Document 71B5kRX04LaDm90oexy6OoGqg

r Ma u . H-25425: Developmental Toxicity Study in Rats___________________________________________ DuPont-11347 TRADE SECRET Study Title H-25425: Developmental Toxicity Study in Rats Laboratory Project ID: DuPont-11347 Test Guidelines: U.S. EPA Health Effects Test Guidelines OPPTS 870.3700 Prenatal Developmental Toxicity Study Author: Susan M. Munley, M.A. Study Completed on: April 21,2003 Performing Laboratory: E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Number:| #4Service Code Number: Page 1 o f 156 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats DuPont-11347 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles o f Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17, except for the item documented below. The item listed does not impact the validity o f the study. The bulk test substance characterization and stability analyses were performed at DuPont Regional Analytical Services (RAS), a non-GLP laboratory. These analyses were in compliance with regulatory guidelines. None o f the aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with IS09002 regulations. All o f the analyses are considered valid and sufficient for the purposes o f this study. Study Director: /^/ylusi Susan M. Muni .A. Research Scientist EX du Pont de Nemours and Company Applicant:________________________________ ______ _________ Applicant Representative Date Sponsor._______________________________________ _________ Sponsor Representative Date 2 Company Sanitized. Does not contain TSC A CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 25425 Dates o f Inspections: Protocol: August 23, 2003 Conduct: September 10,11, 2002 Records, Reports: December 17-19, 2002; February 25-28, 2003; March 1, 2003; April 15-16, 2003 Dates Findings Reported to: Study Director: August 23, 2002; September 11, 2002; March 3, 2003; April 16, 2003 Management: September 11,2002; December 23, 2003; April 21,2003 Reported by: Staff Quality Assurance Auditor Date 3 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. AnalyticalEvaluationsby: CLvLrjb .... ....._ JanetC. Maslanka, B.S. SeniorStaffChemist Date Approvedby: Mylchreest,Ph.D. Manager Zt-tipr-ZO ft Date IssuedbyStudyDirector: -- /H . SlO uL T llM jr SusanM. Munley, MfC. ResearchScientist / - f ip r (005 Date 4 Company Sanitized. Does not contain TSCA C8i H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT..................................... 2 QUALITY ASSURANCE STATEM ENT........................................................................................ 3 CERTIFICATION.................................................................................................................... 4 LIST OF APPENDICES.............................. ....................................................................................... 6 STUDY INFORMATION................................................ 7 STUDY PERSONNEL......................................................................................... 8 SUM M ARY.............................................................................................................................................9 O B J E C T I V E .........................................................................................................................................10 MATERIALS AND M ETHODS................................................................. 10 A. Test Guidelines..........................................................................................................................10 B. Test Substance........................................................................................................................... 10 C. Test Species............................................................................................................................... 10 D. Animal Husbandry.............................. 11 E. Quarantine and Pretest Period.................................................................................................. 12 F. Study Design............................................................................................................. 12 G. Selection o f Dose Levels...........................................................................................................12 H. Randomization.......................................................... 12 I. Preparation, Administration, and Analysis o f Test Formulations........................................ 13 J. Animal Euthanasia..... ...............................................................................................................15 K. Parameters to be Studied...........................................................................................................15 L. Control of B ias...........................................................................................................................16 M. Statistical Analyses.................................................... 16 RESULTS AND DISCUSSION........................................................................................................ 17 ANALYTICAL EVALUATIONS.................................................................................................... 17 A. Chromatography........................................................................................................................17 B. Recovery Sam ples.................................................................................................................... 17 C. Homogeneity and Stability Samples........................................................................................17 D. Concentration Verification Samples........................................................................................18 E. Analytical Conclusions............................................................................................................. 19 DEVELOPMENTAL TOXICOLOGY........................................................................................... 20 5 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 A. Maternal Findings..................................................................................................................... 20 B. Fetal Findings.............................................................................................................................21 C O N C LU SIO N S.................................................................................................................................. 22 RECORDS AND SAM PLE ST O R A G E............................... 22 R EFER EN C ES................................................................... 23 TA BLES.........*.......................................................................................................................................24 A PPEN D IC ES...................................................................................................................................... 39 LIST OF TABLES TABLE 1 SUMMARY OF DOSING SOLUTION ANALYSES................................................................................. 25 TABLE 2 MEAN MATERNAL BODY WEIGHTS ...................... .............................................................................. 26 TABLE 3 MEAN MATERNAL BODY WEIGHT CHANGES................................................................................... 29 TABLE 4 MEAN MATERNAL FOOD CONSUMPTION...........................................................................................31 TABLE 5 CLINICAL OBSERVATIONS........................................................................................................................33 TABLE 6 REPRODUCTIVE OUTCOME.......................................................................................................................34 TABLE 7 INCIDENCE OF FETAL MALFORMATIONS.............................................................................................35 TABLE 8 INCIDENCE OF FETAL VARIATIONS....................................................................................................... 36 LIST OF APPENDICES APPENDIX A ANALYTICAL DATA.............................................................................................................................40 APPENDIX B INDIVIDUAL BODY WEIGHTS...................................................... 47 APPENDIX C INDIVIDUAL BODY WEIGHT CHANGES........................................................................................ 61 APPENDIX D INDIVIDUAL FOOD CONSUMPTION........................................... 71 APPENDIX E INDIVIDUAL CLINICAL OBSERVATIONS....................................................................................... 81 APPENDIX F GROSS POSTMORTEM FINDINGS...................................................................................................... 93 APPENDIX G INDIVIDUAL REPRODUCTIVE DATA...............................................................................................99 APPENDIX H INDIVIDUAL FETAL WEIGHTS AND ALTERATIONS.................................................................105 6 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats STUDY INFORMATION Svnonvms/Codes: Submitter's Notebook Numberisi: Haskell Number: 25425 CAS Registry Number: Composition:! DuPont-11347 Purity: Known Impurities: Physical Characteristics: Amber-yellow-brown solid Stability: The test substance appeared to be stable under the conditions o f the study; no evidence o f instability was observed. Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 - U.S.A. Study Initiated/Completed: August 22, 2002 / (see report cover page) 7 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats STUDY PERSONNEL Study Director: Susan M. Munley, M.A. Management: Eve Mylchreest, Ph.D. Robert M. Parker, Ph.D., D.A.B.T. Primary Technician: William P. Boyer Supervisor: Deborah L. Tyler Analytical Chemist: Janet C. Maslanka, B.S. Management: S. Mark Kennedy, Ph.D. Toxicology Report Preparation: MaryK. LaRoe Management: Nancy S. Selzer, M.S. Laboratory Veterinarian: Thomas W. Mayer, D.V.M., A.C.L.A.M. William Singleton, D.V.M., A.C.L.A.M. DuPont-11347 8 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 SUMMARY H-25425 was administered by gavage to groups o f 22 Crl:CD(SD)IGS BR rats once daily at dose levels o f 0,10,100, or 1000 mg/kg/day. Doses were administered as a suspension in 0.5% aqueous methylcellulose at a volume of 5 mL/kg/day and dosing took place over days 6 through 20 o f gestation (G). Body weight, food consumption, and clinical sign data were collected during the in-life phase. On day 21G, dams were euthanized and subjected to a gross external and internal examination. Uterine contents were described; all fetuses were removed and individually weighed, sexed, and examined for external alterations. Approximately one-half o f the fetuses were subjected to fresh visceral and fixed head evaluations; all fetuses were examined for skeletal alterations. Under the conditions o f this study, there was no evidence o f any maternal or developmental toxicity at any level tested. The data for maternal body weight, weight change, food consumption, clinical observations, survival, and gross postmortem observations did not suggest any toxicity to the dams at either 10, 100, or 1000 mg/kg/day. Data summarizing the reproductive outcomes, embryofetal viability, fetal body weight and sex ratio, and fetal external, visceral, head, and skeletal malformations and variations did not indicate any adverse developmental outcome. The NOEL for maternal and developmental toxicity was, therefore, considered 1000 mg/kg/day. 9 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats DuPont-11347 OBJECTIVE The purpose o f this study was to evaluate the potential maternal and developmental toxicity of H-25425 in rats. MATERIALS AND METHODS A. Test Guidelines The study design complies with the following test guidelines: United States Environmental Protection Agency (EPA), Office o f Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines, OPPTS 870.3700 Prenatal Developmental Toxicity Study (1998). B. Test Substance The test substance (H-25425) was supplied by the sponsor, the DuPont Chemical Solutions Enterprise (DCSE), E. I. Du Pont de Nemours and Company, Wilmington, Delaware. It was assigned Haskell Laboratory Number 25425. The sponsor was responsible for the characterization o f the test substance. Test substance characterization was conducted by DuPont Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. A reserve sample o f the test substance was collected and retained by DuPont 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 o f spontaneous disease. 10 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 Eighty-eight nulliparous time-mated females were received on August 22, 2002 (66 females) and August 23, 2002 (22 females) from Charles River Laboratories, Inc., Raleigh, North Carolina. Body weights on the day the rats were mated, day 0 o f gestation (day 0G), were supplied by the vendor. The rats for this study were at either 1, 2, or 3 days o f gestation upon arrival. D. Animal H usbandry 1. Housing Animal rooms were maintained at an acceptable temperature o f 18-26C (targeted at 22-24C) and maintained at an acceptable relative humidity o f 30%-70% (targeted at 40%-60%). Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours). Animals were housed individually in suspended, wire-mesh, stainless steel cages. Nesting material was not provided because the dams were euthanized prior to parturition. 2. Feed and Water PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 (formerly known as Purina Certified Rodent Chow) was available ad libitum. Water from United Water Delaware was available ad libitum. 3. Identification Each animal was assigned a unique number and was identified with an AVID Microchip implant by the supplier prior to shipping. Upon receipt, each animal was assigned a unique Haskell animal number. Both the Haskell animal number and the AVID Microchip implant number were recorded on each cage card. A master list o f unique Haskell animal numbers and corresponding unique AVID Microchip implant numbers is 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 o f 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 o f key contaminants, including 11 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence o f 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 o f the study. E. Quarantine and Pretest Period Rats were quarantined according to procedures outlined in Haskell Laboratory SOI and then released for the study upon approval of the Laboratory Animal Veterinarian designee" F. Study Design The experimental design is shown below: GrouD Dose (ma/ke/dav) Suspension Concentration fmg/mL) Time-Mated Females I 0b 0 n 10 2 m 100 20 22 22 22 IV 1000 200 22 a Test substance, administered by oral gavage, on days 6-20 o f gestation (G), at a dose volume of 5 mL/kg. b Vehicle (0.5% aqueous methylcellulose in deionized water) G. Selection o f Dose Levels The dose levels for this study were selected by the Sponsor. H. Randomization Dams were assigned to lots according to their gestation day. Then, they were ranked within their respective lots on the basis o f day 0G 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). 12 Company Sanitized. Does not contain TSCA CBI /**'**\ /"""s H-25425: Developmental Toxicity Study in Rats DuPont-11347 I. Preparation, Administration, and Analysis of Test Formulations 1. Test Formulation Preparation Formulations of the test substance suspended in the vehicle (0.5% methylcellulose in deionized water) were prepared daily and stored in a closed container at room temperature until used. The method of mixing the test substance with the vehicle was documented in the study records. 2. Test Formulation Administration The test substance was administered by gavage because the oral route is the route that is recommended by regulatory agencies for this type o f study. The volume administered (5 mL/kg) was based on the most recent body weight. 3. Test Formulation Sampling Samples containing H-25425 at the concentrations o f 0, 2,20, and 200 mg/mL were collected on August 26 and 29, 2002 for uniformity, concentration verification, and 5-hour room temperature stability. Samples at all concentrations were collected on September 4 and 10, 2002 for concentration verification analysis. All dosing formulation samples were collected on the same day the formulations were prepared. 