Document KJBk9g72Boe555gb6ZOMyxRMw

AR226-3183 DuPont-4902 TRADE SECRET Study Title H-24616: Developmental Toxicity Study in Rats Laboratory Project ID: DuPont-4902 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: October 15,2001 Performing Laboratory: 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 Work Request Number:, 1Service Code Number: Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 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. The characterization of the test substance that was conducted prior to the initiation of the study provided the percentage of solids in the test substance. This information was used to calculate the dose levels for the study. Further chemical characterization of the test substance was conducted after the completion of the study and provided the composition of the solids in the test substance. Samples of the test substance were collected on the first and last days of the dosing period and were analyzed; these analyses provided confirmation of the percentage of solids and documented the test substance stability over the course of the study. None of the aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with IS09002 regulations. All of the analyses are considered valid and sufficient for the purposes of this study. Applicant / Sponsor: E. L du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Applicant / Sponsor Research Scientist DuPont Representative Date Date Company Sanitized. Does not contain TSCA CBI -2- I H-24616: Developmental Toxicity Study in Rats DuPont-4902 QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24616 Dates of Inspections: Protocol: October 4,2000 Conduct: October 19,25,26, 2000 Records, Reports: March 15,16,19-21,23, 2001; April 23,26-27, 2001 Dates Findings Reported to: Study Director: March 25,2001; April 29, 2001 Management: April 25, 2001; October 15, 2001 Reported by. JYL^-) u J v r u r Kimberly B. Brebner Quality Assurance Auditor 5-nc+-<20I Date Company Sanitized. Does not contain TSCA CBI -3 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. ADDrovedbvi^ 7 ^ ^ -u b (- ---------- - Robert M. Parker, Ph.D,, D.A.B.T. Director Developmental and Reproductive Toxicology AndNeurobehavioral Toxicology /S- C T-2O 01 Date Susan M. Munley, M.A. 1 Research Scientist /5- J/-2Q D / Date Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT.................................... 2 QUALITY ASSURANCE STATEMENT...................................................................................... 3 CERTIFICATION..............................................................................................................................4 STUDY INFORMATION................................................................................................................. 7 STUDY PERSONNEL....................................................................................................................... 8 SUMMARY......................................................................................................................................... 9 OBJECTIVE 10 MATERIALS AND METHODS.............................................................. A. Test Guidelines................................................................................ B. Test Substance................................................................................. C. Test Species...................................................................................... D. Animal Husbandry........................................................................... 1. Housing............................................................................................................ 2. Feed and W ater................................................................................................ 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 B ias................................................................................. M. Statistical Analyses.......................................................................... RESULTS AND DISCUSSION............................................................... A. Maternal Findings............................................................................ 1. Mortality........................................................................................................... 2. Body W eights................................................................................................... 3. Body Weight Changes..................................................................................... 4. Food Consumption.......................................................................................... 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 Company Sanitized. Doss not contain TSCA CB1 -5- H-24616: Developmental Toxicity Study in Rats TABLE OF CONTENTS (Continued) 5. Clinical Observations................................................................... 6. Postmortem Findings.................................................................... B. Fetal Findings.................................................................... 1. Mortality........................................................................................ 2. Body Weight................................................................................. 3. M alformations.............................................................................. 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 W EIGHTS......................................... 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 DuPont-4902 Page .17 .17 17 .17 .17 .17 .17 18 18 19 ,20 .21 .22 .23 .24 .25 .26 ..28 ,31 .32 .42 .52 .62 .76 .82 .88 Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats STUDY INFORMATION Substance Tested Svnonvms/Codes: H-24616 Haskell Number: 24616 DuPont-4902 Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study initiated/Completed: October 5,2000 / (see report cover page) In-Life Initiated/Completed: October 8, 2000 / November 16, 2000 Comoany Sanitized. Does not contain TSCA CBI -7- H-24616: Developmental Toxicity Study in Rats STUDY PERSONNEL Study Director: Susan M. Munley, M.A. Management: Robert M. Parker, Ph.D., D.A.B.T. Primary Technician: Ronald L. Poore Toxicology Report Preparation: Mary K. LaRoe Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-4902 Company Sanitized. Does not contain TSCA CBt -8 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 SUMMARY H-24616 was administered by oral gavage to groups of 22 time-mated rats at dosages of 0, 50, 250, or 1000 mg/kg/day over days 6-20 of gestation (G). Body weight, food consumption, and clinical observation data were recorded during the in-life portion of the study. On day 21G, the females were euthanized and examined grossly; the uteri were removed, weighed, and uterine content data were collected. Each fetus was weighed, sexed, and examined externally and skeletally. Approximately 50% of the fetuses underwent fresh visceral and fixed head evaluations. There was no compound-related mortality nor were there any compound-related gross postmortem observations at any level tested. Compound-related clinical observations were seen at 250 and 1000 mg/kg/day. These findings were limited to lung noise observed in 2/22 animals at 250 mg/kg/day and 5/22 animals at 1000 mg/kg/day. Minimal, statistically significant reductions in maternal body weights, weight changes, and food consumption were observed at 250 and 1000 mg/kg/day as well. The weight and weight change reductions occurred primarily during the first week of dosing and had minimal impact on mean final weight; final weights were no less than 97% controls at these levels and overall weight changes were no less than 86% controls. With regard to reproductive and fetal outcome, the only compound-related observation that was seen was a minimal statistically significant reduction in mean fetal weight at 1000 mg/kg/day (94% controls). There was no compound-related fetal mortality, nor were there any compound-related fetal malformations and variations. There were no compound-related effects seen at 50 mg/kg/day. Under the conditions of this study, minimal evidence of maternal toxicity including reduced body weight, weight gain, food consumption, and increased lung noise was observed at 250 and 1000 mg/kg/day. No significant or adverse effects were seen in dams dosed at 50 mg/kg/day or lower. Similarly, minimal evidence of developmental toxicity was evident at 1000 mg/kg/day based on a 6% reduction in mean fetal weight. Thus, the maternal no-observed-effect level (NOEL) was considered 50 mg/kg/day; the NOEL for developmental toxicity was considered 250 mg/kg/day. i | 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 (1985) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union (1994). Company Sanitized. Does not contain TSCA CBI -9 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 OBJECTIVE The purpose of this study was to evalu ' H-24616 in rats. H-24616 contains an '' ' '' ' " r 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 H-24616 was supplied by the sponsor, the DuPont Chemical SoIution^interpns^IX^SE), E. I. Du Pont de Nemours andCompany^Jewari^Del aware, as composition.'" H-24616 is a j 0 H i | l H H V including Lhc active in g r e d ie n tJ H H H 11 was assigned the Haskell Laboratory Number 24616. The sponsor was responsible for the characterization 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 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. Sanitized Does not contain TSCA CBf - 10- H-24616: Developmental Toxicity Study in Rats DuPont-4902 Eighty-eight nulliparous, time-mated females, were received on October 5 and 6, 2000 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 0G), were supplied by the vendor; day 0G body weights ranged from 230 to 266 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 the United Water Delaware was available ad libitum. 3. Identification Each animal was assigned a unique number and identified with an ear punch/notch by the supplier prior to shipping. Upon receipt, each animal was assigned a unique Haskell animal number. Both the Haskell animal number and the ear punch/notch number were recorded on each cage card. A master list of unique Haskell animal numbers and corresponding unique ear punch/notch 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 -11 - Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 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 SO and then released for the study upon approval of the Laboratory Animal Veterinarian. F. Study Design The experimental design is shown below: Group Dose (me/ke/dav) Dose Volume^ (mL/ke) Time-Mated Females I 0c 4.08 22 n 50 0.204 22 m '250 1.02 22 IV 1000 4.08 . -22 a H-24616 was administered as weight of test substance, adjusted fo i^ H H a c tiv e ingredient, per kg body weight. It was administered once daily, by gavage, over days 6-20 of gestation (days 6-20G). b H-24616 was administered as received from the sponsor. The neat liquid was not diluted prior to dosing but was given to the animals in varying volumes dependent on the targeted dose and amount (grams) of polymer in the H-24616 preparation. c The control group was dosed with deionized water. G. Selection of Dose Levels The dose levels for the current study were based on results from a 14-day range-finding study in rats. In the range-finder, no toxicity was observed up to the limit dosage level of 1000 mg/kg/day ^H fiT h u s, doses for the current study were selected based on the ability of rats to tolerate the upper limit dose in the range-finder. Company Sanitized. Doe? not TSCA CPI - 12- H-24616: Developmental Toxicity Study in Rats DuPont-4902 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 H-24616 was administered daily to the study animals as received from the sponsor. The neat liquid was not diluted prior to dosing but was given to the animals in varying volumes dependent on the targeted dose and amount (grams) of active ingredient in the H-24616 preparation. The test material was administered by oral gavage because the oral route was deemed to be the most efficient method for delivering an accurate dosage. The volume administered was based on the most recent body weight. The test substance was continuously stirred during dosing to maintain uniformity of the mixture. Control group animals were similarly dosed with deionized water at the same dose volume used for the high-dose group. The test substance was analyzed by the sponsor using samples collected before and after dosing on the first and last days of the dosing period. The analyses were performed by Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. Based on the percent solids, percent fluorine, and pH measurements at each time of analysis, the test substance was considered stable over the course of the study. The results of these analyses are presented below: Sample Date October 8, 2000 predose October 8,2000 postdose October 25, 2000 predose October 25, 2000 postdose % Solids % Fluorine 12.5 12.7 12.5 12.5 pH - 13- Company Sanitized. Does not contain t s c a CBI H-24616: Developmental Toxicity Study in Rats J. Animal Euthanasia DuPont-4902 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 6-21G. Food consumption was measured on days 4, 6, 8,10, 12,14,16,18, 20, and 21G. 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 21G. 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. 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 Bourn's fixative, the heads of decapitated fetuses were examined and alterations were recorded. Examinations were based on the method of Barrow and Taylor.( J 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. - 14- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 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 was p < 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. 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 Jonckheere's test(10) Cochran-Armitage test Linear contrast of least square means(11) - 15 - Company Sanitized. Docs iot contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 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 were minimal, compound-related reductions in mean maternal body weight at > 250 mg/kg/day. At 1000 mg/kg/day, slight (maximally 5% lower than controls), statistically significant reductions in mean maternal body weights were evident beginning on day 8G persisting until the end of the study. Mean final weight (absolute weight or weight adjusted for weight of products of conception) was 3% lower than controls. At 250 mg/kg/day, slight (maximally 3% lower than controls), statistically significant reductions occurred on days 10 and 12G. Mean final weight was 2%/3% lower than controls using the absolute/adjusted mean final weight. There were no compound-related effects on mean maternal weight at 50 mg/kg/day. 3. Body Weight Changes (Table 2, Appendix B) There were minimal, compound-related reductions in mean maternal body weight gain at > 250 mg/kg/day. At 1000 mg/kg/day, overall weight gain was 7%/14% lower than control using the absolute/adjusted final weight to calculate gain over days 6-21G. This overall reduction was statistically significant and was primarily the result of compound-related, statistically significant reductions in mean weight gain over days 6-8 and 8-10G. At 250 mg/kg/day, overall weight gain was 5%/13% lower than control using the absolute/adjusted final weight to calculate gain over days 6-21G. The reduction calculated using the adjusted final weight was statistically significant. As for 1000 mg/kg/day, these reductions primarily resulted from reduction seen early in the dosing period; the gain over days 8-10G for the 250 mg/kg/day group was statistically significantly reduced. At 50 mg/kg/day, the weight gain over days 8-10G was slightly but significantly lower than for controls. This reduction at 50 mg/kg/day was not considered adverse because it was minimal in magnitude and had no impact on either overall body weight gain during the study or on final body weight. 