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H -25231: Developmental Toxicity Study in Rats___________________ _____________________________DuPont-10309
TRADE SECRET
Study Title H-25231: Developmental Toxicity Study in Rats
Laboratory Project ID: DuPont-10309
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T e s t G u id e l in e s : U.S. EPA Health Effects Test Guidelines OPPTS 870.3700 Prenatal Developmental Toxicity Study
A u t h o r : Susan M. Munley, M.A.
S t u d y C o m p l e t e d o n : November 19, 2002
P e r f o r m i n g L a b o r a t o r y : 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
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H -25231: Developmental Toxicity Study in Rats
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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 of the aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with IS09002 regulations. All of the analyses are considered valid and sufficient for the purposes of this study.
Applicant / Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A.
Applicant / Sponsor
Research Scientist DuPont Representative
Date Date
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H-25231: Developmental Toxicity Study in Rats
QUALITY ASSURANCE STATEMENT
DuPont-10309
Haskell Sample Number(s): 25231
Dates o f Inspections: Protocol: March 20, 2002; April 17, 2002 Conduct: April 17,30 2002; May 1, 2002
Records, Reports: September 26,30, 2002; October 9-11,13-14,27-30, 2002
Dates Findings Reported to: Study Director: October 2,14, 2002; November 1, 2002 Management: October 9, 2002; November 13,19, 2002
Reported by:
. uM ruur
imberly B. Brebner Staff Quality Assurance Auditor
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Date
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CERTIFICATION
We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study.
Analytical Evaluations by:
Janet C. Maslanka, B.S. Senior Staff Chemist
/if , Hoo 2_ Date
Approved by:
Robert M. Parker, PhD., D.A.B.T. Manager
Date
Issued by Study Director: O
Susan M. Munley, M.j Research Scientist
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Date
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H -25231: Developmental Toxicity Study in Rats______ __________________________________________DuPont-10309
TABLE OF CONTENTS
Page
GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT.....................................2
QUALITY ASSURANCE STATEMENT........................................................................................3
CERTIFICATION................................................................................................................................ 4
LIST OF APPENDICES..................................................................................................................... 6
STUDY INFORMATION................................................................................................................... 7
STUDY PERSONNEL..........................................................................................................................8
S U M M A R Y ............................................................................................................................................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.......................................................................................................................... 13.
I. Preparation, Administration, and Analysis o f Test Formulations........................................13
J. Animal Euthanasia....................................................................................................................15
K. Parameters to be Studied.......................................................................................................... 15
L. Control o f Bias..............................................
16
M. Statistical Analyses...................................................................................................................17
RESULTS AND DISCUSSION..........................................................
18
ANALYTICAL EVALUATIONS......................................................
18
A. Chromatography.................................................................
18
B. Concentration Verification and Stability Samples.................................................................18
C. Concentration Verification Samples....................................
19
D. Analytical Conclusions.................
19
DEVELOPMENTAL TOXICOLOGY...........................................................................................20
A. Maternal Findings.................................................................................................................... 20
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B. Fetal Findings........................................................................... C O N C L U S IO N S .................................................................................
21 23
RECORDS AND SAMPLE STORAGE.........................................
23
REFERENCES............................................................................................................................... .....24
TABLES................................................................................................................................................ 25
APPENDICES..................................................................................................................................... 40 LIST OF TABLES
TABLE 1 SUMMARY OF DOSING SOLUTION A N A L Y SES............................................................................................26 TABLE 2 MEAN MATERNAL BO DY W EIGHTS.................................................................................................................27 TABLE 3 M EAN MATERNAL BO DY WEIGHT CHANGES...............................................................................................30 TABLE 4 MEAN MATERNAL FOOD CONSUMPTION....................................................................................................... 32 TABLE 5 CLINICAL O BSERVATIO NS..................................................................................................................................... 34 TABLE 6 REPRODUCTIVE OUTCOM E.................................................................................................................................... 35 TABLE 7 INCIDENCE OF FETAL MALFORMATIONS....................................................................................................... 36 TABLE 8 INCIDENCE OF FETAL VARIATIONS...................................................................................................................37
LIST OF APPENDICES
APPENDIX A ANALYTICAL D A T A ...........................................................................................................................................41 APPENDIX B INDIVIDUAL BO DY W EIGHTS....................................................................................................................... 49 APPENDIX C INDIVIDUAL BO DY WEIGHT CH A N G ES.................................................................................................. 63 APPENDIX D INDIVIDUAL FOOD CONSUM PTION...........................................................................................................73 APPENDIX E INDIVIDUAL CLINICAL OBSERVATIONS................................................................................................. 83 APPENDIX F GROSS POSTMORTEM FINDINGS..................................................................................................................94 APPENDIX G INDIVIDUAL REPRODUCTIVE DA TA ........................................................................................................100 APPENDIX H INDIVIDUAL FETAL WEIGHTS AND ALTERATIONS........................................................................ 106
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H -25231: Developmental Toxicity Study in Rats
STUDY INFORMATION Substance Tested: Svnonvms/Codes:
Submitter's Notebook N u m b e ris ):^ ! 02252-150; ELN 00788-5 Haskell Number: 25231
DuPont-10309
Physical Characteristics: Tan liquid 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: April 12, 2002 / (see report cover page) In-Life Initiated/Completed: April 14, 2002 / May 2, 2002
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/*** **%
STUDY PERSONNEL
Study Director: Susan M. Munley, M.A. Management: Robert M. Parker, Ph.D., D.A.B.T.
Primary Technician: Gregory L. Poindexter Management: Scott E. Loveless, Ph.D.
Analytical Chemist: Janet C. Maslanka, B.S. Management: S. Mark Kennedy, Ph.D.
Toxicology Report Preparation: Mary K. LaRoe Management: Nancy S. Selzer, M.S.
Laboratory Veterinarian: William Singleton, D.V.M., A.C.L.A.M.
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H -25231: Developmental Toxicity Study in Rats
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SUMMARY
H-25231 was administered by gavage to groups o f 22 Crl:CD(SD)IGS BR rats once daily at dose levels o f 0, 625, 1250, or 2500 mg/kg/day. Doses were administered as a suspension in deionized water at a volume o f 10 mL/kg/day and dosing took place over days 6 through 20 of 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, maternal toxicity evident as reductions in body weight parameters was observed at 1250 and 2500 mg/kg/day. Effects on maternal food consumption were also reported at 2500 mg/kg/day. Non-adverse maternal effects occurred at 625 mg/kg/day; thus, the maternal no-observed-effect level (NOEL) was considered 625 mg/kg/day. Developmental toxicity was evident at 2500 mg/kg/day evident as reduced mean fetal weight. The NOEL for developmental toxicity was considered 1250 mg/kg/day.
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a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U.S. EPA (1985) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union (1994).
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OBJECTIVE
The purpose o f this study was to evaluate the potential maternal and developmental toxicity of H-25231 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-25231) 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 25231. The sponsor was responsible for the characterization and stability of the test substance. Test substance analyses were 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.
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Eighty-eight nulliparous time-mated females were received on April 11, 2002 (66 females) and April 12, 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 Husbandry
1. Housing
Animal rooms were maintained at an acceptable temperature o f 20-26C (targeted at 23C) and a targeted relative humidity of 50% 10%. Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours). Animals were housed individually in suspended, wire-mesh, stainless steel cages. Nesting material was not provided because the dams were euthanized prior to parturition.
2. Feed and Water
PMINutrition International, Inc. Certified Rodent LabDiet 5002 (formerly known as Purina Certified Rodent Chow) was available ad libitum. Water from the United Water Delaware was available ad libitum.
3. Identification
Each animal was assigned a unique number and 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 of 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 o f 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 firngal 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 specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The
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control group means for the 2500 and 5000 mg/kg/day groups, respectively. Mean overall food consumption (days 6-21G) values were consistent with these body weight effects and were 95% and 89% o f the control group mean at 2500 and 5000 mg/kg/day, respectively. There were no compound-related effects on either maternal weight or food parameters at 625 or 1250 mg/kg/day. There was no evidence of developmental toxicity at any level tested; mean fetal weight, sex ratio, litter size, resorption incidence, and external alteration incidence data were comparable across all groups. Based on these results, the dose levels listed in the table above were selected for the current study.
H. Randomization
Dams were assigned to lots according to their gestation day. Then, they were ranked within their respective lots on the basis of day 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).
I. Preparation, Administration, and Analysis of Test Formulations
1. Test Substance Preparation
Formulations o f the test substance in the vehicle (deionized water) were prepared daily and stored in a closed container at room temperature until used. The method o f mixing the test substance with the vehicle was documented in the study records.
2. Test substance 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 (10 mL/kg) was based on the most recent body weight.
3. Test Substance Sampling
Samples containing H-25231 at the concentrations o f 0, 62.5, 125, and 250 mg/mL were collected on April 16, 2002 for uniformity/concentration verification and 5-hour room temperature stability. Samples at all concentrations were collected on April 23, 2002 and April 30, 2002 for concentration verification analysis.
All dosing solution samples were collected on the same day the solutions were prepared. The solution vehicle was deionized water.
4. Analytical Methods
a. Dosing Solution Treatment
Each 1 mL dosing sample was diluted in 100 mL volumetric with high performance liquid chromatography (HPLC) grade water. The samples were further diluted with 50:50 methanol/water to final concentrations o f 0.000625 mg/mL (0.625 ppm) H-25231. Prior to this
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final dilution, each aliquot was corrected with HPLC grade water so that all samples to be analyzed contained an equivalent amount of water.
Samples submitted for analysis were analyzed the day the solutions were received or were frozen until analyzed.
b. Chromatographic Conditions
LC/MS Method
HPLC Instrument: MS Instrument:
Waters Model 2790 HPLC
Micromass Quattro Micro LC MS with "Z-spray" electrospray
LC parameters: Column:
XTerra MS C 18, 2.1mm x 30mm
Mobile Phase (Time Table), flow rate: 0.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.25 mL/min. 8.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 9.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 9.10 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.40 mL/min. 12.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.50 mL/min. 12.10 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.40 mL/min. 18.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.25 mL/min.
Run Time: Flow rate: Injection Volume: Column Temperature:
18.0 minutes (noted above with mobile phase) 20 microliters 35C
MS parameters: Ionization Mode: Capillary Voltage: Cone Voltage: Source Temperature: Desolvation Temperature: Scan Function:
Electrospray (ESI), negative ions 3.5 kV 40 V 120 300 SIR: 789, 889, 989 and 1089 m/z time: 0-10 minutes
c. Calibration and Quantitation
A stock solution o f the H-25231 test material (separate samples o f H-25231, used as analytical reference) was made in HPLC grade water. Appropriate aliquots o f the stock were diluted with 50:50 methanol/water after a correction with HPLC grade water so that an amount equivalent to
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the dosing samples would be maintained in each diluted standard. These solutions were used as calibration standards that bracketed the target concentration of the diluted dosing samples. Mass to charge ratio (m/z) from LC/MS analysis using negative ion electrospray ionization and selective ion monitoring of these standards over the mass range o f 789 to 1089 (m/z = 789, 889, 989,1089) were used to construct calibration curves by the appropriate regression (see Appendix A, Figure la - Id for representative calibration curves). Measured concentrations for dosing solutions were determined by applying the peak area from replicate injections o f the samples to each calibration curve. The mean result from the concentrations at all selected m/z (n = 4) is reported as the concentration for the sample.
Test substance uniformity in the vehicle was evaluated by calculating the coefficient o f variation (C.V. = standard deviation/mean x 100) of the measured concentrations in duplicate samples for each dosing level. A coefficient of variation o f less than or equal to 10% is the standard criterion at Haskell Laboratory for acceptable distribution o f the test substance throughout the solution.
However, if the test substance has been shown to be difficult to disperse in the vehicle or the analysis has shown variability, a coefficient greater than 10 m aybe acceptable.
The mean result of the duplicate samples for each dosing level was used to determine the concentration o f the test substance for the respective dosing levels.
Stability was evaluated by using the mean result o f the duplicate samples from the concentration verification as the baseline for comparing the corresponding stability results.
J. Animal Euthanasia
Females were euthanized by carbon dioxide asphyxiation. Fetuses were decapitated before proceeding with visceral examinations; those to be viscerally examined without decapitation were injected with sodium pentobarbital. All other fetuses also were injected with sodium pentobarbital before fixation.
K. Parameters to be Studied
1. In-life Observations 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 21G and twice daily on days 6-20G.
2. Postmortem Observations of Females Surviving to Scheduled Euthanasia
The abdominal and thoracic viscera were examined grossly immediately after euthanasia on day 21G. The intact and the empty uterus o f each dam having at least one viable fetus was weighed
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to permit calculation o f 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 of implants (live and dead fetuses, and resorptions) and their relative positions were recorded. The uterus of each apparently "nonpregnant" female was stained with ammonium sulfide(2) to detect very early resorptions.
3. Fetuses 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/3-1 Retarded renal development was classified using the scheme o f Woo and Hoar.(4) In addition, all live fetuses with malformations visible at external examination were examined for soft tissue alterations; decapitation o f these fetuses was at the discretion o f the study director or a designee.
After fixation in Bourn'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.
L. Control o f 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.
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M. Statistical Analyses
Sequential two-tailed 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 of affected fetuses per litter or the litter mean was used as the experimental unit for statistical evaluation. The level o f 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)
Compa" y ^ n m
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RESULTS AND DISCUSSION
ANALYTICAL EVALUATIONS
A. Chromatography Appendix A
H-25231 eluted from the HPLC column as resolved peaks over mass to charge ratio (m/z) range o f approximately 789 to 1089. For the purpose of quantitation, the m/z ratios o f 789, 889, 989,
for determined to be representanv^jfthe H-25231 n n h ^ lo sm g matrix. R epresentativ^X M S chromatograms are shown in Appendix A, Figures 2(a - c). Test substance was not detected in the 0 mg/mL control.
B. Concentration Verification and Stability Samples Table 1, Appendix A
Analytical results from dosing solutions prepared April 16,2002 and analyzed for uniformity/concentration verification and stability are shown in Summary Table 1 and Appendix A, Table I.
The following table summarizes the results for uniformity/concentration verification and stability analyses for the H-25231 sample preparation on April 16, 2002.
Preparation Nominal0 Measured* Average CV Stability0 Day mg/mL mg/mL % Nominal % % Nominal
Test Day 2
62.5 125 250
61.3, 63,6d 113, H 6d 228, 242
100.0 92.0 94.0
3 2 4
91.2 96.0 98.4
a D osing solution concentration mg H-25231/mL, based on 10 mL/kg dose volume.
H -25231 is approxim atelyfcB ftctive ingredient.
b Duplicate samples analyze!
c Stability samples held for 5 hours at room temperature. Percent Nominal based on measured.
d Reported result based on reanalysis o f the original sample.
The results for H-25231 samples prepared on April 16, 2002 show that the test substance was at the targeted concentration, 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.
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C. Concentration Verification Samples Table 1, Appendix A
Analytical results from dosing solutions prepared April 23, 2002 and April 30, 2002 and analyzed for concentration verification are shown in Summary Table 1 and Appendix A, Table EL
The following table summarizes the results for concentration verification analyses for the both sampling days o f the H-25231 sample preparation.
Preparation Day
23-April-2002
Nominal0 mg/mL
62.5 125 250
Measured* mg/mL
65.9, 63.1 119, 128 268, 249
Average % Nominal
103.2 99.2 103.6
CV %
3 5 5
30-April-2002
-
62.5 125 250
60.7, 55.4 127, 118c 213, 228
92.9 6 98.4 5 88.4 5
a Dosing solution concentration mg H-25231/mL, based on 5 mL dose volume. H -25231 is approximatelygp|M ctive ingredient
b Duplicate sam plesper level were analyzed. C.V. calculated to verify uniformity o f mixture. c Reported result based on reanalysis o f the original sample.
The results for samples prepared on April 23,2002 and April 30, 2002 indicate that the test substance was at the targeted levels (target = 11.6% o f nominal) and adequately mixed (CV's less than 10) for all H-25231 samples. Test substance was not detected in the 0 mg/mL samples.
D. Analytical Conclusions
Results from the analysis o f the test substance dosing solutions during the study indicate that the test substance was mixed properly, at the targeted levels, and stable under the conditions o f the study. Test substance was not found in the 0 mg/mL samples.
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DEVELOPMENTAL TOXICOLOGY
A. Maternal Findings
1. Mortality
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 slight, statistically significant, compound-related effects on maternal body weight parameters at 1250 and 2500 mg/kg/day.
At 2500 mg/kg/day, there was a mean body weight loss at the onset of dosing (days 6-8G) that resulted in significantly reduced mean maternal weights (3%-4%) over days 8-14G. The impact o f these reductions was minimal (2%) on absolute final body weight but was more pronounced when the final weight was adjusted for the weight of the products o f conception (4%). Mean overall weight gain at 2500 mg/kg/day was reduced by 7% when compared with the control group; however, when the adjusted final weight was used to calculate the gain, the mean weight gain was reduced 26% when compared with the control group. Otherwise, mean weight gains were significantly increased over days 14-16G and significantly decreased over days 18-20G; these two occurrences were not considered to be o f major toxicological relevance.
At 1250 mg/kg/day, there were also statistically significant reductions in maternal weight gain at the onset o f dosing (days 6-8G). The magnitude o f the body weight effect at 1250 mg/kg/day was similar to but smaller than the effect observed at 2500 mg/kg/day. The impact o f this slight reduction on final body weight was minimal (2%) but was statistically significant (3% reduction)' when the adjusted final body weight mean was considered. Mean overall weight gain at 1250 mg/kg/day was reduced 5% when compared with the control group; however, when the adjusted final weight was used to calculate the gain, the mean weight gain was reduced 22% when compared with the control group.
At 625 mg/kg/day, there was a significant reduction in maternal weight gain over days 6-8G. While this reduction was considered related to the compound, it was not considered adverse because it had no appreciable impact on either final body weight or overall body weight gain at this dose level.
3. Food Consumption (Table 4, Appendix D)
There was a compound-related reduction in mean food consumption at 2500 mg/kg/day. Mean food consumed was significantly reduced at this level over days 6-8, 8-10, and 10-12G. Overall
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food consumption (days 6-21G) was not significantly reduced but was reduced by 8% when compared with the control group.
At 625 and 1250 mg/kg/day, there was a significant decrease in mean food consumption over days 10-12G. These transient reductions were considered spurious and unrelated to the compound.
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 a few animals from each group across all levels including the control group during the study.
5. Postmortem Findings (Appendix F)
There were no compound-related maternal gross postmortem findings observed at any level tested. One rat from the 1250 mg/kg/day group had a firm white mass in the location of a mammary gland; this was not considered to be a compound-related finding.
B. Fetal Findings
1. Mortality (Table 6, Appendix G)
There was no compound-related fetal mortality at any level tested; data for fetal resorptions and dead fetuses were comparable across all groups on study.
2. Body Weight (Table 6, Appendices G and H)
There was a compound-related reduction (4%) in mean fetal weight at 2500 mg/kg/day. Mean fetal weight was unaffected by the compound at doses up to 1250 mg/kg/day.
3. Malformations (Table 7, Appendix H)
There were no compound-related fetal malformations observed at any level tested. One fetus from the 2500 mg/kg/day group was observed with caudal agenesis. Because only one fetus from the whole study was thusly affected, this finding was considered to have occurred by chance and was not considered related to the compound.
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4. Variations (Table 8, Appendix H)
There was a significant increase in the incidence of supernumerary ribs at 2500 mg/kg/day (15 affected fetuses from 11 litters). Although this finding was statistically significant, it was not considered to be toxicologically relevant because the incidence o f this finding was within the range of relevant historical control data (see below); the statistical significance appears to be resulting from the unusually low control group value (3 affected fetuses from 3 litters). There were no other compound-related fetal variations at 2500 mg/kg/day nor were there any at doses o f 1250 mg/kg/day or lower.
Control Group Incidence o f Supernumerary Ribs
Study Reference
W H i) mr
Year Conducted
2001
2001
2001
No. Affected Fetuses (No. Affected Litters)
10(6)
16(5)
22 (8)
w fP S B B "
2000 2000 2000
13(7) 15(11) 14(6)
gfiMPaqr Sanitized, Does not contain TSCA CBI 22
H -25231: Developmental Toxicity Study in Rats
DuPcmt-10309
CONCLUSIONS
Under the conditions o f this study, maternal toxicity evident as reductions in body weight parameters was observed at 1250 and 2500 mg/kg/day. Effects on maternal food consumption were also reported at 2500 mg/kg/day. Non-adverse maternal effects occurred at 625 mg/kg/day; thus, the maternal no-observed-effect level (NOEL)3was considered 625 mg/kg/day. Developmental toxicity was evident at 2500 mg/kg/day evident as reduced mean fetal weight. The NOEL for developmental toxicity was considered 1250 mg/kg/day.