4. Analytical Methods a. Recovery Sample Analysis Concurrent with dosing formulation analyses, recovery o f H-25425 from spiked 0.5 % methylcellulose was tested at the low level (2 mg/mL), at the mid level (20 mg/mL) and at the high level (200 mg/mL) to confirm the analytical method. For the low level, H-25425 was weighed (approximately 12 mg) and diluted with 6 mL o f 0.5% methylcellulose. For the mid and high level, H-25425 was weighed (approximately 60 and 600 mg, respectively) and diluted with 3 mL of 0.5% methylcellulose. All recovery samples were then vortexed for dispersion o f the H-25425 in the methylcellulose. The samples were then processed and analyzed in the same manner as the dosing formulation samples at similar concentrations. b. Dosing Formulation Treatment Each dosing formulation sample was collected in a 15 mL centrifuge tube (5 or 6 mL for 2 mg/mL level and 3 mL for 20 and 200 mg/mL levels). For the first sample set collected, the tubes were centrifuged and the methylcellulose removed. For the remainder o f sample sets collected, 3 mL o f methanol was added to each tube, followed by vortexing for mixing, centrifuging and removal o f the supernatant. After the supernatant was removed, the test substance, remaining as solids, was washed with 3 replicate washes (3 mL) o f methanol with vortexing, centrifuging and removal of the supernatant after each wash. The test substance, remaining as solids, was dried under nitrogen. These solids were then reconstituted in tetrahydrofuran (THF) using sonication to assure all material was dissolved. The 2 mg/mL samples were reconstituted to 2.5 or 3 mL with THF, the 20 mg/mL samples were reconstituted 13 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 to 10 mL with THF and the 200 mg/mL samples were reconstituted to 100 mL with THF. The following target concentrations were then analyzed: 4.0 mg/mL, 6.0 mg/mL and 6.0 mg/mL, respectively. Samples submitted for analysis were analyzed the day they were received. c. Chromatographic Conditions Instrument: Column: Mobile Phase Flow Rate: Injection Volume: Column Temperature: Detection: Hewlett-Packard Model 1100 HPLC Styragel HR 4; 7.8 mm x 300 mm (GPC column) 100% tetrahydrofuran (THF) 1.0 mL/min 50 pi 35C Refractive Index d. Calibration and Quantitation ` ' 1 !o f H-25425 test substance was designated as the analytical reference standard stock solution o f H-25425 in tetrahydrofuran (THF) was used to make canoranon solutions that bracketed the test formulation concentrations. Peak heights from replicate high performance liquid chromatography/gel permeation chromatography/refractive index detector (HPLC/GPC/RI) analysis of each calibration solution were used to construct a calibration curve by least-squares regression. Measured concentrations for each test formulation were determined by applying respective peak heights to the calibration curve. Test substance homogeneity and uniformity in the vehicle was evaluated by calculating the coefficient o f variation (C.V. = standard deviation/mean x 100) o f the measured concentrations in the top, middle, and bottom samples (homogeneity) or duplicate samples (concentration verification) for each dosing level. A coefficient o f variation o f less than or equal to 10% is considered indicative o f acceptable distribution of the test substance throughout the formulation. However, if the test substance has been shown to be difficult to disperse in the vehicle or the analysis has shown variability, a coefficient o f variation greater than 10 may be acceptable. The mean result o f the homogeneity samples (n = 3) or concentration verification samples (n = 2) for each dosing level was used to determine the concentration o f the test substance for the respective dosing formulations. Stability was evaluated by using the mean result o f the homogeneity samples as the baseline for comparing the corresponding stability results. Because o f the procedure used to isolate the test substance in the method for analysis, spiked recovery samples at each level were monitored. A correction based on these recovery samples was applied to the sample results, if the spiked recovery sample analysis was less than 90% of nominal for the level. 14 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats J. Animal Euthanasia DuPont-11347 Adult females were euthanized by carbon dioxide asphyxiation. Fetuses were decapitated before proceeding with visceral examinations; those to be viscerally examined without decapitation were injected intraperitoneally with sodium pentobarbital. All other fetuses also were injected with sodium pentobarbital before fixation. K. Param eters to be Studied 1. In-life Observations o f 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 2 1G 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 o f 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 o f females with viable fetuses was recorded. For each female with visible implantation sites, the types o f implants (live and dead fetuses, and resorptions) and their relative positions were recorded. The uterus o f each apparently "nonpregnant" female was stained with ammonium sulfide(2) to detect very early resorptions. 3. Fetuses o f 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.1^ Retarded renal development was classified using the scheme o f Woo and H oar/4) In addition, all live fetuses with malformations visible at external examination were examined for soft tissue alterations. After fixation in Bouin's fixative, the heads o f decapitated fetuses were examined and alterations were recorded. Examinations were based on the method o f Barrow and Taylor.(5) After alcohol fixation, the alizarin-stained skeletons were examined and skeletal alterations were recorded for all live fetuses, excluding the fetal heads fixed in Bouin's fixative. 15 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 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 Descriptive statistics were performed for all quantitative endpoints listed below. Sequential twotailed trend testing 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 o f 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 o f 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(9) Jonckheere's test(10) Cochran-Armitage test(9) Linear contrast of least square means(u) 16 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 RESULTS AND DISCUSSION ANALYTICAL EVALUATIONS A. Chromatography Appendix A H-25425 eluted from the HPLC/GPC column as a resolved peak over an average retention time o f 8.4 to 8.7 minutes. Representative HPLC/GPC/IR chromatograms are shown in Figures 2 (a - c). Test substance was not detected in the 0 mg/mL control. B. Recovery Samples Appendix A Detailed analytical results o f recovery samples are summarized in Appendix A, Table I. The variability o f the analytical method was demonstrated by the coefficients o f variation o f the recovery results at each targeted dosing concentration (approximately 2, 20, 200 mg/mL) over the course of the study. The measured concentrations o f H-25425 for the 2 mg/mL level were 75.7% to 86.5% o f nominal (mean percent recovery = 82.8% 3.8, C.V. = 5%). The measured concentrations o f H-25425 for the 20 mg/mL level were 87.9% to 103.5% o f nominal (mean percent recovery = 96.9% 5.9, C.V. = 6%). The measured concentrations o f H-25425 for the 200 mg/mL level were 91.4% to 105.8% of nominal (mean percent recovery = 97.5% 6.1, C. V. = 6%). Based on this data, a correction was applied to all sample results when the spiked recovery for the concentration had analyzed below 90% of nominal. C. Homogeneity and Stability Samples Table 1, Appendix A Analytical results from dosing formulation samples collected August 26, 2002 and August 29, 2002 and analyzed for homogeneity, concentration verification, and 5-hour room temperature stability are shown in Summary Table 1 and Appendix A, Table II. 17 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 The following table summarizes the results for homogeneity, concentration verification, and stability analyses for both sampling days o f the H-25425 sample preparation. Sample Day Sample Type 26-Aug-2002 Homogeneity 29-Aug-2002 Homogeneity Nominal mg/mL Measured T,M,Ba mg/mL 0 NDC 2d 1.32,1.26, 1.26 20d 14.1,14.9,14.6 200 179, 185, 204 0 ND 2d 2.11,2.25, 2.23 20 16.1,16.1, 17.3 200 189,188, 188 Mean (T,M,B) % Nominal -- 64.0 73.0 94.7 -- 110.0 82.5 94.0 C.V. Stability*5 (%) % Nominal ---- 3 54.5 3 69.5 7 96.0 ---- 3 110.5 4 87.5 0.3 94.5 a Mean results for the analysis of the top (T), middle (M) and bottom (B) samples, b Samples held 5 hours at room temperature, c Denotes none detected. d Reported results corrected for recovery of the spiked sample at the level (refer to Table I). The results for H-25425 samples prepared on August 26, 2002 show that the test substance was lower than expected for the 2 and 20 mg/mL levels but adequately mixed (CV's less than 10) and stable in the vehicle when held 5 hours at room temperature. Test substance was not detected in the 0 mg/mL samples. The results for H-25425 samples prepared on August 29, 2002 show that the test substance was at the targeted concentrations, adequately mixed (CV's less than 10) and stable in the vehicle when held 5 hours at room temperature. Test substance was not detected in the 0 mg/mL samples. D. Concentration Verification Samples Table 1, Appendix A Analytical results from dosing formulation samples prepared September 4,2002 and September 10, 2002 and analyzed for concentration verification (uniformity) are shown in Appendix A, Table EHand Summary Table 1. 18 Company Sanitized. Does not contain TSCA CBI H-2S425: Developmental Toxicity Study in Rats DuPont-11347 The following table summarizes the results for concentration verification analyses for both sampling days of the H-25425 sample preparation. Preparation Day Nominal mg/mL Measured3 mg/mL Average % Nominal CV % 4-Sept-2002 10-Sept-2002 2b 20 200 2b,c 20 200 2.05, 2.11 16.9, 17.3 190, 191 2.02, 1.79 21.9,21.7 187, 194 104.0 85.5 95.5 95.5 109.0 95.5 2 2 0.4 8 1 3 a Duplicate samples pet level were analyzed. C.V. calculated to verify uniformity of mixture, b Reported results corrected for recovery of the spiked sample at the level (refer to Table I). c Reported results are average of all analyses on the dosing formulations. CV reported based bn the original analysis for the samples (76.0% and 71.5% of nominal, respectively). The results for samples prepared on September 4, 2002 indicate that the test substance was at the targeted levels (target = 14.5% o f nominal) and adequately mixed (CV's less than 10) for all H-25425 samples. Test substance was not detected in the 0 mg/mL samples. The results for samples prepared on September 10, 2002 indicate that the test substance was at the targeted levels (target = 9.0% o f nominal) and adequately mixed (CV's less than 10) for all H-25425 samples. The reported results for the 2 mg/mL and 20 mg/mL levels are based on an average from 3 samplings from both dosing formulations. The initial sampling was lower than expected (76.0% and 71.5% o f nominal, respectively), therefore, the remainder o f the dosing preparation at both levels was re-sampled but not properly re-dispersed before taking the samples. This analysis was lower than the original result for the 2 mg/mL sample (22.2% o f nominal) and higher than expected for the 20 mg/mL sample (123.5% o f nominal). The dosing suspensions were again dispersed and re-sampled for analysis. These results were higher than expected due to the previous poor samplings (188.0% and 132.0% o f nominal, respectively). All results for the 3 samplings were then averaged and reported as the concentrations for the levels. Test substance was not detected in the 0 mg/mL samples. E. Analytical Conclusions Results from the analysis o f the test substance dosing formulations during the study indicate that the test substance was mixed properly, at the targeted levels except for the initial sampling o f the 2 and 20 mg/mL levels and stable under the conditions o f the study. Test substance was not found in the 0 mg/mL samples. 19 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 DEVELOPMENTAL TOXICOLOGY A. Maternal Findings 1. Mortality (Table 6) There was no compound-related mortality at any level tested; all animals on study survived to scheduled sacrifice. 2. Body Weights and Body Weight Changes (Tables 2 and 3, Appendices B and C) There were no compound-related effects on body weight or weight changes at any level tested. Mean body weight gain over the dosing period (days 6-21G) was 91,102, and 94% o f the control group value at 10, 100, and 1000 mg/kg/day, respectively. Mean absolute final body weights were 96.5, 99.8, and 97.2% o f the control group value at the same respective levels. During the predosing period, mean body weight changes were slightly but significantly lower over days 4-6G at 100 and 1000 mg/kg/day. These instances o f statistical significance are considered to have occurred by chance and clearly are not indicative o f any compound-related 3. Food Consumption (Table 4, Appendix D) There was no compound-related effect on maternal food consumption; data were generally comparable across all groups. Mean food consumption over the dosing period (days 6-21G) was 97.8, 98.9, and 97.8% o f the control group value at 10,100, and 1000 mg/kg/day, respectively. 4. Clinical Observations (Table 5, Appendix E) There were no compound-related clinical observations at any level tested. Occasional occurrences o f alopecia were reported for all groups on study. 5. Postmortem Findings (Appendix F) There were no compound-related maternal gross postmortem observations at any level tested. Occurrences o f alopecia generally consistent with the clinical observations were reported for all groups on study. 20 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 B. Fetal Findings 1. Mortality (Table 6, Appendix G) There was no compound-related in utero embryofetal mortality. There were no dead fetuses and incidences o f resorptions were low across all groups on study. 2. Body Weight and Sex Ratio (Table 6, Appendices G and H) There were no compound-related effects on mean fetal weight or sex ratio; data were comparable across all groups on study. 3. Malformations (Table 7, Appendix H) There were no compound-related fetal malformations. Two fetuses from two litters at 1000 mg/kg/day had malformations; one fetus was affected with gastroschisis and a kidney was absent from one fetus. Despite the fact that these fetuses are in the 1000 mg/kg/day level, these findings are not considered compound-related. Both o f these malformations occurred as single incidences and no dose-response relationship was evident. 4. Variations (Table 8, Appendix H) There were no compound-related fetal variations; incidence data for all specific endpoints were generally comparable across the study groups and there was no statistical significance detected for any endpoint. 21 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 CONCLUSIONS Under the conditions o f this study, there was no evidence o f any maternal or developmental toxicity at any level tested. The NOEL for maternal and developmental toxicity was, therefore, considered 1000 mg/kg/day. RECORDS AND SAMPLE STORAGE Laboratory-specific or site-specific raw data, such as personnel files and equipment records were retained by the facility where the work was done. A sample o f the test substance was collected for archive purposes and retained at Haskell Laboratory. Specimens, raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. Characterization data (percent purity, composition, and known impurities) will be stored at a Sponsor facility, Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. Characterization data used to support test substance stability was retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. 22 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats REFERENCES DuPont-11347 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 o f 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 o f Renal Development in Late Gestation o f Rats: The Effect o f 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 o f Trend Tests to Determine a No-Observable-Effect Level in Animal Safety Studies. Journal o f the American College o f Toxicology 14(2):158-168. 7. Haseman, J.K. and Hogan, M.D. (1975). Selection o f 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 o f Mixed Model Analysis. The Journal o f 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 o f Subchronic and Chronic Exposure Studies. Paynter, O.E. et al. United States Environmental Protection Agency, Office o f Pesticide Programs, Washington, D.C., 20460. EPA-540/9-85-020, June 1985. 13. Risk Assessment o f Notified New Substances Technical Guidance Document (XI/283/94-EN), Chapter I, Sections 2.24 and 2.25. 