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M A M - 3 3 1If. 496 evelopmental Toxicity Study in Rats DuPont-10157 TRADE SECRET Study Title developmental Toxicity Study in Rats Laboratory Project ID: DuPont-10157 Test Gu id elin es: United States (U.S.) Environmental Protection Agency CEPA), Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines. OPPTS 870.3700 Prenatal Developmental Toxicity Study. (August 1998). Organisation for Economic Cooperation and Development (OECD/OCDE). Guidelines for Testing of Chemicals, 414. (22nd January 2001). A uth o r: Susan M. Muney, M.A. S tudy Com pleted on: January 30,2004 Perfo r m in g L a bo ra to 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 0m lW ork Req uest N um ber Service Code N umber! Company SanHfz*d. Doe* not contain TSCA CBI Page 1 of 156 >evelopmental Toxicity Study in Rats DuPont-10157 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles of Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17. Test substance characterization was performed at Regional Analytical Services (RAS), Deepwater, NJ . 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 o f this study. Study Director: Susan M. Munley, M.A Research Scientist z o -Jf)t -2 ca j Date Company Sanitised. D oes not contain TSCA CBJ 2 evelopmental Toxicity Study in Rats DuPont-10157 QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24691 Dates of Inspections: Protocol: January 30,2003; February 3, 2003 Conduct: February 20,21, 2003 Records, Reports: May 7, 2003; June 3-6,23, 2003; July 29-30, 2003 Dates Findings Reported to: Study Director: January 30,2003; February 20,26,2003; May 9,2003; June 7, 2003, July 30, 2003 Management: February 20,26,2003; May 9,2003; August 6,2003; January 22,2004 Reported by: _________ ` tP S Staff Quality Assurance Auditor Date Company Sanitized. Does not contain TSCA CBI /Developmental Toxicity Study in Rats DuPont-10157 CERTIFICATION "We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Issued by Study Director! Susan M. Munley, R A . Research Scientist e0 -rJ4 fJ-2 O 4 Date Company Sanitized. Does noi contain TSCA CBI 4 evelopmental Toxicity Study in Rats 0 DuPont-10157 TABLE OF CONTENTS Page GOOD LABORATORY PR A C TIC E COM PLIANCE STA TEM EN T..................................... 2 QUALITY ASSURANCE STA TEM EN T...................................... 3 CERTIFICA TIO N ................................................................ ................................ -..............................4 LIST O F TA B LES.............................................................................. 7 LIST O F A PPEN D IC ES....................................................... ............................................................. 7 STUDY IN FO R M A TIO N ....................................................................................................................8 STUDY IN FO R M A TIO N ................................. 8 STUDY PERSONNEL..................................................................................................... 9 SUMMARY....................................... 10 O B J E C T IV E ............................................................................... 11 SPONSOR AND TEST F A C IL IT Y ............................. 11 Regulatory Com pliance.................... .................................................................. ................*............ 11 Study Design..........................................................................*........................... ..................................12 A. Experimental Design................................................................................................................12 & oup..................................................................................................................................................... 12 MATERIALS AND M E T H O D S...................................................................................................... 12 A. Test Substance............................................................... 12 B. Vehicle................................................................................................................... 12 C. Preparation, Administration, and Analyse^ of Dosing Form ulations..................................13 D. Test Species............................................................................................................................... 15 E. Animal Husbandry....................................................................................................................15 F. Quarantine and Pretest Period..................... 16 Cr. Randomization.......................................................................................................................... 16 H. Parameters Studied....................................................................................................................16 I. Animal Euthanasia....................................................................................................................17 J . Control of Bias.......................................................................................................................... 18 JL . Statistical Analyses..................................... ~.......................................................................... 18 $SU L TS AND DISCU SSIO N ..................................................... .......................................... .......19 Company Sanitized. Does not contain TSCA CM 5  evelopmental Toxicity Study in Rats ANALYTICAL EV A LU A TIO N S.................................................... A. Chromatography........................................................................ B. Recovery Samples......................................... ............................ C. Homogeneity and Stability Samples..................................... ... D. Concentration Verification Samples........................................ E. Analytical Conclusions.............................................................. DEVELOPM ENTAL TO X ICO LO G Y ............................................. A. Mortality, Post Mortem Findings, and Clinical Observations B. Body Weights and Body W eight Changes.................... .......... C. Food Consumption..................................................................... D. Postmortem Findings.............. .................................................. E. Reproductive Outcome and Litter D ata................................. .. F: Fetal Alterations....................................... .................................. G. Malformations............................................................................. H. Variations.................................................. .................................. CONCLUSIONS DuPont-10157 ..19 ..19 ..19 .19 .20 .21 .22 .22 .22 .22 .23 .23 .23 .23 .23 .25 RECORDS AND SAMPLE STORAGE .25 BEFERENCES................................................................................... .26 TABLES.................................. 27 APPENDICES................................................................................................................. 42 Company Sanitized. Does not contain TSCA CBi levelopmental Toxicity Study in Rats DuPont-10157 TRADE SECRET Study Title developmental Toxicity Study in Rats Laboratory Project ID: DuPont-10157 Te st G u id elin es: United States (U.S.) Environmental Protection Agency (EPA), Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines. OPPTS 870.3700 I Prenatal Developmental Toxicity Study. (August 1998). Organisation for Economic Cooperation and Development (OECD/OCDE). Guidelines for Testing of Chemicals, 414. (22nd January 2001). A uth o r: Susan M. Munley, M.A. Study Com pleted o n: January 30,2004 Perfo r m in g L a bo ra to 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 0m lW ork Req uest N um ber Service Code N um ber! C -J Company Santtfead. Does not contain TSCA CBI Page 1 o f 156 evelopmental Toxicity Study in Rats DuPont-10157 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles of Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17. Test substance characterization was performed at Regional Analytical Services (RAS), Deepwater, N.J. 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. Research Scientist Company Satimred. Does not contain TSCA CBt QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24691 Dates of Inspections: Protocol: January 30,2003; February 3,2003 Conduct: February 20,21, 2003 Records, Reports: May 7,2003; June 3-6,23, 2003; July 29-30, 2003 Dates Findings Reported to: Study Director: January 30,2003; February 20,26,2003; May 9,2003; June 7,2003, July 30, 2003 Management: February 20,26,2003; May 9,2003; August 6,2003; ^ January 22,2004 Reported by: Kimberly B. Brenner Staff Quality Assurance Auditor Date Company Sanitized. Does not contain TSCA CBf 3 ^Developmental Toxicity Study in Rats DuPont-10157 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Analytical Evaluations by: JJaanneettCC.MMaassllaannkkaa,,BB..SS.. Senior Staff Chemist (krtS'W' AOOtf- Date Issued by Study Director Research Scientist < 30-rJ4f~> -ZQ L Date Company Sanitized. Does not contain TSCA CBt 'evelopmental Toxicity Study in Rats DuPont-10157 TABLE OF CONTENTS Page GOOD LABORATORY PR A C TIC E COM PLIANCE STA TEM EN T..................................... 2 QUALITY ASSURANCE ST A T E M E N T ........................................................................................ 3 CERTIFICA TIO N ................................................................ ................................ ..............................4 LIST O F TA B LES................................................................................................................................. 7 LIST O F A PPEN D IC ES............................ ........................... ..................;...........................................7 STUDY IN FO R M A TIO N .................................................................................................................... 8 STUDY IN FO R M A TIO N .................................................................................................................... 8 STUDY PERSONNEL.......................................................................................................................... 9 SUMMARY....................................... 10 O B J E C T IV E ................................................................................ 11 SPONSOR AND TEST F A C IL IT Y -------------- -------,--------------------------------------------------11 legulatory C om pliance..................................................................................................................... 11 Study D esign.......................................................................... *....... ....................-..................................12 A. Experimental Design........................................................................................... 12 Group................ ........................ ............................................................................................................12 MATERIALS AND M E T H O D S................................................................................................... ,,.12 A. Test Substance............................................................... .......................................................... 12 B. V ehicle.................................................................................................................... 12 . Preparation, Administration, and Analyses of Dosing Form ulations..................................13 D; Test Species...................................................................................................................... 15 E. Animal Husbandry.................................................................................................................. 15 F. Quarantine and Pretest Period............................ 16 G. Randomization......................................................................................................................... 16 M"' Parameters Studied...................................................................................................................16 I. Animal Euthanasia...................................................................................................................17 L Control of Bias......................................................................................................................... 18 J L . Statistical Analyses...................................... 18 $SU LTS AND DISCU SSIO N ....................................................... .......19 catCompany S aniitod. Does not contai" TSCA 5 Cl evelopmental Toxicity Study in Rats ANALYTICAL EV A LU A TIO N S.................................................... A. Chromatography........................................................................ B. Recovery Samples..................................................................... C. Homogeneity and Stability Samples........................................ D. Concentration Verification Samples........................................ E. Analytical Conclusions.............................................................. DEVELOPM ENTAL TO X ICO LO G Y ............................................. A. Mortality, Post Mortem Findings, and Clinical Observations B. Body Weights and Body Weight Changes.................... .......... C. Food Consumption..................................................................... D. Postmortem Findings.............. .................................................. E. Reproductive Outcome and Litter D ata................................... F: Fetal Alterations......................................................................... G. Malformations............................................................................. H. Variations.................................................................................... CONCLUSIONS DuPont-10157 ..19 ..19 ..19 .19 .20 .21 .22 .22 .22 .22 .23 .23 .23 .23 .23 .25 EECORDS AND SAMPLE STORAGE .25 KEFERENCES ,26 TABLES................................................................................................................................................ 27 APPENDICES......................... ............................................................................................................ 