4. Food Consumption (Table 3, Appendix C) There were minimal, compound-related reductions in mean maternal food consumption at > 250 mg/kg/day. At 1000 mg/kg/day, overall food consumption was 5% lower than controls when averaged over days 6-21G. This reduction was statistically significant and was primarily Company Sanitized. Does not contain T S C A CB1 - 16- H-24616: Developmental Toxicity Study in Rats DuPont-4902 the result of compound-related, statistically significant reductions in mean food consumption over days 6-8, 8-10,10-12, and 12-14G. At 250 mg/kg/day, overall food consumption was 4% lower than control when averaged over days 6-21G. This slight reduction was not statistically significant and resulted from significant reductions in mean food consumption over days 6-8, 8-10, and 10-12G. There were no compound-related effects in mean food consumption at 50 mg/kg/day. 5. Clinical Observations (Table 4, Appendix D) Compound-related clinical observations were seen at > 250 mg/kg/day and were limited to transient lung noise in 2/22 and 5/22 animals from the 250 and 1000 mg/kg/day groups, respectively. The incidence of lung noise at 1000 mg/kg/day was statistically significantly increased. 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; all animals appeared normal upon examination at necropsy. B. Fetal Findings 1. M ortality (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 (6%) reduction in mean fetal weight at 1000 mg/kg/day; this reduction was statistically significant. Mean fetal weights at 50 and 250 mg/kg/day were comparable to control values. 3. M alformations (Table 6, Appendix G) There were no compound-related fetal malformations at any level tested. 4. V ariations (Table 7, Appendix G) There were no compound-related fetal variations at any level tested. - 17- Company Sanitized. Doss not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 CONCLUSIONS Under the conditions of this study, minimal evidence of maternal toxicity including reduced body weight, weight gain, and food consumption and increased lung noise was observed at 250 and 1000 mg/kg/day. No significant or adverse effects were seen in dams dosed at 50 mg/kg/day or lower. Similarly, minimal evidence of developmental toxicity was evident at 1000 mg/kg/day based on a 6% reduction in mean fetal weight. Thus, the maternal no-observed-effect level (NOEL)0 was considered 50 mg/kg/day; the NOEL for developmental toxicity was considered 250 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. Analytical raw 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(IZ) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.03' Company Sanitized. Does not contain T S C A CB1 - 18- H-24616: Developmental Toxicity Study in Rats DuPont-4902 REFERENCES 1. Buck, Robert C. Memorandum containing Composition Summary dated October 2, 2001. Work Request (WR)/Medical Research (MR) file 13422. 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, 6:191 196. 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 (XI/283/94-EN), Chapter I, Sections 2.24 and 2.25. - 19- Company Sanitized. Docs no? contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLES - 20- Company Sanitized. Doss not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 1 MEAN MATERNAL BODY WEIGHTS (grams), b Days Of Gestation Group : Dose (mg/kg/day): n: I 0 22 II III 50 250 22 22 IV 1000 21 0 238. 5 ( 7. 53) c 239. 0 ( 8. 19) 238. 9 ( 8. 57) 238. 4 (10. 27) 6 268 .6 ( 8. 56) 268. 4 (10. 21) 267 .2 ( 8. 06) 265.,5 (13. 46) 8 277 .7 ( 9. 99) 277.,2 (11..79) 273 ..8 ( 9.,55) 266..3 (14.,94) 10 287 ..5 (10. 55) 284..5 (13.,11) 278..6 (12..24) * 272..2 (13.,28) 12 301..2 (10.,86) 299..3 (12..35) 293 .8 (10..07) * 287 ,.8 (14..31) 14 312 .8 (13..69) . 312 .5 (14,.06) 306..9 (11..00) 300,.0 (14..13) 16 330..2 (14..77) 330,.0 (18..90) 324 .9 (11 .84) 321 .5 (15..87) 18 359 .9 (19..07) 363 .1 (16 .87) 352 .9 (13 .66) 349 .7 (18,.23) 20 393 .1 (26..01) 397 .1 <19 .17) 384 .9 (18 .62) 382 .4 (20 .56) 21 417 .1 (30 .53) 422 .4 (20 .68) 407 .5 (19 .72) 403 .6 (22 .45) 21d 322 .2 (15 .72). 325 .7 (15 .04) 313 .6 (13 .86) 311 .7 (18 .77) a Data from one female that was not pregnant were excluded. b Individual animal data are presented in Appendix A. c Standard deviation is presented in parentheses. d 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. -21 - Company Sanitized. Does not contain TSC A CBI % H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 2 MEAN MATERNAL BODY WEIGHT CHANGES (grams).* Days Of Gestation Group: Dose (mg/kg/day): n: I 0 22 II III IV 50 250 1000 22 22 21 0-6 4-6 6-8 8-10 10-12 12-14 14-16 16-18 18-20 20-21 6-21 6-21^ 30.2 ( 4.22)c 13.7 ( 5.03) 9.0 ( 4.30) 9.9 ( 3.87) 13.7 ( 4.04) 11.6 ( 5.17) 17.3 ( 6.86) 29.7 ( 6.68) 33.2 ( 8.79) 24.0 ( 6.40) 148.5 (26.33) 53.6 (11.89) 29.5 ( 7.72) 14.4 ( 3.26) 8.7 ( 5.31) 7.4 ( 4.28)* 14.8 ( 4.97) 13.2 ( 4.36) 17.5 ( 7.54) 33.2 ( 9.32) 34.0 ( 5.25) 25.3 ( 6.49) 154.0 (16.93) 57.3 (10.51) 28.3 ( 6.12) 13.1 ( 3.43) 6.7 ( 7.23) 4.8 ( 8.25)* 15.2 ( 4.90) 13.1 ( 3.86) 18.0 ( 3.83) 28.0 ( 7.49) 32.0 ( 7.52) 22.7 ( 5.82) 140.4 (16.48) 46.5 (10.83)* 27.1 ( 9.48) 14.4 ( 6.48) 0.8 (10.46)* 5.9 ( 9.04)* 15.6 ( 4.85) 12.2 ( 5.04) 21.5 ( 5.35) 28.1 ( 5.33) 32.7 ( 8.36) 21.2 ( 6.34) 138.1 (15.57)* 46.2 (16.42)* a Data from one female that was not pregnant were excluded. b Individual data are presented in Appendix B. c Standard deviation is presented in parentheses. d 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. - 22- Company Sanitized. Does not contain T S C A CBI H-24616: Developmental Toxicity Study in Rats TABLE 3 MEAN MATERNAL FOOD CONSUMPTION (grams/day)a,fc Days Of Gestation Group : Dose (mg/kg/day): n: I 0 22 II III 50 250 22 22 IV 1000 21 4--6 6--8 8--10 10--12 12--14 14--16 16--18 18--20 20--21 6--21 22. 4 (2. 46) c 24. 2 (1..91) 24..8 (1..65) 25..7 (2..21) 26..6 (2..17) 27 .1 (3..01) 30..1 (2 .52) 28..8 <2 .66) 27 .3 (3 .94) 26 .8 (1 .84) 23. 0 (3. 03) 24..1 (3.,21) 24.,8 (3.,20) 26..0 (2..69) 27..2 (2..99) 29 .2 (2,.95) 30,.8 (2..84) 30..4 (2 .62) 28 .7 (4 .12) 27 .6 (2 .45) 22 .6 (1..70) 22 .,5 (2.,29) * 22 .,3 (3..51) * 23 .9 (1..80) * 25..9 (2..37) 27 ,.4 (1..97) 28 .9 (2..58) 28 .4 (2..56) 27 .2 (3..25) 25 .7 (1 .50) a Data from one females that was not pregnant were excluded. b Individual data are presented in Appendix C . c Standard deviation is presented in parentheses. * Significant trend (linear contrast of means); p < 0.05. 22. 4 (1. 81) 20..2 (4.,82)* 21.,7 (2.,32) * 23 .8 (2..66)* 25,.1 (2..67)* 27 .9 (3..03) 29,.5 (2..83) 29 .3 (2..17) 27 .2 (3 .57) 25 .5 <2 .12) * # DuPont-4902 Company Sanitized. Poes not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats TABLE4 CLINICAL OBSERVATIONS" DAY OF GESTATION OBSERVATION: GROUP DOSE (mg/kg/day) NO. EXAMINED 4-5 ALOPECIA 6-21 ALOPECIA DIARRHEA DISCHARGE PERINASAL LUNG NOISE STAIN CHIN _______________ WET PERINEUM___________________________ a Individual data are presented in Appendix D. * Significant trend (Cochran-Armitage test); p ^ 0.05. I 0 22 0 4 0 1 0 0 0 II II II II II II 50 22 2 4 0 0 0 0 0 III IV 250 1000 22 22 10 52 01 00 2 5* 01 01 II II II II II II II II It II II II II IIII II II II II II It II II II II II II II II II II II II II II DuPont-4902 ompany Sanitized. B oes not contain T 5 C A CBt H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 5 REPRODUCTIVE OUTCOME** Group: Dose (mg/kg/day): No. Mated NO. Pregnant N o . Deaths No. With Total Resorptions No. Litters No. Live Fetuses No. Dead Fetuses No. Fetal Resorptions I 0 22 22 0 0 22 298 0 13 II III IV 50 250 1000 22 22 22 22 22 21 0 00 0 00 22 22 21 309 298 00 47 288 0 8 Means Per Litter Mean Corpora Lutea*3 17.5(3.70)c 17.5(2.44) 16.6(3.24) 17.5(3.03) Implantations 14.1(2.21) 14.2(1.69) 13.9(1.67) 14.1(1.58) Resorptions: Total Early Late 0.6(1.53) 0.6(1.53) 0.0 0.2(0.39) 0.1(0.35) 0.0 0.3(0.65) 0.3(0.65) 0.0 0.4(0.74) 0.2(0.44) 0.1(0.48) Dead Fetuses 0.0 0.0 0.0 0.0 Live Fetuses^: Total Males Females 13.5(3.13) 7.4(2.30) 6.2(1.76) 14.0(1.68) 6.5(2.15) 7.5(2.56) 13.5(1.57) 6.6(1.94) 7.0(1.86) 13.7(1.90) 7.0(2.19) 6.7(1.65) Mean Fetal Weight : Total 5.57(0.36) 5.52(0.44) 5.47(0.35) 5.25(0.50)' Sex Ratioe 0.52(0.15) 0.47(0.15) 0.49(0.13) 0.51(0.12) a Individual data are presented in Appendix F . b Statistical analyses are not conducted on mean corpora lutea data; these data are presented for information only. c Standard deviation is reported in parentheses. d 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. e Number male fetuses/total number fetuses per litter. * Significant trend; p < 0.05. Note: The pregnancy rate data, adult mortality data, and the total resorption data were statistically analyzed using the Cochran-Armitage test. All litter mean data (except for fetal weight and sex ratio) were analyzed using Jonckheere's test. Fetal weight and sex ratio were analyzed using a linear contrast of least square means. Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE INCIDENCE OF FETAL MALFORMATIONS Group: Dose (mg/kg/day): I 0 II III 50 250 EXTERNAL N o . Examined^5 Anasarca Cleft palate No. Affected 298[22] 1(1) M 1) 2 [ 2] 309 [22] __ c -- 0[ 0] 298[22] -- -- 0[ 0] IV 1000 288[21] -- -- 0[ 0] VISCERAL N o . Examined Heart &/or Greater Vessels Double Outlet, left ventricle Septal Defect No. Affected 152[22] 160[22] 155[22] 147[21] 1( 1) 2 ( 2) 2 [ 2] -- K 1) 1[ 1] -- -- 0[ 0] -- -- 0[ 0] HEAD N o . Examined Brain Distended Ventricles Hydrocephaly Small brain- hypoplasia Micrognathia Microphthalmia Cleft Palate No. Affected 153 [22] K 1) K 1) K 1) K 1) --K 1) 2 [ 2] 160 [22] -- -- -- -- -- -- 0[ 0] 155[22] -- -- -- -- ---- 0[ 0] 147 I:2i] ----- --- ----- M i) ---- l[ i] - 26- not contain TSCA CBI .^xmpanv Sanitized. Does H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 6 (Continued) INCIDENCE OF FETAL MALFORMATIONS Group : Dose (mg/kg/day): I 0 II III 50 250 IV 1000 SKELETAL N o . Examined Rib - Fused Skull - Fused Vertebra Fused Hemi No. Affected 298[22] 1( 1) 309[22] -- -- 298[22] -- K 1) 288[21] -- -- 2 ( 2) 2 ( 2) 2 [ 2] -- -- 0[ 0] -- -- 1[ 1] -- -- 0[ 0] TOTAL NUMBER AFFECTED 5 ( 5) 1( 1) 1( 1) 1( 1) a Individual fetal alterations are presented in Appendix G. b Number examined and affected, including the number affected with the listed malformations are expressed as Fetuses[Litters] or Fetuses (Litters). c For ease of reading, zeros have been replaced with dashes for the listed malformations. No significant trends were defected. Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam type are presented for information only. - 27- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 7 INCIDENCE OF FETAL VARIATIONS Group: I II III IV . Dose (mg/kg/day): 0 50 250 1000 DEVELOPMENTAL VARIATIONS EXTERNAL N o . Examined-^ No. Affected VISCERAL N o . Examined No. Affected HEAD N o . Examined No. Affected SKELETAL N o . Examined Rib - Rudimentary Cervical Rib - Supernumerary Sternebra - Misaligned Vertebra - Bipartite No. Affected TOTAL WITH DEVELOPMENTAL VARIATIONS 298[22] 0[ 0] 309[22] 0 [0] 298[22] 0 [0] 288[21] 0 [0] 152[22] 0[ 0] 160 [22] 0 [0] 155 [22] 0 [0] 147[21] 0 [0] 153[22] 0 [0] 160[22] 0 [0] 155[22] 0 [0] 147[21] 0 [0] 298[22] 2 ( 2) 13 ( 7) 3 ( 3) 3 ( 2) 18[10] 18(10) 309 [22] __ c 12 ( 5) -- -- 12 [ 5] 12 ( 5) 298 [22] -- 20 ( 7) 1( 1) -- 21 [ 8] 21 ( 8) 288[21] -- 18 ( 7) -- * -18 [ 7] 18 ( 7) - 28- Company Sanitized. Does not contain TSC A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group: Dose (mg/kg/day): I 0 II 50 III IV 250 1000 VARIATIONS DUE TO RETARDED DEVELOPMENT EXTERNAL N o . Examined No. Affected 298 [22] 0[ 0] 309[22] 0[ 0] 298(22] 0[ 0] 288[21] 0[ 0] VISCERAL N o . Examined Heart Sc/or Greater Vessels Patent Ductus Arteriosis Kidney, Papillae^ Small Papilla - Size 1 Small Papilla - Size 2 Papilla - Size 3 No. Affected 152[22] 160 [22] 155(22] 147[22] K 1) 19(12) -- 6 ( 4) 13(11) 20 [13 ] -- 30(15) K 1) 10( 7) 19(10) 30[15] -- 21(10) -- 9 ( 5) 12 ( 7) 2 1 [1 0 ] 2 ( 2) 8 ( 7) K 1) -- 7 ( 6) 10[ 8] HEAD N o . Examined No. Affected SKELETAL N o . Examined Pelvis - Retarded Ossification Rib Retarded Ossification Wavy Skull - Retarded Ossification Sternebra - Retarded Ossification Vertebra - Retarded Ossification No. Affected 153[22] 0[ 0] 160 [22] 0 [0] 155[22] 0 [0] 147[21] 0 [0] 298(22] -- 309 [22] -- 298(22] K 1) 288[21] 2 ( 2) -- M 1) 35 ( 7) 3 ( 2) 115(19) 142([19] -- -- 30(11) 1( 1) 128(22) 144[22] -- -- 25(11) -- 159(22) 172[22] K 1) -- 31(15) 10 ( 4) 107(20) 125 [21] Company Sanitized. Does not contain TSC A CB1 - 29- H-24616: Developmental Toxicity Study in Rats DuPont-4902 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group; Dose (mg/kg/day): I 0 II 50 III IV 250 1000 TOTAL WITH VARIATIONS DUE TO RETARDED DEVELOPMENT 158(21) 158(22) 179(22) 133(21) TOTAL NUMBER FETUSES WITH VARIATIONS 166(21) 165(22) 185(22) 143(21) a Individual fetal alterations are presented in Appendix G. b Number examined and affected, including the number affected with the listed variations, are expressed as Fetuses[Litters] or Fetuses (Litters). c For ease of reading, zeros have been replaced with dashes for the listed variations. d Statistical analyses are conducted on the combined incidences of small renal papillae; the details for each size are presented for information only. No significant trends were detected. Note; Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam are presented for information only. - 30- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDICES -31 - Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDIX A Individual Body Weights - 32- Company Sanitised. Does no! contain TSC A CB1 H-24616: Developmental Toxicity Study in Rats Individual Body Weights Explanatory Notes Footnotes a Maternal body weight minus the weight of the products of conception. b Not pregnant. Data excluded from the calculations. Abbreviations ----- = No Data DuPont-4902 Company Sanitized. Does not contain T S C A CB* H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHTS (grams) GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 0 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 642249 642257 642259 642261 642262 234.0 245.0 230.0 251.0 247.0 237.0 248.0 245.0 236.0 236.0 230.0 234.0 254.0 240.0 234.0 243.0 244.0 237.0 230.0 231.0 230.0 230.0 6 266.2 277.0 257.9 274.6 278.7 264.9 272.2 270.3 266.4 271.9 264.6 255.2 287.6 277.1 264.3 277.1 278.0 268.2 258.6 259.0 256.9 263.2 DAYS OF GESTATION 8 10 12 280.9 292.0 273.1 281.6 290.2 278.1 285.5 282.6 281.3 277.7 272.0 264.3 294.7 282.1 270.3 288.9 282.0 277.9 264.7 263.1 258.1 267.5 292.9 301.6 285.8 294.4 306.5 287.0 294.4 281.7 287.5 287.9 282.7 274.1 306.8 285.9 279.9 301.6 291.7 282.8 280.2 272.2 267.3 280.8 306.3 316.3 294.6 307.2 316.5 298.6 307.1 300.1 296.6 299.8 302.7 288.1 328.1 297.0 288.5 311.1 303.9 298.1 298.4 293.6 277.4 297.0 14 320.2 322.1 307.0 320.8 329.9 314.6 319.5 309.8 312.5 314.6 319.3 300.0 340.4 311.3 295.5 332.2 321.2 307.9 306.3 302.4 278.4 296.4 16 332. 