23 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLES 24 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats TABLE 1 DuPont-11347 SUMMARY OF DOSING SOLUTION ANALYSES Sample Type/Date____________________ Dosing Concentrations and Stability of H-25425 (mg/mL) Homogeneitv/26-Aug-2002 Top Nominal: Middle Bottom Average Measured Conc.c Average Percent N om inal Standard Deviation0 Coefficient of Variation0 Stabilitv/26-Aug-2002 5-hour Room Temperature Homoeeneitv/29-Aus-2002 Top Middle Bottom Average Measured Cone.0 Average Percent Nominal0 Standard Deviation0 Coefficient of Variation0 Stabilitv/29-Aug-2002 5-hour Room Temperature 2.00 1.32a (66.0)b 1.26a (63.0) 1.26a (63.0) 1.28 (64.0) 0.04 3% 1.09a (54.5) 2.1 l a (105.5) 2.25a (112.5) 2.23a (111.5) 2.20 (110.0) 0.07 3% 2.2 l a (110.5) 20.0 14.1a (70.5) 14.9a (74.5) 14.6a (73.0) 14.6 (73.0) 0.40 3% 13.9a (69.5) 16.1 (80.5) 16.1 (80.5) 17.3 (86.5) 16.5 (82.5) 0.69 4% 17.5 (87.5) 200 179 (89.5) 185 (92.5) 204 (102.0) 189 (94.5) 13 7% 192 (96.0) 189 (94.5) 188 (94.0) 188 (94.0) 188 (94.0) 0.58 0.3% 189 (94.5) Concentration Verification^ 4-Sept-2002 10-Sept-2002 2.08a (104.0) 1.9ia,e (95.5) 17.1 (85.5) 21.8d (109.0) 191 (95.5) 191 (95.5) a All reported results corrected based on recovery o f the spiked sample (refer to Appendix A Table I). b Numbers in parentheses are the respective percent o f nominal values. c The average measured concentration, average percent o f nominal (in parentheses), standard deviation, and coefficient of variation o f top, middle, and bottom, d Duplicate samples submitted. Mean result reported. e Mean result for all analysis o f sample. Original analysis was lower than expected (2.0 mg/mL = 76.0% o f nominal and 20.0 mg/mL = 71.5% o f nominal). Duplicate re-sampling o f the dosing suspension analyzed and averaged with the original analysis. 25 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats ) DuPont-11347 GROUP DOSE mg/kg/day I0 II 10 III 100 IV 1000 0 238.1 6.76 20 238.6 8.01 20 237.4 7.27 22 237.7 6.70 20 TABLE 2 MEAN MATERNAL BODY WEIGHTS (grams) DAYS OF GESTATION 4678 9 257.2 8.17 20 255.9 9.40 20 256.8 10.22 22 256.8 6.39 20 272.1 10.06 20 270.8 9.72 20 268.8 11.21 22 269.8 8.47 20 276.1 10.52 20 275.2 9.56 20 273.8 11.01 22 273.6 8.03 20 281.1 12.96 20 278.2 10.00 20 278.5 10.63 22 278.1 7.77 20 285.9 11.90 20 281.9 10.48 20 284.3 10.55 22 282.6 8.44 20 10 291.9 12.73 20 288.4 9.98 20 290.6 11.62 22 288.4 10.78 20 Company Sanitized. Does not contain TSCA C8I 26 H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROUP DOSE mg/kg/day I0 II 10 III 100 IV 1000 11 298.7 13.84 20 294.4 10.73 20 296.7 12.07 22 297.2 10.07 20 TABLE 2 (Continued) MEAN MATERNAL BODY WEIGHTS (grams) DAYS OF GESTATION 12 13 14 15 16 305.0 12.94 20 300.5 11.79 20 303.1 11.58 22 302.3 10.71 20 311.1 15.13 20 306.4 12.38 20 309.4 13.39 22 308.2 10.51 20 317.3 15.79 20 311.2 11.34 20 315.6 13.20 22 313.6 10.91 20 325.0 15.64 20 318.8 13.33 20 324.3 13.52 22 322.2 12.17 20 336.2 16.78 20 329.8 13.74 20 333.9 15.12 22 331.3 13.41 20 17 350.0 17.72 20 343.3 15.43 20 348.9 15.93 22 344.2 14.87 20 Company Sanitized. Does not contain TSCA CBI 27 H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 2 (Continued) MEAN MATERNAL BODY WEIGHTS (grams) GROUP DOSE mg/kg/day 18 DAYS OF GESTATION 19 20 21 I0 II 10 III 100 IV 1000 366.6 19.34 20 359.1 20.40 20 365.4 17.51 22 360.2 17.39 20 381.3 21.34 20 371.6 21.24 20 382.1 18.34 22 374.5 21.45 20 399.3 21.26 20 386.5 26.86 20 398.6 20.98 22 391.5 23.94 20 424.6 25.60 20 409.7 29.32 20 423.8 23.17 22 412.5 27.44 20 21b 324.0 18.80 20 318.4 16.44 20 323.3 18.52 22 318.3 14.76 20 Data arranged: Mean Body Weights (grams) Standard Deviation Number in Group a Data from non-pregnant females were excluded. b Body weight calculated using the final body weight minus the weight of the products of conception. No statistically significant trends (linear contrast of means); p < 0.05. Company Sanitized. Does not contain TSCA CB! 28 I H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROUP DOSE mg/kg/day I0 II 10 III 100 IV 1000 TABLE 3 MEAN MATERNAL BODY WEIGHT CHANGES (grams)a DAYS OF GESTATION 0-4 4-6 6-8 8-10 10-12 12-14 19.1 5.56 20 17.3 5.18 20 19.4 6.90 22 19.1 4.44 20 14.9 2.83 20 14.9 3.32 20 12.0* 4.12 22 13.0* 4.99 20 9.1 5.20 20 7.4 3.70 20 9.7 3.59 22 8.2 3.14 20 10.8 4.54 20 10.1 4.06 20 12.1 3.77 22 10.3 4.84 20 13.1 5.24 20 12.2 4.67 20 12.5 4.08 22 13.9 3.78 20 12.3 5.69 20 10.6 2.70 20 12.5 3.93 22 11.3 3.59 20 14-16 18.9 3.71 20 18.6 4.49 20 18.4 4.41 22 17.7 3.71 20 Company Sanitized. Does not contain TSCA CBi 29 H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 3 (Continued) MEAN MATERNAL BODY WEIGHT CHANGES (grams) GROUP DOSE mg/kg/day 16-18 DAYS OF GESTATION 18-21 6-21 6-21& I0 11 10 III 100 30.4 5.87 20 29.3 10.70 20 31.5 7.54 22 58.1 9.50 20 50.6 15.59 20 58.4 10.56 22 152.6 18.81 20 138.9 24.86 20 155.0 16.39 22 52.0 12.27 20 47.6 10.78 20 54.5 13.62 22 IV 1000 28.9 5.59 20 52.4 12.63 20 142.7 23.30 20 48.4 13.09 20 Data arranged: M e a n B ody Weights (grams) Standard Deviation Number in Group a Data from non-pregnant females were excluded. b 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. Company Sanitized. Does not contain TSCA CBI 30 H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROUP DOSE mg/kg/day I0 II 10 III 100 IV 1000 TABLE 4 MEAN MATERNAL FOOD CONSUMPTION (grams/day) DAYS OF GESTATION 4-6 6-8 8-10 10-12 12-14 14-16 23.9 2.67 20 23.5 2.44 20 23.3 1.96 22 23.7 2.01 20 23.7 4.97 20 23.8 2.04 20 24.4 2.04 22 23.8 1.93 20 26.2 3.53 20 25.0 2.08 20 25.2 2.27 22 24.9 2.04 20 26.2 2.77 20 25.1 2.79 20 26.0 2.09 22 26.0 2.27 20 26.5 3.42 20 26.5 2.29 20 26.5 2.07 22 26.4 1.76 20 27.8 2.79 20 27.9 2.75 20 27.6 2.75 22 27.3 1.84 20 16-18 30.7 3.08 20 30.3 3.35 20 30.3 2.03 22 30.1 3.28 20 Company Sanitized. Does not contain TSCA C8I 31 H-25425: Developmental Toxicity Study in Rats TABLE 4 (Continued) MEAN MATERNAL FOOD CONSUMPTION (grams/day) ______DAYS OF GESTATION GROUP DOSE 18-21 ________ mg/kg/day ____________ 6-21 I 0 30.1 27.5 3.58 2.50 20 20 II 10 III 100 28.7 4.04 20 29.3 3.72 22 26.9 2.29 20 27.2 1.73 22 IV 1000 28.9 4.02 20 26.9 1.99 20 Data arranged: Mean Food Consumption (grams/day) Standard Deviation Number in Group a Data from non-pregnant females were excluded. No statistically significant trends (linear contrast of means); p < 0.05. DuPont-11347 Company Sanitized. Does not contain TSCA CBI 32 ) H-25425: Developmental Toxicity Study in Rats TABLE 5 CLINICAL OBSERVATIONS DAY OF GESTATION OBSERVATION : GROUP : DOSE (mg/kg/day) : NO. EXAMINED : I 0 22 6-21 ALOPECIA 8 No statistically significant trends (Cochran-Armitage test); p < 0.05. Note: During the pretest period (days 4-5G), all animals appeared normal. II 10 22 2 DuPont-11347 III IV 100 1000 22 22 43 Company Sanitized. Does not contain TSCA CBI 33 H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 6 REPRODUCTIVE OUTCOME Group: Dose (mg/kg/day): N o . Mated N o . Pregnant No Delivered Early N o . Deaths No. With Total Resorptions No. Litters I 0 22 20 0 0 0 20 II 10 22 20 0 0 0 20 hi 100 22 22 0 0 0 22 IV 1000 22 20 0 0 0 20 Mean Corpora Luteaa 15.8 (2.1)* 15.3 (3.4) 15.3 (1.5) 15.5 (3.3) Implantations 14.3 (1.8) 13.3 (3.1) 14.5 (1.4) 13.5 (3.3) Resorptions: Total Early Late 0.2 (0.4) 0.2 (0.4) 0.0 0.2 (0.4) 0.2 (0.4) 0.0 0.1 (0.4) 0.1 (0.4) 0.0 0.3 (0.6) 0.2 (0.5) 0.1 (0.3) Dead Fetuses 0.0 0.0 0.0 0.0 Live Fetusesc : Total Males Females 14.2 (1.8) 7.4 (2.5) 6.8 (2.2) 13.2 (3.1) 7.0 (2.4) 6.2 (2.3) 14.4 (1.5) 7.5 (2.4) 6.9 (1.8) 13.3 (3.3) 7.2 (2.2) 6.1 (2.4) Mean Fetal Weight: Total 5.55 (0.34) 5.53 (0.29) 5.48 (0.24) 5.50 (0.31) Sex Ratio`S 0.52 (0.15) 0.52 (0.13) 0.51 (0.14) 0.52 (0.17) a Statistical analyses are not conducted on mean, corpora lutea data; these data are presented for information only. b Standard deviation is reported in parentheses. c Statistical analyses are only conducted on the mean total number of live fetuses per litter. The mean number of males and females are presented for information only. d Number male fetuses/total number fetuses per litter. 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. No significant trends were detected; p < 0.05. 34 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 7 INCIDENCE OF FETAL MALFORMATIONS Group : Dose (mg/kg/day): I 0 II III 10 100 IV 1000 EXTERNAL N o . Examined3 Gastroschisis No. Affected 283 [20] __ b 0[0] 263 [20] --0 [0] 316 [22] --o [0] 265 [20] 1 11) 1 [1] VISCERAL N o . Examined Kidney - Absent No. Affected 147 [20] --0[0] 136 [20] --0[0] 164 [22] --0[0] 138 [20] 1 (1) 1 [1] HEAD N o . Examined No. Affected 147 [20] 136 [20] 164 [22] 0 [0] 0 [0] 0 [0] 138 [20] 0 [0] SKELETAL N o . Examined No. Affected 283 [20] 263 [20] 316 [22] 0[0] 0[0] 0 [0] 265 [20] 0 [0] TOTAL NUMBER AFFECTED 0 (0) 0(0) 0(0) 2 (2) a Number examined and affected, including the number affected with the listed malformations are expressed as Fetuses[Litters] or Fetuses (Litters). b For ease of reading, zeros have been replaced with dashes for the listed malformations. Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam type are presented for information only. No significant trends were detected. 35 Company Sanitized. Does not contain TSCA C SI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 8 INCIDENCE OF FETAL VARIATIONS Group : I II III IV Dose (mg/kg/day): 0 10 100 1000 DEVELOPMENTAL VARIATIONS EXTERNAL N o . Examined3 No. Affected 283 [20] 0 [0] 263 [20] 0 [0] 316 [22] 0 [0] 265 [20] o [03 VISCERAL N o . Examined No. Affected 147 [20] 0 [0] 136 [20] o [o] 164 [22] 0 [0] 138 [20] 0 [0] HEAD N o . Examined No. Affected 147 [20] 0[0] 136 [20] 0 [0] 164 [22] 0[0] 138 [20] 0 [0] SKELETAL N o . Examined Rib - Rudimentary Cervical Rib - Supernumerary No. Affected 283 [20] 1 (1) 6 (3) 6 [3] 263 [20] __ 5 (2) 5 [2] 316 [22] ----- 0 [0] 265 [22] --- 13 (6) 13 [6] TOTAL WITH DEVELOPMENTAL VARIATIONS 6 (3) 5 (2) 0 (0) 13 (6) 36 Company Sanitized. Does not contain TSCA CBI H-2S425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 8 (Continued) INCIDENCE OF FETAL VARIATIONS Group : Dose (mg/kg/day): I 0 II 10 III 100 VARIATIONS DUE TO RETARDED DEVELOPMENT EXTERNAL No . Examined No. Affected 283 [20] 0 [0] 263 [20] 0 [0] 316 [22] o [0 ] IV 1000 265 [20] 0 [0] VISCERAL N o . Examined Kidney Small Papilla - Size 2 Papilla - Size 3 No. Affected HEAD No . Examined No. Affected SKELETAL N o . Examined Wavy rib(s) Skull - Retarded Ossification Sternebra - Retarded Ossification Vertebra - Retarded Ossification No. Affected 147 [20] 136 [20] 164 [22] 138 [20] --4 (4) 4 [4] 1 (1) 4 (3) 5 [3] --3 (3) 3 [31 --2 (2) 2 [2] 147 [20] 0 [0] 136 [20] 0 [0] 164 [22] 0 [0] 138 [20] 0 [0] 283 [20] 1 (1) 16 (7) 1 (1) - 100 (18) 107 [18] 263 [20] --- 10 (4) 1 (1) 114 (19) 117 [19] 316 [22] --- 26 (10) 2 (2) 125 (22) 133 [22] 265 [20] --- 13 (7) --- 98 (19) 103 [19] 37 Com piny Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TABLE 8 (Continued) INCIDENCE OF FETAL VARIATIONS Group: Dose (mg/kg/day): I 0 II 10 TOTAL WITH VARIATIONS DUE TO RETARDED DEVELOPMENT 108 (18) 121 (19) III IV 100 1000 135 (22) 105 (19) TOTAL NUMBER FETUSES WITH VARIATIONS 113 (18) 124 (19) 135 (22) 119 (19) a Number examined and affected, including the number affected with the listed variations, are expressed as Fetuses[Litters] or Fetuses (Litters). b For ease of reading, zeros have been replaced with dashes for the listed variations. Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam are presented for information only. No significant trends were detected. 38 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDICES 39 Company Sanitized. Does not contain TSCA CB) H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX A Analytical Data 40 Company Sanitized. Does not contain TSCA C8i H-25425: Developmental Toxicity Study in Rats DuPont-11347 Table I. Recovery of H-25425 Added to Dosing Vehicle_______ Sample ______ mg/ml H-25425______ Percent Type___________ Nominal_____ Measured Nominal Recovery(A) 1.99 1.64 82.4 Recovery 2.16 1.78 82.4 Recovery 2.84 2.15 75.7 Recovery 2.66 2.30 86.5 Re c o v e r y 2.66 2.27 85.3 Rec o v er y 00 2.98 2.52 84.6 Mean 82.8 3.8, C.V.5% Recovery Recovery Re c o v e r y Recovery Recovery Recovery 19.0 16.7 87.9 19.8 20.5 103.5 20.8 19.1 91.8 19.4 19.2 99.0 19.4 19.7 101.5 19.5 19.0 97.4 Mean 96.9 5.9, C.V. 6% Recovery Recovery Recovery Recovery 187 171 91.4 189 200 105.8 190 181 95.3 188 183 97.3 Mean 97.5 6.1, C.V. 6% (A) Processed with homogeneity/concentration verification samples from dosing prepared August 26,2002. (B) Processed with homogeneity/concentration verification samples from dosing prepared August 29,2002. (C) Processed with concentration verification samples from dosing prepared September 4, 2002. (D) Processed with concentration verification samples from dosing prepared September 10, 2002 (E) Processed with re-sampling of concentration verification samples from dosing prepared September 10, 2002. (F) Processed with second re-sampling o f concentration verification samples from dosing prepared September 10,2002. 41 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 Table II. Homogeneity/Concentration Verification and Stability of H-25425 in Dosing Suspensions Sample mg/mL H-25425 Percent Type___ Nominal Measured Nominal 26-Aug-2002 Homogeneity Control Top M iddle Bottom Top M iddle Bottom Top M iddle Bottom 5 H our(d ) 29-Aug-2002 Homogeneity Control Top M iddle Bottom Top M iddle Bottom Top M iddle Bottom 5 H o u r (d ) 0.00 2.00(B) 2.00(B) 2.00(B) 20.0(B) 20.0(B) 20.0(B) 200 200 200 2.00(B) 20.0(B) 200 0.00 2.00(B) 2.00(B) 2.00(B) 20.0 20.0 20.0 200 200 200 2.00(B) 20.0 200 ND(A) 1.32 1.26 1.26 M e a n iQ : 1.28 0.04 C.V.3% 14.1 14.9 14.6 M ean(C): 14.6 0.40 C.V.3% 179 185 204 M ean(c ) - 189 13 C. V 7% 1.09 13.9 192 ND(A) 2.11 2.25 2.23 M eaniC y 2.200.07 C.V.3% 16.1 16.1 17.3 M e a n ly u .5 0 .6 9 C.V.4% 189 188 188 M e a n ly 188 0.58 C. V. 0.3% 2.21 17.5 189 -- 66.0 63.0 63.0 (64.0%) 70.5 74.5 73.0 (73.0%) 89.5 92.5 102.0 (94.7%) 54.5 69.5 96.0 -- 105.5 112.5 111.5 (110.0%) 80.5 80.5 86.5 (82.5%) 94.5 94.0 94.0 (94.0%) 110.5 87.5 94.5 (A) Denotes not detected. (B) All reported results corrected based on recovery o f the spiked sample (refer to Table I). (C) The average measured concentration, average percent o f nominal (in parentheses), standard deviation, and coefficient of variation o f top, middle, and bottom. (D) Stability samples held 5 hours a room temperature. 42 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 Table III. Concentration Verification of H-25425 in Dosing suspensions Preparation Day Sample Type 4-Sept-2002 Concentration Verification^) mg/mL H-25425 Nominal Measured Control 0.0 n d (b ) Percent Nominal -- 2.00-l(c ) 2.00-2(c ) Mearfi-*); 20.0-1 20.0-2 Mean(D\- 200-1 200-2 M eanf): 2.05 2.11 2.08 0.05 C.V.2%o 16.9 17.3 17.1 0.28 C.V.2% 190 191 191 0.71 C.V. 0.4% 102.5 105.5 (104.0) 84.5 86.5 (85.5) 95.0 95.5 (95.5) 10-Sept-2002 Concentration V erification^) Control 0.0 ndO) -- 2.00-l(c ) 2.00-2(c ) M eanfP): 2.02(E) 1.79(E) 1.91 0.16 C.V 8% 101.0 89.7 (95.5) 20.0-1 20.0-2 M eanf): 21.9(E) 21.7(E) 21.8 0.14 C.V. 1% 109.5 108.5 (109.0) 200-1 187 93.5 200-2 194 97.0 191 4.9 C.V.3% (95.5) (A) Duplicate samples per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity o f mixture. (B) Denotes not detected. (C) All reported results corrected based on recovery o f the spiked sample (refer to Table I). (D) Mean result for analyses on duplicate samples. (E) Mean result for all analysis o f sample. Original analysis was lower than expected (2.0 mg/mL = 76.0% o f nominal and 20.0 mg/mL = 71.5% o f nominal). Duplicate re-sampling o f the dosing suspension analyzed and averaged with the original analysis. 43 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats Figure 1 Representative Analytical Calibration Curves DuPont-11347 Concentration, mg/mL Figure la : Calibration curve showing linear fit (line) to replicate peak height measurements (squares) for calibration solutions of H-25425 diluted with THF over a concentration range o f 2.1411 to 8.0886 mg/mL. 44 Company Sanitized. Does not contain TSCA C B I H-25425: Developmental Toxicity Study in Rats Figure 2 Representative HPLC/GPC/R1 Chromatography Chromatograms RID1 A, R ID A, Refractive Index Signal (082902S1\002-0202.D) nRIU DuPont-11347 4000 3000 2000 -- ,-- ,-- ,-- |-- r-- ,-- i-- |-- -i-- i-- I-- I-- I-- I-- '-- r- 1-- '-- 1-- I-- 1-- 1-- H-- r~ 0 2 4 6 8 10 12 14 mi Figure 2a: Representative HPLC/GPC/RI chromatogram of 0.00 mg/mL dosing suspension of H-25425. Figure 2b: Representative HPLC/GPC/RI chromatogram of 5.9475 mg/mL analytical reference solution of H-25425. 