RECORDS AND SAMPLE STORAGE
Laboratory-specific or site-specific raw data, such as personnel files and equipment records will be retained by the facility where the work was done.
A sample of the test substance was collected for archive purposes and retained at Haskell Laboratory. Specimens, raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. Raw data will be retained at Haskell Laboratory, Newark, Delaware. Characterization data (percent purity, composition, and known impurities) will be stored at Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. Characterization data used to support test substance stability will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware.
a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U.S. EPA(,2) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(13)
Company Sanitised. Does not contain TSCA CBS
23
H -25231: Developmental Toxicity Study in Rats
REFERENCES
DuPont-10309
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.
Sanitized. Does not contain TSCA CW
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H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLES
Bapiflzed. Does not contain TSGA CB|
25
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 1
SUMMARY OF DOSING SOLUTION ANALYSES
Sample Type_______________________________ Dosing Concentrations and Stability o f H -25231 (mg/mL)a
16-April-2002 Concentration Verification
Average Measured Cone.0 Average Percent Nominal0 Standard Deviation0 Coefficient o f Variation0
Nominal:_________ 6225_______________ 125_______________ 250
61.3 113 228
(98.1)0
(90.4)
(91.2)
63.6 116 242
(101.8)
(92.8)
(96.8)
62.5 115 235
(100.0)
(92.0)
(94.0)
1.6
2 .1
9 .9
3% 2% 4%
Stability 0-Day Room Temperature^
5-hour Room Temperature
62.5
(100.0) 57.0 (91.2)
115
(92.0) 120
(96.0)
235
(94.0) 246
(98.4)
Concentration Verification0 23-April-2002
30-April-2002
64.5 (103.2)
58.0 (92.9)
124 (99.2)
123 (98.4)
259 (103.6)
221 (88.4)
a Dosing solution concentration mg H-25231/mL based on 5 mL dose volume. H-25231 is^ P H H H H H H ^ ic tiv e ingredient
b Numbers in parentheses are merespective percent of nominal values. c Mean, S.D. and C.V. for duplicate samples calculated to verify uniformity of mixture. d Mean result for concentration verification samples used as baseline for stability samples. e Duplicate samples submitted. Mean result reported.
0 o m " co m i,, W c a c ( | | 26
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
GROUP
DOSE
m9 /kg/day
I0
II 625
III 1250
IV 2500
0
239.2 8.91
22
237.9 7.56
21
238.3 7.78
22
239.5 9.44
22
TABLE 2
MEAN MATERNAL BODY WEIGHTS (grams)
DAYS OF GESTATION 4678
9
257.8 13.62
22
253.9 11.34
21
258.0 10.02
22
254.7 14.87
22
266.5 12.18
22
265.0 11.28
21
267.2 9.60
22
267.4 16.27
22
271.1 11.15
22
267.6 13.64
21
268.7 9.92
22
263.8 16.65
22
276.6 11.43
22
272.2 11.72
21
273.9 11.62
22
264.2* 19.93
22
281.2 12.30
22
277.4 13.66
21
277.3 9.81
22
270.1* 16.56
22
10
286.8 13.32
22
282.0 13.64
21
283.6 11.99
22
275.6* 17.49
22
Company Sanitized. Doe not contain TSCA CBI
27
)
H -25231: Developmental Toxicity Study in Rats
)
)
DuPont-10309
GROUP
DOSE
m9/kg/day
I0
II 625
III 1250
IV 2500
11
293.9 14.74
22
290.1 14.21
21
290.0 11.17
22
283.6* 17.10
22
TABLE 2 (Continued)
MEAN MATERNAL BODY WEIGHTS (grams)
DAYS OF GESTATION 12 13 14 15
16
300.6 16.42
22
293.2 15.20
21
294.2 13.56
22
290.1* 17.13
22
306 3 15.83
22
300.0 13.95
21
299.8 12.89
22
294.5* 16.20
22
314.0 15.90
22
306.5 14.88
21
307.0 14.42
22
302.3* 17.18
22
320.9 16.51
22
313.1 16.96
21
314.9 15.07
22
309.9 17.83
22
330.7 18.15
22
324.4 19.11
21
326.7 17.42
22
322.5 18.65
22
17
343.0 18.74
22
336.3 19.32
21
339.9 19.92
22
336.0 20.69
22
I
I
1
28
)
H -25231: Developmental Toxicity Study in Rats
)
)
DuPont-10309
TABLE 2 (Continued)
MEAN MATERNAL BODY WEIGHTS (grams)
GROUP
DOSE
mg/kg/day
18
DAYS OF GESTATION 19 20 21
I0 II 625 III 1250 IV 2500
357.7 22.79
22
349.5 18.75
21
355.0 21.92
22
349.9 19.92
22
373.6 22.99
22
364.9 21.85
21
371.0 25.24
22
364.9 23.04
22
390.4 24.67
22
380.0 24.42
21
384.3 27.11
22
378.0 21.82
22
412.1 27.19
22
401.9 28.51
21
405.6 29.16
22
402.3 25.90
22
21-fr
322.0 18.10
22
313.6 18.27
21
310.8* 13.53
22
308.6* 18.83
22
Data arranged:
Mean Body Weights (grams) Standard Deviation Number in Group
a Data from one female that was not pregnant 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.
Sanitized. Does not contain TSCA CSf
29
H-25231 : Developmental Toxicity Study in Rats
)
DuPont-10309
GROUP
DOSE
mg/kg/day
I0
II 625
III 1250
IV 2500
TABLE 3
MEAN MATERNAL BODY WEIGHT CHANGES (grams)
DAYS OF GESTATION
4-6
6-8
8-10
10-12
12-14
14-16
8.7 7.09
22
11.1 7.59
21
9.2 4.99
22
12.7 5.77
22
10.1 4.57
22
7.2* 4.49
21
6.7* 6.89
22
-3.2* 9.27
22
10.2 3.58
22
9.8 4.98
21
9.7 7.10
22
11.4 9.07
22
13.8 5.28
22
11.2 4.53
21
10.6 4.68
22
14.5 5.13
22
13.3 4.20
22
13.3 4.80
21
12.8 6.24
22
12.2 5.53
22
16.7 4.50
22
17.9 5.90
21
19.6 5.68
22
20.3* 4.93
22
16-18
27.0 8.93
22
25.1 7.91
21
28.3 6.43
22
27.4 4.69
22
30
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 3 (Continued)
MEAN MATERNAL BODY WEIGHT CHANGES (grams)
GROUP
DOSE
mg/kg/day
18-20
DAYS OF GESTATION
20-21
6-21
6-21-b
I0
32.7 7.28
22
21.7 5.28
22
145.6 23.73
22
55.5 13.81
22
II 625
30.5 7.81
21
21.8 5.95
21
136.9 23.79
21
48.6 14.20
21
III 1250
29.3 5.81
22
21.4 6.47
22
138.4 23.89
22
43.5* 10.39
22
IV 2500
28.1* 4.18
22
24.3 6.40
22
134.9 16.47
22
41.2* 11.82
22
1 Data arranged: Mean Body Weights (grams)
Standard Deviation Number in Group
a Data from one female that was not pregnant 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.
Sanitized. Does not contain TSCA CBS
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H-25231: Developmental Toxicity Study in Rats
DuPont-10309
GROUP
DOSE
mg/kg/day
I0
II 625
III 1250
IV 2500
TABLE 4
MEAN MATERNAL FOOD CONSUMPTION (grams/day)
DAYS OF GESTATION
4-6
6-8
8-10
10-12
12-14
14-16
21.9 3.44
22
22.7 3.04
21
23.0 3.52
22
23.4 3.74
22
23.1 2.66
22
21.6 2.89
21
21.6 3.48
22
17.7* 4.47
22
23.4 3.07
22
22.3 3.17
21
22.4 2.64
22
20.9* 2.64
22
25.6 3.26
22
23.6* 2.57
21
23.8* 2.71
22
23.8* 2.41
22
26.4 2.70
22
25.1 2.55
21
25.4 3.28
22
24.7 1.88
22
26.9 3.66
22
25.5 3.93
21
26.7 2.95
22
26.3 2.28
22
16-18
28.2 4.33
22
26.1 2.77
21
2 7 .9 2.81
22
27.4 2.25
22
o
32
H -25231: Developmental Toxicity Study in Rats
TABLE 4 (Continued)
MEAN MATERNAL FOOD CONSUMPTION (grams/day)a*
GROUP
DOSE
mg/kg/day
DAYS OF GESTATION
18-20
20-21
6-21
I0
27.6 3.41
22
25.4 3.31
22
25.8 2.79
22
II 625
26.3 3.32
21
24.5 4.50
21
24.4 2.54
21
III 1250
26.1 3.21
22
24.6 3.81
22
24.8 2.46
22
IV 2500
25.4 2.20
22
25.4 4.06
22
23.8 1.25
22
Data arranged:
Mean Food Consumption (grams/day) Standard Deviation Number in Group
a Data from one female that was not pregnant were excluded.
* Significant trend (linear contrast of means); p < 0.05.
DuPont-10309
H -25231: Developmental Toxicity Study in Rats
)
TABLE 5 CLINICAL OBSERVATIONS
DAY OF GESTATION
OBSERVATION:
GROUP : DOSE (mg/kg/day) :
NO. EXAMINED :
I 0 22
II 625 22
4- 6 6-21
ALOPECIA ALOPECIA
30 32
No statistically significant trends (Cochran-Armitage test); p < 0.05.
III 1250 22
0
2
IV 2500 22
0
3
)
DuPont-10309
3 Wo
34
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 6
REPRODUCTIVE OUTCOME
Group: Dose (mg/kg/day):
I 0
II h i IV
625
1250
2500
No. Mated No. Pregnant No Delivered Early No. Deaths No. With Total Resorptions
No. Litters Means Per Litter Mean Corpora Lutea3
22 22 0 0 0 22
16.3 (3.3)*
22 21 0 0 0 21
14.7(2.0)
22 22
0 0 0 22
16.5(2.8)
22 22
0 0 0 22
15.7(2.7)
Implantations
13.3 (2.9)
13.2(2.8)
14.1(2.9)
14.3(1.8)
Resorptions:
Total Early Late
0.2(0.5) 0.2(0.5)
0.0
0.3(0.7) 0.2(0.7)
0.0
0.3(0.6) 0.3(0.6)
0.0
0.3(0.8) 0.3(0.8)
0.0
Dead Fetuses
0.0 0.0 0.0 0.0
Live Fetusesc:
Total Males Females
13.1(2.9) 5.8(2.0) 7.3 (2.4)
12.9(2.6) 6.6(2.0) 6.3(2.6)
13.8(3.1) 7.4(2.8) 6.4 (2.3)
14.0(2.0) 6.7(2.1) 7.3 (2.0)
Mean Fetal Weight: Total Males Females
5.40(0.4) 5.54(0.39) 5.28 (0.42)
5.39(0.3) 5.54(0.28) 5.23(0.23)
5.42(0.2) 5.53(0.22) 5.29(0.24)
5.21(0.4) 5.37(0.40) 5.06(0.36)
Sex Ratio1^
0.45(0.14)
0.52(0.15) 0.53(0.14) 0.48 (0.13)
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.
Company Sanitized. Does not contain TSCA CBS
35
/''"'N.
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 7
INCIDENCE OF FETAL MALFORMATIONS
Group: Dose (mg/kg/day):
I 0
II III 625 1250
EXTERNAL
No. Examined3 Caudal Agenesis
No. Affected
288 [22] __ b 0[0]
271 [21]
--0 [0]
303 [22]
--0 [0]
IV 2500
309 [22] 1(1) 1 [1]
VISCERAL No. Examined
Stomach - Absent No. Affected
150 [22] --0 [0]
142 [21] --o [0 ]
157 [22] --0[0]
158 [22] K l) 1[1]
HEAD No. Examined No. Affected
150[22] 0[0]
142 [21] 0 [0]
157 [22] 0[0]
158 [22] 0 [0]
SKELETAL
No. Examined Appendicular Skeleton - Absent Femur - Absent Rib - Fused Sternebra - Fused
No. Affected
288 [22] 271 [21] 303 [22]
--
----0 [0]
--
----0 [0]
--
----0 [0]
309 [22]
1(1) 1(1)
K l)
1(1) 1 [1]
TOTAL NUMBER AFFECTED
0 (0)
0 (0)
0 (0)
1(1)
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.
No significant trends were detected.
Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam type are presented for information only.
Company Sanitized. Does not contain TSCA CBI
36
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 8
INCIDENCE OF FETAL VARIATIONS
Group: I
II
Dose (mg/kg/day): 0
625
III 1250
IV 2500
DEVELOPMENTAL VARIATIONS
EXTERNAL No. Examined3 No. Affected
288 [22] 271 [21]
0 [01
0 [0]
303 [22]
o [03
309 [22] 0 [0]
VISCERAL No. Examined No. Affected
150 [22] 0 [0]
142 [21] 0 [0]
157[22] 0 [0]
158 [22] 0 [0]
HEAD No. Examined No. Affected
150 [22] 142 [21]
0 [0]
0 [0]
157 [22] 0[0]
158 [22] 0 [0]
SKELETAL No. Examined
Rib - Supernumerary No. Affected
288 [22] 3 (3) 3 [3]
271 [21] 9 (6) 9 [6]
303 [22] 16 (5) 16 [5]
309 [22] 15(11)* 15[11]
TOTAL WITH DEVELOPMENTAL VARIATIONS
3 (3)
9 (6)
16(5)
15(11)
goropang sanitized. Does not contain TSCA CBI
37
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 8 (Continued)
INCIDENCE OF FETAL VARIATIONS
Group: Dose (mg/kg/day):
I 0
II 625
III 1250
VARIATIONS DUE TO RETARDED DEVELOPMENT
EXTERNAL No. Examined No. Affected
288 [22] 0 [0]
271 [21] 0 [0]
303 [22] 0 [0]
IV 2500
309 [22] 0 [0]
VISCERAL No. Examined
Kidney-P Small Papilla - Size 2 Papilla - Size 3
No. Affected
HEAD No. Examined No. Affected
SKELETAL No. Examined
Pelvis - Retarded Ossification Skull - Retarded Ossification Sternebra - Retarded Ossification Vertebra - Retarded Ossification No. Affected
150[22] 142 [21] 157 [22] 158 [22]
2 (2) 7 (5) 9[5]
3 (3) 14(12) 17[13]
2 (2) 5(4) 7 [6]
K l)
7(4) 8 [4]
150 [22] 0 [0]
142 [21] 0 [0]
157 [22] o [03
158 [22] 0 [0]
288 [22] 1(1)
54(IS)
87(13) 123 [21]
271 [21] __ c
33(13) 1(1)
49(12) 75[17]
303 [22] ---
36(14) ---
64(15) 97 [21]
309 [22] 1(1)
57(17) 2 (1)
95(18) 133[21]
Poes not contain TSCACBt
f 38
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
TABLE 8 (Continued)
INCIDENCE OF FETAL VARIATIONS
Group: Dose (mg/kg/day):
I 0
II 525
TOTAL WITH VARIATIONS DUE TO RETARDED DEVELOPMENT
130 (21)
89 (20)
III 1250
102(21)
IV 2500
137(21)
TOTAL NUMBER FETUSES WITH VARIATIONS
131(21)
94 (20)
114(21) 147(22)
a Number examined and affected, including the number affected with the listed variations, are expressed as Fetuses[Litters] or Fetuses (Litters).
b Statistical analyses are conducted on the combined incidences of small renal .papillae; the details for each size are presented for information only,
c For ease of reading, zeros have been replaced with dashes for the listed variations.
* Significant trend (Jonckheere's test); p < 0.05.
Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam are presented for information only.
^npffiqr Sanitized. Does not contain TSCA CBI
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDICES
gpiapanf Sanitized. Does not contain TSCA CB
40
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX A Analytical Data
PqnP ^ V 8 anime Does noi contain TSca CBl
41
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
Table I. Concentration Verification and Stability o f H-25231 in Dosing Solutions
Preparation Day
mg/mL H-25231(A)
Percent
Sample Type 16-April-2002
Nominal
Measured
Nominal
Concentration Verification(B) Control
0.0
n d (c )
--
62.5-1 (D) 62.5-2
Mean(E)
61.3
63.6
62.5 1.6 C.V.3%
98.1 101.8 (100.0)
125-lP) 125-2
Mean(E)
113 116
115 2.1 C.V. 2%
90.4 92.8
(92.0)
250-1 250-2
228 242
91.2 96.8
Mean(ty
235 9.9 C.V. 4%
(94.0)
Stability
62.5 57.0 91.2 125 120 96.0 250 246 98.4
(A) Dosing solution concentrationjng H-25231/mL, based on 5 mL dose volume. H-25231 islB H M H R B H H vC tive ingredient.
(B) Duplicate samples per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity o f mixture. (C) Denotes not detected. (D) Reported results for the 62.5 mg/mL and 125 mg/mL duplicate samples from reanalyses of original samples. (E) Mean result for analyses on duplicate samples.
pom pany Sanitized. Does not contain TSCA CBI
42
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
Table H. Concentration Verification o f H-25231 in Dosing Solutions
Preparation Day
Sample Type 23-April-2002
mg/mL H-25231(A)
Nominal
Measured
Concentration Verification(E) Control
0.0
n d (c )
Percent Nominal
--
62.5-1 62.5-2
Mean(P)
65.9 63.1
64.5 2 .0 C.V.3%o
105.4 101.0
(103.2)
125-1 125-2
Mean^P)
119 128
124 6.4 C.V.5%o
95.2 102.4
(99.2)
30-April-2002
Concentration Verification(E) Control
250-1 250-2
MeantP)
268(E) 249
259 13 C.V. 5%
0.0 ND(C)
107.2 99.6 (103.6)
--
62.5-1 62.5-2
MeantP):
60.7 55.4
58.0 3 .7 C.V. 6%
97.1 88.6
(92.9)
125-1 125-2
Meanf):
127 118
123 6.4 C.V. 5%
101.6 94.4
(98.4)
250-1 250-2
213 228
85.2 91.2
Meant);
221 11 C.V. 5%
(88.4)
(A) Dosing solution concentration mg H-25231/mL based on 5 mL dose volume.
H-25231
ingredient.
(B) Duplicate samples per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture.
(C) Denotes not detected.
(D) Mean result for analyses on duplicate samples.
(E) Mean result for duplicate reanalyzes of original sample. Original analysis not reported due to aliquot error.
Company S a m ia e * Does not contain TSCA
.
43
H -25231: Developmental Toxicity Study ip Rats
Figure 1 Representative Analytical Calibration Curves
DuPont-10309
Figure la : Calibration curve (LC/MS
showing linear fit (line)
to replicate peak area measurements (squares) for calibration
solutions o f H-25231 diluted over a concentration range o f 0.24
to 0.75 ppm (0.00024 to 0.00075 mg/mL).
Figure lb : Calibration curve (LC/MS -B B H R H K h o w in g linear fit (line) to replicate peak area measurements (squares) for calibration solutions o f H-25231 diluted over a concentration range o f 0.24 to 0.75 ppm (0.00024 to 0.00075 mg/mL).
Does not contain TSCA CBI
44
H -25231: Developmental Toxicity Study in Rats
Figure 1 (continued) Representative Analytical Calibration Curve
DuPont-10309
Figure lc: Calibration curve (LC/MS - H H 9 P H |s h o w m g non-linear fit (line) to replicate peak area measurements (squares) for calibration solutions o f H-25231 diluted over a concentration range of 0.24 to 0.75 ppm (0.00024 to 0.00075 mg/mL).
Concentration, ppm
Figure Id: Calibration curve (LC/MS
showing non-linear fit
(line) to replicate peak area measurements (squares) for
calibration solutions of H-25231 diluted over a concentration
range o f 0.24 to 0.75 ppm (0.00024 to 0.00075 mg/mL).
Company Sanitized. Does not plain TSCA GBI
45
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
Figure 2 Representative HPLC/MS Chromatography Chromatograms
050102vc8 Smooth(Mn,2x3)
SIR of 4 channels ,ES-
Figure 2a: Representative HPLC/MS chromatograms of 0.00 mg/mL dosing solution o f H-25231.
Compaflr Sanitized. Does not contain TSCA CB|
46
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
Figure 2 (continued) Representative HPLC/MS Chromatography Chromatograms
050102vc11 Smooth(Mn,2x3)
SIR of 4 channels,ES789.08
Figure 2b: Representative HPLC/MS chromatograms o f 0.51 ppm (0.00051 mg/mL) analytical reference solution of H-25231.
