Ossification (2,6,7,8 bil) VR Retarded Ossification (3-4) VR ----------TSCACP' ^,3.------------ 144. H-24516: Developmental Toxicity Study in Rats DuPont-5991 IN]DIVIDUAL FETAL WiEIGHTS (grams) AMD ALTERA'nous GROUP IV: 500 MG/KG /DAY DAM NO./ FETUS NO. FETUS WT ^. STRUCTURE FIND ING (S) CLASSIFICATION 646262 (Cont.) 8 4.32 9 4.28 10 4.34 11 4.12 12 4.30 13 4.33 Skull Vertebra Pelvis Vertebra Skull Vertebra Skull Vertebra Sfcernebra Retarded Ossification (2,3,7,8 bil) VR Retarded Ossification (cen thl3) VR Retarded Ossification (pubis bil) VR Retarded Ossification (cen thl0,ll,12) VR Retarded Ossification (2,3,8 bil) VR Retarded Ossification (cen thl2) VR Retarded Ossification (2,3 bil;12) VR Retarded Ossification (cen th3) VR Retarded Ossification (4-5) VR 646263 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.50 5.27 5.10 5.21 5.21 4.81 5.36 5.17 5.90 5.15 5.77 5.23 5.20 5.24 5.94 Kidney Vertebra Skull Vertebra Vertebra Skull Vertebra Papilla - Size 3 (bilateral) VR NAD MAD Retarded Ossification (cen thll,12) VR NAD Retarded Ossification (2 bil) VR NAD NAD Retarded Ossification (cen thl2) VR NAD Retarded Ossification (cen fchll) VR Retarded Ossification (2 bil) VR NAD Retarded Ossification (cen thl2) VR NAD 145- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP IV: 500' MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646263 (Cent.) 16 5.72 646270 1 2 5.79 5.74 3 5.33 5.60 5 5 .54 6 5 .78 7 5 .27 8 5 .50 9 5 .87 10 5 .57 11 5 .35 12 5 .16 13 5.94 14 5.62 15 646275 1 2 3 4 5 5.57 5.40 5.47 5.65 5.83 5.53 Vertebra' Rib Vertebra Vertebra Skull Rib Kidney Rib Vertebra Rib Rib Skull Vertebra Vertebra NAD NAD Retarded Ossification (cen thil) VR Rudimentary Cervical (71t) DV Retarded Ossification (cen thlO-11) VR Retarded Ossification (cen fchll) VR NAD NAD NAD Retarded Ossification (6bil) VR Supernumerary (th site 141t) DV NAD Small Papilla - Size 2 (bil) VR Supernumerary (th site 14bil) DV Retarded Ossification (cen thl3) VR Supernumerary (th short 141t,-site rt) DV Wavy (3-13bil) VR Retarded Ossification (l,2;6-8bil) VR Retarded Ossification (cen thll-12) VR NAD NAD NAD Retarded Ossification (cen thil) VR NAD NAD ^oo^TSC^Bl 'ew^ SanWa.^ 146- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500'MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646275 (Ccmt.) 6 5 .54 7 8 9 10 11 12 13 14 646277 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 646281 1 2 3 5 .25 5 .66 5 .11 5 .15 5 .56 6 .06 5 .24 5 .29 4 .34 5 .09 5 .19 4 .08 4 .76 3 .68 4 .49 4 .24 4 .31 4 .79 4 .77 4 .89 4 .84 4 .78 4 .85 4 .15 4 .17 4 .70 Skull ' Vertebra Vertebra Skull Kidney Skull Skull Skull Skull Kidney Skull Skull Retarded Ossification (6 bil) VR Retarded Ossification (cen thl2) VR MAD NAD NAD Retarded Ossification (cen fchl2-13) VR NAD NAD NAD NAD NAD Retarded Ossification (6bil) VR NAD NAD Papilla - Size 3 (bil) VR Retarded Ossification .