45 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats Figure 2 (continued) Representative HPLC/GPC/RI Chromatography Chromatograms DuPont-11347 Figure 2c: Representative HPLC/GPC/RI chromatogram o f200 mg/mL dosing suspension diluted to nominal concentration of 6.00 mg/mL of H-25425. The measured concentration of the representative solution is 190 mg/mL. Figure 2d: Representative HPLC/GPC/RI chromatogram of 189 mg/mL spiked dosing suspension diluted to nominal concentration of 6.00 mg/mL of H-25425. The measured concentration of the representative solution is 199 mg/mL. 46 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX B Individual Body Weights 47 Company Sanitized. Does not contain T SC A CBI H-2542S: Developmental Toxicity Study in Rats Individual Body Weights DuPont-11347 Explanatory Notes Note Reporting of body weight data that were collected prior to study start (day 6G) are limited to day 0 and day 4G because weight data are available for all animals on these days. Any other body weight data for the separate breeding lots o f animals collected on days prior to day 6G are available in the raw data. Footnote a Maternal body weight minus the weight o f the products o f conception. Abbreviations NP = Not Pregnant -----= No Data 48 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 0 663382 663385 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 663464 663465 663467 (NP) (NP) 232.0 237.0 249.0 246.0 235.0 231.0 244.0 238.0 231.0 243.0 242.0 232.0 244.0 235.0 230.0 225.0 238.0 240.0 240.0 245.0 234.0 247.0 INDIVIDUAL BODY WEIGHTS (grams) DAY 4 251.3 244.6 260.6 258.7 261.0 243.2 268.7 260.5 247.8 263.1 247.9 253.2 262.6 261.6 245.8 249.3 255.9 257.5 250.3 268.9 253.1 272.8 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 261.0 262.4 278.6 276.4 275.7 256.7 283.2 275.9 265.6 276.9 260.1 267.2 275.3 277.3 256.0 261.2 273.6 272.6 272.6 287.8 267.4 292.9 269.3 270.4 285.3 277.6 287.9 261.8 284.7 276.3 274.1 284.9 258.8 276.1 278.7 281.0 259.8 261.9 278.1 269.1 275.0 290.6 270.2 295.5 256.0 269.4 293.2 287.3 296.7 264.7 291.5 287.3 275.9 290.4 261.1 275.9 287.5 288.2 264.8 269.3 280.1 277.2 276.8 298.1 277.5 300.1 DuPont-11347 DAY 9 DAY 10 269.5 281.7 298.9 291.4 303.5 276.5 292.8 287.9 284.4 290.6 268.3 284.1 289.2 294.1 271.1 267.0 285.0 280.9 283.9 303.6 275.4 304.1 277.7 280.5 303.0 293.5 309.5 281.9 299.9 299.2 291.7 293.2 270.2 288.0 295.0 298.0 271.0 274.4 294.5 285.5 288.3 312.7 286.9 312.9 49 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 11 INDIVIDUAL BODY WEIGHTS (grams) DAY 12 DAYS OF GESTATION DAY 13 DAY 14 DAY 15 DAY 16 DAY 17 663382 663385 (NP) 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 (NP) 663464 663465 663467 283.7 276.4 305.2 300.6 322.6 287.4 308.2 306.0 294.0 305.9 275.0 297.8 304.0 311.2 280.2 279.5 295.0 291.1 291.1 318.1 288.0 319.5 297.9 275.5 313.7 305.0 326.5 291.7 321.1 310.8 305.9 310.7 285.7 302.5 312.1 315.9 290.2 287.6 299.4 288.7 278.7 321.0 292.1 322.3 289.6 267.5 324.6 311.6 337.3 297.2 324.6 316.6 314.3 322.5 289.5 301.6 309.6 320.6 292.9 293.0 310.3 299.8 285.9 334.0 300.9 331.3 302.1 269.3 334.9 314.4 344.9 306.4 326.3 325.3 314.8 323.9 292.3 313.1 317.0 329.8 293.7 297.1 315.3 305.4 286.0 344.3 308.1 337.0 310.7 269.8 337.2 320.3 350.2 315.5 338.4 335.8 327.5 335.0 299.4 318.1 327.3 336.4 301.1 306.0 319.5 308.2 285.3 349.4 317.7 345.3 320.2 268.1 349.9 338.2 368.7 326.6 348.3 347.0 339.1 347.3 309.8 332.3 330.9 351.1 314.8 313.1 328.8 318.2 283.0 359.7 325.0 354.9 333.0 262.3 363.6 348.0 379.7 337.1 363.7 362.5 355.6 359.8 321.8 342.9 344.3 365.5 323.7 328.6 343.3 336.1 288.3 378.3 339.4 373.4 50 Company Sanitized. Does not contain TSCA C BI H-25425: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 18 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY 21a 663382 663385 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 663464 663465 663467 (NP) (NP) 346.3 267.5 373.7 '370.5 393.9 344.8 384.4 383.4 381.9 380.9 337.1 359.8 359.3 379.4 339.4 338.9 360.4 354.4 292.5 395.6 356.5 391.1 362.2 268.3 385.6 388.1 421.3 357.7 400.6 404.5 391.7 398.7 348.2 373.1 368.9 391.6 357.3 350.2 374.7 365.7 296.3 411.0 370.6 403.6 383.2 267.1 398.8 399.6 437.8 377.4 417.3 419.6 410.6 417.1 366 .0 391.7 395.7 415.9 372.7 364.0 391.6 385.5 287.7 429.6 390.4 422.3 407.0 269.7 420.0 440.7 478.7 392.8 440.1 444.3 432.4 441.3 396.9 415.0 412.6 435.7 392.3 381.8 420.3 405.8 295.0 467.1 416.7 451.3 300.3 339.2 331.3 359.4 302.8 334.5 329.1 314.6 338.3 314.5 313.5 322.8 348.8 304.5 294.7 312.1 303.7. 346.5 321.5 348.7 DuPont-11347 51 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP II: 10 MG/KG/DAY ANIMAL NUMBER DAY 0 INDIVIDUAL BODY WEIGHTS (grams) DAY 4 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 (NP) (NP) 233.0 244.0 255.0 235.0 237.0 230.0 238.0 232.0 231.0 240.0 255.0 245.0 233.0 230.0 237.0 240.0 226.0 249.0 241.0 239.0 239.0 230.0 247.4 264.4 273.5 240.9 260.6 236.9 250.8 247,5 243.1 261.9 267.9 263.4 251.4 250.0 258.2 269.5 241.7 260.6 252.6 252.4 255.8 251.9 260.0 279.9 286.6 252.2 275.0 245.5 265.6 262.6 250.1 274.8 284.1 279.4 263.2 269.5 272.3 277.7 261.6 278.6 267.4 268.5 277.1 266.6 264.8 287.3 293.0 262.3 286.7 256.3 269.3 259.7 246.2 273.9 283.5 284.9 268.0 268.8 278.1 280.2 271.7 279.1 272.3 270.7 282.5 273.8 272.7 293.6 296.0 263.4 286.4 256.0 274.2 267.5 251.7 279.9 290.9 287.6 265.6 274.3 278.4 276.0 273.4 286.1 271.6 274.4 284.5 275.0 DuPont-11347 DAY 9 DAY 10 268.9 301.0 296.1 268.1 291.7 258.3 278.0 269.2 255.0 286.8 289.3 290.6 271.2 275.5 286.5 285.0 275.2 283.9 277.8 277.4 291.3 284.5 279.4 300.0 309.4 275.6 296.3 268.6 285.2 278.5 253.2 292.8 291.1 293.1 277.0 283.5 292.8 281.5 279.7 298.0 284.1 284.9 302.7 288.4 52 Company Sanitized. Does not contain TSCA C81 H-25425: Developmental Toxicity Study in Rats DuPont-11347 INDIVIDUAL BODY WEIGHTS (grams) GROUP II: 10 MG/KG/DAY ANIMAL NUMBER DAY 11 DAY 12 DAYS OP GESTATION DAY 13 DAY 14 DAY 15 DAY 16 DAY 17 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 (NP) (NP) 284.2 303.3 309.1 . 275.2 311.3 268.8 292.4 278.7 249.4 297.4 301.9 301.8 282.5 290.9 299.0 291.6 289.8 296.2 287.4 294.3 308.9 297.8 284.5 316.2 316.5 273.8 312.7 274.4 297.1 291.1 258.5 307.7 306.7 316.3 289.8 297.9 302.2 291.2 295.8 303.3 291.2 299.7 317.3 299.2 293.8 319.8 324.4 269.0 325.5 276.3 305.9 297.0 259.2 309.6 312.4 316.8 291.8 304.6 300.6 300.7 302.0 313.3 295.9 306.4 323.0 308.1 292.9 325.1 326.4 269.3 319.2 287.9 309.6 298.2 258.9 315.4 316.2 324.8 301.8 309.5 312.3 298.1 307.1 317.7 305.5 312.7 328.8 314.6 289.6 332.7 331.9 267.7 333.8 289.5 324.3 311.3 254.4 323.2 322.1 328.9 306.3 320.3 316.0 309.2 316.6 323.3 309.3 320.3 339.0 327.4 302.7 343.0 348.9 271.5 340.8 303.0 335.3 321.9 258.4 331.5 327.6 345.1 316.6 332.8 329.4 311.2 326.2 334.1 323.1 333.1 350.3 339.9 307.6 353.4 360.0 265.3 356.9 314.0 348.6 332.7 266.8 347.1 341.1 362.7 332.5 347.0 342.4 322.6 343.7 346.4 335.2 353.0 362.4 357.3 53 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP II: 10 MG/KG/DAY ANIMAL NUMBER DAY 18 DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY 213 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 (NP) (NP) 310.4 370.4 377.6 265.2 382.1 319.7 366.9 353.7 268.9 365.0 354.5 377.0 345.6 364.3 354.4 332.2 357.3 391.6 362.0 351.8 366.4 378.8 325.7 384.9 398.2 2 74.7 394.6 339.4 380.2 365.3 258.9 380.3 370.4 391.8 330.1 377.4 365.8 347.1 376.1 376.0 363.6 382.4 395.0 387.6 326.4 405.6 411.9 269.0 413.1 341.9 378.1 373.6 265.3 404.8 388.7 416.5 341.3 401.3 383.2 355.2 397.2 390.1 379.6 396.3 417.9 406.6 338.2 431.3 438.9 269.3 440.6 364.8 411.9 406.7, 279.0 426.6 410.6 450.3 360.1 425.7 407.1 371.1 423.0 417.6 402.2 423.8 422.6 420.0 306.3 336.1 345.4 -- 324.4 286.0 317.7 300.0 -- 317.0 324.8 342.6 276.9 327.2 319.1 319.6 320.4 326.5 315.6 320.1 320.0 322.0 DuPont-11347 54 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER DAY 0 DAY 4 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 235.0 250.0 236.0 233.0 232.0 234.0 230.0 250.0 234.0 241.0 244.0 240.0 241.0 233.0 231.0 230.0 225.0 253.0 231.0 242.0 240.0 237.0 255.4 270.9 268.2 248.4 233.6 248.4 249.4 270.0 256.5 253.5 265.2 253.5 259.0 258.4 261.2 248.3 250.2 275.6 242.3 257.2 269.1 255.0 262.0 283.3 282.0 265.0 248.4 265.0 262.1 293.5 269.7 263.9 276.9 267.5 269.7 264.1 270.6 261.0 256.4 283.6 248.8 269.6 281.2 269.1 272.4 288.4 288.4 274.7 258.4 266.0 261.0 298.4 275.2 276.5 280.8 271.6 274.5 269.6 276.6 267.8 264.7 284.9 250.9 273.9 284.5 264.9 271.2 291.8 294.6 279.8 262.6 273.1 269.7 299.0 283.7 281.9 286.8 274.6 279.5 276.3 277.7 270.6 269.6 287.3 253.2 278.2 289.1 277.5 DuPont-11347 DAY 9 DAY 10 277.7 296.7 304.0 280.6 268.5 274.2 273.3 305.7 284.3 289.2 292.9 282.5 285.5 279.6 283.8 279.6 273.6 293.1 266.6 285.2 296.6 282.1 284.0 303.5 301.5 289.3 277.6 281.8 283.7 311.1 301.1 295.7 301.4 284.9 286.5 282.9 295.7 278.8 284.1 298.6 261.8 295.4 307.7 287.0 55 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 INDIVIDUAL BODY WEIGHTS (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER DAY 11 DAY 12 DAYS OP GESTATION DAY 13 DAY 14 DAY 15 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 293.3 312.2 315.7 ' 292.9 282.5 288.7 291.7 323.6 298.5 297.5 305.0 291.1 292.5 287.0 297.7 285.8 292.4 303.7 269.6 301.6 312.2 292.7 299.6 319.7 313.9 299.8 287.3 297.5 293.7 332.4 309.2 309.2 308.5 297.5 297.5 293.3 309.5 298.3 293.1 305.9 281.6 307.4 317.5 295.9 309.3 329.5 321.8 306.6 292.2 302.0 300.6 338.4 316.0 315.5 319.6 301.5 302.4 294.8 315.4 300.7 299.3 311.8 280.5 316.6 326.8 305.8 312.6 340.8 328.8 309.5 299.5 305.7 306.3 342.4 315.1 321.9 324.2 305.9 315.4 307.3 324.0 304.4 306.8 315.2 289.4 321.8 334.2 311.4 310.6 343.0 335.1 318.9 312.9 313.8 318.0 354.4 329.3 337.1 332.5 319.3 317.8 315.3 330.3 314.4 313.1 329.5 294.6 331.4 342.5 320.7 DAY 16 332.3 354.9 345.1 327.0 323.7 326.9 321.0 366.2 336.5 343.3 340.7 321.3 327.7 321.5 346.9 323.3 317.3 340.5 300.3 344.3 355.8 330.1 DAY 17 336.4 373.3 357.2 342.9 338.4 337.9 335.1 386.8 349.6 359.2 357.8 341.0 339.9 343.9 364.1 336.9 339.8 351.4 313.4 355.2 370.9 345.6 56 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER DAY 18 DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY 2Ia 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 350.6 392.3 373.6 356.9 359.5 355.5 356.3 400.1 373.2 381.0 377.5 357.8 353.2 369.3 358.8 350.0 345.3 372.0 326.1 378.9 392.9 358.1 369.0 412.7 395.5 374.3 375.0 363.2 364.8 417.4 392.6 392.8 388.8 373.2 372.3 377.7 388.6 374.4 364.8 391.7 340.3 396.2 409.4 371.6 378.7 428.5 407.8 373.9 394.3 379.5 388.1 441.9 410.4 412.4 414.7 391.3 390.4 383.0 401.2 397.5 380.3 410.9 350.9 418.4 425.0 389.7 405.1 459.4 441.1 387.6 426.6 398.4 408.2 471.0 433.2 437.1 435.3 408.8 418.2 409.4 426.1 422.7 404.0 431.2 377.9 445.6 455.8 421.6 320.0 347.9 334.0 292.3 325.2 308.2 292.4 361.9 335.6 336.9 321.4 312.0 325.6 309.2 338.0 321.7 307.3 323.1 290.3 337.4 342.7 329.5 DuPont-11347 57 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 1000 MG/KG/DAY ANMAL NUMBER DAY 0 DAY 4 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 663381 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 (NP) (NP) 236.0 245.0 245.0 232.0 231.0 236.0 243.0 239.0 233.0 244.0 233.0 240.0 234.0 240.0 226.0 225.0 240.0 247.0 232.0 242.0 233.0 247.0 243.2 260.9 264.4 247.6 242.4 254.4 253.3 262.9 255.2 259.3 233.6 259.1 255.7 262.3 247.7 253.5 258.1 265.2 253.9 256.1 256.2 268.3 255.6 270.8 269.3 251.0 254.9 269.8 267.6 278.0 267.2 275.2 232.2 270.8 267.6 268.9 261.1 271.6 281.6 284.4 261.7 275.2 268.2 281.7 262.3 281.0 274.5 258.5 264.0 274.3 263.9 283.3 267.9 278.0 239.8 272.8 273.4 276.9 262.0 270.7 283.3 283.4 266.9 276.8 272.8 288.0 266.0 278.8 279.7 262.7 265.3 277.7 270.9 285.2 270.5 281.0 241.1 276.6 279.3 283.6 269.0 279.9 287.6 288.5 273.6 281.3 277.0 293.1 DuPont-11347 DAY 9 DAY 10 267.6 291.9 282.3 267.5 269.1 281.5 271.8 288.6 271.9 288.9 246.4 282.2 279.8 288.9 275.3 285.3 295.3 290.6 277.9 287.7 280.9 295.4 271.5 295.0 280.6 265.8 271.7 291.4 279.9 303.1 283.2 292.9 241.6 285.7 285.9 291.7 274.5 289.3 307.0 297.3 285.7 298.1 286.2 303.2 58 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 1000 MG/KG/DAY ANMAL NUMBER DAY 11 DAY 12 DAYS OF GESTATION DAY 13 DAY 14 DAY 15 DAY 16 DAY 17 663381 (NP) 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 (NP) 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 273.0 301.4 291.2 279.9 279.7 302.2 285.5 307.7 287.7 302.2 246.7 297.9 296.2 306.2 285.8 302.6 316.1 305.3 291.5 304.7 292.2 307.3 267.0 306.1 298.1 279.4 283.8 305.3 290.1 318.9 295.5 310.8 248.7 300.8 303.2 314.2 294.0 305.6 320.2 308.1 296.5 308.5 297.8 310.0 264.2 314.4 309.6 292.2 290.6 316.4 291.5 321.7 299.2 318.3 247.7 299.1 311.6 318.0 299.4 308.5 325.4 308.5 302.2 317.8 302.9 316.0 269.1 320.3 311.9 295.6 291.6 317.3 293.9 324.4 306.1 320.1 250.1 309.5 319.4 323.9 308.6 319.8 329.3 319.9 303.1 322.8 312.0 322.8 266.5 327.5 323.6 301.2 296.7 332.7 304.7 339.3 311.0 329.5 252.9 316.1 327.6 330.5 312.3 329.1 339.2 323.2 316.0 332.7 320.4 331.3 267.8 338.1 326.4 307.5 301.2 339.6 313.5 344.2 317.8 337.1 259.2 327.5 339.7 345.3 325.1 339.7 347.4 336.5 324.1 343.0 326.5 346.0 268.6 353.3 339.0 324.0 308.0 351.5 321.2 355.6 330.7 354.0 255.0 341.7 350.9 357.7 339.9 358.2 358.8 349.6 334.5 360.1 334.4 360.0 59 Company Sanitized. Does not contain TSCA CBI .a****, H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER DAY 18 DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY 2Ia 663381 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 (NP) (NP) 271.3 366.2 355.5 340.8 310.4 372.7 337.2 374.0 348.6 368.9 253.2 358.0 369.1 373.0 354.2 372.2 379.8 367.7 349.2 377.4 349.6 378.8 276.2 377.0 376.8 351.2 314.0 387.2 343.1 385.7 356.1 389.1 254.3 375.6 379.7 388.8 367.1 389.6 400.7 389.5 361.6 399.2 364.2 394.3 272.1 393.4 391.6 370.9 320.4 410.2 361.0 406.1 368.8 411.2 258.8 389.7 401.8 403.7 382.0 409.2 416.6 404.5 376.4 420.0 381.1 411.4 280.5 406.3 413.2 400.0 325.2 441.0 385.8 427.5 387.6 435.0 264.6 412.8 425.1 432.1 410.0 429.9 435.5 404.5 394.2 448.0 402.6 434.3 .... 310.9 321.9 297.4 316.6 324.8 310.7 339.5 299.0 326.5 -- 309.9 329.8 334.1 295.0 313.2 332.4 304.5 307.6 351.4 317.1 322.7 DuPont-11347 60 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX C Individual Body Weight Changes 61 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats Individual Body Weight Changes Explanatory Notes Footnote a Maternal body weight minus the weight o f the products o f conception. Abbreviations NP = Not Pregnant -----= No Data DuPont-11347 62 Company Sanitized. Does not contain TSCA CBJ H-25425: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 0-4 663382 663385 (NP) 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 (NP) 663464 663465 663467 19.3 7.6 11.6 12.7 26.0 12.2 24.7 22.5 16.8 20.1 5.9 21.2 18.6 26.6 15.8 24.3 17.9 17.5 10.3 23.9 19.1 25.8 INDIVIDUAL BODY WEIGHT CHANGES (grams) 4-6 9.7 17.8 18.0 17.7 14.7 13.5 14.5 15.4 17.8 13.8 12.2 14.0 12.7 15.7 10.2 11.9 17.7 15.1 22.3 18.9 14.3 20.1 DAYS OF GESTATION 6-8 8-10 10-12 -5.0 7.0 14.6 10.9 21.0 8.0 8.3 11.4 10.3 13.5 1.0 8.7 12.2 10.9 8.8 8.1 6.5 4.6 4.2 10.3 10.1 7.2 21.7 11.1 9.8 6.2 12.8 17.2 8.4 11.9 15.8 2.8 9.1 12.1 7.5 9.8 6.2 5.1 14.4 8.3 11.5 14.6 9.4 12.8 20.2 -5.0 10.7 11.5 17.0 9.8 21.2 11.6 14.2 17.5 15.5 14.5 17.1 17.9 19.2 13.2 4.9 3.2 -9.6 8.3 5.2 9.4 12-14 4.2 -6.2 21.2 9.4 18.4 14.7 5.2 14.5 8.9 13.2 6.6 10.6 4.9 13.9 3.5 9.5 15.9 16.7 7.3 23.3 16.0 14.7 DuPont-11347 14-16 18.1 -1.2 15.0 23.8 23.8 20.2 22.0 21.7 24.3 23.4 17.5 19.2 13.9 21.3 21.1 16.0 13.5 12.8 -3.0 15.4 16.9 17.9 63 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 16-18 S63382 653385 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 663464 663465 663467 ( NP) ( NP) 26.1 -0.6 23.8 32.3 25.2 18.2 36.1 36.4 42.8 33.6 27.3 27.5 28.4 28.3 24.6 25.8 31.6 36.2 9.5 35.9 31.5 36.2 INDIVIDUAL BODY WEIGHT CHANGES (grams) 18-21 60.7 2.2 46.3 70.2 84.8 48.0 55.7 60.9 50.5 60.4 59.8 55.2 53.3 56.3 52.9 42.9 59.9 51.4 2.5 71.5 60.2 60.2 DAYS OF GESTATION 6-21 6-21a 146.0 7.3 141.4 164.3 203.0 136.1 156.9 168.4 166.8 164.4 136.8 147.8 137.3 158.4 136.3 120.6 146.7 133.2 22.4 179.3 149.3 158.4 39.3 -- 60.6 54.9 83.7 46.1 51.3 53.2 49.0 61.4 54.4 46.3 47.5 71.5 48.5 33.5 38.5 31.1 -- 58.7 54.1 55.8 DuPont-11347 64 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 I NDI VI DUAL BODY WEIGHT CHANGES ( g r a m s ) GROUP I I : 1 0 MG/ KG/ DAY ANI MAL NUMBER 0-4 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 14-16 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 ( NP) ( NP) 14.4 20.4 18.5 5.9 23.6 6.9 12.8 15.5 12.1 21.9 12.9 18.4 18.4 20.0 21.2 29.5 15.7 11.6 11.6 13.4 16.8 21.9 12.6 15.5 13.1 11.3 14.4 8.6 14.8 15.1 7.0 12.9 16.2 16.0 11.8 19.5 14.1 8.2 19.9 18.0 14.8 16.1 21.3 14.7 12.7 13.7 9.4 11.2 11.4 10.5 8.6 4.9 1.6 5.1 6.8 8.2 2.4 4.8 6.1 -1.7 11.8 7.5 4.2 5.9 7.4 8.4 6.7 6.4 13.4 12.2 9.9 12.6 11.0 11.0 1.5 12.9 0.2 5.5 11.4 9.2 14.4 5.5 6.3 11.9 12.5 10.5 18.2 13.4 5.1 16.2 7.1 -1.8 16.4 5.8 11.9 12.6 5.3 14.9 15.6 23.2 12.8 14.4 9.4 9.7 16.1 5.3 7.1 14.8 14.6 10.8 8.4 8.9 9.9 -4.5 6.5 13.5 12.5 7.1 0.4 7.7 9.5 8.5 12.0 11.6 10.1 6.9 11.3 14.4 14.3 13.0 11.5 15.4 9.8 17.9 22.5 2.2 21.6 15.1 25.7 23.7 -0.5 16.1 11.4 20.3 14.8 23.3 17.1 13.1 19.1 16.4 17.6 20.4 21.5 25.3 65 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP I I : 1 0 MG/ KG/ DAY ANI MAL NUMBER 16-18 18-21 DAYS OF GESTATION 6-21 6-21a 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 ( NP) ( NP) 7.7 27.4 28.7 -6.3 41.3 16.7 31.6 31.8 10.5 33.5 26.9 31.9 29.0 31.5 25.0 21.0 31.1 57.5 38.9 18.7 16.1 38.9 27.8 60.9 61.3 4.1 58.5 45.1 45.0 53.0 10.1 61.6 56.1 73.3 14.5 61.4 52.7 38.9 65.7 26.0 40.2 72.0 56.2 41.2 78.2 151.4 152.3 17.1 165.6 119.3 146.3 144.1 28.9 151.8 126.5 170.9 96.9 156.2 134.8 93.4 161.4 139.0 134.8 155.3 145.5 153.4 46.3 56.3 58.8 -- 49.4 40.5 52.1 37.4 -- 42.2 40.7 63.2 13.7 57.7 46.8 42.0 58.8 47.9 48.3 51.6 42.9 55.4 DuPont-11347 66 Company Sanitized. Does not contain TSCA C81 /""N H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP III: 100 MG/KG/DAY animal NUMBER 0-4 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 20.4 20.9 32.2 . 