1 337. 7 325. 0 338. 8 349. 1 328. 3 335. 0 320. 8 334. 1 337. 2 326. 5 314. 8 357. 4 328. 7 311. 2 347. 4 337. 8 326. 7 325. 9 328. 6 284. 3 336.,4 Company Sanitized. Does not contain TSC A CB1 H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 18 DAYS OF GESTATION 20 21 21a 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 642249 642257 642259 642261 642262 362.7 364.8 347.3 370.1 384.3 356.1 372.3 345.5 363.9 369.8 375.8 345.9 388.9 358.8 338.4 376.1 366.0 354.5 350.5 357.2 297.1 371.7 403.5 392.5 375.1 407.1 418.2 379.7 404.6 373.9 397.4 413.6 416.4 386.2 436.9 400.7 368.9 407.1 406.2 377.6 382.5 393.6 304.3 401.5 418.9 410.3 403.4 439.0 452.3 405.2 430.2 390.9 418.0 437.1 443.6 413.7 469.5 428.3 388.7 430.5 425.8 400.3 400.5 421.2 313.8 435.0 312.2 325.9 317.3 335.7 338.9 319.6 329.6 300.8 322.0 330.5 336.5 309.6 360.2 307.1 298.6 345.8 332.1 315.7 318.0 320.4 296.6 315.9 DuPont-4902 Company Sanitized. Does not contain TSCA CBt - 35- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHTS (grams) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 0 6 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 258.0 230.0 239.0 244.0 234.0 243.0 249.0 245.0 234.0 230.0 239.0 235.0 248.0 239.0 252.0 231.0 247.0 233.0 232.0 230.0 235.0 230.0 283.9 259.3 255.5 264.9 251.9 271.3 279.1 276.6 263.6 252.2 270.4 263.4 279.4 285.1 271.4 268.0 280.0 274.8 274.5 256.3 267.0 256.5 DAYS OF GESTATION 8 10 12 293.6 268.8 266.4 285.4 257.8 287.4 288.8 291.5 275.2 260.8 282.5 275.5 288.0 286.5 282.1 276.8 290.6 277.3 280.6 257.6 264.9 259.3 296.3 276.8 272.5 291.8 257.8 298.9 292.6 298.6 280.0 263.9 286.6 280.5 293.8 304.2 295.1 282.1 295.0 291.3 293.6 265.6 274.0 268.2 310.9 286.7 286.3 304.2 275.9 312.3 307.6 313.1 295.7 283.4 306.5 295.2 299.2 311.2 303.2 297.3 310.5 317.9 308.3 275.5 293.7 289.6 14 325.6 301.1 299.9 315.1 290.8 330.4 316.3 326.4 312.9 295.8 320.8 308.3 319.6 325.3 318.1 312.9 320.1 337.5 320.4 286.3 301.1 289.8 16 351.4 321.2 320.2 335.5 305.0 355.5 328.9 346.5 329.6 315.4 341.3 329.4 335.4 349.1 340.0 325.4 335.0 356.8 340.5 304.7 314.2 278.1 | Company Sanitized. DS W \ CnianTSCA Cffl -36- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 18 20 21 21a 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 378.8 347.4 351.3 360.4 332.6 383.9 366.4 381.6 364.4 352.6 374.6 359.4 370.7 385.1 379.3 353.4 360.5 392.0 370.4 331.7 344.0 348.2 412.5 375.3 390.2 392.0 372.8 422.0 397.0 417.9 390.3 392.5 412.5 389.2 404.7 425.1 417.0 392.1 396.4 426.0 402.8 354.7 368.0 384.9 443.7 404.6 422.9 419.1 405.3 460.2 419.3 446.4 415.9 421.2 433.2 411.5 424.3 443.8 437.1 401.6 418.4 454.9 428.3 370.5 397.4 ' 413.8 344.8 316.9 319.6 318.8 303.8 358.7 333.1 348.6 322.6 309.7 336.6 322.9 323.3 335.6 332.5 315.3 329.5 344.3 320.6 297.2 316.8 313.6 DuPont-4902 Company Sanitized. Does not contain TSOA CW -37- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHTS (grains) GROUP III: 250 MG/KG/DAY ANIMAL NUMBER 0 6 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 642251 642254 642256 642266 234.0 254.0 233.0 246.0 238.0 252.0 235.0 240.0 251.0 230.0 231.0 233.0 251.0 236.0 248.0 251.0 230.0 231.0 234.0 235.0 232.0 230.0 264.7 270.7 251.1 273.5 266.4 274.5 262.7 268.9 268.6 264.3 258.8 267.3 269.9 265.1 279.9 290.4 258.0 260.0 266.9 269.4 262.1 264.1 DAYS OF GESTATION 8 10 12 276.8 286.8 270.5 275.4 278.0 288.4 274.9 280.0 282.6 272.4 267.2 270.3 267.5 273.5 288.3 291.2 263.2 259.5 270.9 257.6 266.5 262.6 269.8 292.5 267.4 290.6 282.1 295.7 260.9 276.9 282.7 282.3 259.1 279.0 279.2 276.4 299.0 304.5 277.0 273.7 280.7 270.1 264.2 265.5 289.6 311.1 277.5 301.8 297.5 298.0 278.6 292.5 301.9 293.8 279.7 300.8 293.4 293.8 310.8 313.2 290.8 286.5 294.5 285.5 285.7 287.4 14 16 299.8 322.0 298.1 319.7 312.2 315.6 294.3 305.1 313.8 306.8 294.6 313.2 300.8 302.7 327.6 328.3 310.3 295.2 306.6 294.8 294.9 295.3 315.2 342.9 315.4 336.5 326.3 324.7 307.3 325.2 329.0 328.8 308.3 330.1 317.0 325.2 350.7 348.9 325.7 313.7 - 327.0 317.5 318.6 313.6 Company Sanitized. Does not contain TSC A CBf- -38- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP III: 250 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 18 20 21 21a 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 642251 642254 642256 642266 341.8 389.2 334.4 366.5 348.9 357.4 337.7 357.9 361.3 367.1 341.2 362.5 346.4 356.7 369.9 366.4 343.0 345.4 344.8 337.3 344.4 343.2 378.3 424.6 371.3 403.6 380.5 382.8 365.1 381.1 388.6 405.0 365.8 395.4 378.5 396.7 422.5 410.0 372.1 373.9 369.7 358.5 373.8 369.4 402.9 459.2 391.5 436.1 407.9 407.3 390.4 411.8 405.0 429.6 386.5 417.1 398.6 411.0 434.2 429.0 398.3 392.1 397.4 380.6 390.2 388.8 305.7 336.8 304.9 335.8 316.6 321.1 299.9 319.4 319.6 329.4 293.0 311.8 316.0 305.6 331.2 330.3 307.9 301.9 323.4 289.6 299.1 301.0 DuPont-4902 Company Sanitized. Does not contain T S C A CBt - 39- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER 0 6 642183 642191 642193 642196 642197 642210 642212* 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 236. 0 246. 0 240. 0 250 .0 230. 0 234. 0 243. 0 259..0 240..0 230..0 233..0 266..0 250..0 235 .0 234 .0 230 .0 240 .0 230 .0 232 .0 232 .0 230 .0 230 .0 261. 2 272. 7 265. 6 266. 9 257. 0 269. 1 272..7 280..0 268. 8 226..8 264..1 292..0 282 .3 258 .4 259 .2 263 .5 283 .8 268 .0 266 .1 252 .9 264 .7 252 .6 DAYS OF GESTATION 8 10 12 266. 3 286. 8 273. 9 262. 9 268. 8 260..3 276..8 280..6 252..7 252 .5 251..6 300,.7 285 .6 255 .4 266 .4 264 .0 290 .0 267 .5 249 .2 255 .7 255 .2 247 .2 278.3 290.7 277.3 269.7 273.5 262.9 275.4 286.5 266.4 243.2 262.9 274.8 294.3 265.4 273.3 268.9 300.8 273.1 261.9 272.6 266.0 253.7 281.7 305.9 289.6 288.8 281.3 273.4 275.6 305.3 283.9 262.7 275.6 293.2 310.7 281.6 287.3 278.8 324.2 295.3 277.6 288.9 284.3 273.5 14 291.1 311.2 303.2 303.3 289.5 299.6 269.2 323.9 298.1 275.0 295.0 309.4 323.9 290.0 297.1 285.7 332.5 303.9 289.0 301.7 290.2 287.1 16 309.5 332.4 329.2 327.1 318.0 313.5 263.3 342.9 314.4 294.6 308.0 336.6 338.5 309.4 321.2 304.2 363.9 331.6 318.1 319.8 313.9 305.4 /- ~N. Company Sanitized. Does not contain TSC A CB1 - 40- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 18 20 21 21a 642183 642191 642193 642196 642197 642210 642212* 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 337. 5 358..9 360. 9 354..7 343 ..4 351..0 262 .3 372 .8 340..7 325,.2 337 .5 374,.8 371 .0 335 .9 344 .9 328 .6 398 .3 347 .9 348 .4 344 .9 342 .0 323 .9 376. 2 384. 7 398. 3 387. 3 381. 2 383. 4 269. 1 421..9 378..1 357 .3 368..7 405,.0 409,.7 372 .1 392 .3 357 .0 428 .8 371 .0 361 .7 365 .2 369 .0 361 .3 398. 9 406. 1 424. 9 401. 5 407. 7 406. 9 264. 2 441. 0 404..1 380.,7 395..2 427..3 431,.2 387,.7 399 .8 373 .3 458 .5 402 .7 388 .0 384 .3 385 .9 370 .1 299. 3 338. 5 327 .6 309. 6 309.,4 310. 5 --326..7 313..0 306..5 300..9 313..9 343..3 294,.2 290,.2 289 .4 353 .2 327 .6 296 .6 318 .0 291 .3 286 .8 DuPont-4902 Company Sanitized. Does not contain TSCA CBI -41 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDIX B Individual Body Weight Changes Company Sanitized. Does not contanTSCA CB1 - 42- H-24616: Developmental Toxicity Study in Rats Individual Body Weight Changes Explanatory Notes Footnotes a Maternal body weight minus the weight of the products of conception. b Not pregnant. Data excluded from the calculations. Abbreviations ----- = No Data DuPont-4902 o Company Sanitized. Does no? contain T S C A CB1 - 43- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 0-6 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 642249 642257 642259 642261 642262 32.2 32.0 27.9 23.6 31.7 27.9 24.2 25.3 30.4 35.9 34.6 21.2 33.6 37.1 30.3 34.1 34.0 31.2 28.6 28.0 26.9 33.2 DAYS OF GESTATION 4-6 6-8 8-10 14.8 15.3 12.7 26.7 12.8 14.3 14.4 16.5 15.6 18.3 15.7 -2.3 17.0 14.3 13.1 14.8 13.5 11.3 13.6 10.7 8.8 10.2 14.7 15.0 15.2 7.0 11.5 13.2 13.3 12.3 14.9 5.8 7.4 9.1 7.1 5.0 6.0 11.8 4.0 9.7 6.1 4.1 1.2 4.3 12.0 9.6 12.7 12.8 16.3 8.9 8.9 -0.9 6.2 10.2 10.7 9.8 12.1 3.8 9.6 12.7 9.7 4.9 15.5 9.1 9.2 13.3 10-12 13.4 14.7 8.8 12.8 10.0 11.6 12.7 18.4 9.1 11.9 20.0 14.0 21.3 11.1 8.6 9.5 12.2 15.3 18.2 21.4 10.1 16.2 12-14 13.9 5.8 12.4 13.6 13.4 16.0 12.4 9.7 15.9 14.8 16.6 11.9 12.3 14.3 7.0 21.1 17.3 9.8 7.9 8.8 1.0 -0.6 14-16 11.9 15.6 18.0 18.0 19.2 13.7 15.5 11.0 21.6 22.6 7.2 14.8 17.0 17.4 15.7 15.2 16.6 18.8 19.6 26.2 5.9 40.0 Company Sanitized. Does not contain TSCA CB1 -44- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 16-18 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 642249 642257 642259 642261 642262 30.6 27.1 22.3 31.3 35.2 27.8 37.3 24.7 29.8 32.6 49.3 31.1 31.5 30.1 27.2 28.7 28.2 27.8 24.6 28.6 12.8 35.3 DAYS OF GESTATION 18-20 20-21 6-21 40.8 27.7 27.8 37.0 33.9 23.6 32.3 28.4 33.5 43.8 40.6 40.3 48.0 41.9 30.5 31.0 40.2 23.1 32.0 36.4 7.2 29.8 15.4 17.8 28.3 31.9 34.1 25.5 25.6 17.0 20.6 23.5 27.2 27.5 32.6 27.6 19.8 23.4 19.6 22.7 18.0 27.6 9.5 33.5 152.7 133.3 145.5 164.4 173.6 140.3 158.0 120.6 151.6 165.2 179.0 158.5 181.9 151.2 124.4 153.4 147.8 132.1 141.9 162.2 56.9 171.8 6-213 46.0 48.9 59.4 61.1 60.2 54.7 57.4 30.5 55.6 58.6 71.9 54.4 72.6 30.0 34.3 68.6 54.1 47.5 59.4 61.4 39.7 52.7 DuPont-4902 Company Sanitized. Does not contain T S C A CB1 - 45- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHT CHANGES (grains) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 0-6 4-6 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 25.9 29.3 16.5 20.9 17.9 28.3 30.1 31.6 29.6 22.2 31.4 28.4 31.4 46.1 19.4 37.0 33.0 41.8 42.5 26.3 32.0 26.5 13.4 9.0 20.0 10.4 10.9 14.9 13.3 17.3 17.8 11.6 18.3 12.3 11.1 17.8 16.7 13.1 10.0 20.3 13.9 14.6 15.0 15.1 DAYS OF GESTATION 6-8 8-10 10-12 9.7 9.5 10.9 20.5 5.9 16.1 9.7 14.9 11.6 8.6 12.1 12.1 8.6 1.4 10.7 8.8 10.6 2.5 6.1 1.3 -2.1 2.8 2.7 8.0 6.1 6.4 0.0 11.5 3.8 7.1 4.8 3.1 4.1 5.0 5.8 17.7 13.0 5.3 4.4 14.0 13.0 8.0 9.1 8.9 14.6 9.9 13.8 12.4 18.1 13.4 15.0 14.5 15.7 19.5 19.9 14.7 5.4 7.0 8.1 15.2 15.5 26.6 '14.7 9.9 19.7 21.4 12-14 14.7 14.4 13.6 10.9 14.9 18.1 8.7 13.3 17.2 12.4 14.3 13.1 20.4 14.1 14.9 15.6 9.6 19.6 12.1 10.8 7.4 0.2 14-16 25.8 20.1 20.3 20.4 14.2 25.1 12.6 20.1 16.7 19.6 20.5 21.1 15.8 23.8 21.9 12.5 14.9 19.3 20.1 18.4 13.1 -11.7 Company Sanitized. Does not contain T S C A CB1 -46- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-20 20-21 6-21 6-21a 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 27.4 26.2 31.1 24.9 27.6 28.4 37.5 35.1 34.8 37.2 33.3 30.0 35.3 36.0 39.3 28.0 25.5 35.2 29.9 27.0 29.8 70.1 33.7 27.9 38.9 31.6 40.2 38.1 30.6 36.3 25.9 39.9 37.9 29.8 34.0 40.0 37.7 38.7 35.9 34.0 32.4 23.0 24.0 36.7 31.2 29.3 32.7 27.1 32.5 38.2 22.3 28.5 25.6 28.7 20.7 22.3 19.6 18.7 20.1 9.5 22.0 28.9 25.5 15.8 29.4 ' 28.9 159.8 60.9 145.3 57.6 167.4 64.1 154.2 53.9 153.4 51.9 188.9 87.4 140.2 54.0 169.8 72.0 152.3 59.0 169.0 57.5 162.8 66.2 148.1 59.5 144.9 43.9 158.7 50.5 165.7 61.1 133.6 47.3 138.4 49.5 180.1 69.5 153.8 46.1 114.2 40.9 130.4 49.8 157.3 57.1 DuPont-4902 Company Sanitized. Does nei contain T S C CBt H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP III: 250 MG/KG/DAY ANIMAL NUMBER 0-6 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 14-16 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 K 642251 fei 642254 642256 642266 30.7 16.7 18.1 27.5 28.4 22.5 27.7 28.9 17.6 34.3 27.8 34.3 18.9 29.1 31.9 39.4 28.0 29.0 32.9 34.4 30.1 34.1 15.1 15.0 5.3 13.3 13.0 16.9 14.4 14.1 18.4 19.0 10.1 7.7 11.9 12.4 7.1 13.8 16.1 13.4 12.0 15.8 10.9 13.1 12.1 16.1 19.4 1.9 11.6 13.9 12.2 11.1 14.0 8.1 8.4 3.0 -2.4 8.4 8.4 0.8 5.2 -0.5 4.0 -11.8 4.4 -1.5 -7.0 5.7 -3.1 15.2 4.1 7.3 -14.0 -3.1 0.1 9.9 -8.1 8.7 11.7 2.9 10.7 13.3 13.8 14.2 9.8 12.5 -2.3 2.9 19.8 18.6 10.1 11.2 15.4 2.3 17.7 15.6 19.2 11.5 20.6 21.8 14.2 17.4 11.8 8.7 13.8 12.8 13.8 15.4 21.5 21.9 10.2 10.9 20.6 17.9 14.7 17.6 15.7 12.6 11.9 13.0 14.9 12.4 7.4 8.9 16.8 15.1 19.5 8.7 12.1 9.3 9.2 7.9 15.4 20.9 17.3 16.8 14.1 9.1 13.0 20.1 15.2 22.0 13.7 16.9 16.2 22.5 23.1 20.6 15.4 18.5 20.4 22.7 23.7 18.3 "A -48- Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP III: 250 MG/KG/DAY ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-20 20-21 6-21 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 642251 642254 642256 642266 26.6 46.3 19.0 30.0 22.6 32.7 30.4 32.7 32.3 38.3 32.9 32.4 29.4 31.5 19.2 17.5 17.3 31.7 17.8 19.8 25.8 29.6 36.5 35.4 36.9 37.1 31.6 25.4 27.4 23.2 27.3 37.9 24.6 32.9 32.1 40.0 52.6 43.6 29.1 28.5 24.9 21.2 29.4 26.2 24.6 34.6 20.2 32.5 27.4 24.5 25.3 30.7 16.4 24.6 20.7 21.7 20.1 14.3 11.7 19.0 26.2 18.2 27.7 22.1 16.4 19.4 138.2 188.5 140.4 162.6 141.5 132.8 127.7 142.9 136.4 165.3 127.7 149.8 128.7 145.9 154.3 138.6 140.3 132.1 130.5 111.2 128.1 124.7 6-21a 41.0 66.1 53.8 62.3 50.2 46.6 37.2 50.5 51.0 65.1 34.3 44.5 46.1 40.5 51.3 39.9 49.9 41.9 56.5 20.2 37.0 36.9 DuPont-4902 Company Sanitized. Does not contain TSCA CB1 - 49- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL BODY WEIGHT CHANGES (grains) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER 0-6 4-6 642183 642191 642193 642196 642197 642210 642212* 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 25.2 26.7 25.6 16.9 27.0 35.1 29.7 21.0 28.8 -3.2 31.1 26.0 32.3 23.4 25.2 33.5 43.8 38.0 34.1 20.9 34.7 22.6 12.8 8.4 13.7 5.7 14.0 18.6 13.6 18.0 10.7 29.0 16.8 11.9 14.2 5.8 15.1 15.0 12.6 17.1 9.6 7.5 14.4 31.7 DAYS OF GESTATION 6-8 8-10 10-12 5.1 14.1 8.3 -4.0 11.8 -8.8 4.1 0.6 -16.1 25.7 -12.5 8.7 3.3 -3.0 7.2 0.5 6.2 -0.5 -16.9 2.8 -9.5 -5.4 12.0 3.9 3.4 6.8 4.7 2.6 -1.4 5.9 13.7 -9.3 11.3 -25.9 8.7 10.0 6.9 4.9 10.8 5.6 12.7 16.9 10.8 6.5 3.4 15.2 12.3 19.1 7.8 10.5 0.2 18.8 17.5 19.5 12.7 18.4 16.4 16.2 14.0 9.9 23.4 22.2 15.7 16.3 18.3 19.8 12-14 14-16 9.4 5.3 13.6 14.5 8.2 26.2 -6.4 18.6 14.2 12.3 19.4 16.2 13.2 8.4 9.8 6.9 8.3 8.6 11.4 12.8 5.9 13.6 18.4 21.2 26.0 23.8 28.5 13.9 -5.9 19.0 16.3 19.6 13.0 27.2 14.6 19.4 24.1 18.5 31.4 27.7 29.1 18.1 23.7 18.3 Comoany Sanitized. Does not contain TSC A CB1 -50- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) G R O U P IV: 1000 M G / K G / D A Y ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-20 20-21 6-21 to 00 642183 642191 642193 642196 642197 642210 642212* 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 0 26. 5 31. 7 27. 6 25. 