(l,12;6bil) VR NAD Retarded Ossification (6bil) VR NAD Retarded Ossification (6bil) VR NAD Retarded Ossification (6bil) VR Papilla - Size 3 (b'il) VR Retarded Ossification (12;6bil) VR NAD NAD Retarded Ossification (6 bil) VR NAD ^ ^ ^ ppWpanyS(affwizad. ,,,nT^ACBt 147- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646281 (C<mt.) 4 4 .50 5 4 .45 6 4 .91 7 4 .42 8 4 .07 9 4 .68 10 4 .14 11 4 .05 12 3 .90 13 14 15 646283 1 2 3 4 5 6 7 8 9 10 11 4 .27 3 .97 3 .92 5 .90 5 .87 6 .16 6 .19 6 .36 6 .04 6 .03 5 .86 6 .43 6 .27 6 .56 Vertebra Skull Vertebra Vertebra Vertebra Skull Vertebra Sternebra Vertebra Vertebra Kidney Vertebra Vertebra Kidney Retarded Ossification (cen thil) VR NAD Retarded Ossification (6 rt) VR Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (arches ce4 rt) VR NAD Retarded Ossification (7 bil) VR Retarded Ossification (cen thil) VR NAD Retarded Ossification (4) VR NAD Retarded Ossification (cen thil) VR NAD NAD Retarded Ossification (cen th9,ll) VR Small Papilla - Size 2 (rt) VR Retarded Ossification (cen fchll) VR NAD NAD Retarded Ossification (cen thil) VR MAD Papilla - Size 3 (right) VR 148- , . Y ' -- ^ {?;t*4 r T c iO o* - ^ a 1 " " 1 ^ ^iful-i"s--e.i ^0 H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646283 (Cont.) 12 6.11 Vertebra Vertebra 646287 1 2 3 4 5 6 7 8 9 10 11 12 13 14 646289 1 2s. 3- 4 5 6 7 8 9 10 5 .19 5 .47 5 .65 5 .77 5 .55 5 .38 5 .21 5 .54 5 .09 5 .14 5 .72 5 .29 5 .50 5 .43- Rib Rib Skull Rib Rib Skull Subcutis Rib Skull Vertebra Rib Skull Rib Skull 6.10 5.26 5.89 5.75 5.98 5.94 6.30 5.04 5.50 5.55 Retarded Ossification (cen thl2) VR Retarded Ossification (cen thil) VR Supernumerary (th site 14bil) DV Supernumerary (th site 14lt) DV Retarded Ossification (6bil) VR Supernumerary (th site 14rt) DV Supernumerary (th site 14bil) DV NAD Retarded Ossification (6bil) VR NAD Hemorrhage (right, limb*) N NAD Supernumerary (th site 14lt) DV Retarded Ossification (61t) VR Retarded Ossification (cen thl2) VR Supernumerary (th site 14lt) DV Retarded Ossification (61t) VR NAD Supernumerary (th short 14rt,-site 14lt) DV Retarded Ossification (6bil) VR NAD NAD MAD NAD NAD NAD NAD NAD NAD NAD OoTOpany s , ^ . ^ ^ ' - " " TM ^ " 149- H-24516: Developmental ToxicityStudym Rats DuPont-5991 INDIVIDUAL FETAL WEIGHTS (grams) AMD ALTERATIONS GROUP IV: 500 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FIND ING (S) CLASSIFICATION 646289 11 12 13 14s 15 16 (Ctont.) 5 .65 5 .87 5 .58 5 .30 5 .55 5 .78 646293 1 6 .04 2 5 .66 3 5 .53 4 5 .61 5 5 .07 6 5 .54 7 5 .79 8 5 .11 9 4 .80 10 5 .70 11 5 .70 12 5 .98 13 5 .75 14 5 .86 15 5 .25 16 5 .56 17 5 .66 646295 1 2 3 4 5 6 7 8 9 10 5 .88 5 .92 5 .80 5 .37 5 .38 5 .47 5 .25 5 .59 5 .94 5 .40 Vertebra Skull Skull- Skull Kidney Skull Rib Rib Skull NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thil) VR Retarded Ossification (6 rt) VR NAD NAD NAD Retarded Ossification (6 It) VR NAD Retarded Ossification (6 bil) VR NAD NAD NAD NAD Papilla - Size 3 (bil) VR NAD NAD Retarded Ossification (6 It) VR NAD NAD NAD NAD NAD Supernumerary (th site 141t) DV NAD Supernumerary (th site 14bil) DV Retarded Ossification (12) VR NAD NAD .