15.4 1.6 14.4 19.4 20.0 22.5 12.5 21.2 13.5 18.0 25.4 30.2 18.3 25.2 22.6 11.3 15.2 29.1 18.0 6.6 12.4 13.8 16.6 14.8 16.6 12.7 23.5 13.2 10.4 11.7 14.0 10.7 5.7 9.4 12.7 6.2 8.0 6.5 12.4 12.1 14.1 9.2 8.5 12.6 14.8 14.2 8.1 7.6 5.5 14.0 18.0 9.9 7.1 9.8 12.2 7.1 9.6 13.2 3.7 4.4 8.6 7.9 8.4 12.8 11.7 6.9 9.5 15.0 8.7 14.0 12.1 17.4 13.8 14.6 10.3 7.0 6.6 18.0 8.2 14.5 11.3 8.6 17.2 18.6 9.5 15.6 16.2 12.4 10.5 9.7 15.7 10.0 21.3 8.1 13.5 7.1 12.6 11.0 10.4 13.8 19.5 9.0 7.3 19.8 12.0 9.8 8.9 13.0 21.1 14.9 9.7 12.2 8.2 12.6 10.0 5.9 12.7 15.7 8.4 17.9 14.0 14.5 6.1 13.7 9.3 7.8 14.4 16.7 15.5 DuPont-11347 14-16 19.7 14.1 16.3 17.5 24.2 21.2 14.7 23.8 21.4 21.4 16.5 15.4 12.3 14.2 22.9 18.9 10.5 25.3 10.9 22.5 21.6 18.7 67 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats I NDI VI DUAL BODY WEIGHT CHANGES ( g r a ms ) GROUP I I I : 1 0 0 MG/ KG/ DAY ANI MAL NUMBER 16-18 18-21 DAYS OF GESTATION 6-21 6-21 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 18.3 37.4 28.5 29.9 35.8 28.6 35.3 ,33.9 36.7 37.7 36.8 36.5 25.5 47.8 11.9 26.7 28.0 31.5 25.8 34.6 37.1 28.0 54.5 67.1 67.5 30.7 67.1 42.9 51.9 70.9 60.0 56.1 57.8 51.0 65.0 40.1 67.3 72.7 58.7 59.2 51.8 66.7 62.9 63.5 143.1 176.1 159.1 122.6 178.2 133.4 146.1 177.5 163.5 173.2 158.4 141.3 148.5 145.3 155.5 161.7 147.6 147.6 129.1 176.0 174.6 152.5 58.0 64.6 52.0 27.3 76.8 43.2 30.3 68.4 65.9 73.0 44.5 44.5 55.9 45.1 67.4 60.7 50.9 39.6 41.5 67.8 61.5 60.5 DuPont-11347 68 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats I NDI VI DUAL BODY WEIGHT CHANGES ( g r a m s ) GROUP I V: 1 0 0 0 MG/ KG/ DAY ANI MAL NUMBER 0-4 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 663381 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 ( NP) ( NP) 7.2 15.9 19.4 15.6 11.4 18.4 10.3 23.9 22.2 15.3 0.6 19.1 21.7 22.3 21.7 28.5 18.1 18.2 21.9 14.1 23.2 21.3 12.4 9.9 4.9 3.4 12.5 15.4 14.3 15.1 12.0 15.9 -1.4 11.7 11.9 6.6 13.4 18.1 23.5 19.2 7.8 19.1 12.0 13.4 . 10.4 8.0 10.4 11.7 10.4 7.9 3.3 7.2 3.3 5.8 8.9 5.8 11.7 14.7 7.9 8.3 6.0 4.1 11.9 6.1 8.8 11.4 5.5 16.2 0.9 3.1 6.4 13.7 9.0 17.9 12.7 11.9 0.5 9.1 6.6 8.1 5.5 9.4 19.4 8.8 12.1 16.8 9.2 10.1 -4.5 11.1 17.5 13.6 12.1 13.9 10.2 15.8 12.3 17.9 7.1 15.1 17.3 22.5 19.5 16.3 13.2 10.8 10.8 10.4 11.6 6.8 2.1 14.2 13.8 16.2 7.8 12.0 3.8 5.5 10.6 9.3 1.4 8.7 16.2 9.7 14.6 14.2 9.1 11.8 6.6 14.3 14.2 12.8 DuPont-11347 14-16 -1.3 17.8 14.5 11.9 9.6 22.3 19.6 19.8 11.7 17.0 9.1 18.0 20.3 21.4 16.5 19.9 18.1 16.6 21.0 20.2 14.5 23.2 69 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP I V: 1 0 0 0 MG/ KG/ DAY ANI MAL NUMBER 16-18 18-21 DAYS OF GESTATION 6-21 6-21a 663381 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 ( NP) (NP) 3.5 28.1 29.1 33.3 9.2 33.1 23.7 29.8 30.8 31.8 -6.0 30.5 29.4 27.7 29.1 32.5 32.4 31.2 25.1 34.4 23.1 32.8 9.2 40.1 57.7 59.2 14.8 68.3 48.6 53.5 39.0 66.1 11.4 54.8 56.0 59.1 55.8 57.7 55.7 36.8 45.0 70.6 53.0 55.5 24.9 135.5 143.9 149.0 70.3 171.2 118.2 149.5' 120.4 159.8 32.4 142.0 157.5 163.2 148.9 158.3 153.9 120.1 132.5 172.8 134.4 152.6 -- 40.1 52.6 46.4 61.7 55.0 43.1 61.5 31.8 51.3 -- 39.1 62.2 65.3 33.9 41.6 50.8 20.1 45.9 76.2 48.9 41.0 DuPont-11347 70 Company Sanitized. Does not contain TSCA C SI H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX D Individual Food Consumption 71 Company Sanitized. Does not contain TSCA CBI /t0***'. H-25425: Developmental Toxicity Study in Rats Individual Food Consumption Explanatory Notes Abbreviation NP = Not Pregnant DuPont-11347 72 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP I : 0 MG/ KG/ DAY ANI MAL NUMBER 4-6 663382 663385 663386 663389 663391 663399 663406 663408 663414 66341S 663421 663430 663431 663437 663439 663444 663448 663462 663463 663464 663465 663467 ( NP) ( NP) 21.2 21.6 26.0 26.6 28.2 22.6 23.4 26.9 25.6 23.5 18.3 24.1 25.0 25.0 19.5 25.0 23.4 20.0 21.3 24.4 21.6 26.8 INDI VI DUAL FOOD CONSUMPTION ( g r a ms ) 6-8 6.1 22.5 29.0 25.6 29.5 23.6 23.7 27.1 25.4 24.4 18.5 26.5 24.6 23.5 20.6 22.6 23.1 20.9 23.3 27.5 25.9 26.1 DAYS OF GESTATION 8-10 10-12 12-14 36.6 25.2 27.2 25.4 29.7 24,6 26.4 27.1 27.1 24,6 19.1 25.6 25.5 25.2 21.5 23.9 24.9 23.4 24.8 28.9 27.3 29.5 27.5 22.8 29.3 25.5 32.8 25.6 28.8 27.6 27.1 26.1 22.6 26.0 27.4 27.6 22.8 23.8 24.4 20.6 19.1 27.8 23.5 27.6 21.5 17.4 34.2 24.7 32.3 27.5 25.6 27.0 25.6 27.1 22.4 26.0 25.2 29.7 21.6 24.5 26.1 22.2 20.9 29.8 28.0 29.5 14-16 26.1 19.5 32.7 28.8 31.8 28.2 28.1 27.9 28.6 29.6 23.9 26.7 24.8 30.2 25.9 25.4 25.1 22.5 18.9 30.8 26.5 31.5 DuPont-11347 16-18 28.8 14.8 34.1 31.6 34.2 26.6 31.8 28.1 33.9 32.6 28.8 33.1 29.6 33.6 26.5 27.8 26.5 26.3 22.9 33.0 31.4 35.8 73 Company Sanitized. Does not contain TSCA CBJ H-25425: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 18-21 INDIVIDUAL FOOD CONSUMPTION (grams) DAYS OF GESTATION 6-21 663382 663385 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 663464 663465 663467 ( NP) ( NP) 28.1 18.4 30.8 29.5 38.3 25.1 29.3 28.5 28.0 30.0 27.6 34.0 32.7 35.3 35.2 28.9 26.1 23.8 19.9 29.9 30.0 30.1 25.2 20.0 31.0 27.4 33.0 25.8 27.8 27.7 28.0 27.9 23.5 28.7 27.5 29.7 25.5 25.5 25.2 22.9 21.3 29.7 27.7 30.0 DuPont-11347 74 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP I I : 1 0 MG/ KG/ DAY ANI MAL NUMBER 4-6 I NDI VI DUAL FOOD CONSUMPTION ( g r a m s ) DAYS OF GESTATION 6-8 8-10 10-12 12-14 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 ( NP) ( NP) 22.6 21.3 24.1 19.6 25.0 18.3 28.3 25.0 18.9 26.6 20.8 23.4 22.6 23.6 22.0 25.9 23.3 23.0 20.5 23.1 27.6 22.8 22.8 26.7 26.6 21.9 27.9 21.3 25.1 22.9 16.7 24.8 22.3 23.4 21.3 23.4 22.4 21.1 24.0 23.4 23.1 22.9 27.7 23.4 22.3 26.3 25.9 21.9 26.4 20.3 26.3 26.3 20.1 29.1 23.4 23.5 22.5 25.5 26.0 26.1 24.1 23.8 24.4 25.1 28.5 25.0 21.4 24.7 27.6 20.4 29.1 20.8 26.5 26.0 18.6 28.3 23.9 29.0 22.1 27.0 23.4 22.2 25.8 20.9 23.8 26.1 29.3 24.1 23.7 26.2 26.8 15.6 30.1 22.4 27.4 26.7 18.4 28.3 24.8 27.6 24.1 30.0 24.4 27.5 25.5 24.925.9 26.3 31.6 26.8 14-16 25.4 26.9 28.7 18.8 29.4 22.3 30.6 28.8 18.6 28.3 26.3 31.7 25.0 30.8 26.7 24.1 27.1 26.1 26.6 30.2 33.6 28.9 DuPont-11347 16-18 23.8 29.2 34.4 14.3 31.4 25.9 31.3 31.4 22.0 31.2 29.9 32.9 24.6 34.6 35.1 29.6 30.8 24.9 29.1 30.5 33.9 32.4 75 Company Sanitized. Does not contain TSCA CBI H-2S425: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP II: 10 MG/KG/DAY ANIMAL NUMBER 18-21 DAYS OP GESTATION 6-21 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 663466 ( NP) ( NP) 24.8 29.9 34.3 ' 17.5 30.9 22.0 23.7 25.1 16.7 28.2 26.4 30.9 26.6 35.6 25.2 33.8 35.9 27.0 26.6 28.3 31.8 26.6 23.5 27.3 29.5 18.6 29.4 22.1 27.0 26.6 18.6 28.3 25.4 28.6 23.9 30.0 26.1 26.8 28.1 24.6 25.7 27.1 31.0 26.7 DuPont-11347 76 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats I NDI VI DUAL FOOD CONSUMPTION ( g r a m s ) GROUP I I I : 1 0 0 MG/ KG/ DAY ANI MAL NUMBER 4-6 6-8 DAYS OF GESTATION 8-10 10-12 12-14 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 20.5 24.9 25.3 25.3 20.5 23.6 22.9 28.1 23.9 20.5 24.3 23.5 25.6 22.2 24.1 22.3 22.2 21.8 20.7 21.8 24.5 23.5 23.5 27.0 28.0 26.1 22.9 24.1 23.4 28.2 24.5 25.2 25.8 21.0 26.7 23.8 24.4 22.1 21.9 24.2 20.6 24.8 24.6 24.7 21.8 28.1 24.4 25.1 22.7 24.3 25.8 27.4 27.3 25.9 27.6 24.2 30.5 24.3 25.0 22.0 24.5 25.1 20.8 24.8 27.4 25.4 27.2 30.5 28.6 25.3 23.7 25.4 25.8 28.8 28.7 25.2 29.7 25.5 24.7 24.2 26.5 23.3 24.4 25.0 23.1 24.5 26.5 25.8 27.0 31.6 24.0 24.9 24.6 26.6 26.0 26.1 26.3 28.1 27.9 25.0 26.4 25.5 28.3 23.1 25.5 25.3 24.0 28.9 29.4 28.8 14-16 26.1 31.3 25.0 27.7 28.6 26.0 25.7 32.4 29.2 31.8 28.3 26.2 25.6 25.9 30.6 21.9 24.0 26.8 26.3 31.5 29.0 26.2 DuPont-11347 16-18 27.3 33.6 29.1 28.3 28.0 27.9 29.7 33.0 31.6 35.2 30.8 29.9 30.7 30.2 31.7 30.0 29.7 29.8 26.9 30.9 31.6 30.3 77 Company Sanitized. Does not co nta in T S C A C B I H-25425: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP III: 100 MG/KG/DAY ANI MAL NUMBER 18-21 DAYS OF GESTATION 6-21 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 653420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 28.7 31.7 30.3 21.7 31.2 25.1 24.1 31.4 28.3 31.3 27.2 33.3 33.6 35.8 36.8 29.0 28.8 26.0 25.4 28.8 29.5 27.2 26.1 30.6 27.3 25.3 26.3 25.6 25.7 29.7 28.0 29.1 28.1 26.9 28.7 27.7 29.6 24.8 25.8 26.0 24.0 27.8 28.4 26.9 DuPont-11347 78 Company Sanitized. Does not contain TSCA CB H-25425: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP I V: 1 0 0 0 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 4 -6 6-8 8-10 10-12 12-14 663381 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 (NP) ( NP) 18.9 22.8 23.7 . 20.4 22.5 22.3 23.0 21.6 24.1 24.3 19.5 21.8 24.6 22.4 26.5 28.6 25.7 23.6 21.1 25.8 25.3 24.5 22.4 26.0 23.5 20.1 25.9 22.1 21.2 22.8 23.1 23.9 21.6 20.9 25.3 24.4 24.1 27.4 26.2 21.9 23.7 25.5 23.5 24.1 20.4 25.1 22.3 20.0 24.8 23.9 22.7 26.1 24.4 26.0 22.4 23.8 26.4 24.6 24.0 26.9 28.4 23.3 25.3 28.4 26.8 25.3 20.2 29.7 27.8 21.7 26.0 27.5 23.3 27.0 23.1 26.1 22.1 25.0 28.9 28.8 28.9 26.3 27.1 22.9 24.3 26.5 24.2 25.0 18.5 27.1 27.5 23.8 26.9 26.1 22.8 26.3 24.9 27.0 22.4 24.1 28.4 29.2 29.1 27.4 27.6 25.2 24.5 27.4 26.7 25.1 14-16 18.7 26.4 27.4 22.9 27.5 28.6 27.3 28.5 25.9 29.3 23.5 24.5 29.5 29.4 29.1 27.1 29.4 27.1 26.3 29.2 26.4 25.1 DuPont-11347 16-18 19.2 29.8 29.4 25.2 28.9 31.1 32.1 29.8 30.7 29.0 21.6 32.8 33.5 34.4 36.5 34.0 30.3 27.1 23.9 30.3 25.6 26.8 79 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP IV: 1000 MG/KG/DAY ANIMAL NUMBER 18-21 DAYS OF GESTATION 6-21 663381 663388 663394 663400 663401 663404 663409 663411 663419 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 (NP) ( NP) 21.0 26.0 27.0 26.0 27.2 30.3 26.2 25.9 24.2 30.5 27.3 33.7 34.9 34.8 36.0 35.1 28.8 23.6 26.0 30.1 26.3 25.3 20.1 27.1 26.4 23.0 26.8 27.3 25.2 26.6 25.1 27.6 23.3 26.9 29.9 29.7 30.1 29.6 28.3 24.4 24.9 28.3 25.7 25.2 DuPont-11347 80 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX E Individual Clinical Observations 81 Company Sanitized. Does not contain TSCA CBI H-2542S: Developmental Toxicity Study in Rats Individual Clinical Observations DuPont-11347 Explanatory Notes Footnote 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. r 82 Company Sanitized. Does not contain TSCA CBI Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP I : 0 M G/KG/DAY A N IM A L NUMBER: OBSERVATION 663382 A L O P E C IA BOTH FRONT PAW ALO PECIA BOTH FRONT LEG SA CRIFICED BY DESIGN 0 9 / 0 9 / 0 2 663385 SA CRIFICED BY DESIGN 0 9 / 0 9 / 0 2 663386 SA CRIFICED BY DESIG N 0 9 / 0 9 / 0 2 663389 ALOPECIA LEFT SID E SACRIFICED BY DESIGN 09/09/02 663391 A L O P E C IA BOTH FRONT PAW ALO PECIA BOTH FRONT LEG SA CRIFICED BY DESIGN 0 9 / 0 9 / 0 2 663399 ALOPECIA UNDERBODY ALOPECIA RIGHT SID E SA CRIFICED BY DESIG N 0 9 / 0 9 / 0 2 663406 ALO PECIA BOTH FRONT PAW A LO PECIA BOTH FRONT LEG SA C R IFIC ED BYDESIG N 0 9 / 1 0 / 0 2 IN DIV IDU AL C LINIC AL OBSERVATIONS3 DAYS OF G E ST A T IO N ON WHICH S IG N WAS OBSERVED 4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 a: , , , , , ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 b: , , , , , , ,11,12,13,14,15,16,17,18,19,20, a: , , , , , ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 b: , , , , , , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : / / / / / I t / / / I t t f / I21 a : 21t i l l / I I I I / / / / / t , . a : 2 1i t i t i I / / / I t t t t t tM a: I t i l i a:, I t i l i I I I I I / I I I I /<21!. I t I I / t I I ! ! #"21 a: b: , a: b: a: , 1 4 , 1 5 , , 1 6 , , 1 7 , . 1 8 , 1 9 , , 2 0 , , 2 1 ,14, 15,,16,,17, 18,,19,.20, , 1 4 , 1 5 , , 1 6 , , 1 7 , . 1 8 , 1 9 , , 2 0 , , 2 1 ,14,15,,16,.17, 18,.19,,20, / 1' jr 1r i' tp i' 1, 2 1 a: b: , a: , b: , a: I t ,17, ,I1 1 I ,17, , 1/ I t , ,18, 19,20,21 I 1 , ,18, 19,20, 1 1 III , ,21 a: , , , , , 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21 b: , , , , , 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, a: , , , , ,, , , ,13,14,15,16,17,18,19,20,21 b: , , , / ,, , , ,13,14,15,16,17,18,19,20, 21a : / / /I l I!! I I ! ! t ! ! ! * *- 83 DuPont-11347 H-25425: Developmental Toxicity Study in Rats GROUP I : 0 M G/KG/DAY A N IM A L NUMBER: OBSERVATION 663408 SA CRIFICED BY DESIG N 0 9 / 1 0 / 0 2 663414 SA CRIFICED BY DESIGN 0 9 / 1 0 / 0 2 663415 SA CRIFICED BY DESIGN 0 9 / 1 0 / 0 2 663421 A L O P E C IA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SA CRIFICED BY DESIG N 0 9 / 2 0 / 0 2 663430 SA CRIFICED BY DESIGN 0 9 / 1 1 / 0 2 663431 SA CRIFICED BY DESIGN 0 9 / 1 1 / 0 2 663437 SA CRIFICED BY DESIGN 0 9 / 1 1 / 0 2 663439 SA CRIFICED BY DESIGN 0 9 / 1 1 / 0 2 663444 SA CRIFICED BY DESIG N 0 9 / 1 1 / 0 2 663448 SACRIFICED BY DESIGN 0 9 / 1 2 / 0 2 IN D IV ID U A L C L IN IC A L OBSERVATIONS'3 DAYS OF G ESTA TIO N ON WHICH S IG N WAS OBSERVED 4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 a: t / / t f I t i i / / t t t / f21 ^ /ti t t/ / / t i t t i / / / t21 #21 t i t f i i i i i i i i i r i i / / / r f t / / / / / / / / / ,20,21 ^ * / / / # / / / / / / / / / / / #20, & / / / / # / / / / # / / / # / ,20,21 -b / # / / / / / / / / / / / # / 120, ^* ! Il II !t I ! ! t t I ! !I ,21 ,21^ t II II ! ! ! ! / / / ! I / # ^ i t t t t i i i i i i i i i i i 121 21& / Il It I t t I ! ///t !/ / ,21 ! I l I I t / / / # / / / / / / ,21 Il t II ! / # # # I ! t I l / ! I l I I ! t ! I I I I ! / / / ,21 DuPont-11347 Company Sanitized. Does not contain TSCA CB! 84 H-25425: Developmental Toxicity Study in Rats GROUP I: 0 M G /KG/DAY ANIMAL NUMBER: OBSERVATION ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 09/12/02 663463 ALOPECIA LEFT HIND QUARTERS ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 09/12/02 663464 SACRIFICED BY DESIGN 09/12/02 663465 SACRIFICED BY DESIGN 09/12/02 663467 SACRIFICED BY DESIGN 09/12/02 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: ! 1 / / i i / / /i 1 1 11 b: ! / t 1 i i /I l , 1 1 1 I a: / / ! 1 / / r 1 1 / / I I 1 b: / t / / f / i 1 1 1 / / 1 t a: / f1 1 ii i 1 !!/1 !1 ,19,20,21 ,19,20, ,19,20,21 ,19,20, , , ,21 a: 1 ! / J , , 1 0 , 11, 12, 13, 14, 15, 16,17, 18,19,20,21 b: I / / J , ,10, 11, 12, 13, 14, 15, 16,17, 18,19,20, a: / / / f 1 1 1 1 / / l 1 t I , ,20,21 b: / / f / I l ,20,1 1 1 ! 1 / ! 1 , a: / / r / I l t / 1 , 1 t I t , ,20,21 b: / t / / I t ,20,I / 1 1 / I ! / , a: t / / f I l ,211 / / 1 I 1 / / , , a : ,21t 1 r f 1 1 1 1 1 1 1 1 1 1 , , a: / / / / I l ,21I ! ! ! 1 ! l ! , , a: / / i / I t ,211 ! ! 1 1 I ! / , , DuPont-11347 Company Sanitized. Does not contain TSCA CBi 85 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats GROUP II: 10 MG/ K G / D A Y ANIMAL OBSERVATION NUMBER : 663383 SACRIFICED BY DESIGN 09/09/02 663392 SACRIFICED BY DESIGN 09/09/02 663393 SACRIFICED BY DESIGN 09/09/02 663395 SACRIFICED BY DESIGN 09/09/02 663396 SACRIFICED BY DESIGN 09/09/02 663398 SACRIFICED BY DESIGN 09/09/02 663405 SACRIFICED BY DESIGN 09/10/02 663407 ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 09/10/02 663413 SACRIFICED BY DESIGN 09/10/02 663417 SACRIFICED BY DESIGN 09/10/02 663423 SACRIFICED BY DESIGN 09/10/02 663424 SACRIFICED BY DESIGN 09/10/02 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: 1 1 1 1 1 t t t t i t 1 1 III ,21 a: 1i1ffi t i t i a: 111fti t i l i ,21t I 1 t t 1 / 1 I III ,21 a: / / /1 1 itili ! 1 I III ,21 a : 1 / / / / I l I I ! 1 / 1 t t 1 ,21 a : / /1 t l i t i l i //1 III ,21 a : / /t r i i t i l i / / / III ,21 a: ! ,1 1 t t ,11,12,13, 14,15, 16, 17,18,19, 20,21 b: 1 1 t / / ,10,11,12,13, 14,15, 16, 17,18,19, 20, a: 1 / / r I t t i t / / / III ,21 a: / I f t t Il II ! / 1 1 III ,21 a: /1/ t / I t i l i ! t / III ,21 a: / f t / t Il II ! ! ! I III a: / I f / f I t i l i 1 1 1 III ,21 ,21 86 DuPont-11347 H-25425: Developmental Toxicity Study in Rats GROUP I I : 1 0 M G/KG/DAY A N IM A L NUMBER : OBSERVATION 663427 SA C R IFIC ED BY DESIG N 0 9 / 1 1 / 0 2 663428 SA C R IFIC ED BY DESIG N 0 9 / 1 1 / 0 2 663429 SA C R IFIC ED BY DESIG N 0 9 / 1 1 / 0 2 663433 SA C R IFIC E D BY D E SIG N 0 9 / 1 1 / 0 2 663445 SA C R IFIC ED BY D ESIG N 0 9 / 1 1 / 0 2 663447 SA C R IFIC ED BY DESIG N 0 9 / 1 2 / 0 2 663451 SA C R IFIC ED BY DESIG N 0 9 / 1 2 / 0 2 663452 SA C R IFIC ED BY D ESIG N 0 9 / 1 2 / 0 2 663455 A L O P E C IA BOTH FRONT PAW ALO PECIA BOTH FRONT LEG SA C R IFIC ED BY DESIG N 0 9 / 1 2 / 0 2 663466 SA C R IFIC ED BY D ESIG N 0 9 / 1 2 / 0 2 IN DIV IDU AL CLINICAL OBSERVATIONS3 DAYS OF G E ST A T IO N ON WHICH S I G N WAS O BSERVED 4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 a : / / / / / / t , / / / , / , , , ,21 a: , , t i l l / 2 XI I t I I I I i t I & i i l t i i t i i / , t t i t 121 & Il II tt / / ! t / / / f / / / 21 3. Il II t! t // /f/ //// /2 1 ! I l I I ! / / / ! I / / / / / /21 ,21/ /I t I I I ! 