42 Company Sanitized. Does not contain TSCA CBl 6 evelopmental Toxicity Study in Rats DuPont-10157 LIST OF TABLES TAB'LE 1 SUMMARY OF DOSING A N A L Y SES..................................................................................................................... 29 TAB-LE 2 CLINICAL OBSERVATIONS.................................. ................................................................................................... 30 TABLE 3 MEAN M ATERNAL BODY W EIGHTS................................................................................................................... 31 t a b l e 4 m e a n m a t e r n a l b o d y w e i g h t c h a n g e s .............................................................................................34 TABLE 5 M EAN M ATERNAL FOOD CONSUM PTION..................................................................................................... 36 TABLE 6 REPRODUCTIVE OUTCOME....................................................................................................................................38 TABLE 7 INCIDENCE OF FETAL MALFORM ATIONS..................................................................................................... 39 TABLE 8 INCIDENCE OF FETAL VARIATIONS................................................................................................................. AO LIST OF APPENDICES APPENDIX A ANALYTICAL CHEMISTRY REPORT.............................. APPENDIX B INDIVIDUAL CLINICAL OBSERVATIONS............. ..... APPENDIX C INDIVIDUAL BO DY W EIGHTS.................... ...................... APPENDIX D INDIVIDUAL BO DY WEIGHT CHANGES....................... APPENDIX E INDIVIDUAL FOOD CONSUM PTION................................ APJENDIX F INDIVIDUAL REPRODUCTIVE D A T A ............................... AP1ENDK G GROSS POSTMORTEM FIN D IN G S..................................... APfENDIX H INDIVIDUAL FETAL WEIGHTS A ND ALTERATIONS ...43 ...51 ...65 ...79 ...89 ...99 105 111 Company Sanitized. Does not contain TSCA CBI developmental Toxicity Study in Rats STUDY INFORMATION 9th Collective Nomenclature!! Svnonvms/Codes: DuPont-10157 Haskell Number: 24691 CAS Registry Numbej Compositio; Purr Known frnpuritielr Physical Characteristics: White to yellow wax Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was Observed. Sponsor:' 1200 South Hayes Street Arlington, Virginia 22202-5050 U.S.A. Study Initiated/Completed: January 30, 2003 / (see report cover page) In-Life Ihitiated/Completed: February 3, 2003 / February 24, 2003 Company Sanitized. Does not contain TSCA CBi 8 evelopmental Toxicity Study in Rats STUDY PERSONNEL Study Director: Susan M. Munley, M.A. Management: Eve Mylchreest, Ph.D. Supervisor: Deborah L. Tyler Primary Technician: Sandra E. Karr, A.A.S. 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: Thomas W. Mayer, D.V.M., A.C.L.A.M. DuPont-10157 Company Sanitized. Does not contain TSCA CSI 9 'Developmental Toxicity Study in Rats DuPont-10157 SUMMARY JThe objective of this study was to evaluate the potential maternal and developmental toxicity of administered by oral gavage to pregnant rats daily from around the Tim e of implantation toThe end of gestation, days 6-20 of gestation (days 6-20G). Groups of 22 time-mated Crl:CD(SD)IGS BR rats were administered formulations of the test substance in 0.5% aqueous methylcellulose over days 6 through 20 of gestation (G) at daily dose levels of 0,50,200, or 500 mg/kg. During the in-life portion of the study, body weight, food consumption, and clinical observation data were collected. On day 21G, all surviving dams were euthanized and dissected; the abdominal and thoracic viscera were examined grossly. The uterus of each pregnant rat was removed and dissected to permit examination of the uterine contents. The fetuses were removed, individually identified, weighed, sexed, and examined for external, visceral, head, and skeletal alterations. Under the conditions of this study, adverse maternal toxicity was produced at 500 mg/kg/day and consisted of maternal mortality, decreased body weights and body weight gains, and increased clinical observations of toxicity. One litter at 500 mg/kg/day consisted of one early resorption; persistent reductions in food consumption and body-weight gain and increased clinical observations indicative of toxicity were reported during the study for this female. Therefore, this litter consisting of a single early resorption is believed to be secondary to overt maternal toxicity in this dam. Developmental toxicity at 500 mg/kg/day consisted of increased skeletal variations (delayed pelvic bone ossification and wavy ribs). At 200 and 500 mg/kg/day, there were nonadverse, test substance-related, transient reductions in maternal food consumption. In addition, there were slight increases in the incidence of delayed skull bone ossification at 200 and 500 mg/kg/day that were not considered adverse. Thus, the no-observed-effect level (NOEL)i2for both maternal and developmental toxicity was considered 200 mg/kg/day. i 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(13) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.il4) Comoany Sanfilzed. Does not contain TSCA CBI /^P*N developmental Toxicity Study in Rats DuPont-10157 OBJECTIVE ^JThe objective of this study was to evaluate the potential maternal and developmental toxicity of n H | | P | | ^ | | | | n v h e n administered by oral gavage to pregnant rats daily from around the wtTme of implantation OTne end o^gestation, days 6-20 of gestation (days 6-20G). The test s u b s t a n c e B H H H H H ^ f H B i s an organofluorine compound. The 50,200, and 500 mg/kg/day dose levels were "selected for the current study based on findings from two sviously conducted studies. The first study was an 84-day range-finding study(1) with In which dose levels of 5, 25, and 125 mg/kg/day were tested. Evaluation of in-life data from the first few weeks of this study indicated that no compoundrelated toxicity was observed at doses <125 mg/kg/day. The evaluation of data from the 84-day study was limited to that which was collected during the first few weeks of dosing because in a developmental toxicity study, time-mated rats are only dosed for 15 consecutive days. The s e c o n tC tu d ^ Ia ta s e m h a ^ g ^ o n s ^ re d was from a rat developmental toxicity study with a s i m i l J H H | | [ | ^ m H | ^ ^ ^ ^ H S i which dose levels of 50, 200, and 500 mg/kg/day were evalufefed. M aternalanculeveio^aental toxicity were produced at 500 mg/kg/day and were limited to reductions in maternal body weight gain and food consumption, increased clinical signs, and increased fetal skeletal variations. No toxicologically significant or adverse compound-related effects were seen in dams or fetuses at 50 or 200 mg/kg/day. Thus, for the current study, a high dose level of 500 mg/kg/day was expected to produce maternal and developmental toxicity; the intermediate level of 200 mg/kg/day was expected to produce minimal to no toxicity, and the low dose of 50 mg/kg/day was expected to be the no-observedadverse-effect level (NOAEL). SPONSOR AND TEST FACILITY The study was sponsored by t h e f l J | | H H H | H P | B j 2 0 0 South Hayes Street, Arlington, Virginia, 22202-5050. The Sponsor's approval of the protocol was considered effective the date the Sponsor authorized the Work Authorization Form. The study will be conducted at DuPont Haskell Laboratory for Health and Environmental Sciences, E. I. du Pont de Nemours and Company, Newark, Delaware. REGULATORY COMPLIANCE The study design complies with the following test guidelines: United States (U.S.) Environmental Protection Agency (EPA), Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines. OPPTS 870.3700 Prenatal Developmental Toxicity Study. (August 1998). Organisation for Economic Cooperation and Development (OECD/OCDE). Guidelines for Testing of Chemicals, 414, (22nd January 2001). Company SanUbmi* Does not contain TSCA GB| 11 levelopmental Toxicity Study in Rats STUDY DESIGN A. Experimental Design The study design is as follows: Group I Dose3 (mg/kg/day) 0c Concentration (mg/mL)^ 0.0 Time-Mated Females 22 n 50 10.0 22 m 200 40.0 22 IV 500 100.0 22 a Formulations o f test substance in 0.5% aqueous methylcellulose were administered once daily by oral gavage on days 6-20G at a dosing volume o f 5 mL/kg. b To achieve these concentrations o f active ingredient, the formulations were adjusted for sample purity, c The control group animals received vehicle (0.5% aqueous methylcellulose) only at a dosing volume o f 5 mL/kg. DuPont-10157 MATERIALS AND METHODS A.. Test Substance fhe test substance, a waxy solid with known p u r r i y ^ J H k n d composition, was supplied by he Sponsor. The test substance was assigned the m sk ell Laboratory Number H-24691. The Sponsor was responsible for characterization and analysis of identity, stability, and purity of the bulk test substance. Available information on the purity, composition, contaminants, synonyms, CAS.registry number, basic physical properties, hazards, and hazardous material classification(s) m provided by the Sponsor and is available on the Haskell Laboratory Sample Evaluation form. The Sponsor also provided a Certificate of Analysis to the Study Director. The original Sample Evaluation Form and the Certificate of Analysis are retained in the official Work Request fie for the study. A reserve sample of the test substance was collected and retained by the festing Facility. f. Vehicle fhe vehicle was 0.5% aqueous methylcellulose. Lot number(s) and expiration date(s) were pcorded in the study records. tTSCACB' r Developmental Toxicity Study in Rats DuPont-10157 C. Preparation, Administration, and Analyses of Dosing Formulations Formulations of the test substance in the vehicle were prepared daily. The method o f mixing the test substance with the vehicle was documented in the study records. The test substance was administered by oral gavage because this route is recommended by regulatory agencies for this type of study. The volume administered (5 mL/kg) was based on the most recent body weight. Samples of each test formulation were taken 3 times during the study. Analyses addressed concentration, uniformity of mixing, and stability. Samples were submitted shortly after preparation to the Analytical Chemistry Group at Haskell Laboratory. 1. Analytical Methods a. Recovery Sample Analysis Concurrent with dosing formulation analysis, recovery of the test substance from spiked 0.5% methylcellulose was tested at the low level (10 mg/mL), at the mid level (40 mg/mL) and at the high-level (100 mg/mL) to confirm the analytical method. The test substance was weighed (approximately 30 mg, 120 mg, and 330 mg on test days 1 and 11 and approximately 20 mg, 90 mg, and 260 mg on test day 20, respectively) and diluted with 3 mL (2 mL for test days 11 and 20) of 0.5% methylcellulose. All recovery samples were then mixed to disperse the test substance in the methylcellulose. The samples were then processed and analyzed in the same maimer as the samples at similar concentrations. b. Dosing Formulation Treatment Each dosing sample (3 mL for test day 1; 2 mL for test days 11 and 20) was diluted to 100 mL with methanol and mixed to dissolve the test substance in the formulation. The dosing samples were analyzed without further dilution or were further diluted with the 0 mg/mL sample (initial dilution) to an expected concentration of approximately 0.06 mg/mL (a.i.) prior to analysis. Before all final dilutions, the internal standard diluted solution (refer to Calibration and Quantitation Section) was added to each test sample to give a final concentration of ipproximately 0.09 mg/mL. Each sample (final dilution) was adjusted to have an equivalent mount of matrix (final dilution of the 0.0 mg/mL control) when analyzed. Samples submitted for analysis were analyzed the day the formulations were received by the lasting group. c. Chromatographic Conditions Instrument: Column: Injector: Detector: Carrier Gas: Hewlett-Packard Model 6890 GC J & W, DB-1701, 30 m, 0.32 mm ID, 1 um film thickness Split, 250C FED;250C Helium (2.1 mL/min) Company SenW ied, Ones not contain TSCA CBI 13 >evelopmental Toxicity Study in Rats DuPont-10157 Split vent: Injection Volume: Oven Program: Initial Temperature: Initial Time: Level 1 Rate: Level 1 Temperature: Level 1 Time: Total run time: 22.3 mL/min 2 microliter Gradient 100C 1.00 min. 20.0C/min. 260C 0.00 min. 9.00 min. d. Calibration and Quantitation A separate sample of the test substance was obtained to use as the analytical reference standard. A stock solution was prepared in methanol. This stock solution was sonicated to assure that all material was in solution. Before analysis, appropriate aliquots of the stock were diluted with the 0 mg/mL sample (initial dilution) to make calibration standards, which bracketed >ck solution of internal standard 'as prepared in methanol and added to xw nitration of approximately .09 mg/mL. The ratio of the internal standard and the test substance 1 peak heights from replicate GC analysis of these solutions were used to construct a calibration curve by least squares regression (see Appendix A, Figure 1 for a representative curve). Measured concentrations for the dosing samples were determined by applying the peak height ratios from replicate injections o f each sample to the calibration curve. Test substance homogeneity and uniformity in the vehicle was evaluated by calculating the coefficient of variation (C.V. = standard deviation/mean x 100) of the measured concentrations in the top, middle, and bottom samples (homogeneity) or duplicate samples (concentration verification) for each dosing level. A coefficient of variation of less than or equal to 10% is considered indicative of acceptable distribution of the test substance throughout the solution. However, if the test substance has been shown to be difficult to disperse in the vehicle or the analysis has shown variability, a coefficient of variation greater than 10 may be acceptable. The mean result of the homogeneity samples or concentration verification duplicate samples for each dosing level was used to determine the concentration of the test substance for the respective dosing levels. Stability was evaluated by using the mean result of the homogeneity samples as ihe baseline for comparing the corresponding stability results. Spiked recoveries samples at each level were prepared and monitored to show the effect on the (uantitation of the study due to sampling into 100 mL volumetric flasks. Based on the spiked lecovery for each level on the day of the analysis, a correction was applied to all results in the study. Company Sanitized. Does not contain TSCA CBI 14 'Developmental Toxicity Study in Rats DuPont-10157 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 applicable regulatory guidelines. The strain was selected because background data are available from the literature, the supplier, and previous studies at Haskell Laboratory. Eighty-eight nulliparous, time-mated females were received on January 31,2003 (66 females) and February 3,2003 (22 females) from Charles River Laboratories, Inc., Raleigh, North Carolina. Body weights from the day the rats were mated, day 0 of gestation (day 0G), were supplied by the vendor and ranged from 230 to 270 grams. The rats for this study were requested to be approximately 63 days old and at either 1,2, or 3 days of gestation upon receipt. Each rat was assigned a unique number and identified with an AVID microchip implant by the supplier prior to shipping. Upon receipt, each rat was assigned a unique Haskell animal number. Both the Haskell animal number and the number provided by the supplier were recorded on each cage card. A master list of unique Haskell animal numbers and corresponding unique supplierprovided animal numbers was maintained with the study records. E. Animal Husbandry 1. Housing Animal rooms were maintained at an acceptable temperature of 18-26C (targeted at 22-24C) and maintained at an acceptable relative humidity of 30%-70% (targeted at 40 %- 60%). Occasional excursions outside the accepted ranges were minor and did not affect the study. Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours). Animals were housed individually in suspended, wire-mesh, stainless steel cages. Nesting material was not provided because the dams were euthanized prior to parturition. 2. Feed and Water PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 (formerly known as Purina Certified Rodent Chow) was available ad libitum. Water from United Water Delaware was available ad libitum. 3. Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Company Sanitized. Does not contain TSCA CBI 15 evelopmental Toxicity Study in Rats_________________________ DuPont-10157 Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional iequirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study. F. Quarantine and Pretest Period Rats were quarantined according to procedures outlined in Haskell Laboratory SOP LA0Q3-P, and then released for the study upon approval of the Laboratory Animal Veterinarian designee. G. Randomization Dams were assigned to lots according to their gestation day. Then, they were ranked within their respective lots on the basis of day OG body weights and assigned to control and experimental groups by random sampling from the ranked list. The distribution resulted in mean body weights for all groups that were not statistically different (p > 0.05). (L Parameters Studied ------ L Ih-life Observations of Females a. Clinical Observations Clinical observations were recorded on the day after arrival and daily until the end of the study; linical observations were recorded twice daily on days 6-20G. b. Body Weight Jody weights were recorded on the day after arrival and daily until the end of the study. c. Food Consumption food consumption was measured on days 4,6, 8, 10, 12,14,16, 18, 20, and 21G. Company SanKfeed. Does not contain TSCA CBI tevelopmental Toxicity Study in Rats DuPont-10157 2. Postmortem Observations of Females Surviving to Scheduled Euthanasia The abdominal and thoracic viscera were examined grossly immediately after euthanasia on day 21G. The intact and the empty uterus of each dam having at least one viable fetus was weighed to permit calculation of maternal body weight adjusted to exclude the products of conception. The corpora lutea count for each ovary of females with viable fetuses was recorded. For each female with visible implantation sites, the types of implants (live and dead fetuses, and resorptions) and their relative positions were recorded. The uterus of each apparently "nonpregnant" female was stained with ammonium sulfide(3) to detect very early resorptions. 3. Fetuses of Females Surviving to Scheduled Euthanasia For each fetus, the following parameters were recorded: identification number, intrauterine location, sex, and body weight. The external alterations detected for each live fetus were also recorded. For each litter, the first live fetus and every other live fetus thereafter (approximately 50% of the fetuses) were examined for visceral alterations/4* Retarded renal development was classified using the scheme o f Woo and H oar/5* In addition, all live fetuses with malformations visible at external examination were examined for soft tissue alterations; decapitation of these fetuses was at the discretion of the study director or a designee. Aiter fixation in Bouin's fixative, the heads of decapitated fetuses (fetuses that were decapitated prior to visceral examination; approximately 50% of the fetuses) were examined and alterations were recorded. Examinations were based on the method of Barrow and Taylor.(6) 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. I. Animal Euthanasia Females were euthanized by carbon dioxide asphyxiation. Fetuses were decapitated before proceeding with visceral examinations; those to be viscerally examined without decapitation fere injected with sodium pentobarbital. All other fetuses also were injected with sodium pentobarbital before fixation. Co' 17 ,DOs TS'c * 51 [Developmental Toxicity Study in Rats DuPont-10157 J. Control of Bias In addition to random assignment to groups, all females were coded before scheduled euthanasia and remained coded during the collection of postmortem and fetal data. K. Statistical Analyses Descriptive statistics were performed for all quantitative endpoints listed below. Sequential twotailed trend testing(7) 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/85 The level of significance selected was p < 0.05. Where the data were tied and the standard large sample version of Jonckheere's test was not applicable, exact p values were calculated using permutation methodology/95 Parameter Maternal weight Maternal weight changes Maternal food consumption Live fetuses Dead fetuses Resorptions (total, early, late) 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(10) Jonckheere's test*115 Cochran-Armitage test*105 Linear contrast of least square means*125 * Company cSaannitaLaz*ad-. Doe not contain 18 evelopmental Toxicity Study in Rats G DuPont-10157 RESULTS AND DISCUSSION ANALYTICAL EVALUATIONS A. Chromatography (Appendix A) The test substance eluted from the GC column as resolved peak with a retention time of approximately 3.7 minutes. The internal standard eluted from the GC column as a resolved peak with a retention time of approximately 4.1 minutes. Representative GC chromatograms are shown in Figures 2(a - d). Test substance was not detected in the 0 mg/mL control. B. Recovery Samples (Appendix A) Detailed analytical results of recovery samples are summarized in Appendix A, Table ! The variability of the analytical method was demonstrated by the coefficients of variation of the recovery results at each targeted dosing concentration (approximately 10,40,100 mg/mL) over the course of the study. The range of the measured concentrations of the test substance for the 10 mg/mL level was 84.5% to 92.6% of nominal (mean percent recovery = 88.9% 3.3, C. V. = 4%). The range of the measured concentrations of the test substance for the 40 mg/mL level was 81.9%, to 93.5% of nominal (mean percent recovery = 85.5% 4.7, C.V. = 5%). The range of the measured concentrations of the test substance for the 100 mg/mL level was 76.4% to 90.2% of nominal (mean percent recovery = 83.0% 5.1, C.V. = 6%). Based on this data, a correction was applied to all sample results using the spiked recovery for each level on the day of analysis. C. Homogeneity and Stability Samples (Table 1, Appendix A) Analytical results from dosing formulations collected on test day 1 (February 3, 2003) and analyzed for homogeneity, concentration verification, and stability are shown in Summary fable 1 and Appendix A, Table II. Sanitized. Does not contain t sc a c b i Company 19 'Developmental Toxicity Study in Rats DuPont-10157 The following table summarizes the results for all homogeneity and/or concentration verification and stability analyses. Test Day Sample Type Test Day 1 Homogeneity Nominal Measured T,M,Ba'b Mean (T,M,B) mg/mL mg/mL % Nominal 0 NDd 10 8.92e, 8.73e, 10.0 40 40.5,40.0, 39.8 100 96.5, 98.3e, 94.8 92.2 100.3 96.5 C.V. Stability0 (%) % Nominal 7 95.6 1 102.8 2 104.0 a Mean results for the analysis o f the top (T), middle (M), and bottom (B) samples, b All results corrected for spiked recovery based on the level and day o f analysis (Refer to Table I). c Samples held 5 hours at room temperature, d Denotes none detected. e Mean result o f the original analysis and duplicate reanalysis o f the original sample. The data for samples collected on Test Day 1 indicates that the test substance was homogeneously mixed in the vehicle at all levels (C.V.'s = 7 ,1 , and 2, respectively). The test substance was at the targeted concentration in the samples ( 7.8% of nominal) and was stable in the vehicle when held for 5 hours at room temperature. D. Concentration Verification Samples (Table 1, Appendix A) Analytical results from dosing formulations collected test day 11 (February 12,2003) and test day 20 (February 21,2003) and analyzed for concentration verification are shown in Summary Table 1 and Appendix A, Table IH. The following table summarizes the results for concentration verification analyses of the the test substance samples for test days 11 and 20. Preparation Day Nominal mg/mL Measured8' b mg/mL Average %Nominal CV % Test Day 11 Test Day 20 10 40 100 10 40 100 7.28e, 7.23c, 8.71d 39.9, 39.7, 41.l d 100c, 101, 98.2d 9.45, 9.57 35.0, 37.8 94.6, 91.9 77.4 100.5 99.7 95.1 91.0 93.2 11 2 1 1 5 2 a Duplicate samples per level were submitted and analyzed. C.V. calculated to verify uniformity of mixture, b All results corrected for spiked recovery based on the level and day o f analysis (Refer to Table I). c Mean result o f the original analysis and duplicate reanalysis o f the original sample, d Results o f the analysis o f a 3rd sample collected from the dosing preparations. Results from analysis of the samples that were collected on Test Day 11 for concentration verification indicated that test substance was homogenously mixed (CV = 2 ,1 ) and at thetargeted concentration (0.5% of nominal) for all samples except for the 10 mg/mL level not contain Company Sani**4' 0085 20 'evelopmental Toxicity Study in Rats DuPont-10157 (CV = 11, 22.6% of nominal). The 3rd sample collected from the 10 mg/mL level (87.1% of nominal) indicated that the original samplings had been collected before the preparation was adequately mixed and consequently the CV greater than 10 for the replicates and a recovery of less than 20% of nominal for the level. Results from analysis of the samples that were collected on Test Day 20 for concentration verification indicated that test substance was homogenously mixed (CV = 1 , 5 , 2 ) and at the targeted concentration ( 9.0% of nominal) for all samples. E. Analytical Conclusions Results from the analysis of the test substance dosing formulations at the start of the study indicated that the test substance was homogeneously mixed, at the targeted concentrations and stable in the vehicle under the conditions of the study. Results from the analysis of the test substance dosing formulations for the concentration verification indicated that the test substance was at the targeted concentration during the study except for the 10 mg/mL level on the first sampling for the concentration verification analysis on test day 11. Subsequent sampling of this formulation indicated that the original samples had been collected before the formulation was adequately mixed. 1 Company Sanitized. Does not contain TSCA CB1 developmental Toxicity Study in Rats DuPont-10157 DEVELOPMENTAL TOXICOLOGY A. Mortality, Post Mortem Findings, and Clinical Observations (Table 2, Appendices B and G) Test substance-related mortality was produced at 500 mg/kg/day. Four dams were sacrificed in extremis on either day 10,11,12, or 13G and one dam was found dead on day 16G. Clinical observations preceding death in these animals included hunched-over posture, weakness, diarrhea, and wet and/or stained fur. Two of these five dams appeared normal at the gross necropsy whereas three dams had pale kidneys and/or discolored liver or lungs. There was no mortality at either 50 or 200 mg/kg/day. Test substance-related clinical observations were produced at 500 mg/kg/day and included increased occurrences of alopecia, diarrhea, hunched-over posture, weakness, and fur-staining. There were no test substance-related clinical observations at either 50 or 200 mg/kg/day. All other clinical observations recorded were considered incidental and unrelated to the test substance. B. Body Weights and Body Weight Changes (Tables 3 and 4, Appendices C and D) Test substance-related reductions in maternal body weight and weight gain were evident at 500 mg/kg/day. Reductions in maternal weight gain occurred at the onset of the dosing period jnd persisting for the duration of the study. Mean weight gain over the course of the study (days 6-21G) was 25% lower than for the control group; when the final body weights were adjusted for the weight of the uterine contents, the mean weight gain over the same time period was 57% lower than for the control group. These reductions in maternal body weight gain resulted in lower or significantly lower mean maternal body weights beginning as early as day 7G and persisting for the duration of the study; mean final body weights were 9% lower than the control jroup. There were no test substance-related effects or maternal body weight or weight gain at flier 50 or 200 mg/kg/day; data from these two groups were generally comparable to control p u p data. C. Food Consumption (Table 5, Appendix E) {here were slight and occasionally statistically significant test substance-related reductions in (lean maternal food consumption at 200 and 500 mg/kg/day. These reductions were most pronounced over the first few days of dosing but generally were subtle enough such that there fas no appreciable impact on food consumption at these levels when data were averaged over fie course of the dosing period. Therefore, these slight test substance-related, transient eductions were not considered indicative of adverse toxicity. not contain XSCA CBI Comp80* Saniti*1- Does 22 /!