^-----^"^ita141" gg^SW^ 150- H-24516: Developmental Toxicity Study in Rats DuPont-5991 INDIVIDUAL PETAL WEIGHTS (grams) AMD ALTERATIONS GROUP IV: 500'MG/KG/DAY DAM NO./ FETUS MO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 646295 11 12 13 14s (0Dnt.) 5 .42 5 .52 5 .66 5 .69 646301 1 2 5 .49 5 .50 3 5 .44 4 5 .74 5 5 .35 6 5 .00 7 5 .06 8 5 .63 9 5 .30 10 5 .50 11 4 .91 12 5 .30 646304 1 2 3 4 5 6 5 .38 6 .05 5 .60 5 .83 4 .84 5 .06 7 5 .05 8 5 .14 9 5 .17 10 4 .85 11 4 .66 12 5 .45 Skull Vertebra Vertebra Vertebra Vertebra Skull Kidney Skull Vertebra Skull Skull NAD Retarded Ossification (61t) VR NAD NAD NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (cen ttilO) VR NAD Retarded Ossification (cen thl3) VR NAD Retarded Ossification (cen thl2) VR NAD NAD NAD Retarded Ossification (6bil) VR Papilla - Size 3 (bil) VR Retarded Ossification (6bil) VR NAD Retarded Ossification (cen thIO) VR NAD Retarded Ossification (61t) VR NAD NAD NAD Retarded Ossification (6bil) VR C@mpany Sa*^--'"'""'"'"^0'1 151- H-24516: Developmental Toxicity Study in Rats __ _______DuPont-5991 APPENDIX H Analytical Report -^-o-tconwr.'l'S^0* ^^^^{-, w 152. H-24516: Developmental Toxicity Study in Rats DuPont-5991 A. SAMPLE SUBMITTAL Samples containing H-24516 at the concentrations ofO, 5.0, 20.0 and 50.0 mg/mL were collected on March 2, 2001. These samples were analyzed to verify homogeneity, concentration, and 5hour room temperature stability. Samples from the same preparation at the concentrations of 5.0 mg/mL were collected on March 5, 2001 to verify the mixing homogeneity for this level. The refrigerated stability for the levels in th^study had been established in a previous Subcbromc Toxtfitv 90 Day Gavage Study Samples containing H-24516 at the concentrations ofO, 5.0, 20.0 and 50.0 mg/mL were collected on March 9,2001 and March 20,2001. The samples were analyzed to verify concentration. All dosing suspension samples were collected on the same day the suspensions were prepared. They were analyzed when received or were frozen until analyzed. The suspension vehicle was 0.5% aqueous methylcellulose. B. METHODS 1. Analytical Methods a. Dosing Suspension Treatment Each dosing sample was diluted to 100 mL with methanol and sonicated to dissolve the H-24516 in the suspension. The dosing samples were further diluted with the 0 mg/mL sample (initial dilution) to an expected concentration of approximately 0.09 mg/mL (active ingredient [a.i.]) prior to analysis. An internal standard (refer to Calibration and Quantitation Section) at an equivalent amount was added to each sample before the final analysis dilution. C.n.P.nySani.l^."""01"'""""''"'" 153- H-24516. Developmental Toxicity Study in Rats b. Chromatographic Conditions DuPont-5991 Instrument: Column: Injector: Detector: Carrier Gas: Split vent: Injection Volume: Oven Program: Initial Temperature: Initial Time Level 1 Rate: Level 1 Temperature: Level 1 Time: Total run time: Hewlett-Packard Model 6890 GC J & W, DB-1701, 30 m, 0.32 mm ID, 1 urn film thickness Split, 250C FID; 250C Helium (2.1 mL/min) 22.3 mL/min 2 microliter Gradient 100C l.OOmin. 