Company Sanitized. Does not contain TSCA CB1
47
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
Figure 2 (continued) Representative HPLC/MS Chromatography Chromatograms
050102vc16 Smooth{Mn,2x3) 100-
%-
05Q102vc16 Smooth(Mn,2x3) 100-
%-
050102vc16 Smooth(Mn,2x3) 100-
%-
789 6.82 1475.68
SIR of 4 channels,ES789.08
9.490e+003
889 7.40 2093.85
9.12 " min
SIR of 4 channels,ES889.06
1,266e+004
I 9-30 =^4===;====^^
min
989 7.85 1035.81
SIR of4 channels,ES-
989.06 6.321 e+003
0-
050102vc16 Smooth(Mn,2x3)
100-
% - 0.01 V
i
2.00
4.00
min
SIR of 4 channels ,ES-
1089 8.29
1089.04 4.025e+003
646.83
9.54
6.00 8.00
mm
Figure 2c: Representative HPLC/MS chromatograms o f 62.5 mg/mL dosing solution diluted to nominal concentration o f 0.000625 mg/mL (0.625 ppm) o f H-25231. The measured concentration o f the representative solution is 60.7 mg/mL.
fy Sania
Does natccr,tain TSC4 CBt
48
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX B Individual Body Weights
iS C A Ctot
49
H -25231: Developmental Toxicity Study in Rats
Individual Body Weights
DuPont-10309
Explanatory Notes
Note
Reporting o f 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 additional body weight data collected for the separate breeding lots of animals on days prior to day 6G are available in the raw data.
Footnote
a Maternal body weight minus the weight of the products of conception.
Abbreviations
NP = Not Pregnant -----= No Data
c TM .P ^ Santesd. DMSnotrontainTSMcB(
50
H-25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
DAY 0
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
235.0 235.0 251.0 232.0 244.0 250.0 250.0 239.0 248.0 230.0 232.0 241.0 236.0 233.0 237.0 265.0 230.0 240.0 236.0 230.0 231.0 238.0
INDIVIDUAL BODY WEIGHTS (grams)
DAY 4
265.1 252.9 266.5 254.1 257.9 272.7 267.6 250.7 266.5 252.1 220.2 264.8 261.0 250.7 267.8 284.2 235.0 262.3 262.7 240.2 252.6 263.6
DAYS OF GESTATION
DAY 6
DAY 7
DAY 8
285.9 268.6 282.6 266.6 270.1 277.4 269.9 261.1 280.3 260.6 244.8 269.8 270.1 262.7 269.9 285.8 243.5 267.8 256.1 247.0 253.7 268.2
292.9 276.2 286.7 275.7 270.0 281.5 267.9 264.1 284.2 264.3 253.1 267.6 274.6 271.7 272.9 286.4 247.3 269.3 264.9 256.9 263.3 272.0
300.4 279.3 294.7 281.2 274.3 284.4 274.1 265.2 284.3 270.9 260.4 277.9 279.8 270.4 276.8 296.9 255.8 274.6 278.6 261.4 265.2 277.9
DAY 9
304.5 287.7 300.2 287.6 277.2 292.8 278.1 270.7 287.7 273.9 268.2 278.5 288.1 274.5 281.9 300.5 255.5 287.0 279.8 262.1 270.4 279.3
DuPont-10309
Company Sanftoed. Does not contain TSCA C B\
51
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
DAY 10
INDIVIDUAL BODY WEIGHTS (grams)
DAYS OF GESTATION DAY 11 DAY 12 DAY 13 DAY 14
DAY 15
DAY 16
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
316..2 290 .4 307..7 296,.0 279 .0 294 .0 280 .5 274 .7 297 .9 274 .1 273 .7 285 .7 292 .2 284 .1 292 .8 306 .4 261 .2 285 .0 286 .6 270 .4 273 .2 287 .4
331..8 299..8 316..3 305..7 288..8 301..4 288,.2 275,.6 298,.6 284 .8 285 .2 292 .8 294 .4 286,.8 296..1 310..8 265..1 292..2 300 .3 274..6 279,.3 298,.3
342 .6 307..5 333..6 309..1 292..5 305..5 296..2 281..3 307..1 290..7 292..6 302..3 304,.6 290,.1 303 ,.0 319,.5 270..0 296..4 304,.0 283 .8 284 .8 296..7
348 .,6 308.,5 336.,8 314..0 301,.1 309,.6 300 ,.7 288,.2 308..9 297 ,7 300 .8 304 ,.9 309 .3 295 .8 306 ,.9 324 ,.5 274 .9 307..3 312 .6 288 .6 292.,9 307.,1
357 .2 315 .8 337 .2 322 .0 309 .2 311 .7 308 .9 296 .5 314 .9 306 .7 308 .2 317 .1 317 .9 303 .4 317 .9 335 .0 281 .7 319,.2 322 .9 295 .9 296..3 311,.4
363 ,.2 321,.9 340 .4 329..7 313 .2 330,.3 313 .1 310..4 325..5 316 .7 318..6 327 ,.3 326 ,.2 307 ,0 318 ,.4 340,.0 285 ,.1 320 ,.5 335 ,.3 299..5 297,.8 319,.6
379 .8 331..4 354 .2 344 ,.7 325 .,4 329,.4 324 ,.7 312 ,.0 330 ,.9 328 .0 331..6 335 .4 342 .3 310 .9 328 .2 352..0 296..3 329..5 342..7 308 .6 308. 2 329..0
empan? Sanitized. Does not contain TSCA CB1.
52
H -25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
DAY 17
INDIVIDUAL BODY WEIGHTS (grams)
DAYS OF GESTATION DAY 18 DAY 19 DAY 20
DAY 21 DAY 21a
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
390..1 343..8 373 .7 355..3 337..4 340..8 330..3 329,.8 339,.7 344 ,.1 343 ,.7 347 .3 355,.5 320 .7 337 .0 363,.5 305 ,.7 345,.8 357 ,.8 324 ,.9 318 ,.5 340,.9
410 .,9 356..1 395 .3 376..0 325..0 356,,0 335.,7 339 ,.0 354 .8 359,.2 365 ,.7 366,.6 369 .7 338 .5 350 .3 378 .0 316 .5 363 ,.8 382,.2 341,.5 331..5 357..5
420. 7 368. 8 407. 3 390.,5 360..8 374..7 349..6 360 .3 369..0 372 .0 383 .7 387..2 387..4 347..9 362..5 397..7 326..3 379..9 405,,9 350..6 345,.3 371 .9
437 .,0 388 .,9 425 .9 411,.9 377,.0 392..0 358 .2 378 ,.5 385 .6 393 ,.0 404 ,.0 404 ,.1 408 .3 360 .2 375 .6 413 .1 340 .9 400 .8 420 .3 364 .8 358 .0 391 .1
465..6 414..7 452 .0 433 .9 388 ,.3 412 .9 364 .9 393 .6 410..2 414..5 431..5 432,.4 431,.9 384,.7 399,.0 432,.4 364 .2 421,.3 440,.0 388,.4 377,.3 413 .0
361,.2 327 ,.0 360,.5 329 ,.4 300..3 322 ,.6 331..3 301..3 321..2 308 ,.4 323 .6 330..4 333 ,.4 310 ,.3 335,.0 326,.7 284 .0 308..8 326 ,.9 311..0 304 ,.6 325,.6
DuPont-10309
Sanitized. Does not contain TSCACBj
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHTS (grams)
GROUP II: 625 MG/KG/DAY
ANIMAL NUMBER
DAY 0
DAY 4
DAYS OF GESTATION
DAY 6
DAY 7
DAY 8
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
230.0 239.0 239.0 256.0 236.0 241.0 230.0 243.0 254.0 236.0 242.0 242.0 236.0 231.0 235.0 249.0 236.0 236.0 230.0 231.0 235.0 230.0
240.1 260.5 261.8 263.0 226.3 251.6 248.0 274.0 277.3 252.0 257.9 242.9 243.2 257.4 244.7 258.2 252.9 252.6 242.4 257.8 259.7 251.2
259.7 268.2 277.8 287.0 257.5 256.4 256.4
285.1 290.9 258.6 269.2 268.2 252.6 268.8 257.1 257.7 256.4 268.0 257.9 262.7 261.7 255.6
265.8 277.4 287.1 292.2 261.0 247.6 257.6 291.5 289.7 255.5 269.6 267.9 251.9 273.2 251.0 261.2 264.3 269.2 251.5 268.5 268.8 264.0
272.7 278.0 287.7 294.2 264.9 258.5 259.7 289.9 294.2 255.7 272.0 279.0 259.1 277.2 261.0 264.0 268.0 272.5 266.0 278.2 275.7 266.7
DAY 9
273.4 284.3 292.3 308.0 269.9 259.6 267.6 298.7 300.8 264.5 282.3 277.7 261.6 278.9 262.6 260.9 270.3 276.3 275.9 275.8 284.4 276.9
DuPont-10309
Company Sanitized. Does not itain TSCA CB1
54
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL BODY WEIGHTS (grams)
GROUP II: 625I MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION DAY 10 DAY 11 DAY 12 DAY 13 DAY 14
DAY 15
DAY 16
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
277..3 291..3 297..3 316..9 279..8 269..6 269..1 303 .3 303 ,.0 266.,4 283 .6 279..7 271,.7 288 ,.1 272 .6 266..6 276..6 281..6 278 .,3 282..4
275..6 270..0
289.,6 301..1 307.,0 318 .6 288..8 272 .1 277..9 316..3 310 ,.7 276 ,.1 294 .1 279..5 278..3 293 ,.0 271..3 270..3 284 .8 290 .9 285 .6 294 .2 289,.3 282 .3
297. 1 305. 7 311. 8 325. 9 296..7 276..8 277 .6 317..9 315..9 276..6 286.,7 286.,3 280..3 300..5 283..6 272..9 278..7 291..2 289 .5 294..9 294 .0 282 ,.7
293 ..0 302.,8 315. 9 329 ..8 301.,8 282 .,5 286 .3 321,.0 324 .5 282 .1 301..5 285..1 286..1 305 .1 293 .3 280 ,.2 293 .4 305 .4 304 .2 301..5 299..8 290,.8
305 .3 315 .5 322 .1 342 .1 309 .6 288 .4 291 .1 326 .5 325 .8 286 .1 308 .1 295 .7 299 .2 312 .4 295 .5 285 .7 296 .6 314 .3 311 .8 306 .6 301 .4 291 .9
310 .8 325 .0 324 .,6 350.,0 312 .,8 294 .3 291 .9 340 ,.5 332 .8 297..4 319..4 297 ,.4 308 ,.6 319 ,.8 306..1 290..4 282 .4 319..4 321.,9 317 .,2 309 .7 300 .3
325..0 340..2 342 .6 367.,9 329..8 305..1 301..3 350..2 346,.6 298,.9 325 ,.6 281,.5 318 ,.6 328 .2 316,.4 296..9 295 .8 333..6 330.,7 326.,9 324 .,0 308..0
Company Sanitized. Does not contain TSCA CBI
55
./" N
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHTS (grams)
GROUP II: 625 MG/KG/DAY
ANIMAL NUMBER
DAY 17
DAYS OF GESTATION DAY 18 DAY 19 DAY 20
DAY 21
DAY 2Ia
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
336.3 352.4 354.1 381.7 342.1 314.3 316.7 360.7 357.1 308.7 333.7 277.9 335.3 340.1 326.2 302.5 315.8 346.7 343.5 340.5 334.9 319.9
350.0
361.9 362.8 373.8 361.4 327.1 324.1 372.5 371.0 321.1 347.2 283.3 353.7 353.9 341.1 306.4 334.9 370.7 361.6 355.0 354.3 335.7
370.3 377.6 380.3 398.3 375.3 342.5 339.5 398.1 385.6 328.6 363.0 286.6 372.9 367.5 355.2 316.7 344.4 386.4 381.4 365.7 365.4 348.9
390.4 390.0 398.2 419.2 392.7 357.2 351.2 420.1 396.2 347.5 377.0 278.9 388.3 380.9 369.9 322.1 358.4 407.3 397.5 380.6 374.3 361.9
412.3 416.7 424.9 442.5 423.1 373.9 372.1 446.0 417.2 364.6 385.4 280.1 414.1 400.7 389.3 335.6 377.6 433.0 430.9 402.5 401.1 375.8
326.1 335.8 327.4 342.9 320.0 293.1 301.8 341.5 331.0 290.6 290.7
--
298.5 300.9 305.3 309.4 289.3 323.2 340.2 312.7 312.0 294.3
DuPont-10309
Company Sanifead. Does oieonianrscACBI
56
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHTS (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
DAY 0
DAY 4
DAYS OF GESTATION
DAY 6
DAY 7
DAY 8
S58707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
230.,0 256 ..0 233 .,0 230..0 248..0 246.,0 244,.0 241,,0 234 ,.0 255,.0 234 ,.0 244..0 239,.0 241.,0 232 .,0 236 .0 234..0 233 ,.0 237 .0 230 .0 235 ,.0 230 ,.0
260 .6 275 .2 243 ,.8 236 .6 246 .2 253 ,.3 265 .7
257 .5 255 .5 281 .4 256 .7 262 .8 258 .0 270 .6 262,.1 257,.3 255 .2 252 .6 262 ,.0 248 .3 260 .8 254 .2
274.7
283.1 256.3 253.0 262.9 269.1 275.0 269.0
268.1 292.8 268.4 273.6 263.0 274.7 271.4 269.5 258.4 256.0 263.1 258.2 260.5 258.3
281.9 276.3 260.1 259.4 268.5 272.9 272.1 261.4 269.3 289.8 262.1 273.9 271.2 282.2 276.3 270.8 264.2 251.9 273.1 262.6 262.7 248.0
289.9 294.6 257.5 265.7 279.8 276.7 279.5 263.1 267.7 295.6 265.2 273.0 280.0 290.7 282.6 276.3 265.4 258.9 265.6 273.6 265.3 259.9
DAY 9
292.6 292.1 263.2 271.4 280.5 283.3 278.7 273.6 277.5 302.3 271.6 281.3 275.2 269.1 290.0 272.8 272.2 264.2 276.2 273.9 271.1 267.5
DuPont-10309
Company Sanfee! Doe, no. contain TSCA CBI
57
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL BODY WEIGHTS (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
DAY 10
DAY 11
DAYS OF GESTATION DAY 12 DAY 13 DAY 14
DAY 15
DAY 16
S58707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
300 .5 303 ,.8 267..0 279..2 294..4 282..5 286..5 286 .1 282..0 317..3 278. 6 281. 5 279..3 282 ,3 293 .4 277 .5 274 .6 268 .9 282 .2 274 ..5 276..0 271..8
308 .4 301 .2 270 .2 280..8 293 .0 292 .2 293 .9 289 .1 288 .5 322 .7 285 .5 281..4 287 .8 296 .0 298 .7 279 .5 286 .9 286 .8 292 .3 278 .7 281 .8 283 .8
314..5 308 ,.9 272 .2 292 .1 306..1 295..9 292..0 298..4 296..9 329.,0 285. 3 297. 3 278. 3 300..4 309..0 290..3 288.,8 280..7 292..9 279 .1 284 .0 280..1
321,.3 313 ,.0 277..0 295..3 304 ,.4 300 ,.3 287 .2 305 ,.6 294 .9 334 ,.0 290 .7 302 .8 285 ,.1 305 .2 316..4 297..6 295..2 286..5 298.,6 294.,3 298 .2 292 .4
330,.4 325,.2 281,.2 303 ,.3 314..0 308..3 291..0 303 .3 298 .9 347..2 298..4 302.,4 297..4 313 ..0 324 .2 310..0 300..7 296..1 306.,8 302 .,6 298 .,7 301..6
337..9 327..5 281..8 311..0 317..0 315..8 305..4 318 ,.8 315 .0 355,.9 307..4 315 .6 307 ,.6 325..4 333 .5 318 ,.6 305 .8 300 .3 312 .4 303 .6 305 .6 305 .7
355 .,2 344 .2 286,.0 325 .2 341,.7 328 ,.8 318 ,.6 324 ,.1 325 .7 371,,8 311.,4 325 .7 322 .1 326..5 346 ,.7 327 ,.9 315 ,.4 310 ,.7 322 ,.0 321,.8 317,.7 317 ,.2
'9% 0@s Hot r C4 CBI
58
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHTS (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
DAY 17
DAYS OF GESTATION DAY 18 DAY 19 DAY 20
DAY 21
DAY 21*
658707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
373 ,.7 359 ,.9 289,.4 334 ,.5 347 ,.3 345 ,.6 328 ,.6 328 .2 336 ,.8 391..6 328 .7 340 .9 337..0 339,.6 362..2 341..2 324 .3 326 .1 337 .6 336 .8 330 .3 338 .5
388..8 376.,6 296..6 346 .9 363..9 357 .9 339..3 345..7 350..2 409..0 333 .9 356..8 353 .0 361..7 379,.0 358,,9 343 .2 337..3 356,.5 357..8 348..4 348 .0
404..6 397..4 297..4 361..5 386..9 371..0 352.,4 360..2 367..5 430 .1 347,.5 375 ,.1 372,.0 373 ,.5 394 ,.2 377 .5 356 .0 353 ,.8 378 .4 374 .2 362 .6 367 .4
422 ,.7 408..4 307,.0 373 .0 392..0 383 .9 365 .8 373 .0 383 ,.4 452 .8 363 .9 386..5 385 ,.1 392,.8 413,.3 391 .2 369 .6 366 .5 385 .4 385 .2 375 .3 377 .1
444 .3 435 ,.4 311,.2 390 .6 413 .0 399,.6 388,,2 390,,3 416 .2 462 .6 384 .6 414 .,3 413..1 423.,3 434..1 409..1 391..8 388 .9 409..1 407..4 393 .5 403 .4
342,.2 334,.2 296,.5 300 .2 314 ,.8 287,.5 302..6 310 .0 315 .5 334 .0 304 .5 311..9 312 .9 310..7 329..7 301..5 307..6 297..4 305..7 301..7 306..9 309..0
DuPont-10309
Company Sanitized. Does not contain TSCA C8|
59
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHTS (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
DAY 0
DAY 4
DAYS OF GESTATION DAY 6 DAY 7 DAY 8
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
254.0 247.0 235.0 231.0 240.0 234.0 240.0 250.0 245.0 230.0 242.0 233.0 240.0 268.0 243.0 231.0 230.0 230.0 244.0 233.0 234.0 234.0
266.7 259.1 250.9 251.2 243.9 251.3 260.7 272.5 266.1 238.0 261.3 267.5 259.5 291.4 263.4 247.4' 230.9 245.0 262.0 235.5 252.6 227.0