1 I ttItI! a: ! I l II t I I I l I I I I ! ,21 a: , , , , , , , , , , , , , , / 19, 20,21 b: i i t t t t , , , , , , , /19/20/ a : , , , , , , , , , 19, 20,21 b: t i i r i i i i t t i i i i ,19,20, a : t i i i i i , , , , , , , , , , ,21 ^ , , , , , , , , / , , , , , , , ,21 DuPont-11347 Company Sanitized. Does not contain TSCA CBJ 87 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats GROUP III: 100 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 663384 SACRIFICED BY DESIGN 09/09/02 663387 SACRIFICED BY DESIGN 09/09/02 663390 SACRIFICED BY DESIGN 09/09/02 663397 SACRIFICED BY DESIGN 09/09/02 663402 SACRIFICED BY DESIGN 09/09/02 663403 SACRIFICED BY DESIGN 09/10/02 663410 SACRIFICED BY DESIGN 09/10/02 663412 SACRIFICED BY DESIGN 09/10/02 663416 SACRIFICED BY DESIGN 09/10/02 663418 SACRIFICED BY DESIGN 09/10/02 663420 SACRIFICED BY DESIGN 09/10/02 663425 SACRIFICED BY DESIGN 09/ll/02 INDIVIDUAL CLINICAL OBSERVATIONS9 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.: / / / / / / / / / / / / r t / / /21 / / /a: i r t t t t 1 1 r 1 t r 1 ,21 a: / / / / / / / / / / r r / / / / /21 a: 21t 1 1 1 1 t t t 1i r t 1t 11t / / /a: r1 1 1 t 1t1 1 t 1 1 t /21 a: , , , r , , , f , , , , , f , , ,21 a: 1 1 t 1 i t 1 / t t 1 / / / / / , 21 a: / / / 1 1 t i 1 1 r t 1 1 t i t 1 21 a: , , , # / / f f ,21 a: 1 1 t 1 1 t / r 1 t t t 1 r 1 / ,21 a: / / / / / , t / / / / , / , / , ,21 a: / / / / / / / / / t 1 1 r t , , ,21 88 DuPont-11347 H-25425: Developmental Toxicity Study in Rats GROUP I I I : 1 0 0 M G/KG/DAY A N IM A L NUMBER: O B SE R V A T IO N 663426 SA C R IFIC ED BY DESIG N 0 9 / 1 1 / 0 2 663438 SA C R IFIC ED BY D ESIG N 0 9 / 1 1 / 0 2 663440 A L O P E C IA BOTH FRONT PAW A L O PE C IA BOTH FRONT .LEG SA C R IFIC ED BY DESIG N 0 9 / 1 1 / 0 2 663441 SA C R IFIC ED BY D ESIG N 0 9 / 1 1 / 0 2 663443 SACRIFICED BY DESIG N 0 9 / 1 1 / 0 2 663449 A L O P E C IA BOTH FRONT PAW A LO PEC IA BOTH FRONT LEG SA C R IFIC ED BY D ESIG N 0 9 / 1 2 / 0 2 663450 A L O P E C IA BOTH FRONT PAW A LO PEC IA BOTH FRONT LEG SA C R IF IC E D BY D E SIG N 0 9 / 1 2 / 0 2 663456 SA C R IFIC ED BY DESIG N 0 9 / 1 2 / 0 2 INDIV IDU AL CLINICAL OBSERVATIONS3 DAYS OF G E ST A T IO N ON WHICH S IG N WAS OBSERVED 4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 a: / / / / / / / 1 / / l i t ! ! , ,21 a; / t / / * / / / / f I I I 1 / , ,21 a: / / / / / / / t / / I I I I ! , ,2 1 a: t i t / / / t t f / I I I 1 / , ,2 1 a: i i t / / / ! ! l 1 1 1 1 / ' , ,21 a: t i t / / / 1 1 ! / I I I / / , ,21 a: t t / / / t / t S / I I I a: i t / / / ! / / / / I I I b: / / /i / t tf l t III a: t / / / / / / l / / I I I b; / / / / / f / ! / ! I I I a; t i / / t ! / 1 / / I I I a: / / / / t / t t / / I I I a: / / / / f / l , / / I I I b: / / / / / J / t i / I I I a: / / / / / / / / / I I I a; / / / // t / / / III 1 1 , ,21 ! 1 ,20,21 I 1 ,20, / ! ,20,21 1 ,20, 1 1 , ,21 , 1 ,20,21 t I , ,2 1 ! I , 20, t t , ,21 / 1 , ,21 DuPont-11347 Company Sanitized. Does not contain TSCA C8I 89 H-25425: Developmental Toxicity Study in Rats GROUP III: 100 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 663457 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT FRONT LEG ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 09/12/02 663461 SACRIFICED BY DESIGN 09/12/02 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 ,9,10,11,12,13,14,15,16,17,18,19,20,21 b ,9,10,11,12,13,14,15,16,17,18,19,20, a <9, , , , , I , , , , , , a , ,10,11,12,13,14,15,16,17,18,19,20,21 y. , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a I , / / / , / / / , / / ,21 a: ,21 DuPont-11347 Company Sanitized. Does not contain TSCA C SI 90 Company Sanitized. Does not contain TSCA H-25425: Developmental Toxicity Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS3 GROUP IV: 1000 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 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 663381 SACRIFICED BY DESIGN 09/09/02 a: / / / / / / ,211 / ! ! 1 / / I I 1 663388 SACRIFICED BY DESIGN 09/09/02 a: t i t i i i ,21/ /1 1 1! I1I1 663394 SACRIFICED BY DESIGN 09/09/02 a: iiiiii ,21/ /1 1 !1 1111 663400 SACRIFICED BY DESIGN 09/09/02 a: iiiiii ,21/! 1 I ! 1t11 ! 663401 SACRIFICED BY DESIGN 09/09/02 a: iiiiii ,21/1 1 1 1 1111 1 663404 SACRIFICED BY DESIGN 09/10/02 a: iiiiii 211 1 1 1 / 1 ' 1 / I , 663409 SACRIFICED BY DESIGN 09/10/02 663411 SACRIFICED BY DESIGN 09/10/02 663419 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 09/10/02 a: l i l i l ,21' / 1 1 / 1 1 / t 1 a: IIIIII ,211 1 1 1 t ' l 1 1 1 a: i t i / 8 / 9 / 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20,21 b: / / / / 8 / 9 / 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, a: l i l i l / 1 l 1 I / / / / 1 ,21 a: I I I I I I I 1 1 1 1 / / / / I ,21 663422 SACRIFICED BY DESIGN 09/10/02 a: IIIIII 1 ' 1 1 1 / 1 / / 1 ,21 to 663432 O SACRIFICED BY DESIGN 09/11/02 a: I I I I I I 1 !I 1 !!1 //1 CD DuPont-11347 Company Sanitized. Does not contain TSCA CB! H-25425: Developmental Toxicity Study in Rats______________________________________________________________ GROUP I V : 1 0 0 0 M G/KG/DAY A N IM A L NUMBER: OBSERVATION 663434 ALOPECIA RIGHT SID E SA CRIFICED BY DESIG N 0 9 / 1 1 / 0 2 663435 SA CRIFICED BY DESIG N 0 9 / 1 1 / 0 2 663436 SA CRIFICED BY DESIG N 0 9 / 1 1 / 0 2 663442 SACRIFICED BY DESIGN 0 9 / 1 1 / 0 2 663446 A L O P E C IA BOTH FRONT PAW ALO PECIA BOTH FRONT LEG SA CRIFICED BY DESIGN 0 9 / 1 1 / 0 2 663453 SA CRIFICED BY DESIG N 0 9 / 1 2 / 0 2 663454 SA CRIFICED BY DESIG N 0 9 / 1 2 / 0 2 663458 SA CRIFICED BY DESIG N 0 9 / 1 2 / 0 2 663459 SACRIFICED BY DESIG N 0 9 / 1 2 / 0 2 663460 SA CRIFICED BY DESIGN 0 9 / 1 2 / 0 2 663468 SACRIFICED BY DESIG N 0 9 / 1 2 / 0 2 INDIV IDU AL CLINICAL OBSERVATIONS3 DAYS OF G E ST A T IO N ON WHICH S I G N WAS OBSERVED 4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 1 ,1 2 ,1 3 ,1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,2 1 a: , , , , , , , 3o: , , , , , , , ^ , , , , , , , ,,, ,, , ,,, , , ,17,18,19,20,21 , , ,17,18,19,20, / , , , , , ,21 , / , / / / , , , , , , , , , , ,21 cl , , , , , , , , , , , , , , , , , 21 ^ , , , , , , , , , , , , , , , , , 21 cl* , , , , , , a: , , , , , , ,,,,,, , , , , , , , , , , ,21 , , , , , , , , , , ,21 , , , , , , , , , , ,21 , , , , , , , , , , , , , , , , ,21 cl* , , , , , , , , , , , , , , , , , 21 cl* , , , , , , , , , , , , , , , , , 21 ^* , , , , , , , , , , , , , , , , , 21 ^* , , , , , , , , , , , , , , , , ,21 ^* , , , , , , , , , , , , , , , , ,21 92 DuPont-11347 H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX F Gross Postmortem Findings 93 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats Gross Postmortem Findings Explanatory Notes Abbreviations = No Data NAD = No Abnormalities Detected NP = Not Pregnant DuPont-11347 94 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROSS POSTMORTEM FINDINGS Group 1 : 0 mg/kg/day Animal Number 663382 663385 663386 663389 663391 NP 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 663463 NP 663464 663465 663467 Structure(s) Skin -- Skin Skin Skin Skin -- -- -- -- -- -- -- -- -- -- Skin Skin -- -- Findinq(s) Alopecia both front paws and legs NAD NAD Alopecia left side Alopecia both paws and right front leg Alopecia right side Alopecia both front legs NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Alopecia both front paws Alopecia both front paws and left front leg NAD NAD NAD 95 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROSS POSTMORTEM FIN D IN G S G roup II: 10 m g / k g / d a y Animal Number 663383 663392 663393 663395 663396 663398 663405 663407 663413 663417 663423 663424 663427 663428 663429 663433 663445 663447 663451 663452 663455 NP NP 663466 Structure(s) -- -- -- -- -- -- -- Skin -- -- -- -- -- -- -- -- -- -- Skin -- Skin __ Finding(s) NAD NAD NAD NAD NAD NAD NAD Alopecia abdomen NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Alopecia both front paws NAD Alopecia both front paws and legs NAD 96 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROSS POSTMORTEM FIN D IN G S Group III: 100 mg/kg/day Animal Number 663384 663387 663390 663397 663402 663403 663410 663412 663416 663418 663420 663425 663426 663438 663440 663441 663443 663449 663450 663456 663457 663461 Structure(s) -- -- -- -- -- -- Skin -- -- -- -- -- -- -- Skin -- -- Skin Skin -- Skin -- Findinq(s) NAD NAD NAD NAD NAD NAD Alopecia both front paws NAD NAD NAD NAD NAD NAD NAD Alopecia both front paws and legs NAD NAD Alopecia both front paws Alopecia both front paws NAD Alopecia both front paws NAD 97 Company Sanitized. Does not contain TSCA CB! H-25425: Developmental Toxicity Study in Rats DuPont-11347 GROSS POSTMORTEM FIN D IN G S G r o u p IV: 1000 m g / k g / d a y Animal Number 663381 663388 663394 663400 663401 663404 663409 663411 663419 NP 663422 663432 663434 663435 663436 663442 663446 663453 663454 663458 663459 663460 663468 NP Structure(s) _______ -- Skin -- -- -- -- -- Skin -- Skin -- -- -- -- -- -- -- -- -- -- F i n d i n g (s ) NAD NAD Alopecia chest NAD NAD NAD NAD NAD Alopecia both front paws and legs NAD NAD Alopecia right side NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD 98 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX G Individual Reproductive Data 99 Company Sanitized. Does not contain TSCA C S I H-25425: Developmental Toxicity Study in Rats Individual Reproductive Data Explanatory Notes Abbreviations NP = Not Pregnant . . . = No Data DuPont-11347 100 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 INDIVIDUAL REPRODUCTIVE DATA G ROUP I: 0 MG/ K G / D A Y ANIMAL NUMBER CORPORA LUTEA NIDATIONS 663382 6 6 3 3 8 5 (NP) 663386 663389 663391 663399 663406 663408 663414 663415 663421 663430 663431 663437 663439 663444 663448 663462 6 6 3 4 6 3 (NP) 663464 663465 663467 19 14 16 17 13 17 17 16 18 12 16 16 13 14 16 16 15 ... 20 13 17 16 ... 11 16 16 13 15 17 16 16 12 14 14 12 13 13 13 15 17 13 14 RESORPTIONS TOTAL EARLY LATE 00 . 00 11 00 11 00 00 00 00 00 00 11 00 00 00 00 00 . . . ... 00 00 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL WEIG H T (G) 0 16 5 11 0 11 6 5 0 15 4 11 0 16 8 8 0 12 7 5 0 15 8 7 0 17 11 6 0 16 6 10 0 16 10 6 0 12 10 2 0 14 8 6 0 13 6 7 0 12 5 7 0 13 7 6 0 13 8 5 0 13 5 8 0 15 7 8 0 17 7 10 0 13 5 8 0 14 2 12 5 .34 5 .62 5 .77 5 .86 5 .89 5 .60 5 .34 5 .96 5 .10 5 .60 5 .68 5 .48 5 .62 5 .34 4 .55 6 .08 5 .36 5 .56 5 .68 5 .63 Company Sanitized. Does not contain TSCA O CD ) H-25425: Developmental Toxicity Study in Rats ) DuPont-11347 INDIVIDUAL REPRODUCTIVE DATA GROUP II: 10 MG/KG/DAY ANIMAL NUMBER CORPORA LUTEA NIDA TIONS RESORPTIONS TOTAL EARLY LATE DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL WEIGHT (G) 663383 5 4 0 0 0 0 4 2 2 663392 15 14 0 0 0 0 14 7 7 663393 16 13 0 0 0 0 13 7 6 6 6 3 3 9 5 (NP) . ... ... ... 663396 19 16 0 0 0 0 16 4 12 663398 14 12 1 1 0 0 11 5 6 663405 15 15 ' 0 0 0 0 15 5 10 663407 20 18 0 0 0 0 18 11 7 6 6 3 4 1 3 (NP) ... ... ... 663417 19 16 0 0 0 0 16 8 8 663423 14 12 0 0 0 0 12 6 6 663424 17 16 1 1 0 0 15 10 5 663427 14 13 1 1 0 0 12 6 6 663428 16 14 0 0 0 0 14 7 7 663429 15 12 0 0 0 0 12 2 10 663433 10 7 0 0 0 0 7 52 663445 17 15 0 0 0 0 15 8 7 663447 14 13 0 0 0 0 13 5 . 8 663451 13 13 0 0 0 0 13 6 7 663452 17 15 0 0 0 0 15 7 8 663455 17 14 0 0 0 0 14 5 9 663466 19 14 0 0 0 0 14 8 6 6.11 5.54 5.68 5.70 5.70 5.09 4.67 5.45 5.58 5.69 5.45 5.44 5.73 5.63 5.65 5.44 5.34 5.47 5.76 5.47 Company Sanitized. Does not contain TSCA CBI 102 H-25425: Developmental Toxicity Study in Rats DuPont-11347 INDIVIDUAL REPRODUCTIVE DATA GROUP III: 100 MG/KG/DAY ANIMAL NUMBER CORPORA LUTEA NIDA TIONS RESORPTIONS TOTAL EARLY LATE DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL WEIG H T (G) 663384 13 12 1 1 0 0 11 7 4 5.98 663387 16 16 0 0 0 0 16 5 11 5.21 663390 17 16 0 0 0 0 16 9 7 5.06 663397 14 14 0 0 0 0 14 7 7 5.53 663402 16 14 0 0 0 0 14 9 5 5.68 663403 14 13 0 0 0 0 13 6 7 5.45 663410 18 17 0 0 0 0 17 8 9 5.33 663412 16 15 0 0 0 0 15 9 6 5.57 663416 15 15 1 1 0 0 14 10 4 5.43 663418 16 14 0 0 0 0 14 8 6 5.42 663420 17 16 0 0 0 0 16 5 11 5.65 663425 14 13 0 0 0 0 13 4 9 5.87 663426 13 13 0 0 0 0 13 7 6 5.46 663438 15 15 1 1 0 0 14 5 9 5.83 663440 14 13 0 0 0 0 13 10 3 5.40 663441 15 15 0 0 0 0 15 7 8 5.15 663443 14 14 0 0 0 0 14 6 8 5.54 663449 18 16 0 0 0 0 16 8 8 5.16 663450 14 13 0 0 0 0 13 5 8 5.43 663456 16 15 0 0 0 0 15 5 10 5.67 663457 17 17 0 0 0 0 17 5 12 5.28 663461 15 13 0 0 0 0 13 7 6 5.41 Company Sanitized. Does not contain TSCA CB1 103 H-25425: Developmental Toxicity Study in Rats DuPont-11347 INDIVIDUAL REPRODUCTIVE DATA GROUP IV: 1000 M G /KG/DAY ANIMAL NUMBER CORPORA LUTEA NIDA TIONS RESORPTIONS TOTAL EARLY LATE DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE iMEAN FETAL WEIGHT (G) 6 6 3 3 8 1 (NP) 663388 17 14 0 0 0 0 14 68 5.50 663394 14 14 0 0 0 0 14 9 5 5.18 663400 15 15 0 0 0 0 15 7 8 5.48 663401 5 1 0 0 0 0 1 1 0 6.38 663404 18 15 0 0 0 0 15 5 10 5.82 663409 13 11 1 0 1 0 10 2 8 5.54 663411 17 13 0 0 0 0 13 7 6 5.41 663419 13 13 0 0 0 0 13 5 8 5.10 663422 15 14 0 0 0 0 14 6 8 5.97 .6 6 3 4 3 2 (NP) ,,. ... , . ... ... ... 663434 15 14 0 0 0 0 14 6 8 5.32 663435 14 13 0 0 0 0 13 6 7 5.93 663436 16 15 1 1 0 0 14 95 5.48 663442 13 12 0 0 0 0 12 4 8 5.20 663446 20 17 0 0 0 0 17 9 8 5.32 663453 19 15 0 0 0 0 15 7 8 5.44 663454 16 16 2 2 0 0 14 6 8 5.37 663458 15 13 0 0 0 0 13 6 7 5.36 663459 19 15 1 0 1 0 14 3 11 5.63 663460 15 13 00 0 0 13 7 6 5.36 663468 20 17 0 0 0 0 17 11 6 5.31 Company Sanitized. Does not contain TSCA CBI 104 H-25425: Developmental Toxicity Study in Rats DuPont-11347 APPENDIX H Individual Fetal Weights and Alterations 105 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats Individual Fetal Weights and Alterations Explanatory Notes DuPont-11347 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 o f 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 a 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. 106 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-2542 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663382 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 663386 1 2 3 4 5 6 5.33 5.25 5.04 5.16 5.60 5.25 4.87 5.06 5.11 5.76 5.75 5.64 5.49 5.45 5.34 5.34 Vertebra Vertebra Vertebra Rib Vertebra Vertebra Vertebra Rib 5.48 5.24 5.94 5.95 5.85 5.89 Vertebra Vertebra Vertebra Skull Vertebra NAD NAD Retarded Ossification (cen thll) NAD' Retarded Ossification (cen thlO) NAD Retarded Ossification (cen thll) NAD NAD NAD Supernumerary (sitel4 bil) Retarded Ossification (cen thlO) Retarded Ossification (cen thll) Retarded Ossification (cen thlO-11) NAD Supernumerary (pinpoint site 14 bil) NAD Retarded Ossification (cen thlO-13) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll-12) Retarded Ossification (12) Retarded Ossification (cen th5,10-12) VR VR VR DV VR VR VR DV VR VR VR VR vr 107 Corrfpany Sanitized. Does not contain TSCA CBI Ii-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-2542 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663386 (Cont.) 7 5.43 8 5.25 9 4.73 10 5.89 11 6.13 Vertebra Rib Vertebra Vertebra Vertebra Kidney Vertebra 663389 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.86 5.94 6.03 5.75 5.41 5.68 5.72 6.28 5.50 5.84 5.91 5.74 5.32 5.68 5.87 Vertebra Vertebra Vertebra Vertebra Vertebra Kidney Vertebra Vertebra FINDING(S) CLASSIFICATION Retarded Ossification (cen thll-13) Supernumerary (site thl4 bil) Retarded Ossification (cen thl3) Retarded Ossification (cen thl3) Retarded Ossification (cen thlO) Papilla - Size 3 (bil) Retarded Ossification (cen thl2) VR DV VR VR VR VR VR NAD NAD NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) ' Retarded Ossification (cen thll) Papilla - Size 3 (It) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) VR VR VR VR VR VR VR VR 108 Company Sanitized. Does not contain TSCA C SI H-25425: Developmental Toxicity Study in Rats HU-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM .#/ FETUS # FETUS WT. STRUCTURE FENDING(S ) 663391 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 663399 1 2 3 4 5 6 7 8 9 6.04 5.92 5.67 5.15 6.07 6.19 5.80 6.13 5.21 6.17 5.64 5.80 6.01 5.72 6.10 6.13 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 5.97 6.11 6.22 5.85 5.52 5.62 5.99 5.63 6.18 Retarded Ossification (cen thlO,11) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll,12) Retarded Ossification (cen thl3) Retarded Ossification (cen thll) Retarded Ossification (cen thlO,ll) Retarded Ossification (cen th5,11) NAD Retarded Ossification (cen thlO,12) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR VR VR VR 109 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 -IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING (S) CLASSIFICATION 663399 (Cont.) 10 5.74 11 5.83 12 6.06 663406 1 5.74 2 5.71 3 5.66 4 6.03 5 5.74 6 6.03 7 5.35 8 5.03 9 5.67 10 5.29 11 5.28 12 5.50 13 5.70 14 5.50 15 5.71 Vertebra Vertebra Vertebra Skull Skull Vertebra Skull Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 663408 1 2 5.56 5.28 Skull NAD NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (1) Retarded Ossification (2 rt) Retarded Ossification (cen thll) NAD NAD Retarded Ossification (1) Retarded Ossification (cen thll) Retarded Ossification (cen th.10,12) NAD Retarded Ossification (cen thl0,12) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO,12) VR VR VR VR VR VR VR VR VR VR VR VR VR NAD Retarded Ossification (6 bil) VR 110 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 .HN-2542 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663408 (Cont.) 3 5.27 4 5.63 5 5.57 6 4.98 7 5.07 8 5.57 9 5.54 10 5.57 11 5.20 12 5.37 13 5.32 14 5.04 15 16 17 663414 1 2 3 4 5 6 7 8 9 10 11 12 5.28 5.25 5.34 6.28 5.43 6.12 6.17 6.06 6.33 6.01 5.90 6.21 5.81 5.78 5.69 Vertebra Vertebra Vertebra Rib Rib Rib Skull Vertebra Rib Vertebra Vertebra Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Rudimentary Cervical (7 rt) Supernumerary (site thl4 It) NAD NAD NAD Supernumerary (site thl4 bil) NAD NAD Retarded Ossification (1) Retarded Ossification (gen thl3) NAD Supernumerary (site thl4 It) NAD VR VR VR DV DV DV VR VR DV NAD NAD Retarded Ossification (cen thlO) NAD NAD NAD NAD NAD Retarded Ossification (cen thlO) NAD NAD NAD VR VR 111 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425. TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663414 13 14 15 16 (Cont.) 5.70 5.86 6.32 5.68 663415 1 5.88 Vertebra 2 5.18 Vertebra 3 5.24 Vertebra 4 5.37 5 5.44 Vertebra 6 4.14 Skull Skull Skull Vertebra 7 4.96 Vertebra 8 4.71 Vertebra 9 4.87 Vertebra 10 5.07 11 5.41 12 4.93 13 4.88 Vertebra 14 4.83 15 5.25 Vertebra 16 5.43 663421 1 5.49 FINDING(S) CLASSIFICATION NAD NAD NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (2 bill Retarded Ossification (cen thll-13) Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll-12) NAD VR VR VR VR VR VR VR VR VR VR VR VR VR NAD 112 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663421 2 3 4 5 6 7 (Cont.) 6.03 5.72 5.66 5.22 5.47 5.60 8 5.56 9 5.58 10 5.77 11 5.72 12 5.37 663430 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.50 5.83 5.76 6.06 5.95 5.39 5.63 4.81 5.88 5.84 6.18 5.33 5.70 5.66 663431 1 2 3 4 5 6 3.82 5.65 5.76 5.67 5.79 5.56 Vertebra Vertebra Vertebra NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-11347 CLASSIF ICATION VR VR VR 113 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663431 (Cont.) 7 5.71 8 5.23 9 5.42 10 5.54 11 5.49 12 5.79 13 5.87 663437 1 2 5.31 5.51 3 6.06 4 5.90 5 5.34 6 5.73 7 5.49 8 5.56 9 5.30 10 5.40 11 5.90 12 5.95 Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Vertebra Vertebra Vertebra NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl) NAD NAD NAD * VR VR NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen th9,11-13) Retarded Ossification (6 bil) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) Retarded Ossification (1) Retarded Ossification (cen thll-13) NAD NAD Retarded Ossification (cen thll,13) Retarded Ossification (cen thl2) Retarded Ossification (cen thl0-12) Retarded Ossification (cen thll) VR VR VR VR VR VR VR VR VR VR VR 114 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-2542S IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663439 1 2 3 4 5 6 7 8 9 10. - 11 12 13 5.61 5.87 5.65 5.20 5.71 5.07 4.84 5.52 5.19 5.24 5.31 5.09 5.18 Vertebra Vertebra Vertebra Skull Skull Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra 663444 1 2 3 4 5 6 7 8 9 10 11 12 4.83 5.27 4.73 3.90 4.71 4.21 4.75 4.57 4.25 3.44 5.26 4.75 Rib Vertebra F I N D I N G (S) CLASSIFICATION Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (12) Retarded Ossification (2 bil) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl0,12) Retarded Ossification (1) Retarded Ossification (cen thll) VR VR VR VR VR VR VR VR VR VR VR VR NAD NAD NAD NAD NAD Wavy (th6-ll rt 11 lt> NAD NAD Retarded Ossification (cen thl2) NAD NAD NAD VR VR 115 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663444 (Cont.) 13 4.54 663448 1 2 3 4 5 5.96 6.19 5.64 6.11 6.39 6 6.13 7 6.19 8 6.14 9 6.52 10 5.69 11 5.99 12 6.09 13 6.02 Kidney Vertebra Vertebra Vertebra Kidney Vertebra 663462 1 2 3 4 5 6 7 8 9 10 5.26 5.41 5.37 5.41 5.60 5.01 5.24 5.68 5.52 5.56 Vertebra Vertebra Vertebra Vertebra Vertebra Papilla - Size 3 (bil) NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen thl2) NAD NAD Papilla - Size 3 (bil) Retarded Ossification (cen thl2) Retarded Ossification (cen th9,12) NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thlO) NAD NAD NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR VR VR VR 116 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663462 (Cont.) 11 5.20 12 5.20 13 4.81 14 5.67 15 5.41 663464 1 2 3 5.51 5.72 5.70 4 5.25 5 5.47 6 5.52 7 5.62 8 5.92 9 5.33 10 5.20 11 5.77 12 5.74 13 5.52 14 5.74 15 5.77 16 5.41 17 5.35 663465 1 2 3 4 5 6 7 6.03 5.80 5.67 5.86 5.54 5.58 5.80 Vertebra Vertebra Vertebra Vertebra Vertebra Sternebra NAD Retarded Ossification (cen thl0-12) NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thl3) NAD NAD NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification NAD NAD NAD NAD NAD NAD NAD NAD DuPont-11347 CLASSIF ICATION VR VE VR VR VR VR 117 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663465 8 9 10 11 12 (Cont.) 5.57 5.72 5.80 5.37 5.58 13 5.58 663467 1 5.92 2 5.49 3 5.79 4 5.88 5 5.83 6 5.22 7 5.82 8 5.46 9 5.99 10 5.84 11 5.49 12 5.63 13 5.00 14 5.43 Vertebra Vertebra Vertebra Skull Skull FINDING(S) CLASSIF ICATION NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (1) NAD NAD NAD Retarded Ossification (1) NAD NAD NAD NAD VR VR VR VR VR 118 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 653383 1 2 3 4 663392 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663393 1 2 3 4 5 6 7 8 5.96 5.94 6.25 6.30 Vertebra Vertebra Vertebra 5.15 5.41 5.15 5.52 5.83 5.64 5.92 5.75 5.38 6.21 5.21 5.48 5.08 5.83 Skull Vertebra Vertebra Vertebra Vertebra 5.88 5.05 5.83 5.43 6.28 5.86 5.33 5.91 Vertebra Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thlO) Retarded Ossification (cen th9) NAD Retarded Ossification (1) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) NAD NAD Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll,13) NAD NAD NAD NAD NAD NAD VR VR VR VR VR VR VR VR VR 119 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued.) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) 553393 (Cont.) 9 5.91 10 5.38 11 5.37 12 5.41 13 6.26 563396 1 5.92 2 5.71 3 5.87 4 5.75 5 5.60 6 5.57 7 6.14 8 5.45 9 5.77 10 5.87 11 5.68 12 5.19 13 5.86 14 6.10 15 5.45 16 5.21 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Vertebra 663398 1 5.35 Kidney Retarded Ossification (cen thll) NAD Retarded Ossification (cen thlO) NAD NAD Retarded Ossification (cen thl) NAD NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thlO) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl3) NAD NAD Papilla - Size 3 (It) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl,12-13) Papilla - Size 3 (rt) DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR VR VR VR VR VR 120 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 563398 (Cont.) 2 5.61 3 5.19 4 5.56 5 6 7 8 9 10 11 663405 1 2 3 4 5 6 6.07 6.07 5.32 5.64 5.45 6.22 6.21 5.16 5.00 5.20 4.84 5.18 4.91 7 5.36 8 5.18 9 4.75 10 4.90 11 5.19 12 4.95 13 5.33 14 5.08 15 5.38 Vertebra Rib Vertebra Rib Rib Vertebra Rib Skull Skull Vertebra Skull Skull Vertebra Vertebra Retarded Ossification (cen thl3) NAD Supernumerary (site thl4 bil) Retarded Ossification (cen thl2) NAD Supernumerary (site thl4 lt) Supernumerary (site thl4 lt) NAD Retarded Ossification (cen thll-12) NAD Supernumerary (site thl4 lt) VR DV VR DV DV VR DV NAD NAD NAD NAD NAD Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (cen thll) NAD Retarded Ossification (1) Retarded Ossification (12) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD NAD NAD VR VR VR VR VR VR VR 121 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663407 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 663417 1 2 3 4 5 6 5.19 4.75 4.46 4.91 4.99 4.21 3.76 4.44 5.04 5.55 4.43 4.24 4.85 4.77 4.74 4.97 4.14 4.65 Vertebra Vertebra Vertebra Vertebra Subcutis Vertebra Vertebra Rib Vertebra Vertebra Vertebra Vertebra 5.34 5.34 5.32 5.27 6.25 6.15 Vertebra Retarded Ossification (cen thlO-12) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll-13) Retarded Ossification (cen thlO) NAD Hemorrhage (back*) Retarded Ossification (cen thll) Retarded Ossification (cen th9,ll) NAD NAD Supernumerary (sitel4 rt) Retarded Ossification (cen thlO,12) Retarded Ossification (Cen thlO-12) Retarded Ossification (cen thll) Retarded Ossification (cen thlO-12) NAD NAD NAD Retarded Ossification (cen thll,12) NAD NAD NAD NAD NAD DuPont-11347 CLASSIF ICATION VR VR VR VR N VR VR DV VR VR VR VR VR 122 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats HN-25'425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663417 (Cont.) 7 5.12 8 5.20 9 5.56 Vertebra 10 5.36 11 5.52 12 5.38 Vertebra 13 5.60 14 5.13 15 5.57 Vertebra 16 5.12 663423 1 2 3 4 5 6 7 8 9 10 11 12 5.31 5.42 5.45 5.67 5.80 5.80 5.41 5.42 6.00 5.07 5.96 5.64 663424 1 5.90 Vertebra 2 5.69 3 5.81 Vertebra 4 5.90 Vertebra NAD NAD Retarded Ossification (cen thlO) NAD NAD Retarded Ossification (cen thlO) NAD NAD Retarded Ossification (cen thlO) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thlO,12) D u P o n t-11347 CLASSIFICATION VR VR VR VR VR VR 123 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 C HN-25425 TERATOGENICITY STUDY QF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663424 (Cont.) 5 5.92 Vertebra 6 5.43 7 5.71 Vertebra 8 5.87 9 5.70 Vertebra 10 5.44 Vertebra 11 5.52 Vertebra 12 5.36 Vertebra 13 5.51 14 5.63 Vertebra 15 5.99 663427 1 4.89 Vertebra 2 5.57 Skull Vertebra 3 5.45 4 4.95 5 5.36 Vertebra 6 5.51 7 5.60 8 5.66 9 5.59 10 5.63 Vertebra 11 5.70 Vertebra 12 5.53 FINDING(S) CLASSIF.ICATION Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO-ll) Retarded Ossification (cen thl0-13) NAD Retarded Ossification (cen thl2) NAD VR VR VR VR VR VR VR Retarded Ossification (cen thll) Retarded Ossification Retarded Ossification (cen th9) NAD NAD Retarded Ossification (cen th9,ll) NAD NAD NAD NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thl3) NAD (6 rt) VR VR VR VR VR VR 124 Company Sanitized. Does not contain TSCA CSJ H-2542S: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663428 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663429 1 2 3 4 5 6 7 8 9 10 5.34 5.72 5.49 5.72 6.02 5.84 5.56 5.34 5.11 5.37 5.56 4.55 5.25 5.32 Vertebra Vertebra Vertebra Vertebra Sternebra Vertebra 5.03 6.01 5.84 5.71 5.71 5.34 6.03 5.43 5.87 6.21 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD NAD NAD NAD Retarded Ossification (cen thlO,11) Retarded Ossification (cen thl2) Retarded Ossification (3,4,6) Retarded Ossification (cen thl2) NAD NAD' NAD VR VR VR VR VR VR NAD Retarded Ossification (cen thll,13) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll) VR VR VR VR VR VR 125 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats HN-25425 TERATOGENICITY STUDY OP H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663429 (Cont.) 11 5.64 12 5.98 663433 1 5.14 2 5.69 3 5.51 4 6.15 5 5.63 6 5.85 7 5.46 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 663445 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.55 5.25 5.39 6.04 5.78 5.80 5.71 5.36 5.45 5.31 5.63 5.71 5.88 5.71 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll-13) NAD Retarded Ossification (cen th!3) Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thll-12! Retarded Ossification (cen thll-13) Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen th7,12) NAD Retarded Ossification (cen th8,9,10) NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thll) NAD NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR VR VR VR 126 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) 663445 (Cont.) 15 6.12 Vertebra 663447 1 2 3 4 5 6 7 8 9 10 11 12 13 5.46 5.42 5.46 5.25 5.64 5.30 5.11 5.71 5.49 6.01 4.95 5.33 5.57 Vertebra Vertebra Vertebra Vertebra Vertebra 663451 1 2 3 4 5 6 7 8 9 10 11 5.09 5.40 5.54 5.46 5.47 5.20 5.35 5.15 5.20 5.09 5.37 Vertebra Vertebra Vertebra Retarded Ossification (cen thlO,11,12) NAD NAD NAD Retarded Ossification (cen thll) NAD NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thlO) NAD NAD NAD NAD NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR VR 127 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) CLASSIFICATION 663451 (Cont.) 12 5.61 13 5.55 663452 1 5.64 2 5.78 3 5.58 4 5.52 5 5.37 6 5.45 7 5.64 8 5.10 9 4.97 10 5.64 11 5.26 12 5.28 13 5.48 14 5.72 15 5.57 Vertebra Vertebra Vertebra Vertebra Vertebra Skull Skull Vertebra Vertebra Vertebra Vertebra Vertebra Skull Skull Vertebra Vertebra Vertebra Vertebra NAD NAD Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (1) Retarded Ossification 12) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thl2-13) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thl2,13) Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thll) Retarded Ossification (cen th9,ll) VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR 128 Company Sanitized. Does not contain TSC A CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued.) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663455 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663466 1 2 3 4 5 6 7 8 5.76 5.51 5.92 5.68 5.91 5.78 6.05 5.78 6.05 5.97 5.61 5.76 5.27 5.60 Kidney Kidney Vertebra Kidney Vertebra Vertebra 5.37 5.76 5.38 5.65 5.61 5.19 5.78 5.53 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Small Papilla - Size 2 (It) NAD NAD NAD Papilla - Size 3 (bil) Retarded Ossification (cen thl2) NAD Papilla - Size 3 (It) NAD NAD Retarded Ossification (cen thll) NAD NAD NAD Retarded Ossification (cen thll) Retarded Ossification (cen thlO,12) Retarded Ossification (cen thll) Retarded Ossification (cen th9,10,11) Retarded Ossification (cen thlO,11,12) Retarded Ossification (cen thll) Retarded Ossification (cen thl2,13) Retarded Ossification (cen thl2) Retarded Ossification (cen thll,13) VR VR VR VR VR VR VR VR VR VR VR VR VR VR 129 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats HN-25 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 10 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663466 (Cont.) 9 4.97 10 5.28 11 5.71 12 5.45 13 5.29 14 5.57 Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen th9,10,11) NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thlO) DuPont-11347 CLASSIFICATION VR VR VR VR 130 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 663384 1 2 3 4 5 6 7 8 9 10 11 663387 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.78 5.83 6.51 5.64 6.14 5.70 6.20 5.99 6.11 6.01 5.88 Vertebra 5.22 5.33 4.94 5.46 5.18 5.50 5.17 5.49 5.08 5.48 5.11 4.70 5.13 4.96 Vertebra Skull Skull Vertebra Vertebra Vertebra Vertebra Skull Vertebra NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thl3) NAD VR NAD NAD NAD NAD Retarded Ossification (cen thl0-12) Retarded Ossification (1) Retarded Ossification (6,7 rt) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thl0,12) NAD NAD Retarded Ossification (cen thll) Retarded Ossification (6 bil) Retarded Ossification (cen thll) NAD NAD VR VR VR VR VR VR VR VR VR 131 Company Sanitized. Does not contain TSCA CBi H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 663387 (Cont.) 15 5.24 16 5.43 663390 1 2 5.32 4.94 3 4.80 4 4.47 5 5.07 6 4.75 7 8 9 10 11 12 13 14 15 16 663397 1 2 3 4 5 6 5.16 5.08 5.61 4.37 4.99 5.17 5.22 5.36 5.27 5.36 5.45 5.44 5.22 5.65 5.45 5.71 Vertebra Skull Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Retarded Ossification (cen thll-12) NAD NAD Retarded Ossification ( 1 2 ) Retarded Ossification (cen thlO-ll) NAD NAD NAD Retarded Ossification (12) Retarded Ossification (cen thll,13) NAD NAD NAD Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification ( 12) NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) NAD VR VR VR VR VR VR VR VR VR 132 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats HN-25425, TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663397 (Cont.) 7 , 5.43 Vertebra 8 5.05 9 5.52 Vertebra 10 5.48 11 5.97 12 5.67 Vertebra 13 5.57 Kidney 14 5.76 563402 1 2 3 4 5 6 7 8 5.41 5.73 5.87 5.25 5.34 5.77 5.94 5.85 Vertebra 9 6.19 Vertebra 10 5.43 11 5.68 12 5.72 13 5.59 14 5.69 653403 1 2 3 4 5 5.88 5.45 5.16 5.61 5.46 Vertebra 6 5.30 Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl3) NAD NAD Retarded Ossification (cen thll) Papilla - Size 3 (bil) NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR 133 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663403 (Cont.) 7 5.07 Vertebra 8 5.48 9 5.45 Vertebra 10 5.31 11 5.61 12 5.31 Vertebra 13 5.81 663410 1 5.39 Vertebra 2 5.50 Vertebra 3 5.02 Vertebra 4 4.81 Vertebra 5 5.33 6 5.79 Skull Vertebra 7 5.38 Vertebra 8 5.04 9 5.13 10 4.27 11 5.68 12 5.56 13 5.60 Vertebra 14 5 .23 15 5.56 Vertebra 16 5.64 17 5.76 FINDING(S) CLASSIF ICATION Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl3) Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD Retarded Ossification (1) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) NAD NAD VR VR VR VR VR VR VR VR VR VR VR VR 134 Company Sanitized. Does not contain TSCA CB! H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663412 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 663416 1 2 3 4 5 6 7 8 9 5.27 5.84 5.20 5.58 5.86 