20.0C/min. 260C 0.00 min. 9.00 min. c. Calibration and Quantitation A separate sample of H-24516 (-3) was obtained for use as the analytical reference standard m i H n ^ stock solution was prepared in methanol. This stock solution was sonicated to assure that an material was in solution. Before analysis, appropriate aliquots of the stock were diluted with methanol to make calibration standards that bracketed the target concentration of the > c k standarc^HIHH^^H^IIBlR of solution an internal ^^^^^^^^^I^^^^^^^^^^^^^^^^^^^^^^^^^^^^BB^^B ^ was prepared in methanol and addea to each calibration standard A A and test sample to give an equivalent final concentration in all dilutions. The ratio of the peak heights for internal standard and H-24516 at three retention times (3.5, 4.17, and 4.77 minutes) from replicate GC analysis of these solutions were used to construct a calibration curves by least squares regression (see Figure la, Ib, and Ic for a representative curves). Measured concentrations for the dosing samples were determined by applying the peak height ratios from replicate injections of each sample to the respective calibration curve. Test substance homogeneity in the dosing suspensions was evaluated by calculating the coefficient of variation (C.V. = standard deviation/mean x 100) of the measured concentrations in the top, middle, and bottom (T, M, and B) samples or the mean of duplicate samples for each concentration. A coefficient of variation of less than 10% is considered indicative of acceptable distribution of the test substance throughout the dosing suspension. The mean result of the top, middle, and bottom homogeneity samples or of the duplicate concentration verification 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 of the top, middle, and bottom homogeneity samples or of the duplicate concentration verification samples (0-day room temperature) as the baseline for comparing the corresponding room temperature and refrigerated results. ^amTSC^ 154- -SSS&^Q' H-24516: Developmental Toxicity Study in Rats DuPont-5991 C. ANALYTICAL RESULTS 1. Chromatography H-24516 eluted from the GC column as resolved peaks with retention times from 2.9 minutes to approximately 6.0 minutes. For the purpose ofquantitation, resolved peaks at the retention times IBIIHHIBHHIHBHHIB0^10^ , of approximately 3.5,4.17, and 4.77 minutes were used. The internal standardfHH|^HI as a resolved peak at approximSreiy3.99 "minutes. Representative GC chromatograms are shown in Figures 2(a - c). Test substance was not detected in the 0 mg/mL control. 2. Homogeneity, Concentration, and Stability Verification Analytical results from dosing suspensions collected on March 2, 2001 and March 5, 2001 (5.0 mg/mL level) and analyzed for homogeneity, concentration, and stability verification are shown in Analytical Table I and Analytical Summary Table 1. The following table summarizes the results for homogeneity, concentration, and stability verification. Preparation Date 2-Mai-2001 5-Mar-2001 Nominal mg/mL 0 5.0 20.0 50.0 5.0s Measured T,M,B" mg/mL ND0 7.96,4.41,3.99 17.7,20.6,20.9 43.6,44.7,44.1 4.96, 5.06, 5.07 Mean (T,M,B) % Nominal 107.6 98.7 88.3 ^ 100.7 C.V. (%) -- 41 9 1 1 Stability" % Nominal -- 74.7 99.5 87.2 d a Mean results for the analysis of the top (T), middle (M) and bottom (B) samples. b Samples held 5 hours at room temperature. c