4 37 ..5 -1..0 29..9 26..3 30,.6 29..5 38 .2 32 .5 26 .5 23 .7 24 .4 34 .4 16 .3 30 .3 25 .1 28 .1 18 .5 38. 7 25. 8 37 .4 32. 6 37 .8 32 ..4 6. 8 49..1 37 .4 32..1 31..2 30,.2 38 .7 36 .2 47 .4 28 .4 30 .5 23 .1 13 .3 20 .3 27 .0 37 .4 22. 7 21. 4 26. 6 14. 2 26. 5 23. 5 -4.,9 19.,1 26.,0 23..4 26..5 22..3 21,.5 15,.6 7..5 16 .3 29 .7 31 .7 26 .3 19 .1 16 .9 8 .8 137. 7 133. 4 159. 3 134. 6 150. 7 137. 8 -8..5 161..0 135..3 153 ..9 131..1 135..3 148..9 129..3 140..6 109 .8 174 .7 134 .7 121 .9 131 .4 121 .2 117 .5 . 38.1 65.8 62.0 42.7 52.4 41.4 -- 46.7 44.2 79.7 36.8 21.9 61.0 35.8 31.0 25.9 69.4 59.6 30.5 65.0 26.6 34.2 DuPont-4902 Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDIX C Individual Food Consumption - 52- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats Individual Food Consumption Explanatory Notes Footnotes a Not pregnant. Data excluded from the calculations. Abbreviations -----= No Data DuPont-4902 - 53- Company Sanitized. Doss not contain TSCA CBf H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 4-6 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 642249 642257 642259 642261 642262 21.5 22.8 19.1 17.6 24.4 24.6 22.7 22.2 25.2 25.9 21.3 16.5 23.9 26.5 22.2 23.3 23.6 23.6 20.8 21.8 21.8 21.4 6-8 25.1 27.7 24.6 23.3 26.4 27.0 25.8 23.3 25.3 22.6 22.4 24.4 24.7 24.4 20.6 25.3 22.9 25.6 22.6 22.6 20.2 24.5 DAYS OF GESTATION 8-10 10-12 12-14 24.6 26.2 22.8 24.8 28.8 25.8 26.3 21.6 25.1 25.3 23.9 25.6 26.4 24.3 23.3 26.6 25.1 24.5 24.6 22.2 22.6 24.8 26.1 30.3 25.0 25.9 28.3 27.8 28.4 25.9 24.4 25.0 25.2 25.6 29.4 26.1 22.2 23.9 24.8 23.9 24.7 24.9 20.8 26.6 26.8 27.9 25.0 25.7 29.3 28.0 26.3 24.4 26.3 25.2 26.2 29.3 29.6 27.4 23.1 30.2 28.7 27.8 - 24.8 24.2 22.1 26.1 14-16 21.3 30.7 31.0 26.6 30.9 27.4 28.2 24.8 29.7 30.9 24.3 23.1 26.2 28.8 25.2 28.7 27.7 26.4 26.4 26.1 21.3 31.1 16-18 29.6 30.9 29.7 27.9 32.5 31.6 31.5 26.7 31.1 32.2 32.8 28.2 33.3 31.5 26.8 32.5 31.5 28.0 28.7 28.2 24.0 33.5 Company Sanitized. Does net cOnta'n TSC A CBS H-24616: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 18-20 20-21 6-21 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 642249 642257 642259 642261 642262 32.6 29.5 30.3 29.2 30.6 30.7 27.6 26.2 29.2 28.9 30.9 24.6 31.8 30.4 25.9 31.9 29.4 24.1 28.4 27.9 22.6 30.3 26.7 25.6 32.7 29.7 27.1 25.8 29.0 23.-6 25.5 28.9 29.7 31.8 34.9 32.4 22.6 26.5 23.9 23.9 22.6 28.1 18.5 30.0 26.6 28.8 27.3 26.4 29.4 28.2 27.8 24.6 27.2 27.3 26.7 26.2 29.2 27.9 23.8 28.3 26.9 25.6 25.5 25.4 21.7 28.3 DuPont-4902 I - 55- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 4-6 6-8 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 24.1 18.1 20.1 21.1 15.1 23.3 25.6 25.7 25.6 21.3 25.1 24.1 23.1 25.9 20.2 26.3 27.3 25.6 24.2 20.6 21.0 22.8 27.6 21.6 24.1 27.8 19.7 26.6 25.2 25.9 24.1 20.8 26.1 25.7 24.4 24.6 25.0 26.8 27.3 26.5 24.7 15.2 18.7 22.4 DAYS OF GESTATION 8-10 10-12 12-14 24.6 18.9 23.5 26.3 16.6 25.3 24.8 27.5 24.5 21.5 26.5 25.4 24.8 28.4 27.8 29.0 29.6 27.5 25.6 21.8 22.3 23.8 28.4 21.7 24.7 28.5 22.4 27.3 27.8 27.5 26.5 23.8 28.3 27.0 23.6 26.3 25.8 26.5 28.8 30.9 26.8 19.4 23.5 25.9 28.5 22.1 26.4 26.0 21.1 27.4 24.1 27.5 27.9 24.3 28.4 27.6 28.5 28.1 29.4 31.2 28.9 34.7 30.0 25.5 25.6 25.1 14-16 31.1 26.0 29.9 30.1 22.4 32.7 26.6 29.4 30.9 27.4 32.1 31.2 29.5 32.0 33.2 28.5 27.1 33.6 30.7 25.1 25.8 26.9 16-18 29.5 27.9 31.1 30.9 24.8 31.5 32.2 30.5 31.6 28.9 32.8 32.1 31.3 34.3 34.3 32.8 30.4 37.3 31.0 27.4 25.6 29.9 -56- Company Sanitized. Does not contain TSC A C W H-24616: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 18-20 20-21 6-21 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 32.5 27.9 32.3 29.6 28.6 35.6 30.4 30.4 30.2 28.8 32.7 31.7 28.3 29.0 32.5 34.4 29.9 34.0 29.2 25.1 26.1 29.3 30.9 25.0 32.3 27.0 30.6 34.6 29.3 33.4 27.3 31.0 30.3 32.9 31.1 25.6 25.3 20.3 27.8 34.6 28.5 18.9 26.6 29.0 29.0 23.8 27.8 28.3 22.8 29.8 27.4 28.7 27.9 25.5 29.6 29.0 27.5 28.7 29.4 29.2 28.8 32.2 28.3 22.5 24.1 26.4 DuPont-4902 - 57- Company Sanitized, does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP III: 250 MG/KG/DAY ANIMAL NUMBER 4-6 6-8 DAYS OF GESTATION 8-10 10-12 12-14 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 642251 642254 642256 642266 23.6 21.2 17.9 21.9 22.3 24.1 24.1 24.8 22.3 25.3 23.9 22.4 22.7 21.9 20.9 21.7 23.7 22.5 22.1 23.5 19.7 23.9 25.8 26.8 24.6 19.5 23.5 23.5 24.6 23.7 21.8 22.4 23.1 21.8 20.4 22.5 24.2 21.8 22.9 22.3 22.4 16.4 18.9 22.3 20.1 23.5 20.0 23.0 22.3 23.4 13.8 20.2 21.9 25.9 18.8 27.4 24.2 22.8 25.2 26.6 25.8 24.1 24.9 19.8 14.7 '' 21.9 23.4 24.2 21.0 26.1 23.9 22.3 24.1 23.4 25.4 26.4 25.2 27.3 22.4 23.9 26.1 23.2 24.6 24.5 21.0 20.9 22.3 25.2 23.9 26.9 23.7 28.9 26.2 24.4 27.9 22.3 23.7 25.6 25.9 29.9 22.6 24.3 28.3 26.4 31.2 26.8 27.5 23.4 26.3 24.8 14-16 25.6 28.8 23.6 28.4 26.1 23.6 25.6 27.9 24.9 28.1 25.3 30.0 26.1 28.2 29.9 30.0 28.6 28.4 27.2 28.7 29.1 28.5 16-18 26.6 32.6 23.5 31.1 28.3 27.6 29.3 28.8 27.6 30.1 30.9 32.4 29.5 30.6 33.2 29.0 24.6 26.6 25.7 26.9 30.5 30.7 - 58- Company Sanitized. Does not conin'" CR| H-24616: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP III: 250 MG/KG/DAY ANIMAL number DAYS OF GESTATION 18-20 20-21 6-21 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 642251 642254 642256 642266 28. 8 32. 2 26. 1 32. 0 27. 6 25. 4 27..1 26.,4 27.,2 31..6 27 .0 28..9 29,.1 28,.9 31 .5 31 .8 28 .3 28 .1 24 .9 22 .2 30 .0 29 .3 27. 6 35. 6 22. 7 30. 5 29. 0 28.,4 29..1 27 .6 24..7 28..5 26..6 26,.9 27,.0 25 .0 20 .2 30 .1 27 .9 28 .8 29 .1 23 .8 26 .6 22 .5 25. 1 28. 4 23. 2 27. 2 25. 7 24.,6 24.,9 24..9 24..6 27 .3 25..3 28..2 25 ,.1 25,.8 27 .8 27 .2 26 .7 26 .0 25 .1 22 .7 24 .7 25 .8 DuPont-4902 Company Ssnrf'yoft. Dnog not conf^*** -59- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER 4-6 6-8 642183 642191 642193 642196 642197 642210 642212a 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 21.7 22.4 22.9 19.7 18.4 25.4 25.1 23.5 21.3 22.2 23.5 24.6 22.8 23.1 20.0 22.8 23.7 23.8 22.3 19.9 24.8 21.2 23.1 26.1 22.6 19.9 22.5 12.7 18.8 19.5 12.0 26.2 14.6 25.1 22.8 19.3 23.0 20.9 24.5 20.4 9.1 20.5 15.1 23.6 DAYS OF GESTATION 8-10 10-12 12-14 22.4 23.7 20.1 17.7 22.8 20.1 20.1 23.6 19.6 20.6 18.3 19.5 27.1 21.6 23.8 20.5 24.5 21.9 19.3 22.5 23.5 23.2 18.8 29.3 22.5 23.6 22.1 22.2 22.7 27.9 22.8 25.8 23.4 19.3 26.3 23.5 25.6 20.7 26.9 24.5 21.7 22.8 25.1 24.0 20.4 25.6 23.7 23.4 21.9 24.1 18.2 26.9 21.9 25.7 25.5 24.0 26.2 24.3 26.8 21.1 30.9 24.3 25.1 26.8 27.6 30.1 14-16 16-18 23.3 29.5 29.5 28.1 25.7 25.4 20.3 28.7 22.3 29.6 25.4 25.6 28.0 26.1 29.3 25.1 36.2 30.6 28.3 28.7 30.5 29.7 26.6 33.9 29.9 32.3 25.4 28.9 17.8 33.3 25.0 33.8 30.0 29.4 31.5 25.5 30.4 25.4 33.2 29.8 . 28.9 29.6 29.4 27.9 Company Sanitized. Does not contain TSCA CB1 -60- H-24616: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams/day) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 18-20 20-21 6-21 642183 642191 642193 642196 642197 642210 642212a 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 29.6 31.8 31.4 29.8 29.4 28.3 21.9 32.5 27.9 32.3 29.1 25.9 31.3 27.8 28.8 27.2 32.8 27.0 25.1 29.9 27.9 30.3 27.6 28.5 27.2 26.9 27.4 31.8 11.6 32.3 26.4 32.4 29.0 22.9 30.0 23.7 24.9 23.9 29.5 31.8 21.6 29.0 21.5 22.0 23.7 28.5 25.8 25.1 24.5 23.7 19.4 27.8 22.0 28.0 24.1 24.0 27.8 24.0 26.7 23.0 29.8 25.9 22.4 26.0 25.3 26.6 DuPont-4902 Company Sanitized. Does not contain T S C A CB1 -61 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDIX D Individual Clinical Observations Company Sanitized. Does not contain TSC A CB1 - 62- H-24616: Developmental Toxicity Study in Rats Individual Clinical Observations DuPont-4902 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. I V J H) nM TPA r>D| - 63- H-24616: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL OBSERVATION NUMBER: INDIVIDUAL CLINICAL OBSERVATIONS DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 DuPont-4902 642182 ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/23/00 642185 SACRIFICED BY DESIGN 10/23/00 642186 SACRIFICED BY DESIGN 10/23/00 642188 SACRIFICED BY DESIGN 10/23/00 642190 SACRIFICED BY DESIGN 10/23/00 642194 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/23/00 642203 SACRIFICED BY DESIGN 10/24/00 642204 SACRIFICED BY DESIGN 10/24/00 642206 SACRIFICED BY DESIGN 10/24/00 642209 SACRIFICED BY DESIGN 10/24/00 a: a : !1]ll!l2,13'l4!l5!l6!l7'l8!l9,20,21 b : ........................ , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: , , , t , / t I / t21 a: , , , , , , , , , 2*1J* a:.: . i i i i i 21, , / / / i i ' a: , , , , , , , t , / / *21 L: . . . . . . r , , / ' 21 a: $ , . . / / t i /^2,-1L a: ./I , , / / / , t > * **2x1 a : , , , , , > , / / / / ' ' ' ' ' ' 2^-1L a: , / / t t 2tJ1- a: ,,I ,II ,21 , , , , , , , * , , , ,*2*1*- -64- Company Sanitized. Does not contain TSC A CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 GROUP I: 0 MG/KG/DAY ANIMAL OBSERVATION NUMBER: INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642222 SACRIFICED BY DESIGN 10/24/00 642225 SACRIFICED BY DESIGN 10/25/00 642228 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG ALOPECIA PERINEUM ALOPECIA BOTH REAR LEG SACRIFICED BY DESIGN 10/25/00 642232 SACRIFICED BY DESIGN 10/25/00 642233 SACRIFICED BY DESIGN 10/25/00 642236 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/25/00 642242 DISCHARGE PERINASAL RED SACRIFICED BY DESIGN 10/25/00 642249 SACRIFICED BY DESIGN 10/26/00 a: a: a: b: a: b: a: b: a: b: a: a a a: b: a: a: , , ,7, a: , , , , a 11 12 13,14,15,16,17,18,19,20,21 11 12 13,14,15,16,17,18,19,20, , , , ,17,18,19,20,21 , , , ,17,18,19,20, , , , ,17,18,19,20,21 , , , ,17,18,19,20, , , , ,17,18,19,20,21 , , , ,17,18,19,20, ...................21 ,21 ,21 , 20,21 , 20, , ,21 ,21 ,21 Company Sanitized. Does not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 642257 SACRIFICED BY DESIGN 10/26/00 642259 SACRIFICED BY DESIGN 10/26/00 642261 SACRIFICED BY DESIGN 10/26/00 642262 SACRIFICED BY DESIGN 10/26/00 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: t i r i t i i i / 1 1 1 I 1 1 !2**1-*a : i t r i i i / I t ! 1 1 1 1 1 1 i*2**1 a: i t r i 1 1 1 1 t .................. 21 a : f i l i t i 1 1 1 1 / f 1 1 1 1 t2t1J. # DuPont-4902 - 66- Company Sanitized. Does not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL OBSERVATION NUMBER: INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642181 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/23/00 a: b: a: b: a: 642184 SACRIFICED BY DESIGN 10/23/00 a: 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 ,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, iiiii ,,,,, t//tI i , , , , < < ,19,20,21 , , , , , , , < ,19,20, l / 21 642192 SACRIFICED BY DESIGN 10/23/00 a: 642198 SACRIFICED BY DESIGN 10/23/00 a 21 642199 SACRIFICED BY DESIGN 10/23/00 a: , , , , , , , , , , - , , . . - 21 642202 SACRIFICED BY DESIGN 10/23/00 a: 642205 SACRIFICED BY DESIGN 10/24/00 a: 642207 SACRIFICED BY DESIGN 10/24/00 a ,21 DuPont-4902 -67- Company Sanitized. Does not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 GROUP II: 50 MG/KG/DAY ANIMAL OBSERVATION NUMBER: INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642213 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW ALOPECIA LEFT HIND QUARTERS SACRIFICED BY DESIGN 10/24/00 642223 SACRIFICED BY DESIGN 10/24/00 642224 SACRIFICED BY DESIGN 10/24/00 642226 SACRIFICED BY DESIGN 10/25/00 642229 SACRIFICED BY DESIGN 10/25/00 642230 SACRIFICED BY DESIGN 10/25/00 642238 ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 10/25/00 642241 SACRIFICED BY DESIGN 10/25/00 642245 SACRIFICED BY DESIGN 10/25/00 a: , b: , a: b: a: b: a: I ! ,12,13,14,15,16,17,18,19,20,21 I I ,12,13,14,15,16,17,18,19,20, II ,18,19,20,21 ,18,19,20, $I IIt ,18,19,20,21 ,18,19,20, !I III , , , ,21 a : i i i i t i ' 21 a : i i i i i i t t i i 2t1J- I I I ! ! r I t42*1 .a :. i t i l r t i i I / / t2***1- a : 1 1 , 1 1 1 , < , , , , , ' ' ' 21 a : ,5,6,7, , , ,11,12,13,14,15,16,17,18,19,20,21 b : , , , , , ,10,11,12,13,14,15,16,17,18,19,20, a: i i i i i i / t i i i i 21 a: i i i i i i i i / f f ' 21 L: i i i i i i t ' ' ' *21x -68- Company Sanitized. Does not contain T S C A CB l H-24616: Developmental Toxicity Study in Rats GROUP XI: 50 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 642247 SACRIFICED BY DESIGN 10/26/00 642253 SACRIFICED BY DESIGN 10/26/00 642255 ALOPECIA LEFT HIND QUARTERS SACRIFICED BY DESIGN 10/26/00 642264 SACRIFICED BY DESIGN 10/26/00 642265 SACRIFICED BY DESIGN 10/26/00 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19.20,21 a: a: a: , ,6,7,8, , I I i l I I I l I I ! b: , ,6,7, , , t i l t i l I........t.......i.......l.......i......21 a ,21 a: DuPont-4902 - 69- Company Sanitized. Does not contain T S C A CBl H -24616: D evelopm ental T oxicity Study in Rats # DuPont-4902 GROUP I I I : 2 5 0 MG/KG/DAY ANIMAL NUMBER: OBSERVATION INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH S IG N WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642187 ALOPECIA LEFT FRONT LEG SACRIFICED BY DESIGN 10/23/00 642189 SACRIFICED BY DESIGN 10/23/00 642195 SACRIFICED BY DESIGN 10/23/00 642200 LUNG NOISE SACRIFICED BY DESIGN 10/23/00 642201 SACRIFICED BY DESIGN 10/23/00 642208 ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/24/00 642211 SACRIFICED BY DESIGN 10/24/00 642215 SA C R IFIC E D BY D ESIG N 10/24/00 642219 SACRIFICED BY DESIGN 10/24/00 642220 SACRIFICED BY DESIGN 10/24/00 a: 1 , 1 , 1 1 a: , 1 1 1 1 1 III ,21 ,21 a : , , , , , , , , , , , , , , > * ,~21A a : i , , , i i , , i , , < , ' ' ' ,21 a : , , , , , , , , , ,14,15,16, b : , , , , , , , , ,13,14,15,16, , , , , a: I I I ! till ,21 a : ! I l I I ! I I ! I^21 3.: t i i i ^ i i 3: , , i i i i 3: / i , , , , / i i/ * t i i i i t t i 91 i i i i f f /21 31 , l l , , l / I ! i f ,9 1 3 : , , , , ! ! I I I ! ' '^21J- a: , , , , , , :.a : , , , , , , i i i i t 21 / i i / / ' ' *21 Company Sanitized. Does not contain T S C A CB1 -70- H -24616: D evelopm ental T oxicity Study in Rats____________________________________________ D u P o n t-4 9 0 2 GROUP III: 250 MG/KG/DAY ANIMAL OBSERVATION NUMBER: INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642221 SACRIFICED BY DESIGN 10/24/00 642227 SACRIFICED BY DESIGN 10/25/00 642231 SACRIFICED BY DESIGN 10/25/00 642237 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT FRONT PAW LUNG NOISE ALOPECIA LEFT SIDE SACRIFICED BY DESIGN 10/25/00 642243 SACRIFICED BY DESIGN 10/25/00 642244 SACRIFICED BY DESIGN 10/25/00 642248 SACRIFICED BY DESIGN 10/26/00 642250 ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/26/00 01 t ! I l I I ! ! I I f t t 1 ' I* X 3.: I I I I I I I I I ! t 0t1- . 