&*** evelopmental Toxicity Study in Rats DuPont-10157 D. Postmortem Findings (Table 6, Appendix F) With the exception of those gross postmortem findings described previously for animals that were either sacrificed in extremis or found dead, there were no remarkable test substance-related necropsy observations. One dam from the 500 mg/kg/day group had pale kidneys; all other surviving dams at 500 mg/kg/day appeared normal. There were no remarkable, test substancerelated necropsy observations at 50 or 200 mg/kg/day. E. Reproductive Outcome and Litter Data (Table 6, Appendices G and H) There were no test substance-related effects evident in the reproductive outcome and litter data for animals that survived until scheduled euthanasia and had live litters. Litter mean data for corpora ltea and implantation counts, litter sizes, incidences of resorptions, fetal weight, and sex ratio were comparable across all groups on study. There was one dam at 500 mg/kg/day whose litter consisted of one early resorption. Although this dam survived until scheduled euthanasia, this animal was in relatively poor condition by the end of the study. During the course of the study, this animal exhibited persistent reductions in food consumption, body-weight loss, and clinical signs of toxicity. Based on these data, the resorption of one fetus was considered likely to be secondary to overt maternal toxicity. F. Fetal Alterations (Tables 7 and 8, Appendix H) 1. Malformations (Table 7, Appendix H) There were no malformed fetuses in the current study. 2. Variations (Table 8, Appendix H) There were test substance-related and statistically significant increases in fetal skeletal variations tf 200 and 500 mg/kg/day. At 500 mg/kg/day, there were increased occurrences of delayed pelvic bone ossification and wavy ribs. At 200 and 500 mg/kg/day, there were increased ficidences of delayed skull bone ossification. These findings were all considered to be test ubstance-related and are consistent with skeletal variations produced by a similar fluorotelomerjased alcohol. However, the effects on skull bone ossification, in particular, the increase tbserved at 200 mg/kg, were not considered adverse for several reasons. Retarded skull bone jssification is a relatively common observation in general and is therefore, not typically onsidered a tremendously reliable indicator of developmental toxicity, especially in the absence if clear test substance-related effects on fetal body weight. Relevant historical control data are provided in the table below and the incidences for all groups in the current study fall within the ange of historical control data. not contain TSCA CBI Company S a n * * i-0005 S 23 evelopmental Toxicity Study in Rats DuPont-10157 Historical Control Incidence for Retarded Skull Bone Ossification / '" 'N /""'s Om s not contain TSCA CBI 24 evelopmental Toxicity Study in Rats DuPont-10157 CONCLUSIONS Under the conditions o f this study, adverse maternal toxicity was produced at 500 mg/kg/day and consisted of maternal mortality, decreased body weights and body weight gains, and increased clinical observations o f toxicity. One litter at 500 mg/kg/day consisted of one early resorption; persistent reductions in food consumption and body-weight gain and increased clinical observations indicative of toxicity were reported during the study for this female. Therefore, this litter consisting o f a single early resorption is believed to be secondary to overt maternal toxicity in this dam. Developmental toxicity at 500 mg/kg/day consisted of increased skeletal variations (delayed pelvic bone ossification and wavy ribs). At 200 and 500 mg/kg/day, there were nonadverse, test substance-related, transient reductions in maternal food consumption. In addition, there were slight increases in the incidence of delayed skull bone ossification at 200 and 500 mg/kg/day that were not considered adverse. Thus, the no-observed-effect level (NOEL)a for both maternal and developmental toxicity was considered 200 mg/kg/day. RECORDS AND SAMPLE STORAGE Laboratory-specific or site-specific raw data, such as personnel files and equipment records will be retained by the facility where the work was done. A sample of the test substance was collected for archive purposes and retained at H askell Laboratory. Specimens, raw data, test substance characterization data, and the final report 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 tfr-e test substance were not detected. Thus, for this-study, the NOEL is equivalent to the NOEL as defined by the t-J-S. EPA(l3) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(I4) Company Sanitized. not contain TSCACBf 25 6 evelopmental Toxicity Study in Rats REFERENCES DuPont-10157 A***- 3. Salewski, E. (1964). Farbemethode zum makroskopischen Nachweis von Implantationstellen am Uterus der Ratte. Archiv. Path. Exp. Pharmakol. 247:367. 4. Staples, R.E. (1974). Detection of Visceral Alterations in Mammalian Fetuses. Teratology, 9(3):A37-A38. 5. Woo, D.C. and Hoar, R.M. (1972). Apparent Hydronephrosis as a Normal A spect of Renal Development in Late Gestation of Rats: The Effect of Methyl Salicylate. Teratology, 6:191-196. 6. Barrow, M.V. and Taylor, W J . (1969). A Rapid Method for Detecting M alformations in Rat Fetuses. J. Morph., 127(3):291-306. 7. Selwyn, M.R. (1995). The Use of Trend Tests to Determine a No-Observable-Effect Level in Animal Safety Studies. Journal of the American College of Toxicology 14(2): 158-168. 8. Haseman, J.K. and Hogan, M.D. (1975). Selection of the Experimental Unit in Teratology Studies. Teratology, 12:165-171. 9. Patefield, W. (1982). Exact Tests for Trends in Ordered Contingency Tables. A pplied Statistics 31:32-43. 10. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th ed. The Io w a State University Press, Iowa, pp. 246-248,349-352. 11. Jonckheere, A.R. (1-954). A Distribution-Free K-Sample Test Against Ordered Alternatives. Biometrika 41:133-145. 12. Dempster, A.P., Selwyn, M.R., Patel, C.M., and Roth, A J. (1984). Statistical a n d Computational Aspects of Mixed Model Analysis. The Journal of the Royal Statistical Society, Series C (Applied Statistics), 33(2):203-214. 13. Hazard Evaluation Division, Standard Evaluation Procedure, Toxicity Potential: Guidance for Analysis and Evaluation of Subchronic and Chronic Exposure Studies. Payn-ter, O.E. et al. United States Environmental Protection Agency, Office of Pesticide Program s, Washington, D.C., 20460. EPA-540/9-85-020, June 1985. 14. Risk Assessment of Notified New Substances Technical Guidance Document (XI/283/94-EN), Chapter I, Sections 2.24 and 2.25. ___ Comoany Sanitized, Do***certain TSCA C9K 26 developmental Toxicity Study in Rats DuPont-10157 TABLES Company San't'red. Does not contain TSCA CBI r 27 Developmental Toxicity Study in Rats Tables DuPont-10157 Explanatory Notes Notes Day C21 = Corrected final maternal body weight = final maternal body weight m inus the gravid uterine weight plus the empty uterine weight. Abbreviations --= S.D. = S.E. = N= No Data Standard Deviation Standard Error Number in Group Company Sanitized. Does nejKContain TSCA CBf 28 Pevelopmental Toxicity Study in Rats DuPont-10157 TABLE 1 SUMMARY OF DOSING ANALYSES Nominal: Homogeneity Samples Test Day 1 Top M iddle Bottom Average Measured Cone. Average Percent Nominal Standard Deviation Coefficient of Variation Stability Samples 5 Hour Room Temperature Concentration Verification Test Day 11 #1 Dosing Concentration of 8-2 Telomer B Alcohol _________________ (mg/mL)_______________ 12 40 100 8.92" (89.2)b 8.73a (87.3) 10.0 (100.0) 9.22 (92.2) 0.69 7% 9.56 (95.6) 40.5 (101.3) 40.0 (100.0) 39.8 (99.5) 40.1 (100.3) 0.37 1% 41.1 (102.8) 96.5 (96.5) 98.3" (98.3) 94.8 (94.8) 96.5 (96.5) 1.8 2% 104 (104.0) 7.28a (72.8) 39.9a (99.8) 100" (100.0) #2 7.23a 39.7" ' 101" (72.3) (99.3) (101.0) #3 Average Measured Cone. * Average Percent Nominal Standard Deviation Coefficient of Variation * Test Day 20 #1 8.71d (87.1) 7.74 (77.4) 0.84 11% 9.45 (94.5) 41.1d (102.6) 40.2 (100.5) 0.76 2% 35.0 (87.5) 98.2d (98.2) 99.7 (99.7) 1.4 1% 94.6 (94.6) #2 - 9.57 (95.7) 37.8 (94.5) . 91.9 (91.9) Average Measured Cone/ Average Percent Nominal' Standard Deviationr Coefficient of Variation' 9.51 (95.1) 0.09 1% 36.4 (91.0) 2.0 5% 93,2 (93.2) 1.9 2% a Mean result o f the original analysis and duplicate reanalysis o f original sample, b Numbers in parentheses are the respective percent o f nominal values. Statistics based on the average measured concentration o f the top, middle and bottom o f each dosing level. Result o f the analysis for the third sample collected from the dosing preparations, e Statistics based on the average measured concentration o f triplicate samples for the dosing level, f Statistics based on the average measured concentration o f duplicate samples for the dosing level. Cb ft TSCACBi Company SantBwd* 0 * * * * con*ain /? 29 'evelopmental Toxicity Study in Rats TABLE2 CLINICAL OBSERVATIONS DAY OF GESTATION 6-21 OBSERVATION; GROUP : DOSE RATE (MG/KG/DAY): NO. EXAMINED : NO. SACRIFICED IN EXTREMIS NO. FOUND DEAD ALOPECIA DIARRHEA HUNCHED OVER PALLOR SORE STAIN CAGEBOARD STAIN FACE STAIN PERINEUM WEAK WET PERINEUM I 0 22 0 0 5 0 0 0 0 0 0 0 0 0 * S ta tis tic a lly sig n ific a n t trend (Cochran-Armitage te s t); p < 0.05. II 50 22 0 0 2 0 0 0 0 0 0 0 0 0 OQ 3><33 t3aaor, I o 33. 3 7-4) DuPont-10157 III IV 200 500 22 22 0 4* 01 6 10* 0 6* 0 6* 01 01 11 01 0 3* 0 5* 01 evelopmental Toxicity Study in Rats DuPont-10157 TABLE 3 MEAN MATERNAL BODY WEIGHTS (grams)2 DAY 0 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. N 249.4 10.26 2.19 22 DAY 4 265.7 11.68 2.49 22 DAYS OF GESTATION DAY 5 DAY 6 DAY 7 270.2 11.37 2.42 22 277.5 12.33 2.63 22 284.5 11.77 2.51 22 DAY 8 289.9 11.88 2.53 22 DAY 9 293.9 11.65 2.48 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. N 249.6 11.52 2.51 21 264.6 11.61 2.53 21 271.0 12.86 2.81 21 276.3 12.99 2.84 21 281.5 12.38 2.70 21 287.9 11.15 2.43 21 291.6 10.33 2.26 21 GROUP III: 200 MG/KG/DAY GROUP MEAN S.D. S.E. N 249.8 11.38 2.43 22 259.1 16.20 3.45 22 269.2 13.81 2.94 22 274.6 13.09 2.79 22 278.2 12.21 2.60 22 284.8 13.59 2.90 22 287.7 11.90 2.54 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. S 249.7 12.02 3.00 16 263.5 16.57 4.14 16 269.8 16.81 4.20 16 277.8 16.17 4.04 16 271.9* 19.90 4.97 16 278.3* 20.79 5.20 . 16 284.2* 22.40 5.60 16 tsca cbi C o rap W s iM < to * " ,," !OT,al" 31 developmental Toxicity Study in Rats DuPont-10157 TABLE 3 (Continued) MEAN MATERNAL BODY WEIGHTS (grams) DAY 10 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. N 299.6 12.50 2.67 22 DAY 11 306.8 14.74 3.14 22 DAYS OF GESTATION DAY 12 DAY 13 DAY 14 314.3 14.58 3.11 22 322.4 13.49 2.88 22 326.0 15.44 3.29 22 DAY 15 332.8 15.39 3.28 22 DAY 16 344.3 16.87 3.60 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. N 297.1 11.84 2.58 21 304.3 11.02 2.40 21 311.8 11.99 2.62 21 318.5 10.86 2.37 21 324.1 12.77 2.79 21 329.5 10.78 2.35 21 . 340.1 11.37 2.48 21 GROUP III: 200 MG/KG/DAY GROUP MEAN S.D. S.E. N 292.5 11.55 2.46 22 299.3 12.41 2.65 22 308.1 14.38 3.07 22 316.7 15.51 3.31 22 320.7 16.25 3.46 22 330.2 18.81 4.01 -22 341.5 19.07 4.07 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. N 287.8* 17.89 4.47 16 286.8* 21.52 5.38 16 296.0* 25.14 6.29 16 303.7* 23.68 5.92 16 313.2* 20.46 5.12 16 319.8* 23.03 5.76 16 331.2* 23.55 5.89 16 Company Sann ita* D o not oontai TSCACS 32 [Developmental Toxicity Study in Rats DuPont-10157 TABLE 3 (Continued) MEAN MATERNAL BODY WEIGHTS (grams) DAY 17 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. N 358.2 17.52 3.74 22 DAY 18 374.5 18.14 3.87 22 DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY C21 391.1 20.22 4.31 22 409.0 21.87 4.66 22 433.8 25.95 5.53 22 330.3 20.07 4.28 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. N 354.1 12.58 2.74 21 369.5 13.83 3.02 21 385.2 14.86 3.24 21 401.6 15.38 3.36 21 427.1 18.14 3.96 21 332.4 14.87 3.24 21 GROUP III: 200 MG/KG/DAY GROUP MEAN S.D. S.E. N 356.8 21.47 4.58 22 373.2 23.80 5.07 22 389.2 26.02 5.55 22 405.3 29.39 6.27 22 426.5 32.75 6.98 22 325.7 23.20 4.95 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. N 346.1 25.61 6.40 16 360.5 27.43 6.86 16 374.1* 28.59 7.15 16 386.2* 28.17 7.04 16 395.1* 34.57 8.64 16 300.4* 29.09 7.27 16 a Data were excluded from females that were not pregnant, found dead, sa crificed in e x tr e m is , or had l i t t e r s consisting e n tire ly of resorptions. * S ta tis tic a lly sig n ific a n t trend (linear contrast of means); p < 0.05. - 33 Company S a n to ! Doe. noteontaln T 'Developmental Toxicity Study in Rats DuPont-10157 TABLE 4 MEAN MATERNAL BODY WEIGHT CHANGES (grams)a 0-6 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. N 28.1 8.30 1.77 22 DAYS OF GESTATION 4-6 6-8 8-10 10-12 11.8 12.4 9.7 14.7 3.75 4.74 4.60 5.79 0.80 1.01 0.98 1.23 22 22 22 22 12-14 11.8 4.38 0.93 22 14-16 18.2 4.48 0.96 22 GROUP II: 50 MG/KG/DAY GROUP MEAN 26.7 11.7 11.5 9.2 14.8 12.3 16.0 S.D. 6.12 3.67 5.27 4.23 6.61 5.72 7.95 S.E. 1.33 0.80 1.15 0.92 1.44 1.25 1.74 N 21 21 21 21 21 21 21 GROUP III: 200 MG/KG/DAY GROUP MEAN 24.8 15.4 10.2 7.7 15.6 12.6 20.8 S.D. 5.77 7.95 6.47 5.14 5.52 6.31 5.71 S.E. 1.23 1.70 1.38 1.10 1.18 1.35 1.22 N 22 22 22 22 22 22 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN' S.D. S.E. H 28.1 7.99 2.00 16 14.2 5.09 1.27 16 0.5* 9.5 8.2* 17.2* 18.0 9.68 9.26 14.95 10.08 8.65 2.42 2.31 3.74 2.52 2.16 16 16 16 16 16 34 Bpevelopmental Toxicity Study in Rats DuPont-10157 TABLE 4 (Continued) MEAN MATERNAL BODY WEIGHT CHANGES (grams) - 16-18 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. N 30.3 4.18 0.89 22 DAYS OF GESTATION 18-21 6-21 6-C21 59.3 156.4 52.9 9.91 21.46 16.15 2.11 4.58 3.44 22 22 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. N 29.4 6.63 1.45 21 57.6 7.96 1.74 21 150.8 19.57 4.27 21 56.1 13.63 2.97 21 GROUP III: 200 MG/KG/DAY GROUP MEAN 31.8 53.3* S.D. 7.02 11.41 S.E. 1.50 2.43 S 22 22 151.9 28.17 6.01 22 51.1 19.49 4.16 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN 29.3 34.6* 117.4* 22.6* S.D. 7.50 24.96 34.43 30.68 S.E. 1.88 6.24 8.61 7.67 U 16 16 16 16 i Data were excluded from females that were not pregnant, found dead, sa crificed in e x tr e m is , or had l i t t e r s con sisting en tir e ly of resorptions. ' S t a t is t ic a lly sig n ific a n t trend (linear contrast of means); p < 0.05. -- ekmnot eat^ n r s c A c s i 35 ^Developmental Toxicity Study in Rats DuPont-10157 TABLE 5 MEAN MATERNAL FOOD CONSUMPTION (grams/day)a 4-6 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. N 22.8 2.78 0.59 22 DAYS OF GESTATION 6-8 8-10 10-12 12-14 14-16 23.3 24.1 25.5 26.1 27.2 3.47 2.35 2.94 2.68 2.65 0.74 0.50 0.63 0.57 0.56 22 22 22 22 22 16-18 29.3 3.83 0.82 22 GROUP II: 50 MG/KG/DAY GROUP MEAN 23.8 21.9 23.4 25.7 26.4 26.8 30.2 S.D. 2.56 2.42 2.49 2.71 2.29 3.68 3.42 S.E. 0:56 0.53 0.54 0.59 0.50 0.80 0.75 N 21 21 21 21 21 21 21 GROUP III: 200 MG/KG/DAY GROUP MEAN 23.5 21.3* 22.1* 