278.3 278.1 256.7 266.8 271.7 252.3 271.3 288.6 282.2 251.6 275.2 280.3 270.1 310.6 273.6 262.8 241.1 254.7 264.4 249.8 260.8 241.8
281.3 279.9 262.4 265.6 265.4 261.0 256.9 286.9 275.7 240.1 273.8 268.7 259.6 304.8 278.3 245.9 242.2 258.9 254.3 238.6 258.2 245.0
288.9 281.3 258.2 273.4 246.3 247.5 265.2 275.3 281.7 243.4 281.2 280.1 257.9 309.2 280.9 259.0 245.3 259.0 256.8 242.2 260.8 219.4
DAY 9
289.6 288.2 264.8 275.5 258.0 257.1 275.8 279.9 284.4 249.3 264.9 288.0 267.8 314.8 279.9 264.9 244.0 265.3 267.1 252.6 257.3 254.1
DuPont-10309
'feed,
TSCA Cfif
60
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL BODY WEIGHTS (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
DAY 10
DAY 11
DAYS OF GESTATION DAY 12 DAY 13 DAY 14
DAY 15
DAY 16
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
298 ..7 264 .8 269..9 283 .5 274 .8 262 .0 286..2 289..1 290..8 259..4 277.,9 290..7 273 ..6 322 .8 287..1 269..7 252..8 269..0 274,.6 255..3 267..2 243 .6
303 .8 276. 9 277. 3 290..0 283 .,6 275..1 294.,9 295..3 298,.9 264..6 287..9 299 .3 285 .0 329..7 289..2 270..2 256..2 276..6 286,.8 262..6 279,.9 255 .2
308.,9 292 .1 281.,2 292 .6 289..3 271..4 304 .1 309..3 297..8 273 .1 288..7 309..4 294,.8 335..0 297..8 278..8 266 .5 279 .6 294 .5 269 .7 284 .2 263 .3
313.9 295.8 287.5 295.5 296.9 277.6 309.1 311.4 295.8 277.7 293.7 308.8 297.0 335.8 305.5 273.4 266.7 292.3 300.7 276.8 291.9 274.7
311.6 306.8
298.1 299.7 311.7 284.5 312.9 313.6 302.1 282.8 306.8 325.1 302.2 349.8 313.9 285.1 272.4 298.6 310.0 285.2 297.5 279.2
319.6 316.1 294.7
302.8 318.5 293.3 321.4 327.8 313.9 292.6 305.8 333.1 311.0 358.9 320.5 290.3 281.5 312.5 318.7 295.5 301.2 287.1
330.0 333.2 310.0 320.2 332.9 303.1 339.6 341.2 328.7 303.2 316.0 345.2 323.7 372.2 330.7 303.9 290.0 323.1 330.7 308.3 308.7 300.7
co m p m f Sanitized. Does not contain TSCA CBS
61
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHTS (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
DAY 17
DAYS OF GESTATION DAY 18 DAY 19 DAY 20
DAY 21
DAY 2Ia
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
343.1 352.1 323.9 330.8 351.9 314.5 356.9 353.7 336.4 308.1 332.8 361.6 335.4 387.1 346.6 307.2 307.5 342.0 346.6 319.4 322.5 311.0
355.4 362.1 332.7 347.7 368.9 328.8 373.5 363.4 351.1 325.2 345.3 380.3 353.2 393.6 359.6 322.9 318.6 349.1 365.2 336.6 335.5 329.7
369.5 374.7 352.6 365.8 378.3 334.1 391.5 374.1 367.8 333.3 370.1 402.1 368.4 417.0 382.0 338.2 332.6 365.0 380.9 345.8 349.2 335.0
383.0 392.3 362.1 378.2 394.3 353.7 398.3 389.2 377.8 357.1 373.1 419.6 377.8 426.0 391.8 345.8 343.7 380.3 392.6 358.1 358.9 362.3
405.9 404.6 382.0 409.1 414.4 369.5 434.0 419.7 399.5 373.2 400.0 447.0 398.7 461.8 422.9 367.2 366.6 409.1 421.7 384.5 380.1 379.8
321.7 303.2 305.1 312.7 304.3 281.3 336.9 328.2 298.1 284.1 305.0 329.3 298.6 354.4 322.9 296.3 284.7 303.5 324.9 299.7 309.9 283.9
DuPont-10309
e s not irta!r,
62
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX C Individual Body Weight Changes
Company Sanitized. Does not contain TSCA CBS
63
H -25231: Developmental Toxicity Study in Rats
Individual Body Weight Changes Explanatory Notes
Footnote a Maternal body weight minus the weight of the products of conception. Abbreviations NP = Not Pregnant -----= No Data
DuPont-10309
"o'oomMnTSCACBI
64
/"N
H -25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
0-4
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
30.1 17.9 15.5 22.1 13.9 22.7 17.6 11.7 18.5 22.1 -11.8 23.8 25.0 17.7 30.8 19.2
5.0 22.3 26.7 10.2 21.6 25.6
INDIVIDUAL BODY WEIGHT CHANGES (grams)
4-6
20.8 15.7 16.1 12.5 12.2 4.7 2.3 10.4 13.8
8.5 24.6
5.0 9.1 12.0 2.1 1.6 8.5 5.5 -6.6 6.8 1.1 4.6
DAYS OF GESTATION
6-8
8-10
10-12
14.5 10.7 12.1 14.6
4.2 7.0 4.2 4.1 4.0 10.3 15.6 8.1 9.7 7.7 6.9 11.1 12.3 6.8 22.5 14.4 11.5 9.7
15.8 11.1 13.0 14.8
4.7 9.6 6.4 9.5 13.6 3.2 13.3 7.8 12.4 13.7
16.0 9.5 5.4
10.4 8.0 9.0 8.0 9.5
26.4 17.1 25.9 13.1 13.5 11.5 15.7
6.6 9.2 16.6 18.9 16.6 12.4 6.0 10.2 13.1 8.8 11.4 17.4 13.4 11.6 9.3
12-14
14.6 8.3 3.6
12.9 16.7
6.2 12.7 15.2
7.8 16.0 15.6 14.8 13.3 13.3 14.9 15.5 11.7 22.8 18.9 12.1 11.5 14.7
DuPont-10309
14-16
22.6 15.6 17.0 22.7 16.2 17.7 15.8 15.5 16.0 21.3 23.4 18.3 24.4
7.5 10.3 17.0 14.6 10.3 19.8 12.7 11.9 17.6
pgiopsrajK Sanitized. Does net contain TSCA CB|
65
H -25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
16-18
INDIVIDUAL BODY WEIGHT CHANGES (grams)
18-20
DAYS OF GESTATION
20-21
6-21
6-21a
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
31.,1 24 .7 41..1 31..3 -0 .4 26 .6 11..0 27..0 23 .9 31..2 34 .1 31..2 27..4 27 .6 22..1 26 .0 20..2 34 .3 39..5 32..9 23 .3 28 .5
26..1 32 .8 30..6 35..9 52 .0 36,.0 22 .5 39..5 30 .8 33 .8 38..3 37..5 38..6 21..7 25..3 35..1 24..4 37..0 38..1 23 .3 26..5 33 .6
28..6 25..8 26..1 22..0 11..3 20..9
6..7 15..1 24..6 21..5 27..5 28..3 23.,6 24..5 23..4 19..3 23 .3 20..5 19..7 23 .6 19..3 21,.9
179.,7 146..1 169 .4 167 .,3 118 .2 135 .5
95 .0 132 .5 129..9 153 .,9 186..7 162 ..6 161..8 122..0 129..1 146 .6 120 .7 153 .5 183 .,9 141.,4 123 .6 144 .8
75,.3 58 .4 77,.9 62 .8 30 .2 45 .2 61 .4 40,.2 40,.9 47 ,.8 78 ,.8 60..6 63 .3 47,.6 65,.1 40 .9 40 ,.5 41,.0 70..8 64 ,.0 50..9 57 ,.4
DuPont-10309
Company Sanitized. Does
W contain TSCACBI
66
/***.,
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHT CHANGES (grams)
GROUP II: 625 MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION
0-4
4-6
6-8
8-10
10-12
12-14
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
10.1 21.5 22.8
7.0 -9.7 10.6 18.0 31.0 23.3 16.0 15.9
0.9 7.2 26.4 9.7 9.2 16.9 16.6 12.4 26.8 24.7 21.2
19.6 7.7
16.0 24.0 31.2
4.8 8.4 11.1 13.6 6.6 11.3 25.3 9.4 11.4 12.4 -0.5 3.5 15.4 15.5 4.9 2.0 4.4
13.0 9.8 9.9 7.2 7.4 2.1 3.3 4.8 3.3 -2.9 2.8
10.8 6.5 8.4 3.9 6.3
11.6 4.5 8.1
15.5 14.0 11.1
4.6 13.3
9.6 22.7 14.9 11.1
9.4 13.4
8.8 10.7 11.6
0.7 12.6 10.9 11.6
2.6 8.6 9.1 12.3 4.2
- 0.1
3.3
19.8 14.4 14.5
9.0 16.9
7.2 8.5 14.6 12.9 10.2 3.1 6.6 8.6 12.4 11.0 6.3 2.1 9.6 11.2 12.5 18.4 12.7
8.2 9.8 10.3 16.2 12.9 11,6 13.5 8.6 9.9 9.5 21.4 9.4 18.9 11.9 11.9 12.8 17.9 23.1 22.3 11.7 7.4 9.2
DuPont-10309
14-16
19.7 24.7 20.5 25.8 20.2 16.7 10.2 23.7 20.8 12.8 17.5 -14.2 19.4 15.8 20.9 11.2 -0.8 19.3 18.9 20.3 22.6 16.1
BWHpany Sanitized Does not contain TSCA C 8I
67
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHT CHANGES (grams)
GROUP II: 625 MG/KG/DAY
ANIMAL NUMBER
16-18
18-20
DAYS OF GESTATION
20-21
6-21
6-21a
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
25 .0 21..7 20..2
5..9 31..6 22 .0 22 .8 22 .3 24 .4 22 .2 21,.6
1..8 35..1 25..7 24 .7
9..5 39,.1 37..1 30..9 28..1 30..3 27..7
40..4 28..1 35..4 45..4 31..3 30..1 27..1 47,.6 25..2 26..4 29..8 -4..4 34..6 27..0 28,.8 15.,7 23 .5 36..6 35..9 25,.6 20..0 26 .2
21.,9 26.,7 26..7 23..3 30..4 16.,7 20.,9 25..9 21..0 17..1
8..4 1..2 25..8 19.,8 19.,4 13 .5 19..2 25..7 33 ..4 21..9 26..8 13 .9
152 .6 148..5 147 ,.1 155 .5 165 .6 117..5 115 .7 160 ,.9 126..3 106 .0 116 .2
11..9 161..5 131..9 132 .,2
77.,9 121.,2 165..0 173 ,.0 139.,8 139.,4 120.,2
66..4 67..6 49..6 55 .9 62 .5 36..8 45,.4 56..4 40 .2 32 .0 21..5
-45..9 32..1 48..2 51..7 32.,9 55..2 82..3 50.,0 50 .3 38 .7
DuPont-10309
Company Sanitized. Doss no! contain tsca CBI 68
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHT CHANGES (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION
0-4
4-6
6-8
8-10
io-:12
12-14
658707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
30 .6 19 .2 10..8
6 .,6 -1..8
7.,3 21.,7 16..5 21..5 26 ,.4 22 .7 18 .8 19 ,.0 29..6 30..1 21..3 21,.2 19..6 25..0 18 ,.3 25 .8 24 .2
14 .1 7. 9
12. 5 16. 4 16..7 15 ..8
9..3 11..5 12..6 11..4 11.,7 10.,8
5.,0 4 .1 9..3 12 .2 3 .2 3 .4 1..1 9..9 .3- 0 . 4 .1
15. 2 11. 5
1.2 12..7 16..9
7..6 4..5 -5..9 -0..4 2..8 -3..2 -0..6 17..0 16..0 11..2 6,.8 7..0 2 .9 2,.5 15,.4 4..8 1..6
10. 6 9 .2 9..5
13 ..5 14 .,6
5..8 7 .,0 23 .0 14 ,.3 21,.7 13 .4 8 .5 -0 ,.7 -8,.4 10 ,.8 1,.2 9 .2 10 .0 16..6 0 ..9 10..7 11..9
14 .0 5 .1 5 .2
12 .9 11 ,7 13 .4
5 .5 12 .3 14 .9 11 .7
6 .7 15 .8 -1 .0 18 .1 15 .6 12 .8 14 .2 11 .8 10 .7
4 .6 8 .0 8 .3
15..9 16..3
9..0 11,.2
7,.9 12 ,.4 -1,.0
4 ,.9 2,.0 18,.2 13 .1 5,.1 19..1 12..6 15 .2 19 .7 11..9 15 .4 13 .9 23 .5 14 .7 21..5
DuPont-10309
14-16
24 .8 19..0
4 .8 21..9 27..7 20..5 27..6 20.,8 26 .8 24 ,.6 13.,0 23 .3 24 .7 13..5 22..5 17..9 14..7 14..6 15,.2 19,.2 19..0 15..6
Company Sanitized. Does not contain TSCA CBI
69
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHT CHANGES (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
16-18
18-20
DAYS OF GESTATION
20-21
6-21
6-21a
658707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
33 .,6 32 .,4 10.,6 21..7 22 .2 29..1 20 .7 21..6 24 .5 37..2 22 ,.5 31..1 30..9 35 .2 32..3 31.,0 27..8 26.,6 34 .5 36..0 30.,7 30 .,8
33. 9 31..8 10..4 26 .1 28 .1 26..0 26..5 27..3 33 .2 43 .8 30..0 29,.7 32 .1 31..1 34 ,3 32..3 26 .4 29..2 28..9 27 .,4 26,.9 29..1
21. 6 27 .0
4 .2 17.,6 21..0 15..7 22.,4 17.,3 32 .8
9..8 20..7 27..8 28..0 30..5 20,.8 17..9 22 .2 22 ,.4 23..7 22 ,.2 18..2 26..3
169 .6 152 .3
54 ..9 137..6 150..1 130..5 113 .2 121..3 148 .1 169 .8 116 .2 140 .7 150..1 148 .6 162 .7 139.,6 133 .4 132 .9 146..0 149..2 133 .0 145 .1
67..5 51,.1 40 .2 47..2 51..9 18..4 27 ,.6 41,.0 47 .4 41 .2 36 .1 38 .2 49 .9 36 .0 58 .3 32..0 49..2 41..4 42,.6 43 .5 46..4 50 .7
DuPont-10309
Company 70
Does
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHT CHANGES (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION
0--4
4-6
6-8
8-10
10-12
12-14
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
12 .7 12 .1 15 .9 20 .2
3 .9 17 .3 20 .7 22 .5 21,.1
8 ,.0 19,.3 34 ,.5 19,.5 23 ,.4 20,.4 16 ,.4
0 ,.9 15 ,.0 18 ,.0
2 ,5 18 ,.6 -7 ,.0
11. 6 19.,0
5 ..8 15..6 27.,8
1.,0 10 .,6 16 .,1 16..1 13 .,6 13 .9 12.,8 10..6 19..2 10 .2 15..4 10 .2
9 ,.7 2..4 14 .3 8 .2 14 .8
10. 6 3.2 1.,5 6.,6
-25 .,4 -4 .8 -6 .,1
-13 ,.3 -0.,5 -8..2 6..0 -0..2
-12..2 -1..4 7..3 -3..8 4..2 4..3 -7..6 -7..6 0..0
-22..4
9..8 -16.,5
11..7 10 .,1 28 .5 14 .5 21,.0 13 ,.8
9..1 16..0 -3 .3 10 .6 15 ,.7 13 .6
6 ,.2 10 ,.7
7..5 10,.0 17..8 13 .1
6 .4 24 .2
10..2 27..3 11..3
9.,1 14..5
9.,4 17..9 20..2
7.,0 13 ..7 10..8 18 .7 21..2 12 .2 10 .7
9,.1 13 .7 10..6 19 .9 14 .4 17,.0 19..7
2 ,.7 14 .,7 16 .9
7 .1 22 .4 13 .1
8 .8 4 .3 4 .3 9 .,7 18 .,1 15.,7 7..4 14 .8 16.,1 6 .,3 5 .9 19 .,0 15..5 15 .5 13 ,.3 15 ,.9
DuPont-10309
14-16
18..4 26..4 11..9 20..5 21,.2 18 ,.6 26,.7 27..6 26..6 20..4
9..2 20..1 21..5 22..4 16..8 18..8 17 ,.6 24..5 20..7 23 ,.1 11..2 21.,5
company Sanittted. Dow X
TSCA CBI
71
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL BODY WEIGHT CHANGES (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
16-18
18-20
DAYS OF GESTATION
20-21
6-21
6-21a
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
25.4 28.9 22.7 27.5 36.0 25.7 33.9 22.2 22.4 22.0 29.3 35.1 29.5 21.4 28.9 19.0 28.6 26.0 34.5 28.3 26.8 29.0
27.6 30.2 29.4 30.5 25.4 24.9 24.8 25.8 26.7 31.9 27.8 39.3 24.6 32.4 32.2 22.9 25.1 31.2 27.4 21.5 23.4 32.6
22.9 12.3 19.9 30.9 20.1 15.8 35.7 30.5 21.7 16.1 26.9 27.4 20.9 35.8 31.1 21.4 22.9 28.8 29.1 26.4 21.2 17.5
127.6 126.5 125.3 142.3 142.7 117.2 162.7 131.1 117.3 121.6 124.8 166.7 128.6 151.2 149.3 104.4 125.5 154.4 157.3 134.7 119.3 138.0
43.4 25.1 48.4 45.9 32.6 29.0 65.6 39.6 15.9 32.5 29.8 49.0 28.5 43.8 49.3 33.5 43.6 48.9 60.5 49.9 49.1 42.1
DuPont-10309
(Company Sanitized. Does not contain TSCA CB1
72
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX D Individual Food Consumption
Sanitized. Does not
TSCACB1
73
/"N,
H -25231: Developmental Toxicity Study in Rats
Individual Food Consumption Explanatory Notes
Abbreviations NP = Not Pregnant
DuPont-10309
Company Sanitized. Does not contato TSCACBf
74
H-25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
4-6
658708 658713 658718
658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
32.0 25.2 25.1 21.5 21.3 23.2 17.8 19.8 25.6 24.6 16.8 22.9 24.6 22.9 21.1 21.9 19.5 20.8 17.0 19.8 20.1 19.4
INDIVIDUAL FOOD CONSUMPTION (grams)
6-8
30.4 26.1 27.1 23.7 21.9 23.3 23.3 21.1 25.3 23.4 25.8 21.6 23.9 21.6 20.7 24.5 21.1 19.2 22.9 21.3 21.5 19.3
DAYS OF GESTATION
8-10
10-12
12-14
29.1 25.5 28.6 25.1 20.6 23.3 18.1 20.4 28.5 21.6 25.4 21.2 25.5 23.2 25.9 24.8 19.7 21.7 23.7 20.9 22.3 20.0
35.0 27.9
31.3 25.2 21.9 24.5 26.5 21.8 26.3 26.4 27.4 24.8 27.5 22.5 25.9 27.6 23.0 23.8 27.1 23.9 22.3 21.3
33.7 26.3 31.5 26.0 23.9 26.8 29.9 25.1 25.3 27.7 27.4 24.8 26.7 23.0 27.0 26.8 22.9 26.1 28.2 23.8 24.6 23.4
14-16
34.6 25.3 32.9 25.8 23.6 23.0 31.4 27.0 26.3 26.3 26.0 26.1 29.6 20.9 26.1 28.0 23.6 26.9 34.3 24.8 22.7 26.4
DuPont-10309
16-18
35.1 27.9 38.1 28.0 17.1 27.6 33.5 28.6 28.6 28.5 28.9 29.0 30.2 24.5 30.3 27.5 24.1 27.1 31.1 25.9 22.9 24.8
JBpnspsni' ..