21a :. I l t I I ! ! I t / / t ' ' * * ** a : /O/// / / i i I I I a : , , ,8,9,10,11, I I I b : , ,7,8,9,10,11, I I I a: Il II ! ! t III b : /i 1 7 1 , t t III a: Il II ! I ! b: I l II ! t 1 III a: Il II ! ! t III , 20,21 ,20, , ,21 cl: , , , , , , / # 2 1t t t I t t t > a: , , , , , , # < # # # # # < # > #21 aa. # # # # # # # # # # # # # # # # #4211 a : ! Il II ! b: I II II I a: ! Il II ! a : ! Il II ! ,18,19,20, ,18,19,20, ,21 ,21 - 71- Company Sanitized. Does not contain T S C A CBl H-24616: Developmental Toxicity Study in Rats GROUP III: 250 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 642251 SACRIFICED BY DESIGN 10/26/00 642254 SACRIFICED BY DESIGN 10/26/00 642256 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/26/00 642266 SACRIFICED BY DESIGN 10/26/00 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: a: a: ,,6, b : ,, , a: ,, , a ,19,20,21 ,19,20, , , ,21 ,21 # DuPont-4902 Company Sanitized. oes not contain T S C A CBI H-24616: Developmental Toxicity Study in Rats 0 DuPont-4902 GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER: OBSERVATION INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642183 LUNG NOISE SACRIFICED BY DESIGN 10/23/00 642191 SACRIFICED BY DESIGN 10/23/00 642193 SACRIFICED BY DESIGN 10/23/00 642196 DIARRHEA SACRIFICED BY DESIGN 10/23/00 642197 SACRIFICED BY DESIGN 10/23/00 642210 SACRIFICED BY DESIGN 10/24/00 642212 SACRIFICED BY DESIGN 10/24/00 642214 SACRIFICED BY DESIGN 10/24/00 642216 LUNG NOISE SACRIFICED BY DESIGN 10/24/00 642217 SACRIFICED BY DESIGN 10/24/00 a: , , , , , , to: , , , , , , a: , , , , , , , , ,14,15, , , ,13,14,15, i ii t * t , , , ,, , , , ,, t i * i 21 a: I I I I f / / / ! ! t t261A a: , , , , , , ', / / , , , /21 t i / t / / >11/ a : / // >/ / i i ! i i i i i i i/ a: , , l i l i / I a: I l I I ! a: , , , I l l ! I it i ti i / i i i i /2"1*" X21/ / / / / / . I I I I ! /21X ......................................... 21 / / / / / 21 a: I I I I I I a: ! 12 iii , 21 a: i i i i i i i / / * i i i i i21 -73 - Company Sanitized. Does not contain T S C A CBl H-24616: Developmental Toxicity Study in Rats GROUP IV: 1000 MG/KG/DAY ANIMAL OBSERVATION NUMBER: INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 642218 SACRIFICED BY DESIGN 10/24/00 642234 SACRIFICED BY DESIGN 10/25/00 642235 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 10/25/00 642239 SACRIFICED BY DESIGN 10/25/00 642240 SACRIFICED BY DESIGN 10/25/00 642246 SACRIFICED BY DESIGN 10/25/00 642252 LUNG NOISE SACRIFICED BY DESIGN 10/26/00 642258 SACRIFICED BY DESIGN 10/26/00 a : / i< 1 1 , I I /! t i l l / ! i, , ,21 a: 'll '' ' ' ! I I ! t 1 1, , ,21 a: b: a: ,t /I /I /t I I II II II II //t i l l /! t i l l ! ! till 1 1 t, ,20, ! 1 , ,20, I 1 , , ,21 a: - I I I II ! lilt 1 1 , , ,21 a : - , , ,21I I I Il 1 1 lilt' 1 1 a: ! I I I Il , , ,211 ! t i l l 1 1 1 a: b: a: t III II / , ,7, I I /! 1 1 Il !! !/ /1 III III III a: / I I I II / /III III III III III ill ill ,, ,21 , , ,21 DuPont-4902 -74- Company Sanitized. Does not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 642260 WET PERINEUM STAIN CHIN BROWN LUNG NOISE SACRIFICED BY DESIGN 10/26/00 642263 LUNG NOISE SACRIFICED BY DESIGN 10/26/00 642267 ALOPECIA LEFT FRONT LEG 642267 SACRIFICED BY DESIGN 10/26/00 642268 SACRIFICED BY DESIGN 10/26/00 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: I I I t b: 6, , I I I a: ! t b: 6, , I I I a: / I ! I b: 6,7, I! a: t i l l t tI III ,21 a: I l I I ! I ! I Il II II ! b : , , , ,8, , ! Il II II II ! a : ! I / i i i i i / ;^ L a : , , ,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 b : , ,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, ! I l I I ! ! / ! ! ! / / / / ! 21 ! I l I I ! ! ! ! I / I I ! ! I /^ DuPont-4902 nipany Sanitized. Does not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDIX E Gross Postmortem Findings -76- Comoanv S a n d e d . Does not con! T e r n m i H-24616: Developmental Toxicity Study in Rats Gross Postmortem Findings Explanatory Notes Footnotes a Not pregnant. Abbreviations -- = No Data NAD = No Abnormalities Detected DuPont-4902 Comoanv Sanit'zed. Does not contain T S C a -77- H-24616: Developmental Toxicity Study in Rats DuPont-4902 GROSS POSTMORTEM FINDINGS Group I: Omg/kg/day Animal Number 642182 642185 642186 642188 642190 642194 642203 642204 642206 642209 642222 642225 642228 642232 642233 642236 642242 ' 642249 642257 642259 642261 642262 Dam Code 21 8 4 11 15 18 44 33 35 23 25 61 54 46 59 53 51 77 86 67 76 69 Structure(s') -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- Finding(s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Company Sanitized. Does not contain T5CA CB! - 78! H-24616: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-4902 Group II: 50mg/kg/day Animal Number 642181 642184 642192 642198 642199 642202 642205 642207 642213 642223 642224 642226 642229 642230 642238 642241 642245 642247 642253 642255 642264 642265 Dam Code 14 16 9 3 13 6 26 39 40 41 37 56 49 58 52 45 65 87 83 75 78 68 Structure(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- . ----- -- -- -- -- Findingis) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD -nmpany Sanitized. Does not contain TSC A CBl -79- H-24616: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-4902 Group HI: 250mg/kg/day Animal Number 642187 642189 642195 642200 642201 642208 642211 642215 642219 642220 642221 642227 642231 642237 642243 642244 642248 642250 642251 642254 642256 642266 Dam Code 7 2 20 5 22 43 38 28 31 29 24 48 47 62 64 55 72 82 84 79 74 88 Structure(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- Finding(s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD -80- Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-4902 Group IV: 1000 mg/kg/day Animal Number 642183 642191 642193 642196 642197 642210 642212a 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 Dam Code 12 19 1 17 10 30 27 42 32 36 34 63 66 50 60 57 70 73 80 71 85 81 Structure(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- .-- -- -- -- -- . Findings') NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Company Sanitized. Does not contain TSC A CB1 -81 - H-24616: Developmental Toxicity Study in Rats % DuPont-4902 APPENDIX F Individual Reproductive Data -82- Cotnoany Sanitized. Does net contain TSCA CBI H-24616: Developmental Toxicity Study in Rats Individual Reproductive Data Explanatory Notes Footnotes a Not pregnant ' . Abbreviations -- = No Data DuPont-4902 - 83- Sanitized. Does net contain TSC A CBt Comoaiw H-24616: Developmental Toxicity Study in Rats * DuPont-4902 INDIVIDUAL REPRODUCTIVE DATA3 GROUP I: 0 MG/KG/DAY ANIMAL CORPORA NIDA NUMBER LUTEA TIONS 642182 22 17 642185 12 12 642186 15 13 642188 16 15 642190 16 16 642194 12 11 642203 26 16 642204 15 14 642206 15 15 642209 19 15 642222 21 16 642225 17 16 642228 20 17 642232 20 15 642233 16 12 642236 14 12 642242 24 14 642249 15 12 642257 16 12 642259 21 15 642261 15 9 642262 17 17 RESORPTIONS TOTAL EARLY LATE 110 0 0 0 110 000 000 000 000 000 110 000 000 000 220 000 000 000 000 000 000 110 770 000 DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 0 16 6 10 0 12 6 6 0 12 5 7 0 15 6 9 0 16 8 8 0 11 4 7 0 16 7 9 0 14 6 8 0 14 4 10 0 15 7 8 0 16 7 9 0 16 8 8 0 15 7 8 0 15 11 4 0 12 7 5 0 12 5 7 0 14 6 8 0 12 6 6 0 12 6 6 0 14 5 9 0 2 20 0 17 7 10 5.51 5.55 5.47 5.33 5.35 6.00 5.10 5.17 5.52 5.69 5.87 5.30 5.67 5.00 6.22 5.88 5.36 5.33 5.50 5.66 6.51 5.49 Company Sanitized. Does not contain t r c a c r i O' H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL REPRODUCTIVE DATA3 GROUP II: 50 MG/KG/DAY ANIMAL CORPORA NIDA NUMBER LUTEA TIONS 642181 16 14 642184 19 14 642192 16 16 642198 19 14 642199 17 15 642202 20 14 642205 21 13 642207 16 14 642213 14 13 642223 24 19 642224 13 13 642226 18 13 642229 18 15 642230 18 16 642238 15 14 642241 17 14 642245 17 13 642247 17 16 642253 19 16 642255 16 11 642264 20 12 642265 16 14 RESORPTIONS TOTAL EARLY LATE 000 000 110 000 000 000 000 00 110 000 000 000 000 110 101 000 000 000 000 000 000 000 DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 0 14 6 8 0 14 12 2 0 15 8 7 0 14 6 8 0 15 8 7 0 14 9 5 0 13 9 4 0 14 7 7 0 12 5 7 0 19 15 4 0 13 7 6 0 13 4 9 0 15 10 5 0 15 7 8 0 13 5 8 0 14 6 8 0 13 8 5 0 16 7 9 0 16 7 9 0 11 6 5 0 12 9 3 0 14 4 10 5.35 5.10 5.50 6.02 5.53 6.23 5.37 5.73 6.12 4.67 5.88 6.12 5.73 5.59 5.67 4.97 5.07 5.75 5.44 5.12 4.76 5.79 -85- Comoanv Sanitized. Does not contain TSC CB! H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL REPRODUCTIVE DATA3 GROUP III: 250 MG/KG/DAY ANIMAL CORPORA NIDA NUMBER LUTEA TIONS 642187 19 15 642189 20 18 642195 22 13 642200 16 15 642201 23 13 642208 25 11 642211 15 15 642215 16 16 642219 13 13 642220 16 15 642221 18 14 642227 16 15 642231 15 12 642237 15 15 642243 16 14 642244 15 15 642248 16 13 642250 14 13 642251 13 11 642254 15 14 642256 14 12 642266 14 13 RESORPTIONS TOTAL EARLY LATE 000 000 000 110 000 000 110 220 110 000 000 000 000 000 000 220 000 000 000 000 000 000 DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 0 15 10 5 0 18 10 8 0 13 8 5 0 14 4 10 0 13 7 6 0 11 7 4 0 14 9 5 0 14 6 8 0 12 6 6 0 15 5 10 0 14 8 6 0 15 6 9 0 12 9 3 0 15 8 7 0 14 8 6 0 13 6 7 0 13 9 4 0 13 5 8 0 11 4 7 0 14 7 7 0 12 7 5 0 13 4 9 5.13 5.35 5.10 5.48 5.75 6.36 5.03 5.35 5.81 5.24 5.26 5.47 5.27 5.51 5.37 6.02 5.60 5.73 5.54 5.11 5.83 4.98 -86- Company Sanitized. Dogs not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL REPRODUCTIVE DATA3 GROUP IV: 1000 MG/KG/DAY ANIMAL CORPORA NIDA NUMBER LUTEA TIONS 642183 642191 642193 642196 642197 642210 6422123 642214 642216 642217 642218 642234 642235 642239 642240 642246 642252 642258 642260 642263 642267 642268 19 14 14 16 22 15 -- 21 17 16 24 17 17 15 19 16 21 15 21 20 16 13 15 11 13 14 14 14 -- 16 13 14 15 17 13 15 16 14 17 12 14 13 14 12 RESORPTIONS TOTAL EARLY LATE 000 101 000 110 000 000 ------ 000 000 000 110 000 110 110 000 000 000 000 000 312 000 000 DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 0 15 7 8 0 10 5 5 0 13 5 8 0 13 6 7 0 14 7 7 0 14 8 6 ______ -- ---- 0 16 8 8 0 13 5 8 0 14 5 9 0 14 9 5 0 17 8 9 0 12 7 5 0 14 9 5 0 16 8 8 0 14 6 8 0 17 4 13 0 12 5 7 0 14 7 7 0 10 5 5 0 14 7 7 0 12 10 2 5.60 5.40 5.75 5.85 5.51 5.25 -- 5.64 5.53 3.84 5.49 5.20 5.73 5.25 5.53 4.77 4.85 5.48 5.26 4.76 5.28 4.31 -87- Company Sanitized. Does not contain T S C A CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 APPENDIX G Individual Fetal Weights and Alterations -88- Company Sanitized. Does not contain t .s o a PRf H-24616: Developmental Toxicity Study in Rats Individual Fetal Weights and Alterations DuPont-4902 Explanatory Notes 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 Company Sanitized. Does not contain TSC A CBI - 89- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE 642182 1 5.93 Vertebra 2 5.65 3 5.64 Vertebra 4 5.04 Rib Vertebra 5 5.52 Rib Vertebra 6 5.08 Rib 7 5.87 8 5.44 9 5.46 10 5.59 Vertebra 11 5.43 Vertebra 12 5.64 Vertebra 13 5.32 14 5.34 Vertebra 15 5.46 Vertebra 16 5.67 Rib Vertebra FINDING(S) CLASSIFICATION Retarded Ossification (CEN TH10) NAD Retarded Ossification (cen thll) Supernumerary (site 14 bil) Retarded Ossification (cen thl2) Supernumerary (site 14 It) Retarded Ossification (cen thll,13) Supernumerary (site 14 It) NAD NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thlO,12-13) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl0,12) Retarded Ossification (cen thlO) Supernumerary (site 14 bil) Retarded Ossification (cen thlO) VR VR DV VR DV VR DV VR VR VR VR VR DV VR 642185 1 2 3 4 5 6 4.93 5.48 5.75 5.77 5.59 6.04 Kidney Rib Kidney Papilla - Size 3 (bil) NAD . NAD Supernumerary (site 14 bil) Papilla - Size 3 (bil) NAD VR DV VR Company Sanitized. Does not contain TSC A CB1 -90- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grains) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642185 (Cont.) 7 5.55 8 5.31 9 5.25 10 5.35 11 5.71 12 5.91 Rib Vertebra Supernumerary (site 14 It) Retarded Ossification (cen thll) NAD NAD NAD NAD NAD DV VR 642186 1 2 3 4 5 6 7 8 9 10 11 12 5.62 5.74 5.70 5.51 5.28 5.58 5.44 5.26 5.34 5.61 5.21 5.37 Rib Vertebra Rib NAD NAD Supernumerary (site 14 bil) NAD NAD Retarded Ossification (cen thl2) NAD NAD Supernumerary (site 14 rt) NAD NAD NAD DV VR DV 642188 1 2 3 4 5 6 7 8 9 10 11 12 5.97 5.19 5.84 5.62 5.29 4.70 5.30 5.47 5.27 4.98 5.14 4.96 Kidney . Small Papilla - Size 2 (bil) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD VR Company Sanitized. Does not contain TSC A CB1 -91 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642188 (Cont.) 13 5.47 14 5.57 15 5.20 Kidney Small Papilla - Size 2 (bil) NAD NAD VR 642190 1 2 3 4 5 6 7 8 9 10 11 12 13 5.34 Vertebra 5.15 5.77 Subcutis Kidney Vertebra 5.44 Vertebra 5.30 Vertebra 6.24 Vertebra 5.09 5.24 Skull Vertebra 5.51 Vertebra 5.55 Vertebra 5.32 Vertebra 4.18 Rib Sternebra Vertebra Rib Vertebra Vertebra Vertebra 5.13 Kidney Retarded Ossification (cen thl0,12,13) NAD Hemorrhage (chin*) Papilla - Size 3 (bil) Retarded Ossification (cen thlO,12) Retarded Ossification (cen thll,12) Retarded Ossification (cen th9-12) Retarded Ossification (cen thl0-13) NAD Retarded Ossification (2 bil) Retarded Ossification (cen thll) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thlO,11) Rudimentary Cervical (7 bil) Misaligned (2,3,4) Bipartite (cen th7,8) Fused (th4-5,rt) Fused (arch ce2,3,th3,4 rt) Hemi (cen th3,5) Retarded Ossification (cen th9-13) Small Papilla - Size 2 (bil) VR VR VR VR VR VR VR VR VR VR VR DV DV DV M M M VR VR Company Sanitized. Does not contain TSCA CB! -92- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 642190 (Cont.) 14 5.09 15 5.67 16 5.61 Vertebra Skull Vertebra Retarded Ossification (cen thlO-13) NAD Retarded Ossification (2 bil) Retarded Ossification (cen th9-13) VR VR VR 642194 1 2 3 4 5 6 7 8 9 10 11 5.75 6.49 6.20 4.97 6.15 6.41 6.00 6.10 6.44 5.84 5.62 Head Brain Brain Brain Eye Sternebra Subcutis Heart &/or Greater Vessels NAD NAD NAD Domed Distended (ventricles;bil) Hydrocephaly Small (hypoplasia) Micrognathia (left) Misaligned (3,4) NAD NAD Hemorrhage (chin, head*) NAD NAD NAD Patent Ductus Arteriosis N M M M M DV N VR '642203 1 2 3 4 5 5.06 5.50 4.92 5.11 5.03 Rib Skull Vertebra Skull Supernumerary (lui oss site, rt) Retarded Ossification (2,3 bil) Retarded Ossification (cen thll,12) Retarded Ossification (2,3 bil) NAD DV VR VR VR - 93- Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642203 (Cont.) 6 4.97 7 4.49 8 5.04 9 5.51 10 4.83 11 4.83 12 5.01 13 5.05 14 5.60 15 5.69 16 4.97 Skull Vertebra Skull Sternebra Skull Skull Kidney Skull Sternebra Vertebra Retarded Ossification (2,3 bil) Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (2,3 bil) Retarded Ossification (6) Retarded Ossification (2,3 bil) NAD Retarded Ossification(2 bil) Papilla - Size 3 (rt) Retarded Ossification (2,3 bil) Retarded Ossification (6) Retarded Ossification (cen thl2) VR VR VR VR VR VR VR VR VR VR 642204 1 2 3 4 5 6 7 8 9 5.30 4.99 5.62 5.39 5.12 5.26 4.68 5.11 5.08 Kidney Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Sternebra Vertebra Papilla - Size 3 (bil) . Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen th9,11-12) Retarded Ossification (cen thl2) Retarded Ossification (6) Retarded Ossification (cen thl2) VR VR VR VR VR VR VR VR VR Company Sanitized. Does not contain TSCA CBl -94i H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642204 10 11 12 13 (Cont.) 5.14 4.78 5.41 5.33 14 5.12 Rib Vertebra Vertebra NAD NAD NAD Wavy (8-10) Retarded Ossification (cen thl2-13) Retarded Ossification (cen thll,13) VR VR VR 642206 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.56 5.89 5.54 4.58 5.06 6.07 5.23 5.47 5.72 5.90 5.79 5.51 5.14 5.81 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thlO-12) NAD NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll-13) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thlO-11) Retarded Ossification (cen thl0,12) VR VR VR VR VR VR VR VR VR -95 - Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE_________________ FINDING(S)___________ CLASSIFICATION 642209 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 642222 1 2 3 6.16 5.64 5.88 6.20 3.85 Subcutis Skull Entire Body Heart &/or Greater Vessels Heart &/or Greater Vessels Spleen Brain Rib Vertebra Vertebra Vertebra Vertebra 6.38 Vertebra Vertebra 5.44 Vertebra 5.56 5.87 5.84 Kidney Vertebra 5.84 5.60 5.74 5.45 Skull Vertebra 5.85 Kidney 5.76 5.69 5.93 Skull Palate Hemorrhage (chin*) NAD NAD Retarded Ossification (2bil) Anasarca Malformation (double outlet It vent.) N VR M M Septal Defect (interventricular) M Pale Distended (ventricles;bil) Rudimentary Cervical (7 It) Bipartite (cen th.9,10) Fused (arch th8-9,rt) Hemi (cen th8) Retarded Ossification (cen thl-46,7,11,12,lul) Bipartite (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thll-13) NAD Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (cen thl2,13) Papilla - Size 3 (bil) M DV DV M M VR DV VR VR VR VR VR VR VR NAD Retarded Ossification (2 bil) Cleft VR M Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE _________ FINDING(S) CLASSIFICATION 642222 (Cont..) 4 6.17 Palate Vertebra 5 6.19 6 5.81 Vertebra 7 5.39 8 5.87 Skull Vertebra 9 5.85 10 6.03 11 5.67 12 5.66 Skull Vertebra 13 5.78 Vertebra 14 5.77 Skull Vertebra 15 6.12 Vertebra 16 6.20 Skull Vertebra Cleft Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (2 bil) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (2 bil) Retarded Ossification (cen thll,12) Retarded Ossification (cen thl3) Retarded Ossification (2 bil) Retarded Ossification (cen thll,12) Retarded Ossification (cen thll,13) - Retarded Ossification (2 bil) Retarded Ossification (cen thl2) M VR VR VR VR VR VR VR VR VR VR VR VR 642225 1 2 3 4 5 6 5.45 4.54 5.48 5.53 5.87 5.51 Vertebra Vertebra Subcutis Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) NAD NAD NAD Hemorrhage (head*) VR VR N -97- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642225 (Cont.) Vertebra 7 5.34 8 5.03 9 5.49 10 4.68 11 5.19 Vertebra 12 5.49 13 5.27 14 5.33 15 5.21 16 5.46 Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification (cen thll-12) NAD NAD NAD NAD NAD VR VR 642228 1 2 3 4 5 6 7 8 9 10 11 12 5.64 5.37 6.00 5.74 5.46 5.58 6.12 5.59 5.70 5.58 5.67 5.53 Nasal Cavity Vertebra Vertebra Vertebra Kidney Vertebra Heart &/or Greater Vessels Vertebra Vertebra Vertebra Hemorrhage (3rd section*) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) Retarded. Ossification (cen thl3) NAD NAD Papilla - Size 3 (bil) Retarded Ossification - (cen thll) Septal Defect (overriding aorta) Retarded Ossification (cen thl3) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl3) N VR VR VR VR VR M VR VR VR Company Sanitized. D o ss not contain TSCA CB! H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642228 (Cont.) 13 5.75 14 5.19 15 6.09 Vertebra Vertebra Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD VR VR 642232 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 4.76 5.25 Vertebra 5.24 Rib Vertebra 4.86 Vertebra 4.70 Vertebra 5.43 5.42 Vertebra 4.99 Vertebra 5.03 Subcutis Vertebra 5.00 5.22 4.45 Vertebra 4.71 Vertebra 5.14 4.77 NAD Retarded Ossification (cen thl2) Supernumerary (site 14 lt) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thll,13) Retarded Ossification (cen thlO) NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thll) Hemorrhage (chin*) Retarded Ossification (cen thll-12) NAD NAD Retarded Ossification - (cen thl2-13) Retarded Ossification (cen thll-12) NAD NAD VR DV VR VR VR VR VR N VR VR VR 642233 1 7.64 NAD -99- Company Sanitized. Does not contain TSCA CB H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642233 (Cont.) 2 5.87 3 6.28 4 5.82 5 6.84 6 6.75 7 6.89 8 6.47 9 5.62 10 5.84 11 5.58 12 5.04 Skull Skull Vertebra Vertebra Skull Skull Retarded Ossification (2,6 bil) NAD Retarded Ossification (2 bil) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll,12) NAD NAD Retarded Ossification (2,3,6 bil;1,12) NAD Retarded Ossification (2,3 bil;1,12) VR VR VR VR VR VR 642236 1 2 3 4 5 6 7 8 9 10 11 12 5.59 5.49 6.14 5.43 5.87 6.02 6.29 5.79 5.73 6.23 6.00 5.93 Vertebra Kidney Vertebra ' Vertebra Vertebra Retarded Ossification (cen thl2) NAD NAD . NAD Papilla - Size 3 (bil) NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen thl2) VR VR VR VR VR 642242 1 2 5.11 4.90 NAD NAD - 100- Company Sanitized. Does not contain TSCA CB! H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 642242 (Cont.) 3 5.38 4 5.63 5 5.73 Rib Vertebra 6 5.16 7 5.38 Vertebra 8 5.03 Rib Vertebra 9 5.84 Kidney 10 5.09 Vertebra 11 5.73 Vertebra 12 5.22 Vertebra 13 5.37 Vertebra 14 5.42 NAD NAD Supernumerary (site 14 It) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thl2) Supernumerary (site 14 rt) Retarded Ossification (cen thll-13) Papilla - Size 3 (bil) Retarded Ossification (cen thll) Retarded Ossification (cen thlO-13) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD DV VR VR DV VR VR VR VR VR VR 642249 1 2 3 4 5 6 7 8 5.60 5.08 5.02 5.41 5.39 5.55 5.45 5.20 Vertebra Vertebra Vertebra Vertebra Kidney Vertebra Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-13) Retarded Ossification (cen thll-12) Papilla - Size 3 (bil) Retarded Ossification (cen thl0,12) NAD NAD NAD VR VR VR VR VR VR -101 - Company Sanitized. Does not contain TSCA CB! H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642249 (Cont.) 9 5.04 10 5.18 11 5.09 12 5.93 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) VR VR VR VR 642257 1 2 3 4 5 6 7 8 9 10 11 12 642259 1 2 5.72 5.59 5.46 5.49 5.75 5.52 5.54 5.26 5.69 4.49 5.62 5.93 Vertebra Vertebra Kidney Kidney Vertebra Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Kidney 6.10 5.67 Skull Retarded Ossification (cen thll) Retarded Ossification (cen 9-11,13) Small Papilla - Size 2 (bil) NAD Papilla - Size 3 (bil) Retarded Ossification (cen thl3) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll lui) Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Papilla - Size 3 (bil) NAD VR VR VR VR VR VR VR VR VR VR VR VR NAD Retarded Ossification (2,3 bil) VR - 102- Company Sanitized. Does net contain TSCA CBI i H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642259 (Cont..) 3 5.55 4 5.93 5 5.42 6 5.59 7 6.01 8 6.03 9 5.13 10 6.03 11 5.55 12 5.74 13 4.82 14 5.72 Kidney Skull Skull Subcutis Skull Skull Vertebra Skull Vertebra Vertebra Subcutis Skull Papilla - Size 3 (bil) Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil;1) NAD Hemorrhage (back*) Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) Retarded Ossification (2 bil) Retarded Ossification (cen thl2) Retarded Ossification (cen thll,12) Hemorrhage (right hindguarter*) Retarded Ossification (2 bil) VR VR VR N VR VR VR VR VR VR N VR 642261 1 6.66 2 6.37 642262 1 5.87 Rib 2 4.80 Skull 3 5.39 4 5.46 Skull Vertebra NAD NAD Supernumerary (lui oss site, bil) Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thl2) DV VR VR VR - 103- Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642262 (Cont.) 5 5.77 6 5.85 7 5.20 8 5.68 9 5.66 10 5.13 11 5.61 12 5.31 13 5.70 14 5.42 15 5.53 16 5.17 17 5.71 Skull Vertebra Skull Skull Skull Sternebra Skull Skull NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thl2) Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) Misaligned (3,4,5) Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) NAD VR VR VR VR VR DV VR VR Company Sanitized. Does not contain TSCA CBI - 1041 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642181 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.17 Vertebra 4.86 Subcutis Vertebra 5.47 Vertebra 5.20 5.41 Vertebra 5.51 5.78 5.32 5.53 Kidney Vertebra 5.36 Vertebra 5.15 5.23 5.20 5.67 Vertebra Retarded Ossification (cen thl2) Hemorrhage (chin*) Retarded Ossification (cen thlO) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD NAD NAD Papilla - Size 3 (bil) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification . (-cen thl2) VR N VR VR VR VR VR VR VR 642184 1 2 3 4 5 6 4.89 5.20 4.87 4.99 5.06 5.20 Vertebra ' Vertebra Vertebra Subcutis Vertebra NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) Hemorrhage (chin*) Retarded Ossification (cen thll) VR VR VR N VR Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 642184 (Cont.) 7 4.95 8 5.20 9 5.41 10 5.41 11 4.92 12 4.93 13 5.07 14 5.31 Vertebra Subcutis Skull Vertebra Subcutis Vertebra Vertebra Retarded Ossification (cen thl2) Hemorrhage (back. It rear leg*) Retarded Ossification (6 bil) NAD Retarded Ossification (cen thll) Hemorrhage (It shoulder*) Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thl0-ll) VR N VR VR N VR VR 642192 1 2 3 4 5 6 7 8 9 5.84 5.79 5.10 5.79 5.35 5.20 5.78 5.04 5.28 Skull Vertebra Skull Vertebra Vertebra Skull Skull Vertebra NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thlO,11) NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) Retarded Ossification (cen thll,12) Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) NAD VR VR VR VR VR VR VR VR - 106- Company Sanitized. Does not contain TSC A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE____________ FINDING(S) CLASSIFICATION 642192 (Cont..) 10 5.22 Skull Vertebra 11 5.54 Kidney 12 5.80 13 5.58 Vertebra 14 5.63 Skull Vertebra 15 5.51 Kidney 642198 1 2 3 4 6.04 6.05 6.09 5.56 Subcutis Kidney Subcutis Vertebra 5 5.59 6 6.04 7 6.08 8 5.74 9 6.11 10 6.47 Vertebra 11 6.31 Kidney 12 5.72 13 6.32 14 6.17 642199 1 5.43 Kidney Vertebra Retarded Ossification (2,3 bil) Retarded Ossification (cen thlO-12) Papilla - Size 3 (rt) NAD Retarded Ossification (cen thll,12) Retarded Ossification (2,3 bil) Retarded Ossification (cen thlO-12) Papilla - Size 3 (It) VR VR VR VR VR VR VR NAD Hemorrhage (chin*) Papilla - Size 3 (rt) Hemorrhage (chin*) Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD Retarded Ossification (cen thl2-13) Small Papilla - Size 2 (bil) NAD NAD NAD N VR N VR VR VR Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) VR VR - 107- Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642199 (Cont.) 2 5.58 Skull Vertebra 3 5.76 Kidney Rib Vertebra 4 5.17 Skull 5 5.00 Kidney Vertebra 6 5.76 Skull Vertebra 7 5.56 Kidney Vertebra 8 5.84 Subcutis Vertebra 9 5.46 Kidney Vertebra 10 5.64 Vertebra 11 5.29 Kidney 12 ' 5.74 13 5.52 Kidney Vertebra 14 5.52 Skull Vertebra 15 5.67 Kidney Retarded Ossification (2 bil) Retarded Ossification (cen thl2) Papilla - Size 3 (It) Supernumerary (lul short. It) Retarded Ossification (cen thll,12) Retarded Ossification (2 bil) Papilla - Size 3 (It) Retarded Ossification (cen thl2) Retarded Ossification (2 bil) Retarded Ossification (cen thll,13) Small Papilla - Size 2 (bil) Retarded Ossification (cen thl3) Hemorrhage (neck, chin*) Retarded Ossification (cen thll-13) Papilla - Size 3 (bil) Retarded Ossification (cen thl0-13) " Retarded Ossification (cen thl3) Small Papilla - Size 2 (bil) NAD Papilla - Size 3 (bil) Retarded Ossification (cen thll) Retarded Ossification (2 bil) Retarded Ossification (cen thll) Small Papilla - Size 2 (bil) VR VR VR DV VR VR VR VR VR VR VR VR N VR VR VR VR VR VR VR VR VR VR -108- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642202 1 2 3 4 5 6 7 8 9 10 11 12 13 14 6.37 Vertebra 6.61 Vertebra 6.91 6.71 Vertebra 6.80 Kidney Vertebra 5.85 5.83 Vertebra 5.86 Vertebra 5.93 6.24 Vertebra 5.71 Vertebra 6.24 Vertebra 6.10 Vertebra 6.08 Vertebra Retarded Ossification (cen thl2) Retarded Ossification (cen thll-13) NAD Retarded Ossification (cen thll) Small Papilla - Size 2 (bil) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thl0-12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) Retarded Ossification (cen.thl0-ll) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO,12-13) VR VR VR VR VR VR VR VR VR VR VR VR 642205 1 2 3 4 5 6 5.96 5.76 5.45 4.98 5.29 5.20 Rib Vertebra Vertebra Supernumerary (site 14 lt) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD NAD DV VR VR - 109- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S)___________ CLASSIFICATION 642205 (Cont.) 7 5.68 8 5.37 9 5.25 10 4.93 11 5.15 12 5.16 13 5.64 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thlO) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) VR VR VR VR VR VR 642207 1 2 3 4 5 6 7 8 9 10 11 12 5.82 5.67 5.90 5.33 5.58 5.66 5.96 5.89 6.07 6.18 5.66 5.63 Skull Vertebra Ureter Kidney Vertebra Skull Vertebra Skull Vertebra Vertebra Vertebra NAD Retarded Ossification (6 rt) Retarded Ossification (cen thlO-12) Distended (bil) Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) Retarded Ossification (2 bil) NAD Retarded Ossification (cen thll,12) NAD Retarded Ossification (2 bil) Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen h9,11,13,lui) Retarded Ossification (cen thlO-13) VR VR N VR VR VR VR VR VR VR VR - 110- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642207 (Cont.) 13 5.35 Vertebra 14 5.58 Skull 642213 1 5.70 Vertebra 2 6.30 Vertebra 3 6.19 Vertebra 4 5.62 5 6.18 Vertebra 6 6.24 Vertebra 7 5.84 8 5.93 Vertebra 9 6.25 Kidney 10 6.45 Vertebra 11 6.35 12 6.34 Vertebra Retarded Ossification (cen thll,13) Retarded Ossification (1,12) VR VR Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO-13) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen th7) Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) VR VR VR VR VR VR VR VR VR 642223 1 2 3 4 5 6 7 8 9 4.06 4.83 4.55 4.56 5.25 5.26 4.65 5.37 4.83 Heart &/or Greater Vessels Vertebra Septal Defect (interventricular) NAD NAD Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD M VR - Ill - Company Sanitized. Does not contain TSC A CBl H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642223 10 11 12 13 14 15 16 17 18 19 (Cont.) 4.28 4.09 4.44 4.60 4.94 4.17 4.46 4.78 4.64 4.94 NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD 642224 1 2 3 4 5 6 7 8 9 10 11 12 13 642226 1 2 3 4 5 6 6.45 6.19 5.80 6.07 4.92 5.94 5.57 5.88 5.82 5.56 6.05 6.03 6.16 Vertebra Rib Kidney Vertebra Kidney 5.78 6.12 6.39 6.16 5.90 6.13 Vertebra Vertebra NAD Retarded Ossification (cen thl0-12) Supernumerary (site 14 bil) NAD NAD NAD Papilla - Size 3 (It) Retarded Ossification (cen thll) Papilla - Size 3 (bil) NAD NAD NAD NAD Retarded Ossification (cen thl3) NAD NAD Retarded Ossification (cen thll) NAD NAD VR DV VR VR VR VR VR Company Sanitized. Dno nnt -112- t p a i nn) H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642226 (Cont.) 7 6.21 8 6.05 9 5.94 10 6.14 11 6.55 12 6.03 13 6.16 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen thll) VR VR VR : VR 642229 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 642230 1 2 3 5.50 5.90 6.16 6.43 5.34 5.24 5.45 6.05 5.60 5.96 5.76 5.74 6.02 5.29 5.57 Skull Vertebra Skull 5.44 5.94 6.08 Kidney Vertebra NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD NAD Retarded Ossification (cen thll) Retarded Ossification (2,3 bil) NAD NAD NAD VR VR VR NAD