24.6 26.1 28.4 31.9* S.D. 2.39 2.40 2.22 3.65 3.57 3.28 2.96 S.E. 0.51 0.51 0.47 0.78 0.76 0.70 0.63 22 22 22 22 22 22 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN 23.7 19.9* 21.4* 20.6* 25.8 27.9 31.8* S.D. 3.03 5.91 3.25 6.76 4.28 4.44 5.31 S.E. 0.76 1.48 0.81 1.69 1.07 1.11 1.33 16 16 16 16 16 16 16 COmPa",' Sa^ 0- ~ r Sc Ac B, S 36 'evelopmental Toxicity Study in Rats DuPont-10157 TABLE 5 (Continued) MEAN MATERNAL FOOD CONSUMPTION (grams/day)* DAYS OF GESTATION 18-21 6-21 GROUP I: 0 MG/KG/DAY GROUP MEAN S.D. S.E. 28.1 3.84 0.82 22 26.4 2.64 0.56 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. W 28.2 2.47 0.54 21 26.2 2.00 0.44 21 GROUP III: 200 MG/KG/DAY GROUP MEAN S.D. S.E. 28.4 3.88 0.83 22 26.3 2.46 0.52 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. N 25.4 5.55 1.39 16 24.7 2.88 0.72 16 a Data were excluded from females that were, not pregnant, found dead, sa c r ific e d in e x tr e m is , or had l i t t e r s consisting e n tir e ly of resorptions. * S ta tis t ic a lly sig n ific a n t trend (linear contrast of means); p < 0.05. Comoamr S*r**tred. Does notcontain TSCA CBl levelopmental Toxicity Study in Rats DuPont-10157 TABLE REPRODUCTIVE OUTCOME Group: Dose (mg/kg/day): I 0 i i h i IV 50 200 500 No. Mated No. Pregnant No Delivered Early No. Deaths No. With Total Resorptions No. L itters Mean Corpora Luteaa 22 22 0 0 0 22 15.7 (1.61)b 22 21 0 0 0 21 16.0 (3.04) 22 22 0 0 0 22 16.0 (3.40) 22 22 0 5* 1 16 16.1 (2.51) Implantations (Nidations) Resorptions: Total Early Late 14.7 (1.62) 0.0 (0.21) 0.0 (0.21) 0.0 13.9 (1.56) 0.7 (1.06) 0.7 (1.06) 0.0 13.9 (1.64) 0.4 (0.79) 0.4 (0.79) 0.0 13.4 (3.87) 0.4 (0.81) 0.4 (0.81) 0.1 (0.25) Dead Fetuses Live Fetuses0 : Total Males Females 0.0 14.6 (1.56) 7.2 (1.79) 7.5 (1.74) 0.0 13.2 (1.81) 6.0 (1-58) 7.2 (1.69) 0.0 13.5 (1.77) 6.7 (2.16) 6.8 (1.97) 0.0 13.8 (1.95) 7.1 (1.84) 6.7 (1.89) Mean Fetal Weight: Total Males Females 5.55 (0.31) 5.68 (0.33) 5.43 (0.32) 5.66 (0.29) 5.83 (0.34) 5.51 (0.26) 5.77 (0.39) 5.94 (0.40) 5.59 (0.42) 5.40 (0.44) 5.57 (0.47) 5.20 (0.39) Sex Ratio^ 0.49 (0.11) 0.45 (0.11) 0.50 (0.14) 0.51 (0.12) a S t a t is t ic a l analyses are not conducted on mean corpora lutea data; these data are presented for information only. b Standard deviation is reported in parentheses. c S t a t is t ic a l analyses are only conducted on the mean to ta l number of liv e fetuses per l i t t e r and to ta l mean fe ta l weight. The means for males and females are presented for information only. d Number male fe tu s e s /to ta l number fetuses per l i t t e r . Note: . The pregnancy rate data, adult m ortality data, and the to ta l resorption data were s t a t is t ic a ll y analyzed using the Cochran-Armitage t e s t . A ll litter'm ean data (except for fe ta l weight and sex ratio) were analyzed using Jonckheere' s t e s t . Fetal weight and sex ratio were analyzed using a lin ea r contrast of lea st square means. * S ta tis tic a lly sign ificant trend; p < 0.05. Company Sanitized. Does not contain TSCA CBI 38 developmental Toxicity Study in Rats DuPont-10157 EXTERNAL No. Examined3 No. Affected TABLE 7 INCIDENCE OF FETAL MALFORMATIONS Group : Dose (mg/kg/day): I 0 II III 50 200 IV 500 322 [22] 277 [21] 297[22] 0[ 0] 0[ 0] 0[ 0] 220[16] 0[ 0] VISCERAL No. Examined No. Affected 167[22] 142[21] 156 [22] 0[ 0] 0[ 0] 0[ 0] 113[16] 0[ 0] HEAD No. Examined No. Affected 167[22] 142[21] 156[22] 0[ 0] 0[ 0] 0[ 0] 113[16] 0[ 0] SKELETAL No. Examined No. Affected 322[22] 277 [21] 297[22] 0[ 0] 0[ 0] 0[ 0] 220 [16] 0[ 0] TOTAL NUMBER AFFECTED 0{ 0) 0( 0} 0( 0) 0{ 0) a Number examined and affected , including the number affected with the lis t e d malformations are expressed as F etuses[L itters] or Fetuses (L itte r s ). b For ease of reading, zeros have been replaced with dashes for the lis t e d malformations. No sig n ific a n t trends were detected (Jonckheere-Terpstra Trend t e s t ) ; p < 0.05. Note: S ta tis tic a l analyses are only conducted on the individual endpoints. The overall to ta l and to ta ls by exam type are presented for information only. Company Sanitized. Does not contain TSCA CBI 39 Developmental Toxicity Study in Rats DuPont-10157 TABLE 8 INCIDENCE OF FETAL VARIATIONS Group: Dose (mg/kg/day) : I 0 II III 50 200 DEVELOPMENTAL VARIATIONS EXTERNAL No. Examined3 No. Affected 322 [22] 277[21] 297 [22] 0[ 0] 0[ 0] 0[ 0] VISCERAL No. Examined No. Affected 167 [22] 142[21] 156 [22] . 0[ 0] 0[ 0] 0[ 0] HEAD No. Examined No. Affected 167 [22] 142[21] 156[22] 0[ 0] 0[ 0] 0[ 0] SKELETAL No. Examined Rib - Rudimentary Cervical - Supernumerary Skull - Fused No. Affected 322[22] 277 [21] 297 [22] ------ 25(11) -- 25(11) -- _-- 20(13) -- 20(13) 2 ( 1) 32(15) -- 34(16) TOTAL WITH DEVELOPMENTAL VARIATIONS 25(11) 20(13) 34(16) . IV 500 220[16] 0[ 0] 113 [16]0[ 0] 113[16] 0[ 0] 220[16] K 1) 34(10) M 1) 35(11) 35(11) VARIATIONS DDE TO RETARDED DEVELOPMENT EXTERNAL No. Examined3 No. Affected VISCERAL No. Examined Kidney*3 Small Papilla - Size 1 Small Papilla - Size 2 Papilla - Size 3 No. Affected 322[22] 0[ 0] 167 [22] 2 ( 2) 4 ( 3) 6 ( 6) 1.2 [ 9] 277 [21] 0[ 0] 142[21] 2 ( 2) 5 ( 5) 7 [ 7] 297[22] 0[ 0] 156 [22] K 1) 1( 1) 3 ( 3) 5 [ 5] 220[16] 0[ 0] 113[16] 2 ( 2) K 1) 2 ( 1) 5[ 3] Company S a n i t y Dees no* contain TSCACI 40 developmental Toxicity Study in Rats TABLE 8 (Continued) INCIDENCE OF FETAL VARIATIONS DuPont-10157 VARIATIONS DOE TO RETARDED DEVELOPMENT (Continued) HEAD No. Examined 167 [22] No. Affected 0[ 0] 142[21] 0[ 0] 156[22] 0[ 0] 113[16] 0[ 0] SKELETAL No. Examined Pelvis - Retarded O ssification Rib - Wavy Skull - Retarded O ssification Stemebra - Retarded O ssification Vertebra - Retarded O ssification No. Affected 322[22] K 1) 22 ( 8) 5< 3) 37(12) 56([15] 277[21] -- -- 31(12) 2( 2) 30 ( 8) 56[13] 297 [22] -- -- 45(16)* 3 ( 2) 34(13) 72[19] 220[16] 9 ( 5)* 5 ( 2)* 55(12)* 8( 5) 12 ( 6) 73[14] TOTAL WITH VARIATIONS DUE TO RETARDED DEVELOPMENT 66(17) 63(15) 76(19) 78(15) TOTAL NUMBER FETUSES WITH VARIATIONS 89 (21) 80(19) 99(20) 106(15) a Number examined and a ffected , including the number affected with the lis t e d variations, are expressed as Fetuses [Litters] or Fetuses (L itters), b S ta tis tic a l analyses are conducted on the combined incidences of small renal papillae; the d e ta ils for each size are presented for information only. * Significant trend (Jonckheere's test); p < 0.05. Note: S t a tis tic a l analyses are only conducted on the individual endpoints. The overall to ta l and to ta ls by exam are presented for information only. Company Sanitized. Does not contain TSC CBI 41 yelopmental Toxicity Study in Rats DuPont-10157 - APPENDICES Company Sanitized. Does not contain TSCACBI >evelopmental Toxicity Study in Rats DuPont-10157 APPENDIX A Analytical Chemistry Report Company Sanitized. Does not contain TSCA CBf 43 evelopmental Toxicity Study in Rats DuPont-10157 Table I. Recovery ( Sample Type Recovery Recovery Recovery Recovery Recovery Recovery Recovery Recovery Recovery Recovery Recovery me N o riS i 10.5 10.5 14.8 14.8 14.8 11.8 [Added to Dcamg Vehicle Percent Mfeasure^ Nominal 9.37 89.2 9.55 91.0 13.7 92.6 12.5 84.5 12.6 85.1 10.7 90.7 Mean: 88.9 3.3, C.V.4% 40.3 33.0 81.9 58.8 48.2 82.0 58.8 50.0 85.0 58.8 50.0 85.0 44.9 42.0 93.5 Mean: 85.5 4.7, C.V. 5% Recovery Recovery Recovery Recovery Recovery recovery 109 93.7 86.0 109 93.0 85.3 144 110 76.4 144 115 79.9 144 115 79.9 132 119 90.2 Mean: 83.0 5.1, C.V.6% (A) Processed with homogeneity and concentration verification samples collected on test day 1 (February 3,2003). (B) Processed with homogeneity and concentration verification re-analysis samples collected on test day 1 (February 3,2003). (C) Processed with concentration verification samples collected on test day 11 (February 12,2003). (D) Processed with concentration verification duplicate re-analysis o f the original samples collected test day 11 (February 12,2003). (E) Processed with concentration verification analysis for re-sampling o f the original formulations prepared test day 11 (February 12,2003). (F) Processed with concentration verification samples collected on test day 20 (February 21,2003). Skrnipatiy Sanitized. Does not costai TSCA CSI LPevelopmental Toxicity Study in Rats DuPont-10157 Table H Homogeneity and Stability Sample Type Nominai Test Day 1 (3-Feb-2003) H om ogen eity Control 0.00 Top 10-0 10-1 10-2 Middle M ean: 10-0 10-1 10-2 Bottom M ean: 10 M ean: Dosing Formulations MVeasure)d Percent Nominal ND 8.48 9.13 9.15 8.92 8.79 8.62 8.77 8.73 10.0 9.22 + 0.69 C.V. 7% -- 84.8 91.3 91.5 (89.2%) 87.9 86.2 87.7 (87.3%) 100.0 (92.2%) Top Middle Bottom 40 40 40 M ean: 40.5 40.0 39.8 40.1 0 .3 7 C.V. 1% 101.3 100.0 99.5 (100.3%) Top Middle Bottom Stability 5 HOUR 100 100-0 100-1 100-2 M ean: 100 M ean: 10 40 100 96.5 92.0 102 101 98.3 94.8 96.5 + 1.8 C.V.2% 9.56 41.1 104 96.5 92.0 102.0 101.0 (98.3%) 94.8 (96.5%) 95.6 102.8 104.0 (A) All results corrected for spiked recovery based on the level and day o f analysis (Refer to Table I). (B) Denotes not detected. (C) Mean result o f the original analysis ( -0 ) and duplicate reanalysis o f original sample (-1, -2). (D) The average measured concentration, average percent o f nominal (in parentheses), standard deviation, and coefficient o f variation o f top, middle, and bottom. ' (E) Stability samples held 5 hours a room temperature. Company Sanitized. Does not contain TSCA CBI $ developmental Toxicity Study in Rats DuPont-10157 Table IH. Concentration Verification Dosing Solutions Preparation Day Sample Type m g /m lfp H H IW -- Nominal Measured Percent Nominal Test Day 11 (12-Feb-2003) Concentration V erification Control 0.0 10-1 10-1A 10-1B Meanf); 10-2 10-2A 10-2B M ean : 10-3 M ean : nd 6.52 7.63 7.70 7.28 6.32 7.88 7.48 7.23 8.71 7.74 0.84 C.V. 11% -- 65.2 76.3 77.0 72.8 63.2 78.8 74.8 723 87.1 (77.4) 40-1 40-1A 40-1B M ean : 40-2 40-2A 40-2B M ean : 40-3 M ean : 38.9 40.8 39.9 39.9 38.0 40.8 40.2 39.7 41.1 40.2 0.76 C.V.2% 97.3 102.0 99.8 99.8 95.0 102.0 100.5 99.3 102.6 (100.5) 100-1 100-1A 100-1B M ean^h 100-2 100-2A 100-2B Mean( 100-3 Mean: 102 98.7 99.2 100 97.1 102 105 101 - 98.2 99.7 1.4 CV. 1% 102.0 98.7 99.2 100.0 97.1 102.0 105.0 101.0 98.2 (99.7) (A) A ll results corrected for spiked recovery based on the level and day o f analysis (Refer to Table I). (B) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity o f mixture. [Q Denotes not detected. (D) The average measured concentration, average percent o f nominal for duplicate samples (-1, and -2), and duplicate reanalysis analysis o f the original sample (-1A, -IB and - 2 A , -2B). (E) The average measured concentration, average percent o f nominal (in parentheses), standard deviation, and coefficient o f variation for duplicate samples based on footnote (D) and the analysis o f the 3rd sample from the original dosing preparation (-3). Company uSanmititizzeeda.. Does not conta.n TSCA CBl 46 tevelopmental Toxicity Study in Rats DuPont-10157 Table HI. Concentration Verification o Preparation Day Sample Type Test Day 20 (21-Feb-2003) Nomina; Concentration V erification^) Control 0.0 10-1 10-2 Mean(F); n Dosing Solutions (continued) Percent Measured Nominal n d (c ) 9.45 9.57 9.51 0.09 C.V. 1% -- 94.5 95.7 (95.1) 40-1 40-2 Mean(F): 35.0 37.8 36.4 2.0 C.V. 5% 87.5 94.5 (91.0) 100-1 100-2 Mean(F): 94.6 91.9 93.2 1.9 C.V. 2% 94.6 91.9 (93.2) (A) All results corrected for spiked recovery based on the level and day o f analysis (Refer to Table I). (B) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity o f mixture. (C) Denotes not detected. (F) The average measured concentration, average percent o f nominal (in parentheses), standard deviation, and coefficient o f variation for duplicate samples Ts c a c a t oes not coot'" Comp0* Saniti*5 evelopmental Toxicity Study in Rats Figure 1 Representative Analytical Calibration Curve DuPont-10157 Peak Height Ratio Figure 1: Calibration curve showing linear fit (line) to replica measurements (squares) for calibration solutions off diluted over a concentration range of 0.0155 to 0.0927 mg/mL with the 0 mg/mL control diluted sample was used as the zero. not co1 Sani tzed. s Developmental Toxicity Study in Rats DuPont-10157 Figure 2 Representative High Performance Liquid Chromatography Chromatograms 0> 00 Ctho- --- T Figure 2b: Representative HPLC chromatogram of 40.0 mg/r dosing solution diluted to a nominal concentration (5FU.06 mg/mL. The measured concentration of the representative solution is 41.1 mg/mL Company Sanitized. Does not contain TSCAC8 I Developmental Toxicity Study in Rats DuPont-10157 Figure 2 (continued) Representative High Performance Liquid Chromatography Chromatograms 0> 0LhnO0- Figure 2c; ^Representative HPLC chromatogram of 0.0618 mg/i lalytical reference solution. mil O*-) 00 tNo CO Figure 2d: Representative HPLC chromatogram of 40.3 mg/r spiked recovery solution diluted to a nominal concentration of 0.06 mg/mL.' The measured concentration of the representative solution is 33.0 mg/mL. cnmoanv Sanitized. 50 evelopmental Toxicity Study in Rats DuPont-10157 APPENDIX B Individual Clinical Observations Company Sanitized. Does not contain TSCA CBI Developmental Toxicity Study in Rats Individua] Clinical Observations DuPont-10157 Explanatory Notes Note 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 abnormal signs were observed during the study examinations, the "b" entries are omitted from the report. Company Sanitized. Does not contain TSCA CBf ISO V0S1 UlBIUOOiQU800 )) evelopmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL OBSERVATION NUMBER: -- = ~ as " = = = as ss a = = s ; ss s as ss = ; = s =s a = = ; as = = as as s ; a s : 670974 SACRIFICED BY DESIGN 2/18/03 670981 SACRIFICED BY DESIGN 2/18/03 670985 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 2/18/03 670986 SACRIFICED BY DESIGN 2/18/03 670987 SACRIFICED BY DESIGN 2/18/03 670989 SACRIFICED BY DESIGN 2/18/03 670994 SACRIFICED BY DESIGN 02/19/03 670998 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 02/19/03 670999 SACRIFICED BY DESIGN 02/19/03 671002 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 02/19/03 671007 SACRIFICED BY DESIGN 02/19/03 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 ss==:sssss===ss=s===ssassss====ssssss==s=:css==s=s: 3I / / / / / / * / f rt i t ,21 a: ,21 a: ,13,14,15,16,17,18,19,20,21 b: ,13,14,15,16,17,18,19,20, a: ............................................................... 