75
Ooss m># s nof ^ fa m TSCA CBS
H -25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL NUMBER
18-20
INDIVIDUAL FOOD CONSUMPTION (grams)
DAYS OF GESTATION
20-21
6-21
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
30.4 28.6 37.9 27.6 28.6 25.8 31.9 24.4 27.2 28.1 27.6 28.4 28.1 22.0 27.5 27.5 21.1 27.8 30.2 25.3 25.9 25.0
34.6 26.5 30.6 26.4 20.8 27.6 27.5 22.5 21.2 23.6 28.2 27.6 25.8 26.2 26.6 23.6 21.6 22.7 22.8 26.0 23.2 23.4
32.7 26.8 32.4 25.9 22.4
25.1 27.8 23.9 26.4 25.8 27.0 25.3 27.3 22.8 26.2 26.4 22.2 24.5 27.8 23.8 23.2 22.9
DuPont-10309
to m * . Does no, oo,,,ai,, tsca
76
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
GROUP II: 625 MG/KG/DAY
ANIMAL NUMBER
4-6
INDIVIDUAL FOOD CONSUMPTION (grams)
DAYS OF GESTATION
6-8
8-10
10-12
12-14
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
25 .7 20 .9 25 .1 24 .9 17 .1 17 .9 23 .3 28,.6 27 .7 20 .9 22 ,9 20 ,1 21,.2 25,.4 22,.4 21,.7 18,.8 25 .4 22,.1 23,.5 21,.8 19,.6
26 .1 22 .8 23 .8 26 .5 20 .5 17 .1 20 .7 26 .3 23 .8 17 .2 21 .3 25 .2 18,.6 23 ,.2 16..7 20 ,.7 19,.3 21,.7 21,.7 23 ,.0 23 .1 20 ,.4
23 ,.1 23 ,.2 21,.9 30..1 22,.9 17..5 22..0 28..1 24,.8 17,.6 21..4 23 .6 20..2 23..0 20..8 18 .6 19 ,.5 23 ,.0 26..3 21.,4 22.,6 19.,7
25 .8 23 .1 24 .2 26..0 23 ,.8 19,.4 23 ,.5 30..6 27..3 21..6 21..6 24 .1 23 .2 23..7 22 .2 21..4 19..7 23 .8 25..3 23 .0 25..4 21.,7
27 .4 24 .9 25 .4 31 .1 23 .8 21,.6 25,.5 26,.8 27,.1 21 .6 26,.1 23 ,.6 26..1 25..5 25..3 23 .3 22..4 26..5 29.,3 23.,2 22.,9 21.,3
14-16
28 .0 28 .1 25 .8 32 .6 23 .4 21 .5 24..4 26..9 28 .7 22 .4 23 .3 20 .2 24 .9 26,.4 26..0 25 .1 14 ,.1 26,.4 32 ,.8 26..2 25 .9 22 ,.1
16-18
30 .3 28..5 25..4 20,.3 25 ,.8 24 ,.1 26,.5 27,.9 30..8 23..3 24 ,.4 16 .3 26 .4 26,.5 25..7 25 ,.4 23..7 27,.9 31..5 26..4 25.,2 22 .,2
Doss 00, oomoio TSCA CD,
77
H-25231: Developmental Toxicity Study in Rats
INDIVIDUAL FOOD CONSUMPTION (grams)
GROUP II: 625 MG/KG/DAY
ANIMAL NUMBER
18-20
DAYS OF GESTATION
20-21
6-21
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 (NP) 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
31,.1 26..8 25..7 31..7 28..8 24 .2 23 .8 29..2 27 ,.3 23 .0 20..7 19..4 25..5 25..3 25..9 25..8 24 .2 28..6 33 .7 25..7 23 .9 21..1
28..7 25..8 24 .3 29.,1 29.,4 22 .9 23 .5 27..4 29..8 18 .9 13 .0 14 .0 23..8 25..6 22..6 20..8 25..9 25..6 33 .7 22,.5 21..4 20..5
27..5 25..4 24 ,.6 28..4 24..5 20..9 23 .8 27..9 27..3 20..8 22 ,.0 21 .2 23 ,.6 24 ,.9 23,.2 22 .8 20..8 25.,4 29..0 24..0 24..0 21..2
DuPont-10309
C w pany Sauteed. Does eel cenlaie TSCA OBI
78
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL FOOD CONSUMPTION (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION
4-6
6-8
8-10
10-12
12-14
658707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
25.1 25.0 21.6 15.7 12.8 25.5 22.1 24.5 25.6 27.6 25.2 22.0 26.7 23.4 26.1 26.1 21.8 19.8 22.3 23.4
21.1 22.1
25.7 20.5 20.4 21.6 28.0 23.1 20.1 18.2 22.3 22.4 19.4 17.3 26.4 26.8 24.1 26.4 19.8 15.8 18.6 23.0 18.1 17.9
23.8 22.2 20.3 24.6 24.8 22.7 20.1 23.2 26.3 27.1 22.5 17.3 22.6 17.3 26.2 19.3 21.8 20.4 21.5 23.3 21.1
23.9
25.4 21.2 18.1 23.5 23.8 22.1 21.5 25.0 27.8 26.8 23.3 21.2 21.0 28.6 28.9 25.9 24.5 22.1 24.2 22.9 21.5 24.3
29.3 29.6 22.5 28.8 26.6 20.7 19.2 25.6 25.5 29.5 23.6 21.1
25.5 26.7 30.9 29.1 22.9 21.9 24.6 26.6 23.0 25.7
14-16
31.1 27.4 20.8 29.7 29.2 25.0 24.5 25.6 28.6 29.4 25.1 26.0 30.7 25.9 29.8 30.4 23.5 22.5 23.4 28.6 24.1 25.6
DuPont-10309
16-18
31.0 31.1 22.7 28.3 28.3 26.4 26.9 25.7 28.6 31.5 27.6 26.6 30.2 30.0 31.1 33.0 24.1 24.3 26.0 30.1 24.3 27.1
jpempany SaniUzi
Ooesnot
confain TSCA CBf
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL FOOD CONSUMPTION (grams)
GROUP III: 1250 MG/KG/DAY
ANIMAL NUMBER
18-20
DAYS OF GESTATION
20-21
6-21
658707 658709 658715 658717 658722 658724 658728 658731 658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
31..5 30,.7 22 ,.2 27 .8 26..7 23 .6 22,.3 24,.4 27..5 30..0 24..6 22..9 29..9 24 .7 31..5 28 .1 21..9 22 ,.1 26..2 26..6 22..8 25..8
29.,7 28 .2 17..4 25..5 25 .1 19 .1 23 .3 22 .4 31..1 24 .,5 25 .,0 22 .7 26..1 31..8 30,.1 25..3 24..3 21..8 20..9 21,.9 20..6 25..4
28..3 26 .3 20 .8 26 .3 26 .7 23 .1 22 .2 23 .9 27..0 27..9 23 .8 21 .8 26 .6
26 .1 29 .0 27 .3 22 .8 21 .3 23 .3 25 .6 22..0 24..4
DuPont-10309
Company S anits>^
80
T&CA, CBS
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL FOOD CONSUMPTION (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION
4-6
6-8
8-10
10-12
12-14
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
21.6 21.9 19.2 22.3 24.1 19.6 24.6 28.0 28.2 25.4 29.9 25.9 22.1 28.8 23.6 27.5 22.6 20.2 20.3 19.5 24.9 15.0
23.4 22.1 16.3 23.1 10.4 15.3 14.9 18.7 22.8 14.3 24.9 19.3 14.8 21.3 21.9 16.5 19.4 17.6 10.7 11.2 19.3 11.4
24.2 16.1 18.4 21.2 19.8 20.1 22.6 20.6 24.1 21.2 15.0 21.5 20.7 25.4 20.8 23.4 18.3 22.1 22.2 17.6 20.4 23.8
24.6 20.1 20.9 22.3 24.1 21.3 27.3 26.2 26.4 26.3 23.4 26.5 24.3 26.8 22.3 23.3 22.0 21.3 27.6 21.7 23.7 20.3
22.5 26.4 24.5 23.4 26.3 24.7 26.4 23.3 21.2 24.7 26.7 24.3 23.2 27.0 24.3 22.4 21.9 24.8 26.8 24.0 26.9 27.9
14-16
25.0 29.0 23.5 22.8 28.3 27.5 28.3 28.9 25.8 27.3 21.4 26.7 24.7 27.2 23.1 28.0 24.3 26.6 30.0 27.1 24.9 27.4
DuPont-10309
16-18
28.1 27.6 26.8 24.4 29.5 29.8 32.7 29.5 27.7 24.8 28.6 28.4 28.2 26.4 25.7 26.5 25.6 23.3 31.0 26.2 26.0 25.9
Company Sanitized. Does not contain TSCA CBS
81
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL FOOD CONSUMPTION (grams)
GROUP IV: 2500 MG/KG/DAY
ANIMAL NUMBER
DAYS OF GESTATION
18-20
20-21
5-21
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 658785 658790
27.7 26.2 28.9 26.0 24.9 27.6 25.4 24.2 24.2 24.5 25.9 27.3 23.7 24.9 23.9 25.8 24.1 20.6 29.1 20.8 27.6 24.7
25.0 19.0 18.7 27.0 27.8 25.3 33.9 29.6 25.3 24.1 28.3 25.4 21.1 31.9 24.0 25.3 25.3 22.9 32.6 21.6 24.1 21.5
25.1 23.6 22.5 23.5 23.6 23.8 25.9 24.8 24.6 23.3 24.0 24.9 22.7 26.0 23.2 23.8 22.4 22.4 25.8 21.2 24.1 23.0
DuPont-10309
Company Sanitized. Does not contain TSCA CBS
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX E Individual Clinical Observations
Company s ani,,red,, 0i>snoi contain TSCA CBI
H -25231: Developmental Toxicity Study in Rats
Individual Clinical Observations
DuPont-10309
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.
Does no t contain TSCA CBI
84
H-25231: Developmental Toxicity Study in Rats
GROUP I: 0 MG/KG/DAY
ANIMAL OBSERVATION NUMBER:
658708 SACRIFICED BY DESIGN 04/29/02
658713 SACRIFICED BY DESIGN 04/29/02
658718 SACRIFICED BY DESIGN 04/29/02
658719 SACRIFICED BY DESIGN 04/29/02
658725 SACRIFICED BY DESIGN 04/29/02
658727 SACRIFICED BY DESIGN 04/30/02
658729
;fg'O SACRIFICED BY DESIGN 04/30/02
f/;[ 658730
/ SACRIFICED BY DESIGN 04/30/02
/co
fM ix
C7 m
I
S' s'
658739 SACRIFICED BY DESIGN
658741 SACRIFICED BY DESIGN
658742 SACRIFICED BY DESIGN
658748 SACRIFICED BY DESIGN
04/30/02 04/30/02 04/30/02 05/01/02
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
: / / / / / / / / / / / / / t / / ,21
iiiiii
f i t i i / / t t i ,21
i i i i i i / / / / / / / / / f ,21
i i i i i i i i i t i i i / i i ,21
^ i i i i i i
t / / / r t / f / ,21
i i i i i i / / / / / / / / / / ,21
^ I I I I I I t I / ! ! t I / / A ,21
I I I I I I ! ! / / / / / / / ! ,21
9- I I I I I I
t I ! ! ! ! ! / / / ,21
& I I I I I I ! ! ! / / / ! ! / f ,21
& I I I I I I ! / / / / / / / / / ,21 I I I I I I / / ! / / / / # / / ,21
DuPont-10309
Company Sanitized. Does not contain iSCA CBl
)
H -25231: Developmental Toxicity Study in Rats
GROUP I : 0 MG/KG/DAY
ANIMAL OBSERVATION NUMBER: = =s ===s ===s = ===c = = 658753
ALOPECIA LEFT SHOULDER
==
SACRIFICED BY DESIGN 05/01/02
658755 SACRIFICED BY DESIGN 05/01/02
658758 SACRIFICED BY DESIGN 05/01/02
658759 SACRIFICED BY DESIGN 05/01/02
658761 ALOPECIA BOTH FRONT LEG
SACRIFICED BY DESIGN 05/01/02
658773 ALOPECIA BOTH FRONT PAW
ALOPECIA BOTH FRONT LEG
SACRIFICED BY DESIGN 05/02/02
658776 SACRIFICED BY DESIGN 05/02/02
658781 SACRIFICED BY DESIGN 05/02/02
658787 SACRIFICED BY DESIGN 05/02/02
658791 SACRIFICED BY DESIGN 05/02/02
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 : 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 b : 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, a:
a : , , , , , , , , , , , , , , , I ,21 a ,21
a ,21
a: ,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 b : , ,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,
^ f i l i t i
, , , / , t I I I I 1 21
a: 4,5,6,7,8,9,10,11,12,13,14,15,16,17, b: , ,6,7,8,9,10,11,12,13,14,15,16,17, a : ,18,19,20,21 b: ,18,19,20, a : , , , ,21
^ , , , , , , , , , , , , , , , , ,21
& I I I I I I I I I I I I ! ! / , ,21
ACl* / I I I / /
21/ / / /l I f f t l ft**.
* / / / / / /
I t f / r t / / r t /21
86
)
DuPont-10309
ISO VOS1 m iuoo tou saoa pBzm m s ^uecfuiod
)
H -25231: Developmental Toxicity Study in Rats
GROUP II: 625 MG/KG/DAY
ANIMAL OBSERVATION NUMBER:
658705 SACRIFICED BY DESIGN 04/29/02
658706 SACRIFICED BY DESIGN 04/29/02
658712 SACRIFICED BY DESIGN 04/29/02
658720 SACRIFICED BY DESIGN 04/29/02
658721 SACRIFICED BY DESIGN 04/29/02
658734 SACRIFICED BY DESIGN 04/30/02
658736 SACRIFICED BY DESIGN 04/30/02
658738 SACRIFICED BY DESIGN 04/30/02
658740 SACRIFICED BY DESIGN 04/30/02
658743 SACRIFICED BY DESIGN 04/30/02
658745 SACRIFICED BY DESIGN 04/30/02
658749 SACRIFICED BY DESIGN 05/01/02
INDIVIDUAL CLINICAL OBSERVATIONS
DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21
a: , , , , , , , , , , / / , / / , ,21
cl: , , , , , , , , , , , , , / , , ,21
a.: , , , , , ,
, , / , , / , , / , , 21
a: , , , , , , , , , / t / / / / / ,21
a: , , , , , , , , / / / / / / / / <21
a: , , , , , , , , , , / / / / / / /21 a: / , , , , , , , , , / ? # / * / ,21
a: , , , , , , , , , , / / / / / / /21 a: , , , , , , , , , , / / / / / / ,21
a: , , , , , , , , , , , / , , / , ,21
a: , , , , , , , , , , , , , , , , ,21
a: , , , , , , , , , , , , , , , , ,21
87
)
DuPont-10309
)
H -25231: Developmental Toxicity Study in Rats
INDIVIDUAL CLINICAL OBSERVATIONS3
GROUP II: 625 MG/KG/DAY
ANIMAL OBSERVATION NUMBER: ==s=s===:==:r==;=:=ssr===:=s=i=s===::=s3:===r=:=;===s==: 658752
SACRIFICED BY DESIGN 05/01/02
658754 ALOPECIA BOTH FRONT LEG
SACRIFICED BY DESIGN 05/01/02
658762 SACRIFICED BY DESIGN 05/01/02
658763 SACRIFICED BY DESIGN 05/01/02
658770 SACRIFICED BY DESIGN 05/02/02
658772 SACRIFICED BY DESIGN 05/02/02
658775 ALOPECIA LEFT SIDE
SACRIFICED BY DESIGN 05/02/02
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
= s =
=
==
= -- =s = s : = : = = = = : s= 2 s = : j5 : s s s s s s = = = s s e s = : s= = = 2 S = = : ~ s= = = = = =
a: i i i t i i , t i t i i i
, ,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:
t t i' /
f
i' / 4' r
! ///,
,21
a: ,, t t )' /
1
1' / 4' l
1r
/ / , ,21
a:
t l 11 l / 4r / 4t f 1 i / r , , 2 1
a:
! ! 1r / / 1r r it f i' i / / , , 2 1
a:
1 / Ir t
/ 4r t
r t
i
1!
, ,21
a: ,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: ,21
Company Sanitized. Does no!
658777 SACRIFICED BY DESIGN 05/02/02
a
,21
658784 SACRIFICED BY DESIGN 05/02/02
a
,21
658788 SACRIFICED BY DESIGN 05/02/02
3 m
3
a:
,21
)
DuPont-10309
H -25231: Developmental Toxicity Study in Rats
GROUP III: 1250 MG/KG/DAY
ANIMAL OBSERVATION NUMBER:
658707 SACRIFICED BY DESIGN 04/29/02
658709 SACRIFICED BY DESIGN 04/29/02
658715 SACRIFICED BY DESIGN 04/29/02
658717 ALOPECIA RIGHT FRONT LEG
ALOPECIA NECK
SACRIFICED BY DESIGN 04/29/02 0 658722 O SACRIFICED BY DESIGN 04/29/02
1tu g *
m 658724 SACRIFICED BY DESIGN 04/29/02 ft 658728 P" SACRIFICED BY DESIGN 04/30/02 O % 658731
3 SACRIFICED BY DESIGN 04/30/02
SACRIFICED BY DESIGN 04/30/02
58735 SACRIFICED BY DESIGN 04/30/02
58737 SACRIFICED BY DESIGN 04/30/02
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
3: / / / / / /
f t i , / , / / / / /2 1
3 l i l i l ! / ! I I ! t ! ! I I21
I I I I I I I ! ! ! ! / / ! ! ' '*71
a : , , , , , , , ,12,13,14,15,16,17,18,19,20,21
b: , , , , , , , ,12,13,14,15,16,17,18,19,20,
a : ........ , , , , , , , ,
,18,19,20,21
b: I l t I I ! ! I l I I t ! ,18,19,20,
a: t i l t i l I t I I I I I I I ! ,21
219-*
II
t II
t
!
I
I
!
t
t
/
I
r
t
t
3.
tI IlrI
I
!
!
//
//
>/!
!21
& ! I l I I ! ! / / / / / / / * / /21
& i i i i i t / / / / / / / / / ' ,21 l i l i l / / / f / l t ! ! I ,21
& l i l i l I ! t ! / / / / / / /21
,21^ '
t ! t II
!
/ff!
!
!
t
//
/
DuPont-10309
o es not contain TSCA CBI
H -25231: Developmental Toxicity Study in Rats
GROUP III: 1250 MG/KG/DAY
ANIMAL OBSERVATION NUMBER:
658751 SACRIFICED BY DESIGN 05/01/02
658756 SACRIFICED BY DESIGN 05/01/02
658765 SACRIFICED BY DESIGN 05/01/02
658766 ALOPECIA LEFT FRONT LEG
ALOPECIA BOTH FRONT LEG
SACRIFICED BY DESIGN 05/01/02
658767 SACRIFICED BY DESIGN 05/01/02
658771 SACRIFICED BY DESIGN 05/02/02
658778 SACRIFICED BY DESIGN 05/02/02
658779 SACRIFICED BY DESIGN 05/02/02
658782 SACRIFICED BY DESIGN 05/02/02
658786 SACRIFICED BY DESIGN 05/02/02
658789 SACRIFICED BY DESIGN 05/02/02
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 ,21
a ,21
a ,21
a: t i i t i i , , , , , ,16,17,18,19, ,
b : , , , , , , , , , , , ,16,17,18,19, ,
a : i i i i i i i i i i i i i i i ,20,21
b: i i i i i i
, , , , , , , , ,20,
a: i i i i i i
/ f / // / / // r
I I I I I I / ! I I I I / I I I t4*
9-* i i i i i i t t i i t t t t t i
l i l i l ! / I I I I I I I I /21
3- i i i i i i i i / t / / / i / t
3.2 i i i i i i i / / / / / / / / / /21
a ,21
a ,21
90
DuPont-10309
))
H -25231: Developmental Toxicity Study in Rats
GROUP IV: 2500 MG/KG/DAY
ANIMAL OBSERVATION NUMBER:
658704 ALOPECIA BOTH FRONT PAW
SACRIFICED BY DESIGN 04/29/02
658710 SACRIFICED BY DESIGN 04/29/02
658711 SACRIFICED BY DESIGN 04/29/02
658714 SACRIFICED BY DESIGN 04/29/02
658716 SACRIFICED BY DESIGN 04/29/02
658723 SACRIFICED BY DESIGN 04/29/02
658726 SACRIFICED BY DESIGN 04/30/02
658733 SACRIFICED BY DESIGN 04/30/02
658744 ALOPECIA CHEST
ALOPECIA LEFT SIDE
ALOPECIA UNDERBODY
SACRIFICED BY DESIGN 04/30/02
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
, ,9,10,11,12,13,14,15,16,17,18,19,20,21 , ,9,10,11,12,13,14,15,16,17,18,19,20,
111
t / / i / I I I l I !***-
a ,21
a: , , , , , , , , , , , , , , , , ,21
a : , , , , / / , , , , , , , , , , ,21 a 21
a: , , , , , , , , , , , , , , , , ,21
a 21
a 21
i t i i i9/10, 11, 12, 13,,14, 15,.16, 1 1 / 1 / / / / /-9'/10, 11, 12, 13,,14,.15,,16, i 1' 1 1 t i i t i i I / 1 ,14,.15,,16,17, 18,.19,,20,,21
i i i i i i I / 1 ,14,15,,16,17,18,.19,,20, i i i i i i 1 1 , 1 ' 1' /,17,,18,19,,20,,21
i i i i i i l 1 1 f 1' 1' 117,,18,19,,20,
i i i i i i 1 I I t ' 1' ' 1' i' i' 1,21
DuPont-10309
Company Sanitized. Does not contain TSCA CBI
91
Company Sanitized. Does not contain TSCA CBt
)
H -25231: Developmental Toxicity Study in Rats
GROUP IV: 2500 MG/RG/DAY
ANIMAL OBSERVATION NUMBER :
658746 ALOPECIA BOTH FRONT PAW
SACRIFICED BY DESIGN 04/30/02
658747 SACRIFICED BY DESIGN 04/30/02
658750 SACRIFICED BY DESIGN 05/01/02
658757 SACRIFICED BY DESIGN 05/01/02
658760 SACRIFICED BY DESIGN 05/01/02
658764 SACRIFICED BY DESIGN 05/01/02
658768 SACRIFICED BY DESIGN 05/01/02
658769 SACRIFICED BY DESIGN 05/01/02
658774 SACRIFICED BY DESIGN 05/02/02
658780 SACRIFICED BY DESIGN 05/02/02
658783 SACRIFICED BY DESIGN 05/02/02
658785 SACRIFICED BY DESIGN 05/02/02
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
:=:s:=:====
a: , , , , , , b: , , , , , , a: , , , , , ,
, ,12,13,14,15,16,17,18,19,20,21 , ,12,13,14,15,16,17,18,19,20, / / / / / / i , i i '21
a: , , , , , , / / / / / / / / ' ' /21
a: , , , , , , / , , , , / / / / / #21
i t , , , , / / / i / , / / / / ,21
a: , , , , , , a:
/ * , / , f / f ' / /21 , , i i i i , i i , i^Qx*1
a: i i i i i , , i i i i , i > ! i <21
a: , , , , , , i , i , , , , , , i i21
a: i l , , , , i i i i , ! , < ' i i 21
l* / / / / / /
//
l
t
!
t
l
/t
/
91 ,
3 : , r i / t / / t i i ! t i t i t /21
3: , 1 1 1 1 1 / / / i / * t f t t /21
92
)
DuPont-10309
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL CLINICAL OBSERVATIONS3
GROUP IV: 2500 MG/KG/DAY
ANIMAL OBSERVATION
DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED
NUMBER:
4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21
== = =s========= =s===s====s==s==s= =======--==== -- =s=--s=
==s====
658790
SACRIFICED BY DESIGN 05/02/02
a:
21
=
= = ====
==
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX F Gross Postmortem Findings
94 |5snpany Sanitized. Does not contain TSCA CB1
H-25231 : Developmental Toxicity Study in Rats
Gross Postmortem Findings Explanatory Notes
Abbreviations = No Data
NAD = No Abnormalities Detected NP = Not Pregnant
DuPont-10309
95
Ppmpany Sanitized, Does not contain TSCA 8!