Denotes none detected. d 5-hour room temperature sample not collected. The data for samples collected on March 3, 2001 indicates that the test substance was homogeneously mixed in the vehicle except for the 5.0 mg/mL level (C.V. = 41). The test substance was at the targeted concentration in the samples (11.7% of nominal) and was stable in the vehicle when held 5 hours at room temperature. The 5 mg/mL level was insufficiently mixed before the initial sampling. This was not considered to have adversely affected the study because the samples were collected after formulation preparation. Then, the formulations are used for dosing. The formulations are stirred continuously during dosing so it is reasonable to conclude that the suspension was adequately homogeneous during use. This finding was substantiated by the results from the samples collected March 5, 2001 from the same preparation indicating that the test substance was homogeneously mixed in the vehicle (C.V. =1). The stability results for the initial sampling (74.7% of nominal) reflect the mixing irregularity of the sampling and not the stability of the test substance. This conclusion is supported by the results of - 155- gaftHUed^098^conta^S^ CompsW H-24516: Developmental Toxicity Study in Rats_____________________________DuPont-5991 the stability samples for the other levels in the study and by the data from the referenced stability Stud^Um^U| study done for the Subchronic Toxicity 90 Day Gavage substance was not found in the 0 mg/mL samples. Test 3. Stability Study The following table is included for a reference in this study to the refrigerated stability for the ..concentrationrange. It summarizes the results for Subchronic Toxicity 90 Day Gavage Study _ I^^^I^^^BHHhomogeneity/concentration verification (January 8, 2001 and ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^m^ -" ' January 15, 2001) and the 4-day refrigerated stability analyses followed by 5 hours room temperature. Preparation Date Nominal Measured Mean C.V. Sample Type____mg/mL_____mg/mL______% Nominal____(%) 8-Jan-2001 Homogeneitya 0 ND1' 5.0 4.53,4.25,4.39 87.8 3 . 20 19.9,17.7,18.6 93.5 6 50 53.4,52.6,54.0 106.8 1 Stability 4-Day Refrigerated'1 5.0 4.81 96.1 -- Stability % Nominal 92.0 86.0 96.6 97.1 4-Day Refrigerated'1 20 19.6 97.8 -- 88.2 4-Day Refrigerated'1 50 48.9 97.8_______--_____95.7 a Mean results for the analysis of the top (T), middle (M) and bottom (B) samples. b Denotes none detected. c Samples held 5 hours at room temperature. d Mean result of single sample for 4-day refrigerated/concentration verification and a single sample for 4- day refrigerated/5 hour room temperature stability. The data froir^fJ^B------RampIes is included with this study to show that the test substance was stable in the vehicle when held 4 days refrigerated and followed by 5 hours at room temperature for the concentration range of the study. This data supports the mixing and storage conditions of the testing system during this study. ^ i f c e a ^_o_ _e_s---^ --- W " ^ ^ " -' "-.