21 a: , , , , , , , , , , , , , , , , , 2 1 a 21 a: ,21 ,21 a: , , , , , , ,11,12,13,14,15,16,17,18,19,20,21 b: , , , , , , ,11,12,13,14,15,16,17,18,19,20, a: , , , , , , , , , ., , , , , , , ,21 a 21 a: ,18,19,20,21 b: ,18,19,20, a: , , , ,21 21 53 DuPont-10157 Corrm->*w Sanitized. Does not contain TSCA CBf evelopriiental Toxicity Study in Rats IXTOXVXDUKL CLXKICMj OBSERVATIONS GROUP I: 0 MG/KG/DAY ANIMAL OBSERVATION NUMBER: DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED: 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 671015 SACRIFICED BY DESIGN 02/20/03 a; , , , , , , , , # , , , , , , , , 21 671017 SACRIFICED BY DESIGN 02/20/03 a: , , , , , , , , , , , , , , , , , 21 671031 ALOPECIA RIGHT FRONT LEG SACRIFICED BY DESIGN 02/20/03 a: , , , , , , b: , , , , , , a: , , , , , , , , , , , ,16,17,18,19,20, , , , , , ,16,17,18,19, , , , , , , , , , , , , 21 671033 ALOPECIA BOTH FRONT LEG' SACRIFICED BY DESIGN 02/20/03 a: , , , , , , b: , , , , , , a: , , , , , , , , , , , , , ,19,20,21 , , , , , , , , ,19,20, , , , , , , , , , , , 21 671035 SACRIFICED BY DESIGN 02/20/03 a: , , , , , , , , , , , , , , , i , 21 671039 SACRIFICED BY DESIGN 02/24/03 a: , , , , , , , , , , , , , , , , ,21 671042 SACRIFICED BY DESIGN 02/24/03 a: t i i t i i i i i i i i i , , , ,21 671044 SACRIFICED BY DESIGN 02/24/03 a: I I I I i i i i i i i , , 21 671045 SACRIFICED BY DESIGN 02/24/03 a: , , , , , , , , , , , , , , , , , 21 671054 SACRIFICED BY DESIGN 02/24/03 a: i i t i i i i i i i i i , , , , ,21 671055 SACRIFICED BY DESIGN 02/24/03 a: i i i i i i i i i i t , , , , , ,21 54 DuPont-10157 Company Sanitized. Does not contain TSCA CBI developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 670975 SACRIFICED BY DESIGN 2/18/03 670976 SACRIFICED BY DESIGN 2/18/03 670978 SACRIFICED BY DESIGN 2/18/03 670980 SACRIFICED BY DESIGN 2/18/03 670984 SACRIFICED BY DESIGN 2/18/03 670990 SACRIFICED BY DESIGN 2/18/03 670993 SACRIFICED BY DESIGN 02/19/03 6710Q0 SACRIFICED BY DESIGN 02/19/03 671003 SACRIFICED BY DESIGN 02/19/03 671008 SACRIFICED BY DESIGN 02/19/03 671012 SACRIFICED BY DESIGN 02/19/03 671016 SACRIFICED BY DESIGN 02/20/03 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, I l I I ! ! t ! 1 1 ! I 1 1 1 a: ,211 1 I ! ! Ili Itili 11 a: t t I I t 1 I t i l i a: , t i i t l III Itili a: , i i i t i III Itili ! i, ,21 ! <, ,21 , ,21 a: , I I II t III Itili 1 , ,21 a: , i t i t i / t 1 Il II a: a i t i l i < 1 1 1 till ,211t ! , 1 1 , ,21 a: t i f i l i ' I t i till 211 1 , , a: t i t i i fili ! Il ! 1 ! , ,21 a: i t i l i ! Il ! till , , , ,21 a: i t i l i liti till 1 1 , ,21 55 DuPont-10157 Company Sanitized. Does not contain TSCA CBf )) Developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 671019 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT FRONT PAW SACRIFICED BY DESIGN 02/20/03 671020 SACRIFICED BY DESIGN 02/20/03 671025 SACRIFICED BY DESIGN 02/20/03 671026 SACRIFICED BY DESIGN 02/20/03 671034 ALOPECIA BOTH FRONT PAW' ALOPECIA LEFT FRONT LEG ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 02/20/03 671043 SACRIFICED BY DESIGN 02/24/03 671048 SACRIFICED BY DESIGN 02724/03 671050 SACRIFICED BY DESIGN 02/24/03 671052 SACRIFICED BY DESIGN 02/24/03 671056 SACRIFICED BY DESIGN 02/24/03 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: b: a: / / t , b: i t t i a: i i t t 13, 13, ; i4 ,15,16,17,18,19,20,21 ,14,15,16,17,18,19,20, i i i i i t t 121 a: i t t t t i t i t , ,21 S t i t i l l i i i t , , , i i i ,21 ai , , , , , , , , t t i i i i t , 21 a: b: a: b: a: b: t i i a: t i t itili tit tilt ti i ,14,15,16,17,18,19,20,21 ,14,15,16,17,18,19,20, ,14,15, , , , , , ,14,15, , , , , , , , ,16,17,18,19,20,21 , , ,16,17,18,19,20, , , , , , t , ,21 ai t i l t i l i t t i t i t i i i 121 a; i i i t i i , , / i i i t i i i ,21 a; t i i t i i i i t i i i i i t i ,21 a: , , , , , , , , , , , , , , , , , 21 t / , , i i i i i i 71 56 ) DuPont-10157  evelopmental Toxicity Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS DuPont-10157 GROUP III: 200 MG/KG/DAY ANIMAL OBSERVATION NUMBER: DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED: : 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 670970 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 2/18/03 a: , , , , , , b: , , , , , , a: , , , , , , , , ,13,14,15,16,17,18,19,20,21 , , ,13,14,15,16,17,18,19,20, , , , , , , , , , , , 21 670972 SACRIFICED BY DESIGN 2/18/03 ,,,,,, , , , , , , . ,21 670979 SACRIFICED BY DESIGN 2/18/03 ,,,, i i , ,21 670983 SACRIFICED BY DESIGN 2/18/03 I I I I 1 I l I I I I ! ! , , , ,21 670988 SACRIFICED BY DESIGN 2/18/03 I I I ,21 670992 SACRIFICED BY DESIGN 02/19/03 a: ,21 670995 SACRIFICED BY DESIGN 02/19/03 a: iii ,21 670996 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 02/19/03 a: b: a: b: a: , , , , ,14,15,16,17,18,19,20,21 , , , ,13,14,15,16,17,18,19,20, , , ,, ,,1 5 ,1 6 ,1 7 ,1 8 , 1 9 ,2 0 , 2 1 , , , , , ,15,16,17,18,19,20, , , , , , , , , , , , , 21 670997 SACRIFICED BY DESIGN 02/19/03 a: / tt ,21 671009 SACRIFICED BY DESIGN 02/19/03 671010 SACRIFICED BY DESIGN 02/19/03 ,21! I ' l l t t ! I I 1 t I t t ! t i i i , , , , , , , , , , , 21 Company Sanitized. Does not contain TSCA CB 57 evelopmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL CLINICAL OBSERVATIONS GROUP III: 200 MG/KG/DAY ANIMAL OBSERVATION NUMBER: DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED: 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 671024 ALOPECIA BOTH REAR LEG ALOPECIA LEFT HIND QUARTERS ALOPECIA RIGHT REAR LEG SACRIFICED BY DESIGN 02/20/03 a: b: a: b: a: b: a: ,11,12,13,14,15,16,17, , , , ,11,12,13,14,15,16,17, , , , , ,17,18,19,20,21 , ,17,18,19,20, , , ,18,19,20,21 , , ,18,19,20, , , . , , ,21 671027 SACRIFICED BY DESIGN 02/20/03 ,21 671028 SACRIFICED BY DESIGN 02/20/03 ,21 671029 SACRIFICED BY DESIGN 02/20/03 till ,21 671030 ALOPECIA BOTH FRONT LEG oo ALOPECIA CHEST T3>t3J<t SACRIFICED BY DESIGN 02/20/03 671032 to SACRIFICED BY DESIGN 02/20/03 5. -*- 671036 NTaO SACRIFICED BY DESIGN 02/24/03 a: ,11,12,13,14,15,16,17,18,19,20,21 b: I I I 10, 11,12,13,14,15,16,17,18,19,20, a: I I I , , ,13,14,15,16,17,18,19,20,21 b: , , ,13,14,15,16,17,18,19,20, a: , , , I , , , , , I *21 IIII ,21 ,21' oo 671037 STAIN CAGEBOARD RED ID 3O ALOPECIA RIGHT FRONT LEG o e3 SACRIFICED BY DESIGN 02/24/03 $5 ------------ ----------------------- a: b: a: b: a: ,19,20,21 ,19,20, , , ,21 H a Clinical observations for this rat were inadvertently not recorded on gestation day 10. O Detected" for the morning of gestation day 10 and the morning of gestation day 11. > O t o ----------------- ---- ---------------------------------------- - __________________________________________________________________________________________________________________________________ 58 Rat had "No Abnormalities 1 PcYckpieatal Toxicity Studyin Rats DuPont-10157 GROUP III: 200 MG/KG/DAY INDIVIDUAL CLINICAL OBSERVATIONS ANIMAL OBSERVATION NUMBER: = = s s = = c = c s s = = s = = s :s = s s s = s s = = s s = s ;s s : 671038 SACRIFICED BY DESIGN 02/24/03 671040 ALOPECIA ABDOMINAL ALOPECIA LEFT SIDE ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA BOTH SIDE ALOPECIA PERINEUM SACRIFICED BY DESIGN 02/24/03 671049 SACRIFICED BY DESIGN 02/24/03 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===IS5S2=====S=5--=ssss=s=as==sss=s=:ss:Ki==ssssrssss:==s=:==s=s:s====;=s:sss=ss=:s=s=s:ss==:s;===:3s=55===s:=s:=:= ,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: ,10,11,12,13, , , , , , , , b: ,10,11,12,13, , , , , , , , a: , , ,1 2 , , , , , , , , , b: a: , , , ,13!14,15^16,17,18,19,20i21 b: , , , ,13,14,15,16,17,18,19,20, a: , , , , ,14,15,16,17,18,19,20,21 b: , , , , ,14,15,16,17,18,19,20, a: r i i i t i t i i i ,20,21 b: 20, a: , , , , , , , , ,., , ,21 ,21 Company Sanitized. Does not contain TSCA CBI 59 Company Sanitized. Does ) Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 670971 SACRIFICED BY DESIGN 2/18/03 670973 HUNCHED OVER DIARRHEA STAIN PERINEUM BROWN WEAK SACRIFICED IN EXTREMIS 02/10/03 670977 SACRIFICED BY DESIGN 2/18/03 670982 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 2/18/03 670991 SACRIFICED BY DESIGN 2/18/03 671001 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 02/19/03 671004 ALOPECIA LEFT FRONT LEG ALOPECIA BOTH FRONT LEG 3O ALOPECIA ABDOMINAL PALLOR SACRIFICED BY DESIGN 02/19/03 5` H(O>A O09 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 till I It t t I t ,21 a: , 12,13 , , , , , b: 11,12, ,, tI i a: , ,13, , I I I a: , ,13, , I I I , ,13, , I I I a: , ,13, , I I I a: II I ,21 a: ,15,16,17,18,19,20,21 b: ,15,16,17,18,19,20, a: a: 21 a: ,16,17,18,19,20,21 b: ,16,17,18,19,20, a: , , ,18,19,20,21 b: , , ,18,19,20, a: , , , , , ,21 a: ,15,16,17, , , , b: ,15,16,17, , , , a: , , , ,18,19,20,21 b: , , , ,18,19,20, a: , , , , , ,20,21 b: , , , , , .20, a: ................... 21 a: ..................... ..... ,21 60 DuPont-10157 Comoany Sanitized. Does not contain TSCA CBI T evelopmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 671005 ALOPECIA ABDOMINAL HUNCHED OVER DIARRHEA WEAK SACRIFICED IN EXTREMIS 02/10/03 671006 ALOPECIA LEFT FRONT PAW ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 02/19/03 671011 ALOPECIA LEFT HIND QUARTERS ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 02/19/03 671013 SACRIFICED BY DESIGN 02/19/03 671014 ALOPECIA LEFT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA RIGHT SIDE ALOPECIA BOTH SIDE ALOPECIA BACK SACRIFICED BY DESIGN 02/20/03 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: ,9,10,11,12, b: ,9,10,11, , a: , , ,11,12, b: , ,10,11, , a: , , , ,12, b: , , ,11, , a: , , , ,12, a: , , , ,12, a: b: a: b: a: a: I I I b: a: b: a: I I I I I 14, 14, ,15,16,17,18,19,20,21 ,15,16,17,18,19,20, , , , , , , , 21 ,19,20,21 ,19,20, ,19,20,21 ,,19,,20,,21 ,21 a : 1 ' 1 1 | iv / 11 flu , / b: ,10,11,12, , a: 1 1 1 1 , , , ,13, 14,15,16,17,18,19,20,21 b: , # , , , , , ,13, 14,15,16,17,18,19,20, a: 1 I 1 I , , , ,13, 14, , , , , , , b: 14,1 1 1 1 , , , ,13, a: ! 1 t t t 1 1 1 ,15,16,17,18,19,20,21 b: 1 1 1 I 1 1 1 ,15,16,17,18,19,20, a: 1 / t I 1 1 1 ,15,16,17,18,19,20,21 b: / t 1 t / / / I ,15,16,17,18,19,20, a: 1 1 1 1 1 1 1 , , , , , , ,21 61 DuPont-10157 >eveiopmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 671018 ALOPECIA BOTH FRONT LEG ALOPECIA ABDOMINAL ALOPECIA BOTH FRONT PAW ALOPECIA UNDERBODY ALOPECIA BOTH REAR LEG ALOPECIA LEFT HIND QUARTERS ALOPECIA CHEST ALOPECIA BOTH HIND QUARTERS SACRIFICED BY DESIGN 02/20/03 671021 HUNCHED OVER DIARRHEA STAIN FACE BROWN WEAK STAIN PERINEUM BROWN WET PERINEUM SACRIFICED IN EXTREMIS 02/10/03 671022 SACRIFICED BY DESIGN 02/20/03 671023 SACRIFICED BY DESIGN 02/20/03 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: 7,8,9,10, 11,12,13,14,15,16,17,18,19,20,21 b: 7,8,9,10 11,12,13,14,15,16,17,18,19,20, a: ,8,9,10 b: ,8,9, a: , ,9,10 11.12.13.14.15.16.17.18.19.20.21 b: , ,9,10 11.12.13.14.15.16.17.18.19.20, a: b: , ,t t t ,10 11.12.13.14.15.16.17.18.19.20.21 11.12.13.14.15.16.17.18.19.20, a: ,12,13,14,15,16,17, , , , b: ,12,13,14,15,16,17, , , , a: ,12,13,14,15,16, , , , , b: ,12,13,14,15,16, , , , , a: , ,13,14,15,16,17, ,19,20,21 b: , ,13,14,15,16,17, ,19,20, a: ,17,18,19,20,21 b: ,17,18,19,20, a: , , , , ,21 3: t i t 3! i t 3l t 3; i t Si i t 3! r r 3l f ttt tt ttt ttt ttt it tit ,n, , t t t t ,ii, , t t t t ,n, , t t t t ,n, , i t t i ,n, , t t t t ,n, , t i t t ,u, , i t t i a: , / t t t t i t i i t t i ,21 a: , , t i t t t i i t i t t ,21 @*npanyS anitized. Does oa* Ooof 3% % Q 62 DuPont-10157 )) evelopmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 671041 WEAK HUNCHED OVER DIARRHEA STAIN PERINEUM BROWN SACRIFICED IN EXTREMIS 02/13/03 671046 ALOPECIA LEFT HIND QUARTERS ALOPECIA LEFT REAR LEG ALOPECIA PERINEUM ALOPECIA BOTH HIND QUARTERS ALOPECIA BOTH REAR LEG ALOPECIA ABDOMINAL ALOPECIA UNDERBODY SACRIFICED BY DESIGN 02/24/03 671047 SACRIFICED BY DESIGN 02/24/03 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 t t , , ,9,10, , , I I I b t i , , ,9,10, , , i l l a 1 i , , ,9,10, , , / / / b 1 1 , , ,9,10, , , I I I a , , , ,10, , , 1 1 1 b ! ! , , ,9,10, , , I I I a f i i i t 10/ / / I I I b , , , ,10, , III a 1 1 III 1 1 1 1 I I I b 1 , , , ,10, , , I I I 11 /1 11 11 1t 11 !1 I1 11 !/ a I t b* I / a: b: a: b: a: b: a: b: a: b: a: b: a: , ,8,.9,10, , , I I I I 1 1 1 1 , ,8,9,10, , , I I I !i 1 !! ,9,10,11,12, , , , , , , , ,9,10,11,12, , , , , , , , ,9,10,11,12,13,14,15,16,17,18, , ,9,10,11,12,13,14,15,16,17,18, , , , ,11,12,13,14,15,16,17,18,19,20 21 , , ,11,12,13,14,15,16,17,18,19,20 , , , , ,13,14,15,16,17,18,19,20 21 , , , , ,13,14,15,16,17,18,19,20 ,, i i i i i i i ,18, , ,18, ,19,20 21 ,19,20 21 ,21 D u P o n t-1 0 1 5 7 Company Sanitized D oes not contain T9CftC8t 63 IfDevelopmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL OBSERVATION NUMBER: 671051 ALOPECIA ABDOMINAL ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH FRONT LEG DIARRHEA STAIN CAGEBOARD RED SORE RIGHT FRONT LEG HUNCHED OVER SACRIFICED BY DESIGN 02/24/03 671053 HUNCHED OVER NO FEED ON CB DIARRHEA WEAK FOUND DEAD 02/19/03 671057 SACRIFICED BY DESIGN 02/24/03 INDIVIDUAL CLINICAL OBSERVATIONS DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED: ,8 ,9 ,10 ,11 ,12,13, 14,15 16, 17, 18,19,20,21 a: ,8 9 ,10 ,11 ,12,13 14,15 16, 17, 18,19,20,21 b: ,7 ,8 9 ,10 ,11 ,12,13 14,15 ,16, 17, 18,19,20, 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: 1 ,12,13 14,15 ,16, 17, 18,19,20,21 b: I a: t ,12,13 14,15 ,16, 17, 18,19,20, , ,13 14,15 ,16 17 18,19,20,21 b: / , ,13 ,14,15 ,16 17 18,19,20, a: / , ,13 -14, ! r b: , , ,13 / lit a: I b: I !1! /;1 1 / 18*, ', ', a: t b: I ''1 t 1 t till ,18, , , a: f t i 11 ,19,20,21 b: ,/,t t 1 1 ,19,20, a: 1 i i , , t ! , , , ,21 b: a: b: a: a; a: b: a: tti ii iii iii i i iii i i i i iii- III iii Ill iii It it Ill iii III X Ji 1 1 t i l l i , ,13, , , , i i i i /15 f i i t ,13,14,15, , ! , , ,14, , i 141 t i t t ! i t i #15, , 1 i i i i 15, , 15,I i i i i i a: ,21 DuPont-10157 C feed D oes not contain T5CA CBl Company Sanrttead. 