H -25231: Developmental Toxicity Study in Rats
GROSS POSTMORTEM FINDINGS
Group I: 0 mg/kg/day
Animal Number
658708 658713 658718 658719 658725 658727 658729 658730 658739 658741 658742 658748 658753 658755 658758 658759 658761 658773 658776 658781 658787 658791
Structure(s)
-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --
Findinc
NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD
DuPont-10309
96
^ p a n g .Sanitized. Pc not igentaSn T8C Off!
/'""`N
H -25231: Developmental Toxicity Study in Rats
GROSS POSTMORTEM F IN D IN G S
Group II: 625 mg/kg/day
Animal Number
Structure(s)
658705 658706 658712 658720 658721 658734 658736 658738 658740 658743 658745 658749 658752 658754 658762 658763 658770 658772 658775 658777 658784 658788
(NP)
Finding(s)
NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD
DuPont-10309
g^TOpany Sanitized. Does not fein TSC CBS.
97
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
GROSS POSTMORTEM F IN D IN G S
Group III: 1250 mg/kg/day
Animal Number
Structure(s)
658707 658709 658715 658717 658722 658724 658728 658731
-------Skin
658732 658735 658737 658751 658756 658765 658766 658767 658771 658778 658779 658782 658786 658789
Finding (s)
NAD NAD NAD NAD NAD NAD NAD Mass (1.0 X 1.5 cm) white, firm, mammary gland left side NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD
Qompany Sanitized. Does not contain TSCA CB1
H -25231: Developmental Toxicity Study in Rats
GROSS POSTMORTEM F IN D IN G S
Group IV: 2500 mg/kg/day
Animal Number
Structure(s)
658704 658710 658711 658714 658716 658723 658726 658733 658744 658746 658747 658750 658757 658760 658764 658768 658769 658774 658780 658783 58785 658790
-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --
Findinq
NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD
DuPont-10309
lalnTSCACBl pBmpm Sanitized Ooes not con
99
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
APPENDIX G Individual Reproductive Data
100
H -25231: Developmental Toxicity Study in Rats
Individual Reproductive Data Explanatory Notes
Abbreviations NP = Not Pregnant --- = N o Data
DuPont-10309
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL REPRODUCTIVE DATA
GROUP I: 0 MG/KG/DAY
ANIMAL CORPORA NIDA NUMBER LUTEA TIONS
RESORPTIONS TOTAL EARLY LATE
DEAD
LIVE FETUSES
MEAN FETAL
FETUSES TOTAL FEMALE MALE WEIGHT (G)
658708 16 16 0 0 0 0 16 6 10 5.15
658713 14 13 0 0 0 0 13 10 3 5.14
658718 19 13 0 0 0 0 13 10 3 5.27
658719 17 16 0 0 0 0 16 9 7 5.20
658725 18 14 0 0 0 0 14 6 8 4.94
658727 20 13 0 0 0 0 13 6 7 5.18
658729
14
4
0
0
0
0
4 13
6.51
658730 15 14
0
0
0
0 14 6 8
4.88
658739 19 14 1 1 0 0 13 8 5 5.20
658741 17 15 0 0 0 0 15 7 8 5.38
658742 23 17 1 1 0 0 16 10 6 5.44
658748 17 14 0 0 0 0 14 10 4 5.71
658753 16 15
0
0
0
0 15 10 5
4.89
658755 12 11 0 0 0 0 11 6 5 5.33
658758
10
9
0
0
0
0
9 54
5.69
658759 13 13
000
0 13 5 8
6.30
658761 17 12 1 1 0 0 11 6 5 5.58
658773 23 16 0 0 0 0 16 11 5 5.26
658776 17 17 0 0 0 0 17 10 7 5.19
658781 13 11 0 0 0 0 11 6 5 5.37
658787 14 12 2 2 0 0 10 7 3 5.69
658791 15 14 0 0 0 0 14 6 8 5.51
)
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL REPRODUCTIVE DATA
GROUP II: 625 MG/KG/DAY
ANIMAL CORPORA NIDA NUMBER LUTEA TIONS
RESORPTIONS TOTAL EARLY LATE
DEAD
LIVE FETUSES
MEAN FETAL
FETUSES TOTAL FEMALE MALE WEIGHT (G)
658705 12 12 0 0 0 0 12 4 8 5.68 658706 12 12 0 0 0 0 12 3 9 5.84
658712 14 14 0 0 0 0 14 9 5 5.49
658720 15 15
0
00
0 15 6 9
5.13
658721 16 16 0 0 0 0 16 10 6 5.19 658734 15 12 0 0 0 0 12 5 7 5.51
658736 12 10 0 0 0 0 10 3 7 5.53 658738 16 15 0 0 0 0 15 7 8 5.50
658740 17 16 3 3 0 0 13 9 4 5.31 658743 13 12 1 1 0 0 11 4 7 5.52
658745 17 15 0 0 0 0 15 10 5 4.79
658749(NP) --- --
--
--
--
--
---
______
______
___ _
658752 18 18 1 0 1 0 17 8 9 5.11
658754 14 14 1 1 0 0 13 6 7 5.64
658762 12 12 0 0 0 0 12 8 4 5.47
658763
13
4
0
0
0
0 4 13
5.72
658770 14 13 0 0 0 0 13 6 7 5.36
658772 17 15 0 0 0 0 15 5 10 5.50
658775 15 13 0 0 0 0 13 8 5 5.47
658777 16 13 0 0 0 0 13 6 7 5.37
658784 18 13
0
0
0
0 13
58
5.02
658788 13 13
0
0
0
0 13 10 3
4.97
SS0
I
103
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INDIVIDUAL REPRODUCTIVE DATA
GROUP III: 1250 MG/KG/DAY
ANIMAL CORPORA NIDA NUMBER LUTEA TIONS
RESORPTIONS TOTAL EARLY LATE
DEAD
LIVE FETUSES
MEAN FETAL
FETUSES TOTAL FEMALE MALE WEIGHT (G)
658707 15 14 0 0 0 0 14 7 7 5.57
658709 19 15 1 1 0 0 14 8 6 5.53
658715
13
3
1
1
0
0
2 11
5.51
658717 15 15 2 2 0 0 13 7 6 5.59
658722 15 15 1 1 0 0 14 4 10 5.66
658724 17 17 0 0 0 0 17 7 10 5.29
658728 13 12 0 0 0 0 12 8 4 5.57
658731 17 12 0 0 0 0 12 6 6 5.14
658732 26 15 0 0 0 0 15 10 5 5.15
658735 18 17 0 0 0 0 17 5 12 5.71
658737 14 12 1 0 1 0 11 3 8 5.44
658751 16 15 0 0 0 0 15 7 8 5.34
658756 19 15 0 0 0 0 15 7 8 5.36
658765 17 16 0 0 0 0 16 2 14 5.65
658766 15 15 0 0 0 0 15 7 8 5.70
658767 18 16 0 0 0 0 16 11 5 5.33
658771 15 13 0 0 0 0 13 7 6 5.08
658778 17 14 0 0 0 0 14 7 7 5.20
658779 17 16 0 0 0 0 16 6 10 5.00
658782 18 16 0 0 0 0 16 7 9 5.17
658786 14 13
0
0
0
0 13 6 7
5.39
658789 14 14 1 1 0 0 13 8 5 5.77
)) )
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL REPRODUCTIVE DATA
GROUP IV: 2500 MG/KG/DAY
ANIMAL CORPORA NIDA NUMBER LUTEA TIONS
RESORPTIONS TOTAL EARLY LATE
DEAD
LIVE FETUSES
MEAN FETAL
FETUSES TOTAL FEMALE MALE WEIGHT (G)
658704 12 12 0 0 0 0 12 7 5 5.14
658710 15 15 0 0 0 0 15 6 9 5.25
658711 12 12
0
0
0
0 12 6 6
4.91
658714 16 15 0 0 0 0 15 7 8 5.11
658716 16 15 1 1 0 0 14 8 6 6.41
658723 13 13 0 0 0 0 13 9 4 5.33
658726 17 16 0 0 0 0 16 9 7 4.86
658733 16 16 2 2 0 0 14 10 4 5.13
658744 23 14 0 0 0 0 14 7 7 5.08
658746 16 14 0 0 0 0 14 5 9 5.06
658747 15 14 0 0 0 0 14 8 6 5.30
658750 18 17 0 0 0 0 17 7 10 5.18
658757 17 16
0
0
0
0 16 10 6
4.91
658760 16 16 0 0 0 0 16 5 11 5.40
658764 17 16
0
0
0
0 16 11 5
4.94
658768 15 13 3 3 0 0 10 4 6 5.29
658769 13 12 0 0 0 0 12 9 3 5.54
658774 18 17
00
0
0 17 9 8
4.67
658780 19 14 0 0 0 0 14 4 10 5.40
658783 17 13 0 0 0 0 13 6 7 5.10
658785 10 10 0 0 0 0 10 5 5 5.74
658790 15 15 0 0 0 0 15 9 6 4.91
Sanitized Does not conte TSCA CBI
105
H-25231: Developmental Toxicity Study in Rats
DuPont-103 09
APPENDIX H Individual Fetal Weights and Alterations
fpompanf
106
e o u ja ia tS C A C B I
H -25231: Developmental Toxicity Study in Rats
Individual Fetal Weights and Alterations
DuPont-10309
Explanatory Notes
For ease o f 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 o f Renal Development in
Late Gestation o f Rats: The Effect o f Methyl Salicylate. Teratology, 6:191-196.
nol contain TSCACBI
107 CdWP?*
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DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
558708 1 2 3 4 5 5 7 8 9
10 11 12 13 14 15 16
5.23 5.15 5.05 5.37 5.40 5.03 5.24 4.80 5.34 5.12 5.01 5.10 4.93 5.32 5.32 4.94
Kidney
Skull Kidney
Skull Skull Skull
NAD NAD NAD NAD Small Papilla - Size 2 (bil) NAD NAD Retarded Ossification (2 bil) Papilla - Size 3 (bil) NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil)
VR
VR VR
VR VR VR
658713 1 2 3
4 5 6 7
8 9 10 11 12 13
5.53 5.16 5.46
5.29 5.26 3.88 5.30
5.44 4.74 5.06 5.40 5.03 5.28
Vertebra Rib Skull Vertebra
Vertebra
NAD NAD Retarded Ossification
(cen thl2) Supernumerary {site 13 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll) NAD NAD NAD NAD NAD Retarded Ossification
(cen thll-12)
VR DV VR VR
VR
658718 1 2
5.18 5.06
NAD NAD
108
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INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658718 (Cont.) 3 5.30
4 5.59
5 4.90 6 5.47 7 5.19 8 5.00 9 4.81 10 5.51 11 5.35
12 5.67 13 5.42
Vertebra Skull Vertebra
Skull Skull
Vertebra
Retarded Ossification
(cen thl2) Retarded Ossification (2 bil) Retarded Ossification
(cen thll) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD Retarded Ossification
(cen thll) NAD NAD
VR VR VR VR VR
VR
658719 1 2
3 4 5 6
7 8 9
10
11 12
13 14
' 4.69 4.82
4.91 5.36 5.17 5.19
4.99 5.08 5.23
5.25
5.72 5.49
5.06 5.83
Vertebra
Vertebra
Vertebra Vertebra Vertebra Vertebra
NAD Retarded Ossification
(cen thlO,12) NAD NAD NAD Retarded Ossification
(cen thl2) NAD NAD Retarded Ossification
(cen thl2) Retarded Ossification
(cen thl2) NAD
Retarded Ossification (cen thlO-13)
NAD Retarded Ossification
(cen thll-12)
VR
VR
VR VR VR VR
D o @ 5 R 0 i ^ tallTSCA 109
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INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658719 (Cont.) 15 5.33
16 5.04
Vertebra Vertebra
Retarded Ossification (cen thl2)
Retarded Ossification (cen thll)
VR VR
658725 1 2 3 4 5 6 7 8 9
10 11 12 13 14
4.58 4.70 5.67 4.69 5.09 4.57 5.48 5.32 5.05 4.66 4.52 5.11 5.03 4.67
Skull Skull Skull
Skull
Skull
NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil)
VR VR VR
VR
VR
658727 1
2
3
4
5
6 7
8 9
5.26 5.92 5.63 5.13 5.13 4.62 4.90 5.23 4.92
Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull
Retarded Ossification (cen thll)
Retarded Ossification (cen th9-13)
Retarded Ossification (cen thll)
Retarded Ossification (cen th9)
Retarded Ossification (cen thl0,12)
Retarded Ossification (cen thll)
Retarded Ossification (cen thll)
Retarded Ossification (12) NAD
VR VR VR VR VR VR VR VR
- D@nolSO 110
/'" N
H -25231: Developmental Toxicity Study in Rats_________________________ _______________________ DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./
FETUS NO . FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658727 (Cont.) 10 5.79 11 4.75
12 4.98 13 5.06
Vertebra Vertebra
NAD Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen thll-12)
VR VR
658729 1
2 3 4
6.55
6.77 6.48 6.25
Kidney Vertebra
Vertebra
Vertebra
Vertebra
Papilla - Size 3 (bil) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thlO,12) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl2)
VR VR VR VR VR
658730 1 2 3 4
5
6
7
8 9 10 11 12
4.95 5.00 4.62 5.24
4.50
4.97
4.18
5.40 5.13 4.41 4.65 5.12
Subcutis Skull
Skull Vertebra
Vertebra
Skull Vertebra
Vertebra
Skull
Skull
Skull
Hemorrhage (left ear*) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll,13) Retarded Ossification
(cen thlO) Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thl2) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD
Retarded Ossification (2 bil)
N VR
VR
VR
VR VR
VR
VR VR
VR
VR
CpmPm ! SanitMd. Does no conisto TSCA OB
111
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INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658730 (Cont.)
13 5.21 14 4.98
Vertebra Vertebra Skull
Retarded Ossification (cen thll)
Retarded Ossification (cen thl2)
Retarded Ossification (2 bil)
VR
VR VR
658739 1 2
3
4
5
6
7
8 9 10
11 12 13
5.53 5.36 5.24 5.32 4.59 5.49
5.32 5.69 4.75 4.80
4.85 5.15 5.49
Subcutis Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra
Vertebra Vertebra
Hemorrhage (neck*) Retarded Ossification
(cen thll) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thl0-12) Retarded Ossification
(cen thl2) Retarded Ossification (2 bil) Retarded Ossification
(cen thll) Retarded Ossification
(cen thl2) NAD NAD Retarded Ossification
(cen lul4) Retarded Ossification
(cen thll-13) NAD NAD NAD
N VR VR VR VR VR VR VR
VR VR
658741 1 2 3 4 5 6
5.89 5.61 5.17 5.40 5.54 5.58
Kidney Skull
Papilla - Sire 3 (It) . Retarded Ossification (2 bil) NAD NAD NAD NAD
VR VR
Company Sanitized. Does not contain TSCA C ii
112
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INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE_______________ FINDING (S)__________ CLASSIFICATION
658741 (Cont.) 7 5.23
8 5.29 9 4.69 10 5.47 11 5.54 12 5.57 13 5.29 14 5.27 15 5.21
Subcutis Kidney Skull
Skull Skull
Hemorrhage (left rear paw*) Papilla - Size 3 (bil) Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD
N VR VR
VR VR
658742 1 2 3
4
5 6 7 8
9 10
11
12 13 14
15
5.18 5.41 5.83
5.78
5.86 5.13 5.30 5.17
5.59 5.42
5.53
5.10 5.15 5.44
5.43
Vertebra Vertebra
Skull Vertebra
Vertebra Vertebra Skull Skull Vertebra Vertebra
NAD NAD Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll) NAD NAD NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen th4) Retarded Ossification
(cen thll) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll) Retarded Ossification
(cen thll)
VR VR
VR VR
VR VR VR VR VR VR
jpfippap gagjitiaett Does not contain 1SCA..C1M
113
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INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658742 (Cont.) 16 5.66 Vertebra
658748 1 2 3 4
5 6 7 8 9 10 11 12 13 14
6.30 5.80 5.84 5.20
5.60 5.93 5.73 5.59 5.67 5.55 5.74 5.41 5.99 5.54
Vertebra
Skull Skull Skull Vertebra
Vertebra
Vertebra
Vertebra
Vertebra Vertebra
Vertebra
Vertebra Vertebra
Vertebra
Vertebra
658753 1 2 3
4.76 4.73 4.96
Retarded Ossification (cen thl2)
VR
NAD NAD Retarded Ossification
(cen thll) Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (2 bil) Retarded Ossification
(cen thio-ll) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl.0-13) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll) Retarded Ossification
(cen thll,13) Retarded Ossification
(cen thl0-ll) Retarded Ossification
(cen thll) Retarded Ossification
(cen thlO-11)
VR VR VR VR
VR
VR
VR
VR
VR
VR
VR
VR
VR
VR
VR
NAD NAD NAD
Sanitized. Do notcontaln 114
H -25231: Developmental Toxicity Study in Rats________________________________________________ DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
S58753 (Cont.) 4 5.00 5 5.14 6 5.35
7 4.52 8 4.84 9 4.61 10 5.78 11 5.20 12 4.70 13 4.43 14 4.41 15 4.85
Pelvis
NAD NAD Retarded Ossification
(pubis It) NAD NAD NAD NAD NAD NAD NAD NAD NAD
VR
658755 1 2 3 4 5 6 7 8 9
10 11
658758 1 2
3 4 5 6
7 8
5.68 5.74 5.17 5.28 5.27 5.24 5.63 5.20 4.93 5.48 5.01
Skull
5.53 5.97
5.89 5.57 5.22 5.68
5.89 5.62
Vertebra Vertebra
NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD NAD NAD NAD NAD
VR
NAD Retarded Ossification
(cen thll) NAD NAD NAD Retarded Ossification
(cen thl2) NAD NAD
VR VR
--------
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS W T . STRUCTURE
FINDING(S)
CLASSIFICATION
658758 (Cont.) 9 5.85
NAD
58759 1 2 3
4 5 6 7 8
9 10 11 12 13
6.11 6.48 5.84
6.00 6.29 6.17 6.58 6.30
6.26 6.59 6.42 6.77 6.15
Vertebra
Rib Vertebra
Vertebra
Vertebra
Vertebra
Vertebra
Skull Vertebra
Vertebra
Vertebra
Skull Skull Vertebra
NAD Retarded Ossification
(cen thll-12) Supernumerary (site 14 rt) Retarded Ossification
(cen thl4) Retarded Ossification
(cen thlO-11,13) Retarded Ossification
(cen thl3) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll-12) Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen thll,13) Retarded Ossification (2 rt) Retarded Ossification (8 bil) Retarded Ossification
(cen thll-12)
VR DV
VR
VR
VR
VR
VR VR
VR
VR
VR VR VR
VR
58761 1 2 3 4 5 6 7
5.36 5.51 5.27 5.40 5.60 5.70 6.03
NAD NAD NAD NAD NAD NAD NAD
116
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INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658761 (Cont.) 8 5.84 9 5.53
10 5.62 11 5.48
NAD NAD NAD NAD
658773 1 2
3 4 5 6
7 8 9 10 11 12
13 14 15 16
5.06 5.52
5.30 5.46 5.02 5.32
5.49 5.57 3.52 5.16 5.41 5.37
5.14 5.95 5.35 5.55
Skull Skull Vertebra Vertebra Skull Skull
Skull Vertebra
Vertebra Skull Skull
Skull Vertebra Vertebra
Vertebra Skull
NAD Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thl2-13) Retarded Ossification (12) Retarded Ossification (2 bil) NAD Retarded Ossification (12) Retarded Ossification
(cen thl0-12) NAD NAD Retarded Ossification
(cen thll) Retarded Ossification (1) Retarded Ossification (12) NAD Retarded Ossification (12) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thlO) NAD Retarded Ossification
(cen thl2) Retarded Ossification (1)
VR VR VR
VR VR VR VR
VR
VR VR VR VR VR VR
VR VR
658776 1
4.78
NAD
-- -----SQgfaglx ftanteW P w net ooniain TSCACBI
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP I: 0 MG/KG/DAY
DAM NO./ FETUS :NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658776 (Cont .) 2 5.20 3 5.36 4 5.41 5 5.41 6 5.44 7 5.59 8 5.47 9 4.83
10 5.15 11 5.45 12 5.18 13 4.85 14 4.85 15 5.08 16 5.03 17 5.18
Skull
Skull Skull
Kidney
Retarded Ossification (2 bil) NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD NAD NAD NAD Papilla - Size 3 (bil)
VR
VR VR
VR
658781 1 2 3 4 5 6 7 8 9
10 11
5.33 5.34 5.33 5.92 5.03 5.45 5.46 5.32 5.38 5.13 5.42
Skull Skull Skull Skull Skull
NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD
VR VR VR VR VR
658787 1 2 3 4 5 6 7
5.95 6.33 5.66 5.73 5.27 5.48 5.36
Skull
NAD Retarded Ossification (2 bil) NAD NAD NAD NAD NAD
VR
118
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTERATIONS
GROUP I : 0 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658787 (Cont.) 8 5.48 9 5.87
10 5.77
NAD NAD NAD
658791 1 2
3
4 5
6
7
8 9 10 11
12
13 14
5.90 5.66
5.80
5.86 5.07
5.36
5.67
5.79 5.32 5.91 5.02
5.61
5.04 5.08
Kidney Vertebra Kidney Vertebra
Vertebra Vertebra Rib Vertebra
Vertebra Vertebra Kidney
Papilla - Size 3 (bil) Retarded Ossification
(cen th9-12) Papilla - Size 3 (bil) Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen thll) Retarded Ossification
(cen thll) Supernumerary (site 14 rt) Retarded Ossification
(cen thl2) NAD NAD NAD Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl2) Small Papilla - Size 2 (It) NAD
VR VR VR VR
VR VR DV VR
VR VR VR
119
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
58705 1 2 3 4 5 6 7 8 9
10 11 12
6.01 5.54 5.93 5.44 6.24 5.35 5.51 5.82 5.52
5.23 5.90 5.63
Rib Rib
Kidney
NAD Supernumerary (short 13 rt) NAD Supernumerary (site 13 It) NAD NAD NAD NAD Papilla - Size 3 (bil) NAD NAD NAD
DV DV
VR
658706 1 2 3 4 5
6 7 8 9 10 11 12
658712 1 2 3 4 5 6 7 8
5.61 6.02 6.23 5.85 6.01
5.64 5.41 6.19 5.81 5.85 5.87 5.55
Vertebra
5.05 5.28 5.39 5.44 5.12 5.52 5.13 4.93
NAD NAD NAD NAD Retarded Ossification
(cen thl2) NAD NAD NAD NAD NAD NAD NAD
NAD NAD NAD NAD NAD NAD NAD NAD
VR
Company Sanitised. Does not contain T8CA Cl
120
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658712 (Cont.) 9 5.55
10 5.68 11 6.32 12 6.00 13 5.67 14 5.82
Kidney
Papilla - Size 3 (rt) NAD NAD NAD NAD NAD
VR
658720 1 2
3 4
5 6
7 8
9 10
11
12 13
14
15
658721 1 2 3 4
5.33 4.81
5.62 5.08
5.33 5.26
4.79 5.11
5.34 5.80
5.30
4.88 5.44
4.92
4.00
Skull Vertebra
Vertebra
Vertebra
Vertebra
Vertebra Vertebra Skull Vertebra Vertebra
5.43 5.65 5.49 5.18
Kidney
NAD
Retarded Ossification (2 bil) Retarded Ossification
(cen thl0-12) NAD Retarded Ossification
(cen thlO-12) NAD Retarded Ossification
(cen th.12) NAD Retarded Ossification
(cen thlO-12) NAD Retarded Ossification
(cen thl0-12) Retarded Ossification
(cen thl2) Retarded Ossification (2 bil) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thll) NAD
VR VR
VR
VR
VR
VR VR VR VR VR
NAD NAD Small Papilla - Size 2 (It) NAD
VR
r?