NAD Papilla - Size 3 (bil) Retarded Ossification (cen thl3) VR VR Company Sanitized. Does not contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642230 4 5 6 7 (Cont.) 5.85 5.91 5.75 5.64 8 5.39 9 5.30 10 5.55 11 5.77 12 4.72 13 5.66 14 5.23 15 5.55 Skull Kidney Vertebra Vertebra Vertebra Kidney Kidney Sternebra Retarded Ossification (6 It) NAD NAD Papilla - Size 3 (bil) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thl2) NAD NAD Papilla - Size 3 (bil) NAD Papilla - Size 3 (bil) Retarded Ossification (6) VR VR VR VR VR VR VR VR 642238 1 2 3 4 5 6 7 8 9 10 5.47 5.76 5.58 5.56 5.60 6.07 5.81 5.68 6.03 5.37 Brain Vertebra Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Vertebra NAD NAD Hemorrhage (left ventricle*) Retarded Ossification (cen thll,12) Retarded Ossification (cen thll,12) Retarded Ossification (cen thl2) - Retarded Ossification (cen thlO-12) Papilla - Size 3 (bil) Retarded Ossification (cen thll,12) Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD N VR VR VR VR VR VR VR VR - 114- icm pany Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 . INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642238 (Cont.) 11 5.12 12 5.71 13 5.98 Skull Vertebra NAD Retarded Ossification (6,7,8 bil) Retarded Ossification (cen thl3) NAD VR VR 642241 1 2 3 4 5 6 7 8 9 10 11 12 13 14 4.77 Rib 5.04 Rib Vertebra 4.70 Rib Vertebra 4.94 5.00 Rib Vertebra 5.33 Rib 4.93 Vertebra 5.01 4.99 5.11 5.02 5.00 Skull Rib Rib Ureter Kidney Rib 4.95 Kidney Vertebra 4.83 Supernumerary (site 14 rt, full 14 It) Supernumerary (full 14 bil) Retarded Ossification (cen thl2) Supernumerary (site 14 bil) Retarded Ossification (cen thl2) NAD Supernumerary (site 14 bil) Retarded Ossification (cen thl3) Supernumerary (SITE 14 BIL) Retarded Ossification (.cen thll-13) Retarded Ossification (3 bil) Supernumerary (site 14 bil) Supernumerary (14 full bil) Distended (bil) Small Papilla - Size 1 (bil) Supernumerary (site 14 rt, short 14 It) Papilla - Size 3 (bil) Retarded Ossification (cen thl2-13) NAD DV DV VR DV VR DV VR DV VR VR DV DV N VR DV VR VR "ompany Sanitized. Does not contain TSCA CBf - 115- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) ' CLASSIFICATION 642245 1 2 3 4 5 6 7 8 9 10 11 12 13 5.20 Vertebra 5.02 Vertebra 4.95 Vertebra 4.90 Skull Vertebra 5.64 Vertebra 5.39 Skull Vertebra 4.86 4.63 Vertebra 5.33 Kidney Vertebra 5.08 Skull Vertebra 5.32 Vertebra 5.31 4.34 Vertebra Retarded Ossification (cen th9-12) Retarded Ossification (cen thll,12) Retarded Ossification (cen thl3) Retarded Ossification (2,4,5,6,7 bil;l) Retarded Ossification (cen thll-13) Retarded Ossification (cen thl2) Retarded Ossification (6 bil) Retarded Ossification (cen thll,12) NAD Retarded Ossification (cen thll) Papilla - Size 3 (bil) Retarded Ossification (cen thll) Retarded Ossification (2,5,6 bil;1,12) Retarded Ossification (cen thl0,ll) Retarded Ossification (cen thll,12) NAD Retarded Ossification (cen th.8,10-13) VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR 642247 1 2 5.50 5.77 Vertebra Vertebra Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) VR VR ompany Sanitized. Doss not'contain TSC A CBI - 116- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE_________________ FINDING(S) __________ 642247 (Cont,.) 3 5.54 Vertebra 4 5.37 5 5.75 Vertebra 6 6.33 7 6.04 Vertebra 8 5.52 9 5.82 10 5.64 11 5.74 Vertebra 12 5.74 Rib Vertebra 13 6.12 Vertebra 14 5.58 15 5.91 16 5.57 642253 1 2 5.32 5.24 Skull 3 5.09 4 5.17 Skull Vertebra 5 5.24 Vertebra 6 5.44 Skull 7 5.48 Kidney 8 5.53 9 5.72 Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (cen thll) Supernumerary(site 14 It) Retarded Ossification (cen thl0-12) Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (2,3 bil) Papilla - Size 3 (It) NAD NAD VP VR VR VR DV VR VR VR VR VR VR VR VR ompany Sanitized. Does not contain TSCA CBt H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642253 (Cont.) 10 5.56 11 5.41 12 5.65 13 5.38 14 5.64 15 5.58 16 5.62 ' Skull Kidney Skull NAD NAD Retarded Ossification (2,3 bil) Papilla - Size 3 (bil) Retarded Ossification (2,3 bil) NAD NAD VR VR VR 642255 1 2 3 4 5 6 7 8 9 10 11 5.13 5.13 5.36 5.10 5.20 5.37 4.93 5.28 5.19 5.11 4.48 Vertebra Skull Skull Vertebra NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (2,3 bil) NAD Retarded Ossification Retarded Ossification (cen thl2) (2 bil) VR VR VR VR .642264 1 2 3 4 5 6 5.20 4.79 5.37 5.11 4.81 4.35 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) NAD VR VR VR VR '- " N iJ Company Sanitized. Does noi contain - 118- /m H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642264 (Cont.) 7 4.90 8 3.75 9 4.95 10 4.91 11 4.86 12 4.18 Kidney Vertebra Vertebra Vertebra Subcutis Vertebra Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) Hemorrhage (back*) Retarded Ossification (cen thl2) NAD NAD VR VR VR VR N VR 642265 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.67 5.47 5.80 5.76 5.82 5.49 6.14 5.57 6.00 6.29 5.90 5.41 5.84 5.96 Vertebra Subcutis Subcutis Subcutis Subcutis Subcutis Subcutis Kidney NAD NAD NAD Retarded Ossification (cen thll) VR NAD NAD Hemorrhage (back*) N Hemorrhage (back*). N Hemorrhage (left front limb*) N 'Hemorrhage (back*) N . Hemorrhage (back*) N NAD Hemorrhage (back*) - Small Papilla - Size 2 (bil) N VR NAD Company Sarutfzed. Does not cnnfa'r t q ^ a no - 119- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM N O ./ FETUS NO. FETUS WT. STRUCTURE _____ FINDING(S) CLASSIFICATION 642187 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 4.64 Vertebra 5.01 4.90 5.52 Skull Vertebra 5.34 Vertebra 5.10 Skull Vertebra 5.38 4.68 5.34 Vertebra 5.47 5.15 Vertebra 5.77 4.88 4.73 Skull Vertebra 5.02 Vertebra Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (7 rt) Retarded Ossification (cen thlO) Retarded Ossification (cen thlO-12) Retarded Ossification (6-7 bil) Retarded Ossification (cen thll-12) NAD NAD Retarded Ossification (cen th9-12) NAD Retarded Ossification (cen thll) Retarded Ossification (7 rt) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) VR VR VR VR VR VR VR VR VR VR VR 642189 1 2 3 4 5 6 5.17 5.50 5.45 5.34 5.17 5.64 Vertebra Vertebra Retarded Ossification (cen thll-12) NAD NAD Retarded Ossification (cen thll-12) NAD NAD VR VR - 120- Company Sanitized. Does not contain TSC A C B1 I H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642189 (Cont.) 7 5.38 8 5.98 9 5.13 10 4.87 11 4.91 12 5.21 13 5.70 14 5.34 15 5.18 16 5.32 17 5.84 18 5.16 Vertebra Subcutis Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thlO) Hemorrhage (chin*) Retarded Ossification (cen thll) Retarded Ossification (cen thl0,12) NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl0,12) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) VR N VR VR VR VR VR VR 642195 1 2 3 4 5 6 7 8 4.95 5.53 5.19 4.93 4.84 4.01 5.37 5.24 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) VR VR VR VR VR VR VR - 121 - Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642195 (Cont.) 9 5.70 10 5.23 11 5.05 12 5.23 13 5.09 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO-11) VR VR VR VR 642200 1 2 3 5.00 5.11 5.57 Vertebra Vertebra Vertebra 4 5.42 5 5.52 Vertebra 6 5.66 7 5.32 Vertebra 8 5.58 Skull Vertebra 9 . 5.59 Vertebra 10 5.34 11 5.67 Vertebra 12 5.79 Vertebra 13 5.33 14 5.82 Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thlO-11) - Retarded Ossification (6 bil) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD NAD VR VR VR VR VR VR VR VR VR VR ompany Sanitized. Doss not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM N O ./ FETUS NO. FETUS WT. STRUCTURE ___________ FINDING(S) _________ CLASSIFICATION 642201 1 2 3 4 5 6 7 8 9 10 11 12 13 642208 1 2 3 4 5 6 7 8 9 10 11 5.49 5.27 6.03 5.62 5.84 5.60 6.18 5.56 6.13 6.03 5.74 5.30 5.90 Vertebra Vertebra Vertebra Subcutis Kidney Vertebra 6.37 6.43 6.20 6.53 6.27 6.18 6.26 6.88 6.14 6.63 6.04 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl2-13) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) NAD NAD Hemorrhage (neck*) NAD Papilla - Size 3 (bil) NAD NAD Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification (cen thlO-12) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll-13) Retarded Ossification (cen thl2) VR VR VR N VR VR VR VR VR VR VR VR Company Sanitized. Does not contain TSCA CB1 - 123- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE 642211 1 2 3 4 5.47 5.19 5.45 5.87 Vertebra Vertebra 5 4.17 Head Vertebra 6 4.84 7 5.16 8 5.00 Skull 9 4.82 10 4.70 11 4.86 Vertebra 12 4.84 Skull Vertebra 13 4.97 Vertebra 14 5.02 Vertebra FINDING(S) CLASSIFICATION NAD NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) Domed Retarded Ossification (cen thll-12) NAD NAD Retarded Ossification (1;2,6 BIL) NAD NAD Retarded Ossification (cen thll-12) Retarded Ossification (1; 2,6 bil) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll) . VR VR N VR VR VR VR VR VR VR 642215 1 2 3 4 5 6 5.89 5.52 5.49 4.79 5.11 5.34 Vertebra Skull Vertebra Vertebra Vertebra Retarded Ossification ' (cen thll) Retarded Ossification (6 lt) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) VR VR VR VR VR Company Sanitized. Does not contain TSCA CB! H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642215 (Cont.) 7 5.52 Kidney Vertebra 8 5.41 Vertebra 9 4.89 Kidney Vertebra 10 5.34 Skull 11 5.37 Kidney Vertebra 12 5.10 13 5.39 14 5.75 642219 1 2 3 4 5 6 7 8 9 10 11 12 6.06 5.88 5.68 5.63 6.33 5.92 5.61 5.47 5.88 5.89 5.73 5.58 Vertebra Small Papilla - Size 2 (bil) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl0-ll) Small Papilla - Size 2 (bil) Retarded Ossification (cen thl2) Retarded Ossification (6 bil) Small Papilla - Size 2 (It) Retarded Ossification (cen thlO) NAD NAD NAD VR VR VR VR VR VR VR VR NAD NAD NAD NAD NAD ' NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thll) VR 642220 1 2 3 4 5 5.26 5.43 5.44 4.74 5.33 Rib Rib Rib Supernumerary (site 14 bil) Supernumerary (site 14 rt) Supernumerary (site 14 rt) NAD NAD DV DV DV - 125- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642220 (Cont.) 6 5.39 7 4.97 8 5.30 9 5.43 10 5.14 11 5.16 12 5.26 13 5.57 14 5.12 15 5.05 Vertebra Skull Vertebra Rib Vertebra Vertebra Rib Rib Vertebra Retarded Ossification (cen thll) NAD Retarded Ossification (2 bil) Retarded Ossification (cen thl2) Supernumerary (site 14 bil) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Supernumerary (site 14 rt) Supernumerary (site 14 It) Retarded Ossification (cen thl2) VR VR VR DV VR VR DV DV VR 642221 1 2 3 4 5 6 7 8 9 10 11 5.50 5.79 5.27 4.69 5.15 5.07 5.17 5.90 5.23 5.04 5.05 Kidney Skull Skull Rib Skull Vertebra Papilla - Size 3 (bil) NAD NAD Retarded Ossification (2,3 bil) NAD Retarded Ossification (2,3 bil) NAD NAD NAD Supernumerary (lui oss. site, It) Retarded Ossification (2,3 bil) Retarded Ossification (cen thll-13) NAD VR VR . VR DV VR VR - 126- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S ) CLASSIFICATION 642221 (Cont.) 12 4.95 13 5.05 14 5.71 Skull Vertebra Rib Vertebra Skull Retarded Ossification (2,3,5,6 bil) Retarded Ossification (cen thlO-13) Supernumerary (luishort, rt) Retarded Ossification (cen thll,12) Retarded Ossification (6 b i l ;1) VR VR DV VR VR 642227 1 2 3 4 5 6 7 8 9 10 11 12 4.47 Vertebra 5.50 5.82 Kidney Vertebra 5.74 Skull Vertebra 5.49 Vertebra 5.45 5.22 Vertebra 5.79 Vertebra 5.27 Vertebra 5.45 Skull Vertebra 5.82 Kidney 5.53 Vertebra Retarded Ossification (cen thll) NAD Papilla - Size 3 (bil) Retarded Ossification (cen thll) Retarded Ossification (2 bil) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD - Retarded Ossification (cen thll,12) Retarded Ossification (cen thlO-13) Retarded Ossification (cen thll-13) Retarded Ossification (2,3 bil) Retarded Ossification (ceri thll,12) Papilla - Size 3 (bil) Retarded Ossification (cen thl2) VR VR VR VR VR VR VR VR VR VR VR VR VR - 127- Company Sanitized. Doss no! contain TSCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642227 (Cont.) 13 5.12 14 5.57 15 5.77 Rib Vertebra Subcutis Skull Vertebra Kidney Vertebra Supernumerary (lul oss site, It) Retarded Ossification (cen thl2) Hemorrhage (head*) Retarded Ossification (2 bil) Retarded Ossification (cen thll) Papilla - Size 3 (bil) Retarded Ossification (cen thl0,12) DV VR N VR VR VR VR 642231 1 2 3 .4 5 6 7' 8 9 10 11 4.76 6.01 4.81 4.89 5.03 5.31 5.47 5.75 5.24 5.36 5.05 Kidney Vertebra Vertebra Kidney Sternebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Papilla - Size 3 (bil) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll-13) Papilla - Size 3 (bil) Misaligned (4) Retarded Ossification (cen thl2) Retarded Ossification (cen thl3) Retarded Ossification (cen thll-13) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) VR VR VR VR DV VR VR VR VR VR VR VR VR Company Sanitized. D ogs net contain T3CA CB1 - 128- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642231 (Cont.) 12 5.57 Vertebra Retarded Ossification (cen thll) VR 642237 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.32 Subcutis Vertebra 5.37 Rib Vertebra 4.80 Rib Vertebra 5.25 Vertebra 5.05 Vertebra 5.94 Rib Vertebra 5.67 Vertebra 5.61 5.95 5.81 Rib Vertebra 5.91 5.82 Rib Vertebra 5.67 Rib Vertebra 4.99 Rib Vertebra 5.52 Hemorrhage (chin*) Retarded Ossification (cen thll-13) Supernumerary (site 14bil) Retarded Ossification (cen thll) Supernumerary (site 14 rt) Retarded Ossification (cen thl0-13) Retarded Ossification (cen thll) Retarded Ossification (cen thll-13) Supernumerary (site 14 bil) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) Supernumerary (site 14 bil) NAD Retarded Ossification (cen thll-13) NAD Supernumerary (site 14 It) ' Retarded Ossification (cen thll-13) Supernumerary (site 14 rt) Retarded Ossification (cen thlO-12) Supernumerary (site 14 bil) Retarded Ossification (cen thlO-12) NAD N VR DV VR DV VR VR VR DV VR VR DV VR DV VR DV VR DV VR -129- Company Sanitized. To s net contain TSCA CBI I H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642243 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.24 Rib Vertebra 5.27 Rib Skull Vertebra 5.40 Vertebra 5.24 5.21 Vertebra 5.16 5.30 Vertebra 4.60 5.63 5.01 6.74 Vertebra 5.45 Vertebra 5.47 Vertebra 5.39 Vertebra Supernumerary (short rt 13) Retarded Ossification (cen thlO) Supernumerary (site 14 rt) Retarded Ossification (7 BIL) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl0)~ . Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) DV VR DV VR VR VR VR VR VR VR VR VR 642244 1 2 3 4 5 5.74 5.77 5.80 5.78 6.33 Skull Vertebra Skull NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thl2) NAD Retarded Ossification NAD (2 bil) VR VR VR Company Sanitized. Ho~z net contain TBCA CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grains) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642244 (Cont.) 6 5.33 Skull 7 6.66 Kidney 8 6.19 Skull 9 6.32 10 5.96 Vertebra 11 6.28 Vertebra 12 5.91 Skull Vertebra 13 6.14 642248 1 2 3 4 5 6 7 8 '9 10 11 12 5.69 5.67 6.96 5.49 4.90 5.11 5.44 5.37 5.24 5.48 5.69 6.01 Vertebra Vertebra Vertebra 13 5.71 Vertebra Retarded Ossification (2,3 bil) Small Papilla - Size 2 (bil) Retarded Ossification (2,3 bil) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) NAD VR VR VR VR VR VR VR NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl3) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO) VR VR VR VR 642250 1 5.70 NAD Company Sanitized. Does not contain TSC A CB1 - 131 - H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642250 (Cont.) 2 5.93 Vertebra 3 5.83 Vertebra 4 5.85 5 5.83 Vertebra 6 5.79 Vertebra 7 5.82 8 5.37 9 5.47 Kidney Vertebra 10 5.81 11 5.53 Vertebra 12 5.67 13 5.89 Kidney Vertebra Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) NAD NAD Small Papilla - Size 2 (bil) Retarded Ossification . (cen thll-12) NAD Retarded Ossification (cen thl2) NAD Papilla - Size 3 (bil) Retarded Ossification (cen thl2) VR VR VR VR VR VR VR VR VR 642251 1 2 3 - 4 5 6 7 5.35 5.47 5.88 5.31 5.17 5.77 5.51 Vertebra Kidney Vertebra Skull Rib Vertebra Kidney " NAD Retarded Ossification (cen thlO 12-13) Papilla - Size 3 (bil) Retarded Ossification (cen thl2-13) Retarded Ossification (1,12 ;2,5,6-8 bil) Supernumerary (site 14 rt) Retarded Ossification (cen thl2) NAD Small Papilla - Size 2 (bil) VR VR VR VR DV VR VR Company Sanitised. Does not contain TSCA CBI - 132- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642251 (Cont.) 8 5.60 9 5.37 10 6.01 11 5.53 Vertebra Kidney Pelvis Vertebra Vertebra Kidney Vertebra Retarded Ossification (cen thll,13) Papilla - Size 3 (bil) Retarded Ossification (ischium It) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Papilla - Size 3 (It) Retarded Ossification (cen thll-12) VR VR VR VR VR VR VR 642254 1 2 3 4 5 6 7 8 '9 10 11 12 13 14 5.06 Kidney 5.32 Vertebra 5.08 Vertebra 5.13 4.74 5.26 4.85 Subcutis Vertebra 5.43 5.38 5.00 5.12 Vertebra 5.29 4.88 Subcutis Vertebra 5.02 Skull Papilla - Size 3 (bil) Retarded Ossification (cen thll) Retarded Ossification (cen thlO) NAD NAD NAD Hemorrhage (back*) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (cen thll) NAD Hemorrhage (back*) Retarded Ossification (cen thlO) Retarded Ossification (2,3 bil) VR VR VR N VR VR N VR VR - 133- Company Sanitized. Does net contain TSCA CBI % H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642256 1 2 3 4 5 6 7 8 9 10 11 12 5.72 Vertebra 6.03 5.66 Vertebra 5.81 Vertebra 5.56 5.80 Vertebra 6.29 5.45 5.78 Skull Vertebra 5.69 Vertebra 5.81 6.42 Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD Fused (5) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD NAD VR VR VR VR M VR VR 642266 1 2 3 4 5 6 7 8 5.28 5.11 5.44 5.62 4.50 4.98 4.83 5.04 Vertebra Vertebra Vertebra Subcutis Rib Vertebra Vertebra Kidney Vertebra Vertebra Retarded Ossification (cen thl2) Retarded Ossification . (cen thl2) Retarded Ossification (cen thll-12) Hemorrhage (back*) Supernumerary (site 14 It) Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO) Small Papilla - Size 2 (bil) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) VR VR VR N DV VR VR VR VR VR Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 250 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642266 (Cont.) 9 4.54 10 4.83 11 4.55 12 4.70 13 5.31 Vertebra Vertebra Subcutis Kidney Vertebra Vertebra Kidney Vertebra Retarded Ossification (cen thll-13) Retarded Ossification (cen thlO-12) Hemorrhage (back*) Small Papilla - Size 2(bil) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thl2) Small Papilla - Size 2 (It) Retarded Ossification (cen thll) VR VR N VR VR VR VR VR - 135 - Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE '______ FINDING(S) CLASSIFICATION 642183 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 642191 1 2 3 4 5 6 7 8 9 5.78 Vertebra 5.81 5.75 Vertebra 5.58 Skull 5.66 Vertebra 5.57 Vertebra 5.53 5.49 5.46 5.42 5.95 5.41 5.56 5.25 Vertebra 5.74 Kidney 5.52 5.52 5.96 5.80 6.00 4.86 5.46 5.06 5.71 Vertebra Vertebra Vertebra Ureter Kidney . Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification (2,3 bil) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thlO-12) Papilla - Size 3 (rt) NAD . NAD .- Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll-12) NAD Distended (rt) Small Papilla - Size 1 (rt) VR VR VR VR VR VR VR VR VR VR N VR - 136- Dompany Sanitized. Does not contain T S C A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642191 (Cont.) 10 4.07 Vertebra Retarded Ossification (cen thll-12) VR 642193 1 2 3 4 5 6 7 8 9 10 11 12 13 642196 1 2 3 4 5 6 7 5.61 Vertebra 5.94 5.58 6.15 5.55 5.67 5.84 6.10 5.73 5.08 5.71 5.75 Kidney Skull Vertebra 5.98 5.56 6.29 5.92 5.97 5.52 5.90 5.87 Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD NAD NAD NAD Papilla - Size 3 (bil) Retarded Ossification (6 lt) Retarded Ossification (cen thll) NAD VR VR VR VR Retarded Ossification (cen thll,12) Retarded Ossification (cen thl2) Retarded Ossification (cen th9-13) Retarded Ossification (cen thll,13) NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) Retarded Ossification (cen thl0,ll) VR VR VR VR VR VR VR - 137- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642196 (Cont.) 8 6.50 9 5.62 10 5.88 11 5.49 12 5.65 13 5.93 Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Retarded Ossification (cen thll-13) NAD Retarded Ossification Retarded Ossification (cen thll,12) Retarded Ossification (cen thl2) Retarded Ossification Retarded Ossification (cen thl2,13) Retarded Ossification (cen thll) (2bil) (2 bil) VR VR VR VR VR VR VR 642197 1 2 3 4 5 6 7 8 9 10 11 12 13 14 642210 1 2 5.71 5.55 5.56 5.57 5.39 5.36 5.23 5.38 5.82 6.02 5.69 5.07 5.10 5.62 Skull Kidney Vertebra Vertebra Kidney Vertebra 6.23 Subcutis 5.61 NAD Retarded Ossification (6 It) Papilla - Size 3 (bil) Retarded Ossification (cen thl2) NAD NAD . NAD Retarded Ossification (cen thll-12) Papilla - Size 3 (rt) NAD Retarded Ossification (cen thl2) NAD NAD NAD VR VR VR VR VR VR Hemorrhage (BACK*) NAD N - 138- Company Sanitized. Does not contain TSCA CBl H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642210 (Cont.) 3 5.29 Vertebra 4 5.04 Rib 5 4.03 Eye Rib Sternebra 6 5.06 7 5.50 Vertebra 8 5.46 Vertebra 9 4.95 Rib Vertebra 10 5.45 Skull Vertebra 11 5.29 12 4.96 Vertebra 13 4.99 14 5.66 Retarded Ossification (cen thl0,12) Supernumerary (site 14 lt) Microphthalmia (right) Supernumerary (site 14 rt) Retarded Ossification (6) NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thll) Supernumerary (site 14 lt) Retarded Ossification (cen thl2) Retarded Ossification (6 bil) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll-12) NAD NAD . VR DV M DV VR VR VR DV VR VR VR VR 642214 1 2 3 4 5 6 7 8 9 10 5.79 6.06 5.20 5.73 5.81 5.28 5.40 5.75 5.60 5.56 Kidney Vertebra Rib Rib Vertebra Rib Papilla - Size 3 (bil) NAD Retarded Ossification (cen th8,12) NAD NAD NAD Supernumerary (site 14 bil) Supernumerary (site 14 lt) Retarded Ossification (cen thll) Supernumerary (site 14 lt) NAD VR VR DV DV VR DV -139- Company Sanitized. Does net contain TSC A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE___________ FINDING(S) CLASSIFICATION 642214 (Cont.) 11 6.30 12 5.84 Rib Rib Vertebra 13 5.43. Vertebra 14 5.10 15 6.13 16 5.21 Rib 642216 1 5.73 Vertebra 2 5.25 Subcutis 3 5.74 Vertebra 4 5.57 Vertebra 5 5.74 6 4.79 7 5.51 Vertebra 8 6.17 9 5.59 10 5.60 Skull . 11 5.54 12 5.36 13 5.34 Vertebra Supernumerary (site 14 It) Supernumerary (site 14 rt) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD NAD Supernumerary (site 14 It) DV DV VR VR DV Retarded Ossification (cen thl2-13) Hemorrhage (head*) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (6 RT) NAD NAD Retarded Ossification (cen thl0,12) VR N VR VR VR VR VR 642217 1 2 3 4 4.85 4.89 5.22 3.46 Vertebra Skull Sternebra Vertebra NAD NAD Retarded Ossification (cen thl2) Retarded Ossification Retarded Ossification Retarded Ossification (cen thll) (3 bil) (6) VR VR VR VR A V Company Sanitized. Does not contain TSCA CBI - 140- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE ______ FINDING(S)__________ CLASSIFICATION 642217 (Cont..) 5 2.70 6 2.98 7 3.51 8 5.06 9 4.79 10 4.56 Head Tail Brain Sternebra Skull Sternebra Sternebra Vertebra 11 3.12 Head Vertebra 12 3.23 Skull Sternebra Vertebra 13 2.55 Head Tail Pelvis Sternebra Vertebra 14 2.84 Skull Sternebra Vertebra Domed Bent Distended (ventricles;bil) Retarded Ossification (6) Retarded Ossification (3 bil) Retarded Ossification (6) Retarded Ossification (6) NAD NAD Retarded Ossification (cen thll) Domed Retarded Ossification (cen thl0,12) Retarded Ossification (3 bil) Retarded Ossification (6) Retarded Ossification (cen thll) Domed Bent Retarded Ossification (pubis bil) Retarded Ossification (4,6) Retarded Ossification (cen thl2) Retarded Ossification (2,3 bil) Retarded Ossification (1,4,6) Retarded Ossification (cen thll-12) N N M VR VR VR VR VR N VR VR VR VR N N VR VR VR VR VR VR 642218 1 2 3 5.34 5.57 5.71 Vertebra Retarded Ossification (cen thll) NAD NAD VR - 141 - Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642218 (Cont.) 4 5.74 5 5.20 6 5.34 7 5.50 8 5.76 9 5.24 10 5.89 11 5.42 12 5.37 13 5.38 14 5.42 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thll,12) Retarded Ossification (2,3 bil) Retarded Ossification (cen thl0,12) VR VR VR VR VR VR VR VR 642234 1 2 3 4 5 6 7 8 9 . 4.47 4.71 5.79 5.40 4.95 5.61 5.60 5.33 4.47 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra NAD NAD Retarded Ossification (cen thl0,12) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thl0-12) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) VR VR VR VR VR VR Company Sanitized. Does net contain TSCA CBI - 142- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642234 (Cont.) 10 4.96 11 5.67 12 4.82 13 5.93 14 5.52 15 4.95 16 5.05 17 5.14 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO) Retarded Ossification (cen thl2-13) NAD Retarded Ossification (cen thl3) NAD VR VR VR VR VR VR 642235 1 2 3 4 5 6 7 8 9 10 11 5.50 5.76 6.18 5.36 Vertebra Vertebra 5.98 Vertebra 5.48 6.17 Kidney Vertebra 6.19 5.44 Vertebra 5.45 Skull Vertebra 5.81 NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thll,13) NAD Papilla - Size 3 (bil) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) Retarded Ossification (2,6 bil;1) Retarded Ossification (cen thll) NAD VR VR VR VR VR VR VR VR P Company Sanitized. Does not contain T S C A CB1 - 143- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642235 (Cont.) 12 5.43 Vertebra Retarded Ossification (cen thll) VR 642239 1 2 3 4 5 6 7 8 X9 10 11 12 13 14 5.17 4.86 Vertebra 5.06 Vertebra 5.62 Skull Vertebra 5.52 Vertebra 5.54 5.39 5.06 Skull Vertebra 4.80 5.48 Pelvis Rib Skull Vertebra 4.97 Vertebra 4.96 5.66 5.40 Skull NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2) Retarded Ossification (1,6-8 bil, 7 rt) Retarded Ossification (ce arch 6-7 lt) Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (8 bil, 6-7 rt) Retarded Ossification (ce arch 5-6 bil) NAD . Retarded Ossification (pubis, ISCHIUM BIL) Retarded Ossification (th9-ll rt) Retarded Ossification (1,12;2-8 bil) Retarded Ossification (cen thl0;arch ce4-7 bil) Retarded Ossification (cen thll-12;arch ce4-5 rt) NAD NAD Retarded Ossification (12;2 bil; 8 rt) VR VR VR VR VR VR VR VR VR VR VR VR VR - 144- Company Sanitized. Does not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642240 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 642246 1 2 3 4 5 6 7 8 9 10 11 12 7.18 5.49 5.24 5.58 5.39 5.16 5.33 5.62 5.57 5.33 5.55 5.78 5.15 5.24 5.08 5.76 Skull Skull Rib 4.15 4.42 4.62 5.00 3.69 4.69 3.99 4.52 5.44 5.13 5.61 4.49 Heart &/or Greater Vessels Rib Sternebra Vertebra Skull NAD Retarded Ossification (3 bil) NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (1; 2 RT) Supernumerary (site 14 It) NAD NAD NAD VR VR DV NAD NAD Patent Ductus Arteriosis NAD NAD NAD Supernumerary (site 14 rt) Retarded Ossification (6) Retarded Ossification (cen th3,ll) NAD NAD NAD NAD Retarded Ossification (1,12; 2-3 bil) VR DV VR VR VR - 145- Company Sanitized. Does not contain TSC A CB1 H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE __________ FINDING(S) CLASSIFICATION 13 14 642252 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 642258 1 2 3 4 ; 4.96 6.07 Vertebra 4.37 5.09 5.21 5.14 5.10 3.63 3.95 4.52 4.64 5.51 4.68 4.88 4.96 5.00 5.09 5.13 5.50 Vertebra Vertebra Vertebra Vertebra 5.64 5.34 5.75 5.42 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll) NAD NAD NAD NAD NAD Retarded Ossification (cen thlO) NAD NAD Retarded Ossification (cen thl3) NAD NAD NAD NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll,13) NAD NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO) Retarded Ossification (cen thl2) Retarded Ossification (cen thl0-ll) VR VR VR VR VR VR VR VR VR - 146- Company Sanitized. Doos not contain TSCA CBI H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642258 (Cont.) 5 5.46 6 5.55 7 5.72 8 4.63 9 5.07 10 5.89 11 5.60 12 5.70 Vertebra Vertebra Skull Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification (1; 2-3 bil;7-8 It) Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO-11) Retarded Ossification (cen th.10,13) Retarded Ossification (cen thlO) NAD VR VR VR VR VR VR VR 642260 1 2 3 4 5 6 7 8 9 10 11 3.29 4.73 5.60 5.71 5.23 5.86 4.87 5.29 5.45 5.77 5.18 Skull Skull Vertebra Vertebra Sternebra Vertebra Skull NAD Retarded Ossification (2,3 bil;1,12) NAD . NAD NAD Retarded Ossification (2,3 bil) Retarded Ossification (cen thll,12) Retarded Ossification (cen thll) NAD Retarded Ossification Retarded Ossification (cen th8-12) Retarded Ossification (2,3 bil) NAD (6) VR VR VR VR VR VR VR ? r-mpany Sanitized. D oss not containTSCA CB1 - 147- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642260 (Cont.) 12 5.78 13 5.23 14 5.62 Skull Rib Retarded Ossification (2,3 bil) NAD Supernumerary (lul oss site, bil) VR DV 642263 1 2 3 4 5 6 7 8 9 10 4.76 4.03 4.57 4.93 4.99 5.09 4.76 4.68 4.57 5.22 Rib Skull Vertebra Skull Rib Skull Rib Skull Vertebra Rib Skull NAD Supernumerary (lul oss site, rt) Retarded Ossification (2,3 bil;1,12) Retarded Ossification (cen thl2,13) Retarded Ossification (2,3 bil) Supernumerary (lul oss site, It) Retarded Ossification (2,3 bil) Supernumerary (lul short, bil) Retarded Ossification (2,3 bil) Retarded Ossification (cen thll) NAD Supernumerary (lul short, bil) Retarded Ossification ' (2,3 bil) DV VR VR VR DV VR DV VR VR DV VR 642267 1 2 3 4 5 6 5.13 5.35 5.00 5.44 5.68 5.42 NAD NAD NAD NAD NAD NAD Company Sanitized. Decs not contain T S C A CB1 - 148- H-24616: Developmental Toxicity Study in Rats DuPont-4902 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 1000 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 642267 (Cont..) 7 5.15 8 5.26 9 4.94 10 5.37 11 5.24 12 5.33 13 5.11 14 5.56 Vertebra Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD NAD VR 642268 1 2 3 4 5 6 7 8 9 10 11 12 3.69 4.71 4.53 3.81 3.95 4.45 4.76 4.78 3.61 3.74 5.22 4.50 Vertebra Heart &/or Greater Vessels Kidney Rib Vertebra Vertebra Vertebra Rib Retarded Ossification (cen thll) NAD NAD NAD Patent Ductus Arteriosis NAD Papilla - Size 3 (bil) Supernumerary (short 13 rt) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) . Retarded Ossification (cen thll) NAD NAD Supernumerary (short It 13) VR VR VR DV VR VR VR DV Company Sanitized. Dots not contain TSCA CB! - 149-