64 evelopmental Toxicity Study in Rats DuPont-10157 APPENDIX C Individual Body Weights Company Sanitized. Does not contain TSCA CBI n (Developmental Toxicity Study in Rats Individual Body Weights DuPont-10157 Explanatory Notes Notes Day C21 = Corrected final maternal body weight = final maternal body weight minus the gravid uterine weight plus the empty uterine weight. Reporting of body weight data that were collected prior to study start (day 6G) are limited to day 0 , 4G, and 5G 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. Abbreviations -- = No Data S.D. = Standard Deviation S.E. SS Standard Error N =' Number in Group NP = Not Pregnant FD = Found Dead SE = Sacrificed in extremis R = Litter totally resorbed Company Sanitized. Doe wot contain T M *C Sf 66 Developmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 0 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015' 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 256.0 248.0 248.0 247.0 246.0 243.0 230.0 246.0 245.0 255.0 244.0 270.0 241.0 248.0 259.0 263.0 246.0 242.0 249.0 231.0 265.0 264.0 GROUP MEAN Sn R T*\ s 249.4 10.26 2.19 22 INDIVIDUAL ADULT BODY WEIGHTS DAYS OF GESTATION DAY 4 DAY 5 DAY 6 276.7 267.3 263.3 267.8 256.2 255.3 248.6 268.4 251.5 272.0 257.4 284.6 274.1 277.7 274.2 278.0 252.8 257.5 260.1 243.3 281.2 276.7 277.0 266.0 269.8 274.9 266.0 262.4 257.6 269.4 255.7 280.6 270.6 290.0 281.9 283.9 282.7 277.3 258.2 257.6 263.9 244.0 274.5 280.2 285.1 274.7 277.1 280.6 263.6 266.9 264.9 281.8 266.4 291.6 273.7 295.8 290.1 292.7 285.0 292.2 263.7 263.1 270.1 251.5 287.6 285.9 265.7 11.68 2.49 22 270.2 11.37 2.42 22 277.5 12.33 2.63 22 DAY 7 293.3 281.3 277.3 283.9 268.7 272.7 277.4 292.5 270.9 297.8 283.4 298.4 299.9 296.9 292.2 289.9 275.0 273.3 28-0.8 258.5 297.4 297.0 284.5 11.77 2.51 22 DAY 8 300.7 283.5 283.7 293.9 277.5 283.8 277.3 297.7 276.2 307.5 290.0 299.8 306.0 305.9 293.7 290.9 277.3 281.2 281.5 265.3 301.5 303.0 289.9 11.88 2.53 22 DAY 9 308.8 291.2 285.0 298.6 286.1 292.8 283.0 300.2 ^0/ *5 311.1 297.4 305.0 313.1 303.3 293.6 298.6 278.2 282.7 283.0 268.3 299.2 303.2 293.9 11.65 2.48 22 tS C A C B l Company Santti*0 -" Does * c00tain 67 )evelopmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY ANIMAL HUMBER DAY 10 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 312.3 298.9 292.4 307.3 294.2 300.1 290.6 301.1 287.2 314.5 294.3 307.9 324.0 313.2 299.0 303.1 286.2 287.5 283.4 271.6 313.1 308.3 GROUP MEAN S.D. S.E. S 299.6 12.50 2.67 22 INDIVIDUAL ADULT BODY WEIGHTS DAYS OF GESTATION DAY 11 DAY 12 DAY 13 DAY 14 320.3 299.0 291.1 312.8 297.3 296.4 295.3 309.0 296.4 323.5 300.1 315.7 341.8 330.8 310.6 312.1 296.4 296.8 289.4 281.3 316.9 316.0 324.5 300.4 301.7 324.2 308.4 304.3 306.9 316.0 306.1 339.2 311.0 323.9 348.3 333.1 318.8 312.6 305.5 297.2 299.7 288.1 322.7 321.6 337.9 315.0 310.7 334.5 316.0 319.5 315.3 328.2 311.0 342.8 321.3 325.0 352.6 335.8 321.5 320.6 312.5 308.9 306.4 294.7 332.4 330.1 341.0 317.1 310.2 337.9 318.8 324.9 316.3 333.5 315.4 347.9 320.4 327.8 366.2 343.7 328.3 317.5 321.3 310.7 306.8 299.3 336.4 331.4 306.8 14.74 3.14 22 314.3 14.58 3.11 22 322.4 13.49 2.88 22 326.0 15.44 3.29 22 DAY 15 346.7 323.9 315.4 351.2 328.7 326.4 328.6 337.0 322.3 359.7 325.7 335.3 364.4 345.9 336.5 327.9 330.6 317.0 305.1 307.7 345.9 339.4 332.8 15.39 3.28 22 DAY 16 362.9 339.0 328.7 359.8 336.2 345.2 341.0 357.7 336.1 373.0 335.1 340.5 380.5 357.2 343.4 329.5 340.8 326.0 315.5 316.5 356.9 352.6 344.3 16.87 3.60 22 ,,o, contain TSCA CM CompOTf S*"1"" 4 0 0 *' 68 Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY AumaL 1TOM3ER DAY 17 INDIVIDUAL ADULT BODY WEIGHTS DAYS OF GESTATION DAY 18 DAY 19 DAY 20 DAY 21 DAY C21 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 GROUP MEAN S.D. S.E. 380.6 355.5 341.0 374.7 353.9 360.2 345.2 370.5 350.8 385.8 347.7 354.6 393.0 371.4 355.3 352.8 352.6 341.6 323.6 329.0 373.1 367.5 358.2 17.52 3.74 22 391.4 365.3 352.9 387.0 363.9 368.4 367.2 390.4 370.4 402.8 372.5 369.1 414.6 387.1 374.8 365.6 372.3 358.6 339.3 346.8 393.9 385.7 374.5 18.14 3.87 22 412.3 389.0 370.0 407.4 381.2 385.2 381.5 411.6 385.1 428.8 391.2 384.5 428.9 402.2 383.8 382.2 385.7 367.1 349.3 364.6 412.4 400.0 391.1 20.22 4.31 22 429.0 404.9 389.2 437.9 392.9 407.3 402.6 430.9 398.4 442.8 412.6 399.0 454.4 417.2 393.3 396.0 406.4 387.6 364.0 384.1 432.3 416.1 409.0 21.87 4.66 22 465.1 435.1 406.2 457.0 410.2 428.2 427.4 440.6 431.0 482.4 433.9 422.6 489.5 448.0 419.4 419.3 432.2 409.2 382.5 402.3 459.5 442.4 433.8 25.95 5.53 22 355.8 321.2 314.5 338.5' 315.1 321.6 319.4 322.1 325.3 366.9 322.8 316.5 381.2 353.5 334.1 326.2 336.1 324.6 296.1 301.9 339.8 334.1 330.3 20.07 4.28 22 DuPont-10157 Company Sanitized. Does not contain TSCA CB! 69 developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHTS GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAY 0 DAYS OF GESTATION DAY 4 DAY 5 DAY 6 DAY 7 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 (NP) 671012 671016 671019 571020 671025 671026 671034 671043 671048 671050 671052 671056 239.0 261.0 246.0 256.0 248.0 242.0 250.0 232.0 237.0 254.0 253.0 270.0 268.0 234.0 257.0 258.0 249.0 242.0 237.0 251.0 242.0 270.0 250. 6 267. 9 260. 3 264. 6 260. 2 260. 8 268. 1 247. 5 256. 4280. 6 261. 5 289. 0 283. 7 257. i 279. 3 269. 1 267. 2 251. 8 253. 7 265. 9 256. 4 285. 8 259.4 278.1 267.5 273.6 269.2 266.0 280.4 251.6 254.6 287.6 270.6 294.8 285.1 266.4 283.8 273.6 280.3 252.8 254.0 266.0 267.1 296.2 263.6 282.4 276.1 273.8 268.0 265.8 283.9 255.3 270.5 291.6 276.1 299.5 301.5 272.5 291.5 281.7 280.6 258.1 264.7 270.8 269.1 297.4 269. 4 288. 5 276. 7 279. 1 274.,8 269..1 293..0 261..0 271. 3 302 .2 280.,4 301. 1 305. 7 279. 1 295. 5 284. 6 275. 1 270. 4 271..2 285. 2 277. 4 303. 9 GROUP MEAN s n. fi R. N 249.8 11.28 2.40 22 265. 4 11.83 2.52 22 271.8 13.03 2.78 22 277.0 13.09 2.79 22 282. 5 12.86 2.74 22 DAY 8 277.1 296.3 289.0 287.6 284.3 281.0 298.9 268.3 279.8 307.2 286.0 309.6 308.3 285.4 294.9 284.9 279.3 273.2 278.8 292.7 284.4 305.3 288.7 11.63 2.48 22 DuPont-10157 DAY 9 282.4 299.5 296.0 295.3 291.3 290.6 297.4 272.7 291.0 312.4 295.5 307.2 313.2 285.5 296.1 285.5 283.9 278.8 277.5 292.8 284.0 307.8 292.6 11.02 2.35 22 Company Sanitized Does not contain TSCACBI 70 ^Developmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAY 10 DAYS OF GESTATION DAY 11 DAY 12 DAY 13 DAY 14 670975 670976 670978 670980 670984 670990 670993 67X000 671003 671008 (NP) 671012 671016 671019 571020 571025 571026 671034 671043 671048 671050 671052 671056 287.5 308.0 306.4 300.1 297.1 296.1 306.0 275.0 293.5 313.1 296.4 315.7 317.5 291.3 302.4 288.9 293.5 280.7 279.6 300.1 287.4 315.3 291.4 313.5 307.3 305.2 303.6 297.2 308.8 285.9 297.8 316.5 299.6 322.3 330.4 303.9 311.2 300.5 - 301.0 294.9 288.1 304.8 302.5 320.4 299.4 320.1 313.9 308.5 306.7 297.7 319.2 300.9 312.6 322.2 304.7 326.1 342.7 312.5 318.4 303.0 304.3 302.1 292.9 319.1 313.4 330.3 309.6 336.2 325.2 321.0 320.0 315.9 325.3 307.5 315.3 316.6 314.8 328.5 341.9 314.3 319.2 306.2 304.4 307.1 300.7 322.4 319.6 333.9 313.1 343.5 332.4 331.3 326.9 319.2 330.1 312.1 319.9 305.7 313.6 335.3 351.9 323.3 324.9 310.3 306.9 310.7 304.2 331.3 323.9 341.1 GROUP MEAN g .D. S.E. K 297.8 12.05 2.57 22 304.9 11.06 2.36 22 312.3 11.91 2.54 22 318.4 10.61 2.26 22 323.3 13.06 2.78 22 DAY 15 319.4 326.4 338.0 333.1 333.6 321.6 342.9 32b .4 322.7 309.9 328.4 336.2 353.7 328.4 329.4 316.1 316.8 315.8 312.8 333.9 338.7 345.9 328.6 11.32 2.41 22 DAY 16 331.9 334.5 357.0 343.4 343.0 335.4 354.3 338.5 334.7 315.6 335.7 347.3 357.6 339.4 338.2 323.6 324.6 325.8 322.6 343.7 352.8 358.8 339.0 12.27 2.62 22 Company Sanitised Does not contain TSCA CBi developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHTS GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAY 17 DAYS OF GESTATION DAY 18 DAY 19 DAY 20 DAY 21 DAY C21 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 (NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 345.8 357.8 369.9 363.0 351.3 337.6 365.2 351.4 347.7 317.2 353.7 364.3 372.2 348.0 355.4 340.2 335.7 336.3 336.6 361.6 375.9 366.1 359.7 380.3 384.0 378.4 370.8 351.3 384.5 373.6 362.8 312.7 367.1 380.0 382.5 361.0 365.8 354.7 348.2 355.0 344.5 378.5 392.7 383.8 375.9 395.5 404.9 387.7 389.4 375.1 399.5 391.0 378.0 318.6 382.9 397.8 392.1 376.6 385.7 369.2 359.3 363.7 359.1 391.7 412.1 402.5 395.5 415.6 421.8 402.7 404.0 393.5 411.1 404.7 386.7 317.9 396.0 416.6 406.1 395.3 396.0 384.2 373.9 382.2 381.3 413.1 434.3 418.5 421.9 442.4 454.3 423.8 428.9 407.2 443.0 433.5 412.0 324.6 421.7 442.6 421.2 417.1 432.1 408.3 397.5 410.5 400.2 440.4 466.1 444.1 315.1 347.0 345.2 331.4 336.2 308.5 345.2 325.9 325.3 -- 329.1 336.1 363.0 326.7 337.4 316.8 309.2 321.5 316.7 347.7 349.9 346.4 GROUP MEAN S.D. S.E. N 352.4 14.58 3.11 22 366.9 18.13 3.87 22 382.2 20.30 4.33 22 397.8 23.31 4.97 22 422.4 28.12 5.99 22 332.4 14.87 3.24 21 DuPont-10157 Company SanRteed Does no* n o * , TSCA C H 72 /""K Developmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP III: 200 MG/KG/DAY ANIMAL NUMBER DAY 0 DAYS OF GESTATION DAY 4 DAY 5 DAY 6 DAY 7 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 245 .0 254 .0 244 .0 254 .0 242 .0 239 .0 235 .0 250 .0 249 .0 263 .0 237 .0 268 .0 265 .0 270 .0 242 .0 237 .0 255 .0 240 .0 270 .0 251 .0 237 .0 249 .0 232..7 264..0 256..6 267..1 242..9 258..9 253..7 270..6 226..0 256..3 253..4 283..5 279..1 284..8 254..1 249..3 256..6 250..8 291..0 263..9 243..1 262..6 254..6 272..8 268..9 278..1 265..3 262,.3 252,.3 279..9 253;.8 283..5 262..7 294 .8 287..3 292..1 258..5 253..5 267 .8 261..4 289..8 268,.6 249,.9 264..3 261..9 276..1 268..7 278..0 267..6 267..7 270..6 284..4 260..8 286..1 266..1 299..7 294..5 296..9 264..7 262..1 275..9 262..7 296..1 277..9 257..9 264..1 268..8 280.. 8 275..7 283 . 0 272..7 273 .9 277.. 9 290..0 265..3 293..4 274..7 294..4 292..4 300..4 264..3 260..4 271..9 268..9 298.. 6 275..7 258,.4 279.. 3 GROUP MEAN S D. S.E. N 249.8 11.38 2.43 22 259.1 16.20 3.45 22 269.2 13.81 2.94 22 274.6 13.09 2.79 22 278.2 12.21 2.60 22 DAY 8 279. 7 292. 0 284. 5 295. 4 288. 2 276. 7 281. 6 299..0 273.,6 298..4 280.,7 301.,3 304..1 305..3 2 66.. 6 261..5 271..9 272 . 3 304..1 283 . 5 264..3 280..7 284.8 13.59 2.90 22 DAY 9 285.1 301.1 288.1 297.5 293.6 283.2 281.2 305.3 277.4 301.1 285.1 299.9 300.0 302.4 273.8 266.9 276.2 270.8 302.2 282.2 275.3 281.7 287.7 11.90 2.54 22 Company S a p u te * Oom M e m ttn 73 [Developmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP III: 200 MG/KG/DAY ANIMAL TOMBER DAYS OF GESTATION DAY 10 DAY 11 DAY 12 DAY : DAY 14 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 571032 671036 671037 671038 671040 671049 291.3 306.0 292.0 301.4 296.0 287.3 285.8 308.4 286.7 309.9 279.4 301.7 306.0 310.1 277.7 272.8 283.2 286.3 301.2 285.0 276.9 289.4 288.5 308.6 295.8 307.2 302.1 297.9 294.5 320.6 290.1 322.1 285.4 306.9 313.0 319.6 285.5 285.0 290.7 283.9 303.9 306.2 288.0 288.6 303.9 313.6 299.2 317.9 309.3 308.4 305.3 331.1 301.1 339.8 298.7 321.9 321.1 327.1 283.6 284.1 301.5 301.4 316.3 299.7 292.5 299.6 316.7 329.8 318.8 328.3 336.4 314.6 314.1 337.0 305.5 344.9 303.9 327.4 327.1 327.7 286.4 287.2 308.6 302.8 328.3 312.5 303.4 305.5 325.2 331.4 313.5 336.2 336.2 317.7 316.6 345.3 305.0 352.1 298.7 326.5 332.2 336.7 289.0 294.1 312.3 313.1 329.0 321.9 308.5 313.7 GROUP MEAN S.D. S.E. jj 292.5 11.55 2.46 22 299.3 12.41 2.65 22 308.1 14.38 3.07 22 316.7 15.51 3.31 22 320.7 16.25 3.46 22 DAY 15 331.0 334.3 316.7 344.0 344.2 328.2 326.8 364.2 328.0 370.0 306.2 338.3 342.0 344.4 298.6 298.6 310.4 318.6 349.6 329.8 317.7 323.6 330.2 18.81 4.01 22 DAY 16 346.3 346.9 335.3 356.9 352.6 329.6 339.6 372.2 328.9 383.0 322.2 353.2 351.2 356.7 310.3 305.2 321.3 334.9 360.3 345.0 326.9 333.5 341.5 19.07 4.07 22 frainy __ 74 g;  developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHTS GROUP III: 200 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION DAY 17 DAY 18 DAY 19 DAY 20 DAY 21 DAY C21 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 364. 9 357. 5 346. 1 367. 6 370. 5 349. 1 364. 3 401. 7 344. 5 405. 6 336. 5 365. 8 368. 6 367. 4 326. 1 317. 7 338. 0 344. 2 374. 6 355. 9 337. 8 345. 6 382.3 381.9 359.2 383.8 391.0 363.9 382.1 419.6 360.5 427.3 346.3 380.5 383.2 380.8 336.4 327.0 350.2 359.6 393.2 37'3.2 362.1 366.7 403. 4 400. 3 376. 3 397. 3 403. 7 379. 8 391. 2 434. 7 374. 4 453. 5 355. 3 400. 9 401. 3 397. 9 345. 1 339. 4 367. 7 378. 8 408. 4 386. 8 383. 7 383. 6 416. 0 420. 2 388. 8 411. 8 421. 3 396. 1 414. 0 455. 8 391. 2 479. 3 370. 1 415. 9 416. 0 413. 9 355. 6 351. 0 384. 4 399. 3 432. 4 406. 6 381. 5 394. 8 444 .9 451 .1 405 . 6 439 . 8 441 .3 413 . 6 434 .2 473 . 0 414 . 5 507 .4 376 .9 440 .3 437 .1 432 .0 367 .3 363 .3 402 .3 427 . 6 449 .9 429 .3 413 .4 418 .3 332.9 332.0 311.4 343.3 336.0 340.4 310.0 359.5 330.7 373.2 285.2 337.9 345.4 330.8 .1 286.7 299.2 317.6 343 . I 330.6 321.5 314.2 GROUP MEAN fi ,D. S.E. N 356. 8 21.47 4.58 22 373.2 23.80 5.07 22 389. 2 26.02 5.55 22 405. 3 29.39 6.27 22 426 .5 32.'75 6.:98 22 325.7 23.20 4.95 22 DuPont-10157 Company SwflEzefL Booem tcoftlam T5CA CBI 75 DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP XV: 500 MG/KG/DAY ANIMAL NUMBER DAY 0 DAYS OF GESTATION DAY 4 DAY 5 DAY 6 DAY 7 670971 670973 (SE) 670977 670982 670991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 671021 (SE) 671022 671023 671041 (SE) 67046 671047 671051 (R) 671053 (FD) 671057 244.0 250.0 23R. 0 255 -0 249.0 242.0 2S4.0 250.0 2Sfi _0 251.0 236.0 243.0 269.0 250.0 253.0 252.0 264.0 232.0 234.0 247.0 251.0 269.0 235.0 273.1 246.0 282.6 260.1 260.5 272.7 238.3 269.7 272.4 258.9 246.7 284.0 266.8 277.2 281.9 275.8 240.3 246.7 256.4 264.7 282.0 246.2 274.5 257.4 2 87. 8 272.3 265.1 285.8 251.4 278.9 273.2 265.9 254.9 285.8 279.8 287.5 284.6 271.2 238.0 247.0 267.3 266.8 286.2 258.8 277.2 263.1 299.8 275.7 274.4 293.7 254.9 285.8 278.9 275.4 265.7 292.9 280.0 292.0 292.6 286.1 246.7 255.3 279.5 273.5 293.7 261.7 255.8 241.0 289.9 264.7 269.6 294.3 255.2 289.6 285.9 271.1 247.9 289.8 268.2 290.2 278.0 279.2 249.5 235.4 266.8 263.3 291.5 GROUP MEAN S.D. S.E. 249.4 11.48 2.45 22 263.3 15.52 3.31 22 269.4 14.98 3.19 22 277.1 14.69 3.13 22 269.9 17.67 3.77 22 DAY 8 247.2 262.4 254.1 304.2 281.1 272.0 293.0 237.4 297.3 290.3 288.3 245.1 283.7 263.5 293.8 290.6 256.0 255.3 252.7 285.7 276.5 304.4 274.3 20.50 4.37 22 DAY 9 271.2 246.0 226.2 308.0 290.5 279.2 301.4 224.3 304.6 297.8 290.8 265.8 292.3 242.8 300.6 295.4 243.1 257.6 261.2 tt) . tl 277.2 303.9 275.8 26.25 5.60 22 Compaq 76 TSCACBI levelopmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER DAY 10 DAYS OF GESTATION DAY 11 DAY 12 DAY 13 DAY 14 670971 670973 (SE) 670977 670982 670991 571001 671004 571005 (SE) 571006 671011 671013 671014 671018 671021 (SE) 671022 671023 671041 (SE) 671046 671047 671051 (R) 671053 (KD) 671057 281.8 231.5 260.3 298.5 297.1 278.8 308.5 209.9 305.3 302.3 294.6 254.8 292.4 222.7 302.9 297.7 226.4 258.4 271.3 267.0 282.0 300.5 264.6 220.2 265.6 317.9 300.1 280.5 312.1 196.4 312.5 301.8 305.5 276.9 282.7 214.0 280.5 290.6 261.6 241.3 249.7 258.8 295.2 261.3 209.8 277.3 327.3 304.3 295.4 334.1 183.0 327.3 315.0 313.3 261.7 290.6 -- 288.2 299.0 272.8 255.0 229.8 246.8 313.1 290.2 194.4 293.2 336.5 318.6 300.7 335.0 -- 316.2 316.2 316.6 247.3 310.9 -- 306.7 296.1 276.3 274.3 215.3 233.9 324.6 291.9 304.6 340.3 324.9 309.0 345.3 -- 328.1 322.2 316.8 277.6 323.8 ______ 318.7 307.7 ______ 286.6 281.4 231.5 220.7 332.1 GROUP MEAN S.D. S.E. ST 274.8 29.90 6.37 22 272.8 33.83 7.38 21 280.3 40.73 9.11 20 289.6 40.33 9-25 19 303.5 34.15 8.05 18 DAY 15 304.7 311.5 345.1 328.0 320.0 354.6 -- 338.8 337.2 331.1 276.7 332.4 -- 324.5 297.5 -- 289.2 286.3 247.9 207.7 338.6 309.5 37.41 8.82 18 DAY 16 325.5 331.5 360.2 344.7 327.4 364.6 -- 347.4 339.6 338.9 287.8 344.3 -- 340.3 301.3 -- 294.8 299.6 247.4 -- 350.8 326.2 30.54 7.41 17 not contain TSCACBl Sanitised. Does Campa* 77 s 0*^ 'Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHTS GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER DAY 17 DAYS OF GESTATION DAY 18 DAY 19 DAY 20 670971 670973 (SE) 670977 670982 670991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 671021 (SE) 671022 671023 671041 (SE) 671046 671047 671051 (R) 671053 (FD) 671057 337.8 339.6 379.0 346.0 348.1 378.8 373.4 360.3 347.5 301.7 363.7 358.2 330.2 298.8 309.3 254.2 364.8 353.0 355.2 396.6 368.2 360.3 392.6 384.0 373.6 356.5 318.2 387.9 368.9 333.0 310.3 322.3 236.1 387.4 373.4 379.0 414.1 384.2 375.8 400.4 402.1 383.0 372.5 326.4 396.1 378.7 352.0 315.5 333.5 221.3 399.1 393.7 390.5 429.9 399.7 390.8 407.8 417.6 400.4 383.6 340.7 395.5 384.6 363.2 330.5 343.7 229.6 407.5 DAY 21 DAY C21 411.7 412.3 448.5 429.3 401.0 368.5 423.0 402.7 410.3 338.5 412.2 378.1 324.7 364.5 . 