Company Sanitized. Does m i coertam TSCA C 8I
121
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP II: 525 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658721 (Cont .) 5 5.46 6 5.12 7 3.80 8 5.49 9 5.41
10 5.19 11 5.39
12 4.69 13 5.47 14 4.85 15 5.04 16 5.44
Kidney
NAD NAD NAD NAD NAD NAD NAD NAD Papilla - Size 3 (bil)
NAD NAD NAD
VR
658734 1 2 3 4 5 6 7 8 9
10 11 12
5.22 5.53 5.79 5.78 4.89 5.77 5.13 5.81 5.55 5.22 5.86 5.53
Kidney Skull Skull
Small Papilla - Size 2 (bil) NAD NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) NAD NAD NAD NAD
VR VR VR
658736 1 2 3 4 5 6 7 8 9
10
5.65 5.51 5.38 6.08 5.12 5.93 5.08 5.21 5.61 5.70
Kidney Skull
Skull
Papilla - Size 3 (bil) Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) NAD NAD NAD NAD
VR VR
VR
compan, Sanitized. Does not contain TSCA CB.
122
H-25231 : Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658738 1 2 3 4 5 6 7 8 9
10 11 12 13 14 15
658740 1 2 3 4
5 6 7 8 9 10 11 12 13
658743 1 2
5.63 5.80 5.39 5.78 5.35 5.33 5.59 5.99 5.59 4.58 5.29 5.88 5.10 5.44 5.81
Kidney Rib
Skull Skull
5.23 5.22 5.58 5.63
-
5.51 5.14 5.41 5.24 5.62 5.24 4.97 5.43 4.86
Vertebra Kidney Kidney
5.53 5.07 Skull
Vertebra
Papilla - Size 3 (bil) NAD NAD Supernumerary (site 13 It) NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD
VR DV
VR VR
NAD NAD NAD Retarded Ossification
(cen thll) NAD NAD Small Papilla - Size 2 (bil) NAD NAD NAD Papilla - Size 3 (bil) NAD NAD
VR VR VR
NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thlO-11)
VR VR
H-25231: Developmental Toxicity Study in Rats________________________ ______________________DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658743 (Cont.) 3 5.59
4 5.71 5 5.16 6 5.63 7 5.71 8 5.35 9 5.88
10 5.27 11 5.82
Vertebra
Kidney Vertebra Vertebra
Retarded Ossification (cen thlO)
NAD NAD NAD NAD NAD Papilla - Size 3 (bil) Retarded Ossification
(cen thl2) NAD Retarded Ossification
(cen thl0-ll)
VR
VR VR VR
658745 1 2 3
4
5 6
7
8 9 10 11 12
4.98 5.09 4.63
4.75
4.57 5.41
4.63
4.72 4.20 4.84 4.59 4.82
Vertebra
Skull Rib Vertebra
Skull Skull Skull
Skull Vertebra
Kidney Vertebra
Vertebra
Vertebra
Retarded Ossification (cen thlO-13)
Retarded Ossification (2 bil) Supernumerary (site 14 rt) Retarded Ossification
(cen thlO,12) Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) Papilla - Size 3 (rt) Retarded Ossification
(cen thll) Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen thll-12) NAD NAD
VR VR DV
VR VR VR VR
TO
TO TO
TO
TO
TO
J5prapspSanitized. Does not a?n TSCA CBI
124
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS W T . STRUCTURE
FINDING(S)
CLASSIFICATION
658745 (Cont.) 13 5.05 14 4.83
15 4.74
Kidney Vertebra
Papilla - Size 3 (bil) Retarded Ossification
(cen thlO,13) NAD
VR VR
658752 1
2
3 4 5
6 7 8 9 10
11
12
13
14 15 16
17
658754 1 2
5.25
5.45
5.21 5.51 5.12
5.25 5.42 5.18 5.13 5.02
5.06
4.95
4.64
5.09 4.81 4.62
5.09
Vertebra Vertebra
Vertebra
Vertebra Vertebra Vertebra Vertebra
Kidney Skull Vertebra Rib Vertebra
5.57 6.04
Retarded Ossification (cen thll-13)
Retarded Ossification (cen thll)
NAD NAD Retarded Ossification
(cen thll,13) NAD NAD NAD NAD Retarded Ossification
(cen thl2) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl2) NAD Papilla - Size 3 (bil) Retarded Ossification (12 bil) Retarded Ossification
(cen thlO) Supernumerary (site 14 It) Retarded Ossification
(cen thll-12)
VR VR
VR
VR VR VR VR VR VR VR DV VR
NAD NAD
not contain T SCA CBl >any &.anitteed. Doss 125
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL PETAL WEIGHTS (grams) AN D ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658754 (Cont.) 3 6.18 4 5.46 5 5.51
6 5.72 7 5.23 8 5.69 9 5.61 10 5.93
11 5.17
12 5.71 13 5.54
Vertebra Skull
Vertebra Kidney Vertebra
NAD NAD Retarded Ossification
(cen thll) Retarded Ossification (1) NAD NAD NAD Retarded Ossification
(cen thll) Papilla - Size 3 (It) Retarded Ossification
(cen thll) NAD NAD
VR VR
VR VR VR
658762 1 2
3 4 5
6 7
8 9 10 11 12
658763 1 2 3 4
5.57 5.18
5.13 5.22 5.15
6.30 5.26
6.10 5.71 5.31 5.13 5.61
Vertebra Vertebra Vertebra
5.91 5.81 5.84 5.32
NAD Retarded Ossification
(cen thll-13) NAD NAD Retarded Ossification
(cen thl3) NAD Retarded Ossification
(cen thll) NAD . NAD NAD NAD NAD
NAD NAD NAD NAD
VR VR VR
126
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658770 1 2 3 4 5 6 7 8 9
10 11 12 13
5.63 5.53 5.38 5.29 5.13 5.46 5.39 5.49 4.89 5.25 5.60 5.34 5.30
Skull
Skull Kidney Skull
Skull
NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) Papilla - Size 3 (bil) Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) NAD
VR
VR VR VR
VR
658772 1 2 3 4 5 6 7
a
9
10
11 12 13 14 15
5.48 5.01 5.22 5.44 5.66 5.71 5.76 5.42 5.53 5.53
5.57 5.61 5.06 5.42 6.11
Skull
Kidney Skull Rib Rib Skull
Skull Rib Skull Kidney
NAD Retarded Ossification (2 bil) NAD NAD NAD NAD
Papilla - Size 3 (bil) Retarded Ossification (2 bil) Supernumerary (site 13 It) Supernumerary (site 13 rt) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Supernumerary (site 13 rt) Retarded Ossification (2 bil) Papilla - Size 3 (bil)
VR
VR VR DV DV VR
VR DV VR VR
658775 1 2 3 4 5
5.66 5.25 4.91 5.25 5.86
Skull
NAD NAD NAD Retarded Ossification (2 bil) NAD
VR
Compan*
127
Does not contain TSCA CBI
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658775 (Cont.) 6 5.52 7 5.39 8 5.17 9 6.15
10 5.54 11 5.54 12 5.30 13 5.60
Vertebra
NAD NAD NAD
Retarded Ossification (cen thl2)
NAD NAD NAD NAD
VR
658777 1
2
3
4
5
6 7
8 "s
9 10
11 12
13
5.36 5.71 5.47 5.36 5.16 5.05 5.10 5.56 5.29 5.51 5.37 5.59
5.29
Vertebra Vertebra Vertebra Vertebra Vertebra
Vertebra Vertebra
Vertebra
Subcutis Vertebra Vertebra
658784 1
4.61
Retarded Ossification (cen thl0-ll)
Retarded Ossification (cen thll)
Retarded Ossification (cen thl0-ll)
Retarded Ossification (cen thll-12)
Retarded Ossification (cen thl2)
NAD Retarded Ossification
(cen thl0,l2) Retarded Ossification
(cen thlO-13) NAD Retarded Ossification
(cen th.9,13) NAD Hemorrhage (chin*) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl2-13)
NAD
VR VR VR VR VR
VR VR
VR N VR VR
Company Sanitized. Does not contain TSCA CBI
128
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP II: 625 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658784 (Cont.) 2 5.05 3 5.17 4 5.15 5 5.22
6 5.03 7 5.05 8 5.09 9 5.11 10 4.70
11 5.08 12 5.18 13 4.79
Skull
Skull Vertebra
Skull
Skull
Rib Skull
Skull
Retarded Ossification (2 bil) NAD
Retarded Ossification (2 bil) Retarded Ossification
(cen thl3) Retarded Ossification (2 bil) NAD
Retarded Ossification (2 bil) NAD
Supernumerary (site 10 It) Retarded Ossification (2 bil) NAD
Retarded Ossification (2 bil) NAD
VR
VR
VR VR
VR
DV VR
VR
658788 1 2
3 4 5 6 7 8 9 10 11 12 13
5.07 2.69
5.15 5.38 5.26 5.33 5.13 5.09 5.38 4.94 4.94 5.16 5.11
Skull Sternebra Vertebra
NAD Retarded Ossification (2 bil) Retarded Ossification (1,3-4) Retarded Ossification
(cen thl0-13) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD
VR VR
VR
^ _____ -nntanTSCA CBl
C oWPan^
129
/ '"""'N
H -25231: Developmental Toxicity Study in Rats ____________ ________________________________ DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658707
1 2
3 4
5
6
7 8 9 10 11 12
13 14
5.32 5.59 5.52 5.29
5.38 5.34 5.24 5.72 5.82 6.06 5.81 5.88 5.70 5.33
Skull
NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD NAD NAD NAD NAD NAD
VR
658709 1
2
3 4 5
6
7
8 9
10
11
12 13
5.58
5.41
6.02 5.39 5.35
5.05
6.04
5.58 5.68
5.50
5.50
5.47 5.60
Vertebra Vertebra
Vertebra Vertebra Vertebra
Vertebra Vertebra Vertebra
Retarded Ossification (cen thll-12)
Retarded Ossification (cen thll-12)
NAD NAD
Retarded Ossification (cen thll)
Retarded Ossification (cen thlO)
Retarded Ossification (cen thlO-ll)
NAD
Retarded Ossification (cen thlO)
Retarded Ossification (cen thlO)
Retarded Ossification (cen thlO,13)
NAD NAD
VR VR
VR VR VR
VR VR VR
Company Sanitized. Does not contain TSC Ci
130
Z**""*'*'
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS :NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658709 (Cont.) 14 5.29 Vertebra
Retarded Ossification (cen thll-12)
VR
658715 1 2
5.56 5.46 Vertebra
NAD Retarded Ossification
(cen thl2)
VR
658717 1 2 3 4 5 6 7 8 9
10 11
12
13
5.59 5.76 6.06 5.67 5.57 5.52 5.28 5.54 5.31 5.33 5.68
5.66
5.64
Kidney
Vertebra Vertebra
NAD NAD NAD NAD
Papilla - Size 3 (It) NAD NAD NAD NAD NAD Retarded Ossification
(cen thl2) Retarded Ossification
(cen thl2) NAD
VR
VR VR
658722 1 2 3 4 5 6 7 8 9
10
5.97 5.51 5.64 5.47 5.98 5.77 5.38 5.67 5.33 6.00
Rib Rib Rib Rib Rib
Rib
Supernumerary (site 13 bil) Supernumerary (site 14 It) Supernumerary (site 14 bil) NAD Supernumerary (site 14 rt) Supernumerary (site 14 bil) NAD NAD NAD Supernumerary (site 14 bil)
DV DV DV DV DV
DV
Company Sanitized. Does not contain TSC CBi
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL PETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658722 (Cont.)