--(>. " -156- H-24516: Developmental Toxicity Study in Rats DuPont-5991 4. Concentration Verification Analytical results from dosing suspensions collected on March 9,2001 and March 20,2001 and analyzed for concentration verification are shown in Table ffl and Summary Table 1. 1 The following table sufemarizes the results for concentration verification analyses. Preparation Date 9-Mar-2001 ^ Nominal mg/mL 0 5.0 20.0 50.0 Measured0 mg/mL ND6 4.44,4.48 18.0'1,18.5 44.6, 46.0 Mean % Nominal -- 89.2 91.3 90.7 C.V1'. (%) -- 1 2 2 20-Mar-2001 0 5.0 20.0 50.0 ND' 4.33,4.38 17.6,17.7 46.7,46.1 ,, ---- 87.0 1 88.3 1 92.8 1 a Mean results for the analysis of the duplicate samples. b C.V. for the duplicate samples used to confirm uniformity of mixture. c Denotes none detected. d Mean result of duplicate re-sampling from the original sample. Original analysis was lower than expected and will not be reported. The data for samples collected on March 9, 2001 indicate that the test substance was uniformly mixed in the vehicle at all levels. The test substance was at the targeted concentration in the samples ( 10.8% of nominal). The data for samples collected on March 20, 2001 indicate that the test substance was uniformly mixed in the vehicle at all levels. The test substance was at the targeted concentration in the samples ( 13.0% of nominal). Test substance was not found in the 0 mg/mL samples. 5. Conclusions Data from the analysis of the samples during the study indicate that the test substance was homogeneously mixed, at the targeted levels and was stable under all conditions used in the study. Test substance was not found in the 0 mg/mL samples. -157. H-24516: Developmental Toxicity Study in Rats ANALYTICAL SUMMARY TABLE 1 DuPont-5991 SUMMARY OF DOSING ANALYSES Nominal: Homogeneity Samples 3-Mar-2001 Top Middle Bottom Average Measured Cone.11 Average Percent Nominal Standard Deviation1' Coefficient of Variation13 Dosing Concentration of H-24516 (mg/mL) 5.0 20.0 50.0 7.96 (^J)8 4.41 (88.1) 3.99 (79.7) 5.38 (107.6) 2.2 41% 17.7 (88.5) 20.6 (103.2) 20.9 (104.3) 19.7 (98.7) 1.8 9% 43.6 (87.3) 44.7 (89.3) 44.1 (88.2) 44.1 (88.3) 0.5 1% Stability Samples 5-Hour Room Temperature 5-Mar-2001 Homogeneity Samples Top 3.73 (74.7) 4.96 (99.3) 19.9 (99.5) 43.6 (87.2) Middle 5.06 (101.3) Bottom 5.07 (101.5) Average Measured Cone.1' Average Percent Nominal Standard Deviation1' Coefficient of Variation1' 5.03 (100.7) 0.06 1% Numbers in parentheses are the respective percent of nominal values. Statistics based on the average measured .concentration (ppm) of the top, middle, and bottom of each dosing level. Samples not required for study. i i-TC^ft rvt Company SanWzed,.Does"^0^" -158- .gp^nS.eSiB^-^- 'evTOpa'^5^1"' H-24516: Developmental Toxicity Study in Rats_____________________________DuPont-5991 ANALYTICAL SUMMARY TABLE 1 (Continued) SUMMARY OF DOSING ANALYSES Nominal: Concentration Verification0 9-Mar-2001 #1 #2 Dosing Concentration of H-24516 (mg/mL) 5.0 20.0 50.0 4.44 (88.7)3 4.48 (89.6) 18.0" (90.0) 18.5 (92.5) 44.6 (89.3) 46.0 (92.1) Average Measured Cone.0 Average Percent Nominal Standard Deviation0 Coefficient of Variation0 20-Mar-2001 #1 #2 4.46 (89.2) 0.03 1% 4.33 (86.5) 4.38 (87.5) 18.3 (91.3) 0.4 2% 17.6 (87.8) 17.7 (88.7) 45.3 (90.7) 1.0 2% 46.7 (93.4) 46.1 (92.3) Average Measured Cone.0 Average Percent Nominal Standard Deviation0 Coefficient of Variation0 4.35 (87.0) 0.04 1% 17.7 (88.3) 0.1 1% 46.4 (92.8) 0.4 1% a Numbers in parentheses are the respective percent of nominal values. b Mean result of duplicate re-sampling of the original sample. Original analysis was lower than expected and will not be reported. C Statistics based on the average measured concentration (ppm) of duplicate samples. C,n,pan,San-^.Do.sn.>co.,.."^.-. 159- H-24516: Developmental Toxicity Study in Rats ANALYTICAL SUMMARY TABLE 1 (Continued) DuPont-5991 SUMMARY OF DOSING ANALYSES Stability Study" Nominal: Homogeneity Samples Dosing Concentration of H-24516 (mg/mL) 5.0 20.0 50.0 Top Middle Bottom Average Measured Cone.0 Average Percent Nominal Standard Deviation0 Coefficient of Variation0 4.53 (90.6)1' 4.25 (85.0) 4.39 (87.8) 4.39 (87.8) 0.14 3% 19.9 (99.5) 17.7 (88.5) 18.6 (93.0) 18.7 (93.5) 1.1 6% 53.4 (106.8) 52.6 (105.2) 54.0 (108.0) 53.4 (106.8) 0.7 1% Stability Samples 0-Day Room Temperature'1 4.39 (87.8) 18.7 (93.5) 53.4 (106.8) 4-Day Refrigerated 4.81 (96.1) 19.6 (97.8) 48.9 (97.8) 4-Day Refrigerated/5 hr. 4.85 (97.1) 17.6 (88.2) 47.9 (95.7) a^Samgles prepared January 8,2001 for Subchronic Toxicity 90 Day Gavage Study b Numbers in parentheses are the respective percent of nominal values. c Statistics based on the average measured concentration (ppm) of the top, middle, and bottom of each dosing level. d The mean measured values from analysis of homogeneity samples (considered fresh/0-day room temperature samples) were used as baselines for comparison with the respective stability samples. ^ . r ^ * - ^ ' ' 6 1 -Con-s--p,,-a:,ns/s^n"i'tte"- -160. H-24516: Developmental Toxicity Study in Rats DuPont-5991 Analytical Table:L Homogenieity and Stability of H-24516 in:Dosing Suspensions Sample mg/mL H-24516 Percent Type Nommal Measured Nominal 2-Mar-2001 Homoeeneitv CONTROL 0.00 ND(A) TOP MIDDLE BOTTOM TOP MIDDLE BOTTOM TOP MIDDLE BOTTOM StabilitvCQ 5.0 5.0 5.0 20.0 20.0 20.0 50.0 50.0 50.0 MeanW: 7.96 4.41 3.99 5.381.2.2 C.V.41% MeanW: 17.7 20.6 20.9 19.71.8 C.V.9% MeanW: 43.6 44.7 44.1 44.M5 C.V.1% 5.0 20.0 50.0 3.73 19.9 43.6 159.3 88.1 79.7 (107.6%) 88.5 103.2 104.3 (98.7%) 87.3 89.3 88.2 (88.3%) 74.7 99.5 87.2 TOP 5.0 4.96 99.3 MIDDLE 5.0 5.06 101.3 BOTTOM 5.0 5.07 101.5 MeanW: 5.03^0.06 (100.7%) C.V.1% (A) Denotes not detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of top, middle, and bottom are based on measured concentration for each level. (C) Stability samples held 5 hours at room temperature. Pompahy Sani$!zed. Does not contain TSCA CB 161- H-24516: Developmental Toxicity Study in Rats DuPont-5991 Analytical Table n. Stalnlity Study of H-2.4516 in Dosing Su;sponsions Preparation Date mg/mL H-24516 Percent Sample Type Nominal Measured Nominal 8-Jan-200l(A) O-DAY ROOM 5.0 TEMPERATUREC13) 4.39 87.8 4-DAY REFRIGERATED 5.0 4-DAY REFRIGERATED/5 5.0 HOUR RT 4.81 4.85 96.1 97.1 O-DAY ROOM TEMPERATUREC8) 4-DAY REFRIGERATED 4-DAY REFRIGERATED/5 HOURRT 20.0 20.0 20.0 18.7 19.6 17.6 93.5 97.8 88.2 O-DAY ROOM 50.0 53.4 106.8 TEMPERATL^13) 4-DAY REFRIGERATED 50.0 48.9 97.8 4-DAY REFRIGERATED/5 HOUR RT 50.0 47.9 95.7 Stud:fmUUB!w- ^ (A) Samples from Subchronic Toxicity 90 Day Gavage J (B) The average measured concentration of top, middle, and Bottom tor the homogeneit samples (0-Day Room Temperature) used as baseline for stability comparison. 