5.80 6.11 5.18 6.00 5.54 5.55 5.89 4.97 5.43 5.31 Vertebra Skull Vertebra Vertebra Vertebra Vertebra 5.43 5.49 5.14 5.23 5.49 5.81 5.40 5.86 4.98 Vertebra Vertebra Kidney Vertebra Vertebra Vertebra NAD Retarded Ossification (cen thl) NAD Retarded Ossification (6 It) NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD NAD VR VR VR VR VR VR Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO.) Papilla - Size 3 (bil) Retarded Ossification (cen thll,13) Retarded Ossification (cen thlO,12) Retarded Ossification (cen thll) NAD NAD NAD NAD VR VR VR VR VR VR 135 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) CLASSIFICATION G63416 (Cont.) 10 5.37 11 5.30 12 5.86 13 4.94 14 5.73 663418 1 2 3 4 5.63 5.59 5.24 5.39 5 5.23 6 5.43 7 5.49 8 5.53 9 5.65 10 5.37 11 5.37 12 5.52 13 5.01 14 5.37 Vertebra Vertebra Vertebra Skull Vertebra Vertebra Vertebra 663420 1 2 3 4 5 6 6.07 6.18 6.34 5.44 5.90 4.24 Vertebra Vertebra Vertebra Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thlO) NAD Retarded Ossification (cen thll-12) NAD Retarded Ossification Retarded Ossification (cen thlO) Retarded Ossification (cen thlO) NAD NAD NAD Retarded Ossification (cen thl2) (1) Retarded Ossification (cen th.12) Retarded Ossification (cen thlO,12) NAD Retarded Ossification (cen thl2) NAD NAD VR VR VR VR VR VR VR VR VR VR 136 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 3HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663420 (Cont.) 7 5.56 8 5.24 9 5.74 10 5.15 11 5.85 12 6.07 13 5.72 14 5.95 15 5.38 16 5.51 Vertebra Vertebra Vertebra Vertebra Vertebra 663425 1 2 3 4 5 6 7 8 9 10 11 12 13 5.76 5.96 4.75 5.97 5.73 6.03 5.84 5.83 5.90 5.58 6.47 6.36 6.15 Vertebra Vertebra Sternebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thl0,ll) NAD NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) Retarded Ossification (cen th6,11,12) Retarded Ossification (cen thlO-11) Retarded Ossification (cen thl2) Retarded Ossification Retarded Ossification (cen thlO,13) NAD Retarded Ossification (cen thlO-11) Retarded Ossification (cen thll) NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD (6) CLASSIF ICATION VR VR VR VR VR VR VR VR VR VR VR VR 137 Company Sanitized. Does not contain TSCA C SI H-25425: Developmental Toxicity Study ip Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 663426 1 2 3 4 5 6 7 8 9 10 11 12 13 663438 1 2 3 4 5 6 7 5.26 5.93 5.22 5.48 5.77 5.33 5.47 5.63 5.05 4.99 5.13 6.00 5.78 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 5.46 5.94 5.98 6.34 5.77 5.93 5.47 Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra NAD Retarded Ossification (cen th.9) NAD Retarded Ossification (cen th9,10) NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen tb.9,11) NAD Retarded Ossification (cen thl0,12) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thlO,11) VR VR VR VR VR VR VR Retarded Ossification (cen thl0-12) Retarded Ossification (cen th9,11-12) Retarded Ossification (centhlO,12) Retarded Ossification (cen thl0-ll,13) Retarded Ossification (cen thlO-14) Retarded Ossification (2 bil) Retarded Ossification (cen th.12) Retarded Ossification (cen thll-12) VR VR VR VR VR VR VR VR 138 Company Sanitized. Does not contain TSCA CB) H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) CLASSIFICATION 663438 (Cont.) 8 5.85 9 10 11 12 13 14 663440 1 2 3 4 5 6 7 8 9 10 11 12 13 5.98 5.42 5.48 6.27 5.76 5.95 5.82 5.58 5.78 5.11 5.70 5.34 5.49 5.05 5.17 5.47 5.25 5.03 b.45 Skull Vertebra Vertebra Vertebra Vertebra Vertebra Skull Skull Vertebra Vertebra Skull Skull Vertebra Vertebra Vertebra Vertebra Retarded Ossification Retarded Ossification (cen thlO,12) Retarded Ossification (cen thll,13) NAD Retarded Ossification (cen thll-13) NAD Retarded Ossification (cen thl2) NAD (1 bil) VR VR VR VR VR NAD NAD Retarded Ossification (cen thll-12) Retarded Ossification Retarded Ossification Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) Retarded Ossification Retarded Ossification Retarded Ossification (cen thlO-ll) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thl2-13) Retarded Ossification (cen thll) (1) (12) (1) (12) VR VR VR VR VR VR VR VR VR VR VR 139 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663441 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 663443 1 2 3 4 5 6 4.79 4.86 4.79 4.83 5.30 5.09 5.49 5.56 5.12 5.34 5.22 5.33 4.95 5.32 5.23 Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Vertebra 5.63 5.85 5.51 5.66 5.23 5.64 Vertebra Skull Skull Vertebra Vertebra Skull Skull Retarded Ossification (cen thlO-13) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen til2) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) NAD NAD (6 rt) VR VR VR VR VR VR VR VR VR Retarded Ossification (cen thlO-11) Retarded Ossification Retarded Ossification Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD NAD Retarded Ossification Retarded Ossification (1) (2 It) (1) (2 bil) VR VR VR VR VR VR VR 140 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 663443 (Cont.) 7 5.93 a 5.17 9 5.72 10 5.64 11 5.57 12 5.37 13 5.11 14 5.46 Skull Vertebra Vertebra Skull Vertebra Skull Vertebra Vertebra Vertebra 663449 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 4.43 4.93 5.49 4.79 5.27 5.12 4.87 5.65 5.60 4.82 5.24 5.17 5.14 5.26 5.25 5.58 Sternebra Vertebra Vertebra Retarded Ossification (7 rt) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) Retarded Ossification (1) Retarded Ossification (cen thl2) NAD Retarded Ossification (1) Retarded Ossification (cen thl0,12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) VR VR VR VR VR VR VR VR VR NAD NAD NAD Retarded Ossification NAD Retarded Ossification (cen th9) NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thlO) NAD (6) VR VR VR 141 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats HN-2542! TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 653450 1 2 3 4 5 6 7 8 9 10 11 12 13 663456 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.19 5.50 5.94 5.14 5.26 5.46 5.35 5.59 5.63 5.60 5.52 5.24 5.22 Vertebra Vertebra 5.26 5.13 5.72 6.09 5.97 5.87 5.80 6.15 5.71 5.53 5.71 6.08 5.35 5.44 5.24 Vertebra Vertebra Kidney Vertebra Vertebra Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thll) NAD Papilla - Size 3 (It) Retarded Ossification (cen thll,12) NAD NAD NAD NAD NAD Retarded Ossification (cen thl3) NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR 142 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 63457 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 IS 17 663461 1 2 3 5.37 5.09 5.52 5.30 5.29 5.30 5.54 5.39 5.17 5.16 5.56 5.15 5.33 4.89 5.09 5.12 5.44 Skull Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra 6.46 5.25 5.31 Vertebra FINDING(S) CLASSIF ICATION NAD Retarded Ossification (6 It) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll-12) Retarded Ossification (cen thlO,12) Retarded Ossification (1) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll,13) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (1) Retarded Ossification (cen thlO) NAD VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR Retarded Ossification (cen thlO) NAD NAD VR 143 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 100 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) 663461 (Cont.) 4 5.56 5 5.15 6 4.97 7 5.41 8 5.75 9 5.18 10 4.96 11 5.68 12 5.21 13 5.47 Vertebra Vertebra Subcutis NAD NAD Retarded Ossification (cen th.9,12) NAD Retarded Ossification (cen thlO) NAD NAD NAD Hemorrhage (chin*) NAD DuPont-11347 CLASSIFICATION VR VR N 144 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663388 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663394 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663400 1 5.20 5.77 5.39 5.48 5.52 5.62 5.38 5.55 5.10 5.82 5.94 5.54 5.57 5.17 Subcutis Kidney Vertebra Vertebra Kidney 5.30 5.41 5.06 4.95 5.31 5.13 4.80 4.79 5.22 5.10 5.46 5.41 5.37 5.21 Vertebra Vertebra Rib 5.63 FINDING(S) CIASSIFICATION Hemorrhage (neck*) NAD NAD NAD Absent (rt) Retarded Ossification .(cen thl2) NAD NAD NAD Retarded Ossification (cen thll) Papilla - Size 3 (bil) NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD Supernumerary (site thl4 It) NAD NAD NAD NAD NAD N M VR VR VR VR VR DV 145 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663400 (Cont.) 2 5.39 3 5.38 4 5.56 5 6.35 6 4.93 7 5.45 8 5.73 9 5.53 10 5.62 11 5.03 12 5.68 13 5.11 14 5.12 15 5.73 663401 1 6.38 663404 1 6.45 2 5.89 3 5.85 4 6.14 5 5.64 6 5.59 Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Vertebra Vertebra Vertebra F I N D I N G (S) CLASSIFICATION Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen thl3) NAD Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD VR VR VR VR NAD Retarded Ossification (cen thl0-12) Retarded Ossification (2 bil) Retarded Ossification (cen th9-13) Retarded Ossification (cen thlO-13) Retarded Ossification (cen thlO-11) Retarded Ossification (cen th9-13) Retarded Ossification (cen thlO,12) VR VR VR VR VR VR VR 146 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663404 (Cont.) 7 5.66 8 5.47 9 6.02 10 5.81 11 5.66 12 5.89 13 5.78 14 5.90 15 5.57 Vertebra Vertebra Vertebra Skull Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 663409 1 2 3 4 5 6 7 8 9 10 663411 1 2 5.42 5.57 5.95 5.40 5.53 5.82 5.90 4.84 5.58 5.37 Vertebra 5.23 5.32 F I N D I N G (S) CLASSIFICATION Retarded Ossification (cen thll-13) Retarded Ossification (cen thlO-13) Retarded Ossification (cen thll-13) Retarded Ossification Retarded Ossification (cen thlO,12-13) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-12) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thlO-13) (1) - NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thlO) NAD NAD NAD NAD NAD VR VR VR VR VR VR VR VR VR VR VR 147 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats 3HN-25425 TERATOGENICITY STODY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) 663411 (Cont.) 3 5.47 4 5.17 5 5.40 6 5.00 7 5.72 8 5.99 9 5.54 10 5.53 11 5.51 12 5.51 13 4.95 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 663419 1 2 3 4 5 6 7 8 9 10 11 12 13 5.10 4.07 5.14 5.26 4.99 4.89 5.16 4.90 5.17 5.17 5.34 5.75 5.34 Rib Skull Vertebra Retarded Ossification (cen thl2) Retarded Ossification (cen till1,12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll,12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll,13) NAD Retarded Ossification (cen thl3) Retarded Ossification (cen thll,12) NAD Supernumerary (thl4 rt pinpoint) NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (6,7,8 rt) Retarded Ossification (cen th5,ll) DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR DV VR VR 148 Company Sanitized. Does not contain TSCA CBI H-2S425: Developmental Toxicity Study in Rats TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 663422 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663434 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663435 1 5.81 6.29 6.29 5.66 6.27 5.73 6.32 5.64 6.03 5.41 6.49 6.08 5.73 5.87 Vertebra Vertebra Vertebra 5.08 5.49 5.27 5.76 5.76 5.02 5.19 5.41 5.29 5.53 4.74 5.21 5.36 5.42 Vertebra Vertebra 5.76 NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thl3) Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD NAD NAD NAD NAD Retarded Ossification (cen thl0,12) NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD NAD DuPont-11347 CLASSIF ICATION VR VR VR VR VR 149 Company Sanitized. Does not contain TSCA CBt H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE 663435 2 3 4 5 (Cont.) 6.16 6.11 6.07 5.63 6 5.98 7 5.91 8 5.75 9 6.29 10 6.04 11 5.24 12 6.18 13 5.98 663436 1 5.29 2 5.73 3 5.23 4 5.60 5 5.20 6 5.23 7 5.48 8 5.69 9 5.71 10 5.25 11 5.41 12 5.16 13 5.80 14 5.87 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra FINDING(S) CLASSIFICATION NAD NAD NAD Retarded Ossification (cen th.ll) NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thll-13) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD Retarded Ossification (12) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll) NAD NAD VR VR VR VR VR VR VR VR VR 150 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 *HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING (S) class: ICAT: 663442 1 2 3 4 5 6 7 8 9 10 11 12 663446 1 2 3 4 5 6 7 8 9 10 4.11 5.31 5.65 5.21 5.21 5.48 4.99 5.30 5.38 5.13 5.51 5.15 Vertebra Rib Vertebra Vertebra Rib Vertebra Rib Rib Rib Skull Skull Vertebra 5.14 5.38 4.95 5.13 5.80 5.28 5.37 5.39 4.85 5.58 Vertebra Skull Vertebra Vertebra Skull Retarded Ossification (cen thlO) NAD Supernumerary (thl4 short bil) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thlO) Supernumerary (thl4 short bil) Retarded Ossification (cen thll-12) NAD Supernumerary (thl4 short bil) NAD Supernumerary (thl4 short bil) Supernumerary (site thl4 rt) Retarded Ossification (1) Retarded Ossification (6 It) Retarded Ossification (cen thll) VR DV VR VR DV VR DV DV DV VR VR VR NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD Retarded Ossification (12) Retarded Ossification (cen thll) Retarded Ossification (cen thlO-11) Retarded Ossification (1) VR VR VR VR VR 151 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS W T . STRUCTURE 663446 (Cont.) 11 5.20 12 5.08 13 4.95 14 5.23 15 4.74 16 6.26 17 6.06 Vertebra Skull Skull Vertebra Vertebra 663453 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.42 5.39 5.33 5.43 5.65 5.73 5.60 5.69 5.48 5.43 5.38 5.28 5.03 5.31 5.48 Abdomen Vertebra Rib Vertebra Vertebra Subcutis Vertebra Vertebra Skull Vertebra Vertebra FINDING(S) CLASSIF ICATION Retarded Ossification (cen thll-12) 1 NAD NAD. NAD Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thl2) VR ` VR VR VR VR Gastroschisis Retarded Ossification (cen thll) Supernumerary (pinpoint 141t) Retarded Ossification (cen thl3) NAD Retarded Ossification (cen th7) NAD Hemorrhage (It front leg*) Retarded Ossification (cen thl2) Retarded Ossification (cen th9) NAD Retarded Ossification (6 bil) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD NAD M VR DV VR VR N VR VR VR VR VR 152 Company Sanitized. Does not contain TSCA C8I H-2542S: Developmental Toxicity Study in Rats TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) 663454 1 2 3 4 5 6 7 8 9 10 11 12 13 14 663458 1 2 3 4 5 6 7 8 9 10 11 5.69 5.05 5.37 5.27 5.45 5.34 5.16 5.04 5.46 5.22 5.47 5.48 5.43 5.73 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 5.80 5.61 5.40 5.08 5.39 5.33 4.88 5.06 5.34 5.36 5.31 Vertebra Vertebra Vertebra Retarded Ossification (cen thll) NAD Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thlO,12) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) Retarded Ossification (cen thlO-12) NAD NAD NAD NAD NAD NAD Retarded Ossification (cen th9,10) NAD NAD NAD NAD Retarded Ossification (cen thlO) Retarded Ossification (cen thll) NAD NAD NAD DuPont-11347 CLASSIFICATION VR VR VR VR VR VR VR VR VR 153 Company Sanitized. Does not contain TSC A CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) CLASSIFICATION 663458 (Cont.) 12 5.87 Vertebra 13 5.20 663459 1 5.47 Vertebra 2 5.56 Vertebra 3 5.66 4 5.65 Skull 5 6.08 Vertebra 6 5.53 Skull Vertebra 7 5.68 Rib Vertebra 8 5.58 Vertebra 9 5.65 10 5.36 Rib Vertebra 11 5.68 Vertebra 12 5.93 13 5.53 Rib Vertebra 14 5.40 663460 1 2 5.29 4.B9 Vertebra Retarded Ossification (cen thll) NAD VR Retarded Ossification (cen thll,13) Retarded Ossification (cen thlO-13) NAD Retarded Ossification (12) Retarded Ossification (cen thl2) Retarded Ossification (1) Retarded Ossification (cen thll-12) Supernumerary (site thl6 bil) Retarded Ossification (cen thll-12) Retarded Ossification (cen thll-13) NAD Supernumerary (site t h i s bil) Retarded Ossification (cen thl2) Retarded Ossification (cen thll-12) NAD Supernumerary (site t h i s bil) Retarded Ossification (cen thlO-14) NAD VR VR VR VR VR VR DV VR VR DV VR VR DV VR NAD Retarded Ossification (cen thll) VR 154 Company Sanitized. Does not contain TSCA CBI H-25425: Developmental Toxicity Study in Rats DuPont-11347 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (cont inued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE F I N D I N G (S) CLASSIFICATION 663460 (Cont.) 3 5.66 4 5.38 5 5.46 6 5.88 7 5.04 8 5.48 9 5.39 10 5.59 11 5.22 12 4.82 13 5.53 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 663468 1 2 3 4 5 6 7 8 9 10 11 12 13 4.91 5.55 5.68 5.42 5.13 5.73 4.78 4.66 5.42 5.43 5.66 5.38 5.27 Vertebra Vertebra Rib Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD NAD Supernumerary (site thl4 It) NAD Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD VR VR VR VR VR VR VR VR DV VR VR VR VR 155 Company Sanitized. Does not contain TSCA C8I H-25425: Developmental Toxicity Study in Rats DuPont-11347 HN-25425 TERATOGENICITY STUDY OF H-25425 IN THE RAT APPENDIX (continued) ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 1000 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 563468 (Cont.) 14 5.39 15 5.63 16 5.03 17 5.24 Rib Vertebra Vertebra Kidney Supernumerary (sitethl4 It) Retarded Ossification (cen thll-12) NAD Retarded Ossification (cen thio) Papilla - Size 3 (bil) DV VR VR VR 156 Company Sanitized. Does not contain TSCA CBI