11 5.78 12 5.67 13 5.13 14 5.87
Vertebra
Rib Rib
Rib
Retarded Ossification (cen thll)
Supernumerary (site 14 It) Supernumerary (site 14 rt) NAD Supernumerary (site 14 It)
VR DV DV
DV
658724 1 2
3 4 5 6 7 8
9
10
11 12 13 14
15 16 17
5.12 5.35
5.47 5.24 5.68 5.29 5.24 5.43
4.97
5.35
5.60 4.86 5.56 5.25
4.89 5.28 5.41
Vertebra
Rib Skull Vertebra Kidney Rib Vertebra
Skull Skull
NAD Retarded Ossification
(cen thlO) NAD NAD Supernumerary (site 13 It) Retarded Ossification (2 bil) NAD Retarded Ossification
(cen thl2) Small Papilla - Size 2 (rt) Supernumerary (site 13 rt) Retarded Ossification
(cen thl2) NAD Retarded Ossification (2 bil) NAD Retarded Ossification
(2,6 bil) NAD NAD NAD
VR
DV VR
VR VR DV VR VR
VR
658728 1 2 3 4 5 6
5.97 5.86 5.21 5.34 5.70 5.21
NAD NAD NAD NAD NAD NAD
Company Sanitized. Does not contain TSCA CBI
132
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658728 (Cont.) 7 5.68 8 5.50 9 5.20
10 5.44 11 5.84 12 5.87
NAD NAD NAD NAD NAD NAD
658731 1
2 3
4
5
6
7 8
9 10 11 12
4.71
5.17 4.87
5.49
5.14
5.36
5.26 4.47
5.51 5.11 5.32 5.31
Vertebra Skull Vertebra Vertebra Vertebra Vertebra
Skull Vertebra
Skull Skull
Retarded Ossification (cen th9,11-12)
Retarded Ossification (2 bil) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll) Retarded Ossification
(cen thll) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thl2-13) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil)
VR VR VR VR VR VR VR VR VR VR
658732 1 2 3 4
5 6 7 8
5.58 5.64 5.04 4.94
5.05 5.23 4.52 5.22
Vertebra
NAD NAD NAD Retarded Ossification
(cen thl2) NAD NAD NAD NAD
VR
Company Sanitized. Does not contain TSCA CBl
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658732 (Cont.) 9 5.21
10 5.02
11 5.23 12 5.10 13 4.82 14 5.56 15 5.06
658735 1 2 3 4 5 6 7 8 9
10 11 12 13 14 15 16 17
5.98 5.72 5.63 5.76 5.94 5.81 5.74 5.58 5.50 5.93 5.88 5.48 5.33 5.97 5.73 5.83 5.33
658737 1 2 3 4 5 6
5.08 5.45 5.36 5.46 5.34 4.99
Vertebra Vertebra Skull
Skull Skull Skull
Skull Skull
Subcutis Subcutis Vertebra
Retarded Ossification (cen thl3)
Retarded Ossification (cen thll)
NAD Retarded Ossification (6 rt) NAD NAD NAD
VR VR VR
NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD
VR VR VR
VR VR
NAD Hemorrhage (left hindquarter*) Hemorrhage (chin*) NAD NAD Retarded Ossification
(cen thll-12)
N N
VR
Com pW Sanitized. Does not contain TSCA OBI
134
,'******
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658737 (Cont.) 7 5.40 8 5.40 9 5.74
10 6.05 11 5.57
Rib Skull
Supernumerary (site 13 It) NAD
NAD
Retarded Ossification (2 bil) NAD
DV VR
658751 1 2 3 4 5 6 7 8 9
10 11 12
13 14 15
5.38 5.15 5.56 5.73 4.86 5.43 5.52 5.00 5.34 5.70 5.48 5.16 5.41 5.47 4.96
Skull Kidney
Skull
NAD NAD NAD NAD NAD Retarded Ossification (2 bil) Papilla - Size 3 (bil) NAD NAD NAD NAD
Retarded Ossification (2 bil) NAD NAD NAD
VR VR
VR
658756 1 2 3 4 5 6
5.04 5.34 5.22 5.19 5.19 5.64
Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra
Retarded Ossification (cen thlO)
Retarded Ossification (cen thll)
Retarded Ossification (cen thll)
Retarded Ossification (cen thl2)
Retarded Ossification (cen thll)
Retarded Ossification (cen thl2)
VR VR VR VR VR VR
/'"'"N
Company Sanitized. Does not contain TSCA CBI
135
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS W T . STRUCTURE
FINDING(S)
CLASSIFICATION
658756 (Cont.) 7 4.87
8 5.16 9 5.33 10 5.46
11 5.45 12 5.89
13 5.44
14 5.79
15 5.32
Vertebra
Vertebra
Vertebra Vertebra Vertebra Vertebra
Retarded Ossification (cen thlO,12)
NAD NAD Retarded Ossification
(cen thll-12) NAD Retarded Ossification
(cen thl3) Retarded Ossification
(cen thll) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll-12)
VR
VR
VR VR VR VR
658765 1 2 3 4
5
6 7 8
9 10 11 12 13 14 15 16
5.49 5.88 6.11 5.71
5.46
5.25 5.54 5.60
5.70 5.64 5.62 5.60 5.67 5.70 5.93 5.54
Vertebra Vertebra
Vertebra Kidney
NAD NAD NAD Retarded Ossification
(cen thl2) Retarded Ossification
(cen thll) NAD NAD Retarded Ossification
(cen thlO) Small Papilla - Size 2 (bil) NAD NAD NAD NAD NAD NAD NAD
VR VR
VR VR
Company Sanitized. Does not contain TSCA CBI
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658766 1 2 3 4 5 6
7 8
9 10 11 12 13 14 15
5.75 5.84 6.07 5.82 5.69 5.90
5.46 5.42
5.81 5.38 5.63 5.47 5.56 5.96 5.76
Vertebra Skull Vertebra Skull
Vertebra
NAD NAD NAD NAD NAD Retarded Ossification
(cen thll) NAD Retarded Ossification (12) Retarded Ossification
(cen thl0-13) NAD Retarded Ossification (12) NAD NAD NAD NAD Retarded Ossification
(cen thll)
VR VR VR VR
VR
658767 1 2 3 4 5 6 7 8 9
10 11
12 13 14 15 16
5.28 5.16 5.51 5.43 5.24 5.19 5.33 5.20 5.42 5.22 5.54
5.18 5.68 5.49 5.13 5.24
Rib
Kidney Rib Rib Skull
NAD NAD Supernumerary (site 13 rt) NAD NAD NAD NAD NAD NAD NAD Papilla - Size 3 (bil) Supernumerary (site 13 bil) Supernumerary (site 13 bil) NAD Retarded Ossification (6 It) NAD NAD
DV
VR DV DV VR
Company Sanitized. Does not contain TB C A CBf
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658771 1 2 3 4
5 6 7 8 9 10 11 12 13
5.32 5.20 4.94 4.43
5.34 4.99 4.97 4.56 5.39 5.07 5.64 5.07 5.18
Skull
Rib Skull
NAD Retarded Ossification (2 bil) NAD Supernumerary (site 13 lt) Retarded Ossification (2 bil) NAD NAD NAD NAD NAD NAD NAD NAD NAD
VR
DV VR
658778 1
2
3
4
5
6 7
8
9 10 11 12 13 14
5.15
5.28
5.30
5.79
5.08
4.82 5.14
4.65
5.60 5.34 5.20 4.80 5.29 5.39
Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Subcutis Vertebra
Skull
Retarded Ossification (cen thll)
Retarded Ossification
(cen thl0,12) Retarded Ossification
(cen thl0-ll) Retarded Ossification
(cen thll) Retarded Ossification
(cen thl0-13) Retarded Ossification (12) Retarded Ossification
(cen thll,13) Hemorrhage (chin*) Retarded Ossification
(cen thll) NAD Retarded Ossification (12) NAD NAD NAD NAD
VR
VR
VR
VR
VR VR
VR N
VR
VR
Compaq Sanitized. Des
138
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658779 1 2 3 4 5 6 7 8 9
10
11 12 13 14 15 16
5.26 4.88 5.18 5.33 4.41 3.64 4.96 4.85 4.85 5.05
5.53 5.32 5.04 5.43 5.41 4.93
Skull Skull Skull Vertebra
Skull Skull Skull
NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thlO) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil)
VR VR VR VR VR VR VR
658782 1
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
4.94
5.27 5.69 5.35 4.90 5.38 5.07 4.82 4.98 5.09 5.25 4.89 5.50 5.40 5.06 5.12
Vertebra Skull
Skull
Retarded Ossification (cen thlO)
NAD NAD Retarded Ossification (2 bil) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (2 bil)
VR VR
VR
Company Sanitized. Does not contain TSGA CB5
139
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE_______________ FINDING (S)__________ CLASSIFICATION
658786 1
2
3
4
5 6
7
8 9
10
11
12
13
658789 1 2 3 4 5 6 7 8 9
10
5.31 Vertebra
5.34 Vertebra
5.29 Vertebra
5.46 Vertebra
5.25 4.95 Vertebra
5.34 Vertebra
5.86 5.35
Kidney Vertebra
5.63 Vertebra
5.49 Vertebra
5.32 Vertebra
5.43 Kidney Vertebra
5.80 5.53 5.78 5.28 6.02 5.51 5.38 6.02 5.72 5.32
Skull Skull
Skull
Retarded Ossification (cen th.12)
Retarded Ossification (cen thll)
Retarded Ossification (cen thl2)
Retarded Ossification (cen thlO-ll)
NAD Retarded Ossification
(cen thll) Retarded Ossification
(cen thll-12) NAD Papilla - Size 3 (bil) Retarded Ossification
(ceh thll-12) Retarded Ossification
(cen thlO-12) Retarded Ossification
(cen thl2) Retarded Ossification
(cen thlO,12) Papilla - Size 3 (bil) Retarded Ossification
(cen th.12)
VR VR VR VR
VR VR VR VR VR VR VR VR VR
NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) NAD NAD
VR VR
VR
Company Sanitized. Doss not contain TSCA CBI
140
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP III: 1250 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658789 (Cont.) 11 6.61 12 5.72 13 6.30
Skull
NAD Retarded Ossification (2 bil) NAD
VR
not contain T8CAC8t Company san ili * -Does
141
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING (S)
CLASSIFICATION
658704 1 2
3
4 5 6 7 8 9
10 11 12
5.20 5.19
5.28
4.91 5.13 5.34 5.06 5.01 5.21
4.31 5.48 5.53
Kidney Skull Skull Vertebra
Skull Kidney Vertebra
Vertebra
Papilla - Size 3 (It) Retarded Ossification (1) Retarded Ossification (6 bil) Retarded Ossification
(cen thlO,12) NAD NAD NAD NAD Retarded Ossification (1) Papilla - Size 3 (bil) Retarded Ossification
(cen thll-12) NAD NAD Retarded Ossification
(cen thll)
VR VR VR VR
VR VR VR
VR
658710 1 2 3 4 5 6 7
8
9
10 11 12 13 14 15
4.99 5.36 5.43 5.12 5.53 5.53 5.31
5.24
5.44
4.47 5.12 5.53 5.28 5.08 5.29
Vertebra Vertebra Vertebra
NAD NAD NAD NAD NAD NAD
Retarded Ossification (cen thl0-ll)
Retarded Ossification (cen thll)
Retarded Ossification (cen thll)
NAD NAD NAD NAD NAD NAD
VR VR VR
Does not contad T s * Company Santtzed'
142
i#***\.
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658711 1 2 3 4 5 6 7
8
9 10 11 12
4.53 4.68 4.86 4.62 4.55 5.26 5.17
5.16
4.84 5.30 4.98 5.02
Vertebra
Kidney Vertebra Skull Vertebra Vertebra Vertebra
Vertebra
NAD NAD Retarded Ossification
(cen th.10,12) NAD NAD NAD Papilla - Size 3 (bil) Retarded Ossification
(cen thlO) Retarded Ossification
(site 6 bil) Retarded Ossification
(cen Lui) Retarded Ossification
(cen thlO-12) Retarded Ossification
(cen thlO-13) NAD Retarded Ossification
(cen thl2) NAD
VR
VR VR VR VR VR VR
VR
658714 1 2 3 4 5
6
5.60 5.39 5.42 5.49 2.48
5.26
Skull Rib
Abdomen Stomach
Appendicular Skeleton Femur Rib Sternebra
NAD Retarded Ossification (2 bil) Supernumerary (site 13 It) NAD Malformation (caudal agenesis) Absent
(kidney,ureter,esophagus) Absent (th4-caudal)
VR DV
M
M M
Absent (rt;lt fibula only) Fused (thl-31t) Fused (1-6) NAD
M M M
ClMlltteed Does not contain TSCA CBl Company Sanrtize
143
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS W T . STRUCTURE
FINDING(S)
CLASSIFICATION
558714 (Cont.) 7 5.59
8 5.01 9 5.77 10 5.23
11 5.06 12 5.13 13 5.22 14 4.71
15 5.32
Vertebra
Skull
Vertebra
Skull Rib Skull Vertebra
Retarded Ossification
(cen thll) Retarded Ossification (2 bil) NAD Retarded Ossification
(cen thlO) NAD Retarded Ossification (2 bil) Supernumerary (site 13 bil) Retarded Ossification (2 bil) Retarded Ossification
(cen thlO) NAD
VR VR
VR
VR DV VR
VR
658716 1 2 3 4 5
6 7 8
9
10
11 12
13 14
6.48 6.57 6.35 6.46 6.28
6.36 6.59 6.31
6.73
6.13
6.56 6.48
6.00 6.49
Vertebra
Vertebra Vertebra Vertebra Vertebra
NAD NAD NAD NAD Retarded Ossification
(cen thlO) NAD NAD Retarded Ossification
(cen thll) Retarded Ossification
(cen thll) Retarded Ossification
(cen thll-12) NAD Retarded Ossification
(cen thll) NAD NAD
VR
VR VR VR VR
658723 1
5.62
NAD
Saw CotnPan^
n0t contain .Does
H -25231: Developmental Toxicity Stiidy in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
558723 (Cont.) 2 5.78 3 5.48 4 5.61 5 5.28 6 4.95 7 5.66 8 4.79 9 4.95
10 5.37
11 5.37 12 4.97 13 5.41
Skull
Skull Skull Skull Rib Skull Skull
Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD Supernumerary (site 13 rt) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD
VR VR VR VR DV VR VR
658726 1
2
3 4
5 6 7 8 9
10
5.13
4.51
4.83 4.86
4.63 4.70 5.14 5.25 3.45
5.12
Subcutis Vertebra
Skull Vertebra
Skull Vertebra
Vertebra
Rib Vertebra
Tongue Pelvis
Vertebra
Hemorrhage (right rear paw *) Retarded Ossification
(cen thl2) Retarded Ossification (2 bil) Retarded Ossification
(cen thlO) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll-12) NAD Retarded Ossification
(cen thll) Supernumerary (site 13 It) Retarded Ossification
(cen thl2) Protruding Retarded Ossification
(ischium bil) Retarded Ossification
(cen thll-12) NAD
N VR VR VR VR VR
VR DV VR N VR VR
notcniaio1SC -- * BC"
145
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658726 (Cont.) 11 5.03
12 4.55
13 14
15
16
658733 1
2
3
4 5 6
7 8 9 10
11 12
13
5.31 4.59
5.36
5.25
4.93 5.31
5.39 5.25 5.25 5.38
5.17 5.11 5.03 5.06 5.01 4.66 5.20
Vertebra Subcutis Skull Vertebra
Subcutis Vertebra Subcutis Vertebra
Vertebra Skull Vertebra Vertebra Skull Skull Vertebra
Skull Rib Vertebra
Vertebra
Retarded Ossification (cen thll)
Hemorrhage (chin*) Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) NAD Hemorrhage (chin*) Retarded Ossification
(cen thll) Hemorrhage (chin*) Retarded Ossification
(cen thll) NAD
VR N VR
VR
N
VR N
VR
Retarded Ossification (cen thll)
Retarded Ossification (8 bil) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thll) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) NAD Retarded Ossification (8 bil) Supernumerary (short 13It) Retarded Ossification
(cen thl2) NAD Retarded Ossification
(cen thll) NAD
VR VR VR
VR VR VR VR
VR DV VR
VR
146
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO / FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658733 (Cont.) 14 5.01 Vertebra
Retarded Ossification (cen thll,13)
VR
658744 1 2 3 4 5 6 7 8 9
10
11 12 13 14
4.93 5.24 5.41 5.18 5.37 5.24 5.05 5.16 5.36 5.27
4.62 4.33 5.40 4.54
Skull Skull
Subcutis Skull Subcutis
Skull
NAD NAD NAD Retarded Ossification (7 rt) NAD Retarded Ossification (2 bil) NAD NAD NAD
Hemorrhage (chin*) Retarded Ossification (2 bil) Hemorrhage (chin*) NAD NAD Retarded Ossification (2 bil)
VR VR
N VR N
VR
658746 1 2
3 4 5
6
7 8 9 10 11 12 13
5.39 4.49
4.97 5.67 4.47
5.37
5.10 5.67 5.26 5.34 5.28 4.95 4.68
Skull Skull Skull
Vertebra
Skull Skull
Kidney
Kidney Skull
NAD Retarded Ossification (1) Retarded Ossification (12) Retarded Ossification (2 bil) NAD NAD Retarded Ossification
(cen thl2) Retarded Ossification (1) Retarded Ossification (2 bil) NAD NAD Papilla - Size 3 (bil) NAD Papilla - Size 3 (It) Retarded Ossification (2 bil) NAD
VR VR VR
VR VR VR
VR
VR VR
,,,,i'# T S W 147
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP XV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658746 (Cont.) 14 4.27
Skull Skull Vertebra
Retarded Ossification (1) Retarded Ossification (2 bil) Retarded Ossification
(cen thl2)
VR VR
VR
658747 1 2 3 4 5 6
7 8 9 10 11 12 13 14
5.15 5.34 5.82 5.65 5.14 5.32
5.19 4.44 5.43 5.42 5.43 5.15 5.15 5.60
Rib Vertebra
Skull Skull
Skull Vertebra
NAD NAD NAD NAD Supernumerary (site 13 It) Retarded Ossification
(cen thl2) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thl3)
DV VR VR VR
VR VR
658750 1
2
3
4 5 6 7
5.83
4.59
5.63
5.17 5.17 5.38 4.90
Vertebra Vertebra Vertebra
Skull Vertebra
Retarded Ossification (cen thll)
Retarded Ossification (cen thl2)
Retarded Ossification (cen thl2)
NAD NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll-12)
VR VR VR
VR VR
nol contad TSCA< c o m ^ " * BGd-DOBS
148
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV:: 2500 MG/KG/DAY
DAM NO./ FETUS NO . FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658750 (Cont.) 8 5.02 9 5.25
10 5.15 11 4.95 12 4.82 13 5.22 14 5.12 15 5.16 16 4.98 17 5.68
Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra
Retarded Ossification (cen thll-12)
Retarded Ossification (cen thl0-ll)
Retarded Ossification (cen thlO-12)
Retarded Ossification (cen thll)
Retarded Ossification (cen thl2)
Retarded Ossification (cen thlO-12)
Retarded Ossification '
(cen thll) Retarded Ossification
(cen thll) Retarded Ossification
(cen thlO-12) Retarded Ossification
(cen thll)
VR VR VR VR VR VR VR VR VR VR
658757 1 2 3 4 5 6 7 8 9
10 11 12
13 14 15
5.15 5.20 4.89 4.74 5.03 5.14 4.86 5.02 4.99 4.80 5.05 4.90
4.77 4.41 4.63
Rib Skull Sternebra Skull
Skull Rib
Skull Sternebra
Rib
Supernumerary (site 14 rt) Retarded Ossification (2 bil) Retarded Ossification (6) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Supernumerary (site 13 rt) NAD NAD NAD NAD Retarded Ossification (2 bil) Retarded Ossification (6) NAD Supernumerary (site 13 It) NAD
DV VR VR VR
VR DV
VR VR
DV
Compaq 149
H -2 5 2 3 1: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658757 (Cont.) 16 4.91 Skull
Retarded Ossification (2 bil) VR
658760 1 2 3 4 5 6 7
8 .9 10 11 12 13 14 15 16
5.91 5.12 5.79 5.73 5.07 5.81 5.06
5.43 5.48 5.26 4.92 5.62 4.93 5.73 5.47 5.03
Skull Vertebra Subcutis
Vertebra
NAD Retarded Ossification (2 bil) NAD NAD NAD NAD Retarded Ossification
(cen thl2) Hemorrhage (chin*) NAD NAD NAD NAD NAD NAD NAD Retarded Ossification
(cen thll)
VR VR N
VR
658764 1 2 3 4 5 6 7 8 9
10
11
5.25 4.96 4.85 5.09 5.83 4.68 4.94 4.66 5.13 4.94
4.65
Skull
Skull Vertebra
Vertebra
NAD NAD NAD NAD NAD . NAD NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll) Retarded Ossification
(cen thl3)
VR VR VR VR
t\0iteo1 150
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658764 (Cont.) 12 4.81 13 4.82
14 4.96
15 4.72 16 4.82
Skull Vertebra
Skull Vertebra
Vertebra
Retarded Ossification (2 bil) Retarded Ossification
(cen thlO) Retarded Ossification (2 bil) Retarded Ossification
(cen thlO) Retarded Ossification
(cen thlO) NAD
VR
VR VR
VR
VR
658768 1 2 3 4
5 6 7
8 9
10
5.56 5.77 5.74 5.14
4.74 5.41 4.54
5.58 5.63
4.82
Vertebra
Skull Vertebra
Skull Vertebra
NAD NAD NAD Retarded Ossification
(cen th.12-13) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) Retarded Ossification (2 bil) Retarded Ossification
(cen thl2) NAD
VR
TO
TO VR
TO
658769 1 2 3 4 5 6 7 8 9
10 11
5.87 6.02 5.80 5.08 5.61 6.02 5.31 5.48 4.96 5.63 5.47
NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD
pees if
151
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
558769 (Cont .) 12 5.19 Rib
Supernumerary (site 13 lt)
DV
658774 1 2 3 4 5
6 7 8
9 10 11 12 13
14 15 16 17
4.57 4.78 4.75 4.83 4.90
4.83 4.52 4.64
4.73 4.62 4.40 4.66 4.84
4.51 4.47 4.55 4.86
Vertebra Skull Rib Vertebra Vertebra
Skull Vertebra Vertebra Vertebra
Vertebra Rib Vertebra Vertebra Vertebra Vertebra
NAD NAD Retarded Ossification
(cen thll-12) Retarded Ossification (2 bil) Supernumerary (short bil) Retarded Ossification
(cen thll) Retarded Ossification
(cen thl2) NAD Retarded Ossification (2 bil) Retarded Ossification
(cen thll-13) Retarded Ossification
(cen thl3) Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen thll) Supernumerary (short 13 lt) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen thll-13) Retarded Ossification
(cen thl3) Retarded Ossification
(cen thlO,12) NAD
VR VR DV VR VR VR VR VR VR
VR DV VR VR VR VR
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658780 1 2
3 4
5 6 7 8 9 10 11
12 13 14
5.49 5.42
5.01 5.42
5.03 5.76 5.74 5.63 5.32 5.47 5.25
5.23 5.63 5.14
Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Vertebra
Vertebra Vertebra
Rib Vertebra Vertebra Vertebra Vertebra
Retarded Ossification (cen thl0-13)
Retarded Ossification (12) Retarded Ossification
(cen thll-12) Retarded Ossification
(cen th9-12) Retarded Ossification (12) Retarded Ossification
(cen thll,13) Retarded Ossification
(cen thl0,12) Retarded Ossification
(cen thl2) NAD Retarded Ossification
(cen thll,13) Retarded Ossification
(cen thl0-12) NAD Supernumerary (14 rt) Retarded Ossification
(cen thlO-12) Retarded Ossification
(cen thll-13) Retarded Ossification
(cen thll-13) Retarded Ossification
(cen thl0-12)
VR VR VR VR VR VR VR VR
VR VR DV VR VR VR VR
658783 1 2 3 4 5 6 7
5.34 5.15 5.26 5.28 5.00 4.64 4.57
Skull Skull
NAD Retarded Ossification (2 bil) NAD NAD NAD Retarded Ossification (6 bil) NAD
VR VR
sO0 * c o ^ "tS' 153
H -25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO / FETUS NO. FETUS WT . STRUCTURE
FINDING(S)
CLASSIFICATION
658783 (Cont.) 8 5.03 9 4.93
10 5.40 11 5.14 12 5.39 13 5.17
Skull Vertebra
Skull
Retarded Ossification (2 bil) Retarded Ossification
(cen thl3) Retarded Ossification (2 bil) NAD NAD NAD
VR
VR VR
658785 1 2 3
4 5 6 7
8
9 10
6.47 5.69 6.13
6.12 5.55 5.53 5.37
5.73
5.30 5.49
Kidney Kidney Vertebra
Kidney Rib Vertebra Vertebra
Vertebra
Small Papilla - Size 2 (bil) NAD Papilla - Size 3 (bil) Retarded Ossification
(cen thl2) NAD NAD NAD Papilla - Size 3 (It) Supernumerary (site 14 bil) Retarded Ossification
(cen thll-13) Retarded Ossification
(cen thll) NAD Retarded Ossification
(cen thll)
VR VR VR
VR DV VR VR
VR
658790 1 2 3 4
5 6 7 8
5.20 5.23 4.74 4.86
5.23 4.88 5.39 4.16
Vertebra Rib
NAD NAD NAD Retarded Ossification
(cen thll) NAD NAD NAD Supernumerary (site 14 bil)
VR DV
, o t c o n ^ tSC 154
H-25231: Developmental Toxicity Study in Rats
DuPont-10309
INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS
GROUP IV: 2500 MG/KG/DAY
DAM NO./ FETUS NO. FETUS WT. STRUCTURE
FINDING(S)
CLASSIFICATION
658790 (Cont.) 9 4.70
10 5.10 11 4.85 12 5.17 13 4.84 14 4.62 15 4.66
Vertebra
Retarded Ossification (cen thll)
NAD NAD NAD NAD NAD NAD
CO*' 155