162- '"'(-mpany &an;s.teA Does net wnisi-. TSCA ^ H-24516: Developmental Toxicity Study in Rats DuPont-5991 Analytical Table in. Concentration Verification of H-24516 in Dosing Suspensions Sample _______mg/mL H-24516_______ Percent Type________Nominal_______Measured_______Nominal 9-Mar-2001 CONTROL 0.00 NDC^ #1 #2 #1 #2 #1 #2 20-Mar-2001 CONTROL 5.0 4.44 5.0 4.48 MeanW: 4.460.03 C.V.1% 20.0 ig.o(C) 20.0 18.5 MeanW: 18.30.4 C.V.2% 50.0 44.6 50.0 46.0 MeanW: 45.3^1.0 C.V.2% 0.00 ND(A) 88.7 89.6 (89.2%) 90.0 92.5 (91.3%) 89.3 92.1 (90.7%) #1 5.0 4.33 , 86.5^ #2 5.0 4.38 87.5 MeanW: 4.35f0.04 (87.0%) C.V.1 % #1 20.0 17.6 87.8 #2 20.0 17.7 88.7 MeanW: 1W0.1 (88.3%) C.V.1% #1 50.0 46.7 93.4 #2 50.0 46.1 92.3 MeanW: 46.4^0.4 (92.8%) C.V.1% (A) Denotes not detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples are based on measured concentration for each level and reported to verify uniformity of mixing. (C) Mean result of duplicate re-sampling from the original sample. Original analysis was lower than expected and will not be reported. Company Sanifizea. DoesribI contain TSRA nw 163- H-24516: Developmental Toxicity Study in Rats Figure 1 Representative Analytical Calibration Curve DuPont-5991 -a 0.6-^ 0.08 0.10 0.12 0.14 Concentration mg/mL (a) 0.08 0.10 0.12 0.14 Concentration mg/mL (b) 0.10 0.12 0.14 Concentration mg/mL (C) Figure 1: Calibration curve showing linear fit (line) to replicate peak height ratio measurements (squares) for calibration solutions of H-24516 diluted over a concentration range of 0.0525 to 0.1576 mg/mL. [(a) Retention time =3.5 minutes, (b) Retention =4.17 minutes, (c) Retention time = 4.77 minutes.] ,^nt^^ 164- foii.t'.".1^^-,"-'j' DtjSsBQ' -------- '?";'- H-24516: Developmental Toxicity Study in Rats DuPont-5991 Figure 2 Representative High Performance Liquid Chromatography Chromatograms FID1 B, (010309SRi002F0201.D) PA1 45- 40 - 35- CO s f 1 30 - 25 -: 20 - 15 -. 10- ^JV-JL-^^. 5- 0 9 Figure 2a: approximately j.5, 3.9 minutes. FID1 B, (010309SR\009F0902.D) PAl 45 - 4 6 8 frtr, io{0 mg/mL ^control) sample with internal standard added. Retention time for H-24516 is i time for internal standard is approximately 40- 35-: C0130 - ' 252015- 10 - 5- t^ g g Oi co 1 M 1 U-A--J g ! ! a 11 1 1 t 1 . (1 Figure 2b: 7 4 6 8 ,,,,, Representative GC chromatogram of 5.0 mg/mL H-24516 dosing solution diluted to a nominal concentration of 0.09 mg/mL. The average measured concentration of the representative solution is 4.48 mg/mL. FID1 B, (010309SRW05F05D2.D) PA" 45- 40 - i 35- (<0 30- CO 25- s e CM f l i i ?I f 20-: T IT" 111 j 1 ! YA.A : 15- 10 - 8 ^ 1 1 1,1 5- 0 ? 4 6 8 m;n Figure 2c: Representative GC chromatogram of 0.1051 mg/mL H-24516 analytical reference solution. -165- ^CompanyS^feed. Does nolcontain TSCA CB1