368.3 241.5 428.7 307.7 310.0 353.3 337.4 289.0 280.5 314.2 296.0 333.7 258.8 296.1 282.5 245.5 277.3 294.6 241.4 330.1 SROUP MEAN S.D. S.E. U 340.7 33.34 8.09 17 353.2 40.20 9-75 17 365.1 46.26 11.22 17 377.0 46.76 11.34 17 386.1 50.09 12.15 17 296.9 31.60 7.66 17 DuPont-10157 Company SanRised. Does m l contain TSCA CBI Developmental Toxicity Study in Rats DuPont-10157 APPENDIX D Individual Body Weight Changes CompanySanftfeed Doe* not contain TSCA CBf Developmental Toxicity Study in Rats Individual Body Weight Changes Explanatory Notes DuPont-10157 Notes 6-C21 = Corrected final maternal body weight = final maternal body weight minus the gravid uterine weight plus the empty uterine weight. Abbreviations = No Data S.D. = Standard Deviation S.E. = Standard Error N = Number in Group NP = Not Pregnant ED = Found Dead SE = Sacrificed in extremis R = Litter Totally Resorbed not contain TSCACBI Com paq Sanitte**-0005 Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP I: 0 MG/KG/DAY ANIMAL HUMBER 0-6 DAYS OF GESTATION 6-8 8-10 10-12 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 29.1 26.7 29.1 33.6 17.6 23.9 34.9 35.8 21.4 36.6 29.7 25.8 49.1 44.7 26.0 29.2 17.7 21.1 21.1 20.5 22.6- 21.9 8.4 7.4 13.8 12.8 7.4 11.6 16.3 13.4 14.9 19.6 16.3 11.2 16.0 15.0 10.8 14.2 10-9 5.6 10.0 8.2 6.4 9.2 15.6 8.8 6.6 13.3 13.9 16.9 12.4 15.9 9.8 15.9 16.3 4.0 15.9 13.2 8.7 -1.3 13.6 18.1 11.4 13.8 13.9 17.1 11.6 15.4 8.7 13.4 16.7 16.3 13.3 3.4 11.0 7.0 4.3 8.1 18.0 7.3 5.3 12.2 8.9 6.3 1.9 6.3 11.6 5.3 12 .'2 1.5 9.3 16.9 14.2 4.2 16.3 14.9 18.9 24.7 16.7 16.0 24.3 19.9 19.8 9.5 19.3 9.7 16.3 16.5 9.6 13.3 GROUP MEAN S.D. S.E. N 28.1 8.30 1.77 22 11.8 3.75 0.80 22 12.4 4.74 1.01 22 9.7 4.60 0.98 22 14.7 5.79 1.23 22 12-14 16.5 16.7 8.5 13.7 10.4 20.6 9.4 17.5 9.3 8.7 9.4 3.9 17.9 10.6 9.5 4.9 15.8 13.5 7.1 11.2 13.7 9.8 11.8 4.38 0.93 22 DuPont-10157 14-16 21.9 21.9 18.5 21.9 17.4 20.3 24.7 24.2 20.7 25.1 14.7 12.7 14.3 13.5 15.1 12.0 19.5 15.3 8.7 17.2 20.5 21.2 18.2 4.48 0.96 22 Com""' z*'?** rVwMS TSCA OBf 81 'evelopmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP 1 : 0 MG/KG/DAY ANIMAL NUMBER 16-:18 DAYS OF GESTATION 18-21 6-21 6-C21 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 28 .5 26 .3 24 .2 27 .2 27 .7 23 .2 26 .2 32 .7 34 .3 29 .8 37 .4 28 .6 34 .1 29 .9 31 .4 36 .1 31 .5 32 .6 23 .8 30 .3 37 .0 33 .1 73 .7 180 .0 70.7 69 .8 160 .4 46.5 53 .3 129 .1 37.4 70 .0 176 .4 57.9 46 .3 146 . 6 59 .8 161 .3 60 .2 162 . 5 51.5 54.7 54.5 50 .2 158 . 8 ' 40.3 60 .6 164 . 6 58.9 79 .6 190 .8 75.3 61 .4 160 .2 49.1 53 .5 126 .8 20.7 74 .9 199 .4 91.1 60 .9 155 .3 60.8 44 .6 134 .4 49.1 53 .7 127 .1 34.0 59 .9 168 .5 72.4 50 .6 146 . 1 61.5 43 .2 112 .4 26,0 55 .5 150 .8 50.4 65 .6 171 .9 52.2 56 .7 156 . 5 48.2 GROUP MEAN q n. q f If 30 .3 4.:18 0.189 22 59 .3 9. 191 2.:11 22 156 .4 21.'46 4.!58 22 52.9 16.15 3.44 22 DuPont-10157 pom pai 82 0oeSRt contain f SCA CBl Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 0-6 DAYS OF GESTATION 4-6 6-8 8-10 10-12 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 (NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 24.6 21.4 30.1 17.8 20.0 23.8 33.9 23.3 33.5 37.6 23.1 29.5 33.5 38.5 34.5 23.7 31.6 16.1 27.7 19.8 27.1 27.4 13.0 14.5 15.8 9.2 7.8 5.0 15.8 7.8 14.1 11.0 14.6 10.5 17.8 15.0 12.2 12.6 13.4 6.3 11.0 4.9 12.7 11.6 13.5 13.9 12.9 13.8 16.3 15.2 15.0 13.0 9.3 15.6 9.9 10.1 6.8 12.9 3.4 3.2 -1.3 15.1 14.1 21.9 15.3 7.9 10.4 11.7 17.4 12.5 12.8 15.1 7.1 6.7 13.7 5.9 10.4 6.1 9.2 5.9 7.5 4.0 14.2 7.5 0.8 7.4 3.0 10.0 11.9 12.1 7.5 8.4 9.6 1.6 13.2 25.9 19.1 9.1 8.3 10.4 25.2 21.2 16.0 14.1 10.8 21.4 13.3 19.0 26.0 15.0 GROUP MEAN S.D. S.E. N 27.2 6.40 1.37 22 11.7 3.58 0.76 22 11.7 5.21 1.11 22 9.1 4.18 0.89 22 14.5 6.56 1.40 22 12-14 13.7 23.4 18.5 22.8 20.2 21.5 10.9 11.2 7.3 -16.5 8.9 9.2 9.2 10.8 6.5 7.3 2.6 8.6 11.3 12.2 10.5 10.8 11.0 8.29 1.77 22 DuPont-10157 14-16 18.8 -9.0 24.6 12.1 16.1 16.2 24.2 26.4 14.8 9.9 22.1 12.0 5.7 16.1 13.3 13.3 17.7 15.1 18.4 12.4 28.9 17.7 15.8 7.87 1.68 22 ized.Does not co n tai Con'Pany Saw 83 evelopmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-21 6-21 6-C21 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 (NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 27.8 45.8 27.0 35.0 27.8 15.9 30.2 35.1 28.1 -2.9 31.4 32.7 24.9 21.6 27.6 31.1 23.6 29.2 21.9 34.8 39.9 25.0 62.2 158.3 62.1 160.0 70.3 178.2 45.4 150.0 58.1 160.9 55.9 141.4 58.5 159.1 59.9 178.2 49.2 141.5 11.9 33.0 54.6 145.6 62.6 143.1 38.7 119.7 56.1 144.6 66.3 140.6 53.6 126.6 49.3 116.9 55.5 152.4 55.7 135.5 61.9 169.6 73.4 197.0 60.3 146.7 51.5 64.6 69.1 57.6 68.2 42.8 61.3 70.6 54.8 -- 53.0 36.6 61.5 54.2 45.9 35.1 28.6 63.4 52.0 76.9 80.8 49.0 GROUP MEAN S.D. S.E. tt 27.9 9.44 2.01 22 55.5 12.46 2.66 22 145.4 31.55 6.73 22 56.1 13.63 2.97 21 DuPont-10157 Company Sanitized. Does not contain TSCA CBI 84 'evelopmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP III: 200 MG/KG/DAY ANIMAL NUMBER 0-6 DAYS OF GESTATION 4-6 6-8 8-10 10-12 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 16.9 22.1 24.7 24.0 25.6 28.7 35.6 34.4 11.8 23.1 29.1 31.7 29.5 26.9 22.7 25.1 20.9 22.7 26.1 26.9 20.9 15.1 29.2 12.1 12.1 10.9 24.7 8.8 16.9 13.8 34.8 29.8 12.7 16.2 15.4 12.1 10.6 12.8 19.3 11.9 5.1 14.0 14.8 1.5 17.8 15.9 15.8 17.4 20.6 9.0 11.0 14.6 12.8 12.3 14.6 1.6 9.6 8.4 1.9 -0.6 -4.0 9.6 8.0 5.6 6.4 16.6 11.6 14.0 7.5 6.0 7.8 10.6 4.2 9.4 13.1 11.5 -1.3 0.4 1.9 4.8 11.1 11.3 11.3 14.0 -2.9 1.5 12.6 8.7 12.6 7.6 7.2 16.5 13.3 21.1 19.5 22.7 14.4 29.9 19.3 20.2 15.1 17.0 5.9 11.3 18.3 15.1 15.1 14.7 15.6 10.2 SROUP MEAN an q tc. s 24.8 5.77 1.23 22 15.4 7.95 1.70 22 10.2 6.47 1.38 22 7.7 5.14 1.10 22 15.6 5.52 1.18 22 DuPont-10157 12-14 21.3 17.8 14.3 18.3 26.9 9.3 11.3 14.2 3.9 12.3 0.0 4.6 i i .i 9.6 5.4 10.0 10.8 11.7 12.7 22.2 lb . 14.1 12.6 6.31 1.35 22 14-16 21.1 15.5 21.8 20.7 16.4 11.9 23.0 26.9 23.9 30.9 23.5 26.7 19.0 20.0 21.3 11.1 9.0 21.8 31.3 23.1 18.4 19.8 20.8 5.71 1.22 22 Company Sanitized. Does not contain TSCA C8I ^Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP III: 200 MG/KG/DAY ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-21 6-21 6-C21 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 36.0 62.6 183.0 71.0 35.0 23.9 69.2 175.0 46.4 136.9 55.9 42.6 26.9 38.4 56.0 161.8 50.3 173.7 65.3 68.4 34.3 42.5 49.7 145.9 52.1 163.6 72.7 39.4 47.4 53.4 188.6 75.1 31.6 44.3 54.0 153.7 80.1 221.3 69.9 87.1 24.1 27.3 30.6 110.8 59.8 140.6 19.1 38.2 32.0 53.9 142.6 50.9 24.1 26.1 21.8 51.2 135.1 30.9 102.6 36.3 101.2 33.9 19.4 24.6 28.9 24.7 52.1 126.4 68.0 164.9 23.3 54.9 32.9 28.2 35.2 33.2 56.7 153.8 56.1 151.4 51.3 155.5 51.6 154.2 47.0 52.8 63.6 50.1 GROUP MEAN S.D. S.E. N 31.8 7.02 1.50 22 53.3 11.41 2.43 22 151.9 28.17 6.01 22 51.1 19.49 4.16 22 DuPont-10157 esnof contain Ts c a CBI 86 'evelopmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER 0-6 DAYS OF GESTATION 4-6 6-8 8-10 670971 670973 (SE) 670977 670982 670991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 671021 (SE) 671022 671023 671041 (SE) 671046 671047 671051 (R) 671053 (FD) 671057 14.8 27.2 25.1 36.8 26.7 32.4 39.7 24.9 29.8 27.9 39.4 22.7 23.9 30.0 39.0 30.6 22.1 14.7 21.3 32.5 22.5 24.7 23.8 -11.6 34.6 -20.5 4.1 -14.8 -30.9 -21.7 17.1 -9.0 6.2 17.0 17.2 4.4 -5.7 28.8 15.6 5.4 16.0 7.2 13.9 -2.4 6.8 16.6 21.0 -0.7 15.5 25.6 16.6 -17.5 -27.5 -26.9 16.1 11.5 8.0 22.0 6.5 11.4 12.0 12.7 16.5 12.9 6.3 18.7 19.0 -20.6 9.7 6.9 8.9 -9.2 8.7 -1.8 13.2 -16.5 -40.8 -- 14.8 1.8 9.1 -14.7 10.7 -2.0 7.1 1.3 10.3 -30.1 -29.6 -- 6.4 8.6 3.1 14.4 8.6 -2.6 18.6 -16.3 23.1 6.2 -18.7 -37.2 8.8 3.0 5.5 -35.2 11.7 10.7 -3.9 12.6 GROUP MEAN S.D. 5.E. H 27.7 7.08 1.51 22 13.8 -2.8 0.5 0.5 5.42 11.94 18.72 20.81 1.16 2.54 3.99 4.65 22 22 22 20 DuPont-10157 12-14 14-16 30.6 -- 27.3 13.0 20.6 13.6 11.2 . -- 0.8 7.2 3.5 15.9 33.2 -- 30.5 8.7 -- 13.8 26.4 1.7 -26.1 19.0 33.6 -- 26.9 19.9 19.8 18.4 19.3 -- 19.3 17.4 22.1 10.2 20.5 -- 21.6 -6.4 -- 8.2 18.2 15.9 -- 18.7 13.9 14.24 3.36 18 17.9 8.39 2.03 17 Company Sanftfred. Does not contain TSCA CBf 87 z***-^. leve-lopmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER 16-18 DAYS OF GESTATION 18-21 6-21 6-C21 670971 670973 (SE) 670977 670982 670991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 671021 (SE) 671022 671023 671041 (SE) 671046 671047 671051 (R) 671053 (FD) 671057 27.5 -- 23.7 36.4 23.5 32.9 28.0 -- 36.6 34.0 17.6 30.4 43.6 -- 28.6 31.7 -- 15.5 22.7 -11.3 -- 36.6 58.7 -- 57.1 51.9 61.1 40.7 -24.1 -- 39.0 29.1 53.8 20.3 24.3 -- 9.2 -8.3 ______ 54.2 46.0 5.4 -- 41.3 152.9 -- 149.2 148.7 153.6 126.6 74.8 -- 137.2 123.8 134.9 72.8 119.3 -- 86.1 32.1 -- 117.8 113.0 -38.0 -- 135.0 48.9 -- 46.9 53.5 61.7 14.6 -13.2 -- 28.4 17.1 58.3 -6.9 3.2 -- -9.5 -47.1 -- 30.6 39.3 -38.1 -- 36.4 GROUP MEAN S.D. S.E. N 26.9 12.24 2.97 17 32.9 25.19 6.11 17 108.2 50.31 12.20 17 19.1 33.16 8.04 17 DuPont-10157 Company Sanitized. Does not contain TSCACBI 88 evelopmental Toxicity Study in Rats DuPont-10157 APPENDIXE Individual Food Consumption Company Sanffeed. Does not contain TSCA CBl evelopmental Toxicity Study in Rats Individual Food Consumption Explanatory Notes Abbreviations --= S.D. = S.E. = N= NP = FD = SE = R= No Data Standard Deviation Standard Error Number in Group Not Pregnant Found Dead Sacrificed in extremis Litter totally resorbed DuPont-10157 Company Sanitized. Does r>otcontain TSCACB, 90 /''"'N )evelopmental Toxicity Study in Rats DuPont-10157 individual mean daily feed consumption GROUP I: 0 MG/KG/DAY AMTMATi NUMBER 4-6 DAYS OF GESTATION 6-8 8-:10 10-12 12- 14 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 25.2 21.0 22.4 24.3 20.3 19.2 16.2 21.9 21.4 26.4 20.0 22.9 .29.4 25.3 24.0 22.6 22.5 21.3 25.5 22.4 24.6 23.1 27.3 21.1 21.8 24.6 20.8 24.3 22.2 24.1 23.6 25.7 23.4 16.9 31.1 26.9 22.8 31.1 20.1 20.9 20.4 21.1 21.4 21.1 27 .2 22 .8 20 .4 25 .8 24 .1 26 .2 22 .6 22 .6 24 .6 25 .9 24 .9' 26 .4 30 .7 24 .1 23 .0 24 .4 22 .9 21 .1 22 .5 23 .1 23 .4 20 .9 30. 9 21. 8 24..8 29. 4 24. 8 24.A 22..7 25. 1 25. 4 29. 2 24. 7 24. 5 32. 9 27. 4 22. 6 21. 4 27. 4 24. 2 24. 2 26. 0 23. 4 23. 9 28 .4 25 .0 21 .8 27 .3 21 .8 26 .4 24 .4 28 .3 26 .3 30 .0 26 .4 24 .3 33 . 5 27 .0 23 .7 24 .4 28 .6 25 .1 25 .6 26 .8 25 .8 23 .4 GROUP MEAN qP S.E. N 22.8 2.78 0.59 22 23.3 3.47 0.74 22 24.1 2.35 0.50 22 25.5 2.94 0.63 22 26 .1 2.158 0.!57 22 14- 16 31 .4 25 . 4 23 .9 31 .4 24 .8 2b . 8 26 . 0 29 . 9 24 . 5 29 . 8 26 . 5 24 . i 33 .4 29 . i 27 .3 2b .7 28 . 4 25 . 8. 25 .0 26 .2 27 . 6 24 .9 27 .2 2.i65 0.!56 22 16-18 34.8 28.3 21.5 26.4 27.2 31.1 26.8 33.5 31.4 32.3 30.4 27.0 39.4 32.7 28.6 29.4 2b. 3 26.5 24.6 28.2 29.1 2b . 1 29.3 3.83 0.82 22 C0mpaily S a n i t y &oeg contain TSCA CBf 91 evelopmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 18-21 DAYS OF GESTATION 6-21 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 31.9 28.9 24.7 39.8 25.7 28.4 25.7 29.2 25.1 31.1 30.5 23.2 33.8 29.4 26.0 25.4 29.6 26.5 23.1 26.5 29.1 25.5 . 30.4 25.0 22.8 29.9 24.3 26.9 24.4 27.6 25.8 29.3 26.9 23.8 33.6 28.2 25.0 25.9 26.7 24.4 23.6 25.5 25.9 23.8 GROUP MEAN S.D. S.E. N 28.1 3.84 0.82 22 26.4 2.64 0.56 22 DuPont-10157 92 *Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 570975 670976 670978 670980 670984 570990 670993 671000 671003 671008 (NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 23.8 22.0 26.0 20.4 19.3 20.9 24.8 23.1 22.8 24.4 24.1 23.9 27.4 26.3 22.8 21.6 23.6 22.4 22.3 26.9 25.8 29.9 23.3 22.8 22.8 19.5 19.9 21.0 25.6 21.4 21.7 24.5 24.4 24.8 26.3 24.9 22.3 20.2 17.9 19.3 19.7 22.1 22.5 18.0 23.4 23.8 29.8 26.1 21.8 22.4 25.1 22.6 23.4 22.4 25.3 23.8 25.4 27.1 21.9 21.5 22.2 20.5 18.5 23.3 21.5 21.5 25.7 26.4 29.4 26.3 29.5 23.3 23.9 27.1 27.1 24.7 22.4 23.7 29.8 27.2 22.3 20.9 22.1 28.0 22.4 26.6 27.9 27.1 24.2 26.9 31-0 27.5 24.7 26.2 28.2 26.2 26.4 20.6 26.7 24.7 27.9 29.5 23.9 23.6 22.4 25.4 24.6 31.0 27.1 26.6 GROUP MEAN S.D. S.E. N 23.8 2.50 0.53 22 22.0 2.43 0.52 22 23.3 2.44 0.52 22 25.6 2.66 0.57 22 26.1 2.55 0.54 22 14-16 27.3 14.5 30.3 24.6 28.9 23.8 29.9 29.5 26.9 18.1 26.8 24.6 30.1 32.4 26.6 25.3 26.0 27.6 24.6 25.8 30.6 26.0 26.4 4.04 0.86 22 DuPont-10157 16-18 31.3 29.4 37.1 34.6 31.1 29.1 31.5 33.2 31.3 22.8 30.3 28.3 33.3 32.8 30.1 28.1 26.3 26.6 23.1 28.7 33.4 24.2 29.8 3.69 0.79 22 c m,'Party ^oe "OiCOi,r>tsin rCA CBl 93 Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP II: 50 MG/KG/DAY ANIMAL fJUMBER 18-21 DAYS OF GESTATION 6-21 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 (NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 26.3 31.6 31.1 28.3 29.2 27.9 29.1 29.5 27.2 19.1 26.3 28.8 30.6 30.5 28.7 24.8 22.7 26.3 27.1 30.5 31.4 24.2 25.9 25.5 30.3 26.8 26.7 25.0 27.7 27.2 26.3 21.6 26.0 25.7 29.1 29.3 25.4 23.6 22.8 24.9 23.1 27.1 28.0 24.0 GROUP MEAN S.D. 5.E. i 27.8 3.09 0.66 22 26.0 2.19 0.47 22 DuPont-10157 Company Sanitized. Does not contain TSCA CBf 94 evelopmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP III: 200 MG/KG/DAY ANTMAT, NUMBER 4-6 DAYS OF GESTATION 6-8 8-10 10-12 12-14 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 20.8 25.6 19.6 22.6 25.4 22.6 18.4 22.8 22.8 24.4 21.3 26.7 25.3 24.1 23.3 21.1 25.1 24.3 27.6 27.3 22.7 23.9 21.9 23.5 18.9 21.9 26.9 20.6 21.6 23.9 26.1 21.9 19.1 21.8 21.1 23.6 20.5 17.7 19.9 20.3 20.6 19.8 17.1 20.9 20.1 26.4 19.1 21.3 25.9 22.8 19.9 24.6 24.5 23.8 17.7 19.5 22.3 22.6 23.3 20.6 22.7 21.8 20.4 21.6 23.8 22.0 25. 1 28. 8 20. 9 24. 8 32. 1 26. 9 23. 0 27. 1 22. 5 29. 8 21. 7 18. 4 23. 4 23. 0 18. 0 25. 3 23. 8 25. 1 20. 9 30. 2 27 . 0 24. 2 26.9 25.9 21.3 25.6 33.9 26.4 25.2 27.8 24.0 28.2 19.6 23.3 25.9 23.9 20.1 22.8 25.6 27.6 31.4 31.2 29.2 27.8 GROUP MEAN c? n <3 f. N 23.5 2.39 0.51 22 21.3 2.40 0.51 22 22.1 2.22 0.47 22 24.6 3.65 0.78 22 26.1 3.57 0.76 22 14-16 26.3 25.4 24.3 27.3 35.0 25.9 26.0 31.8 30.3 32.3 21.4 32.9 31.4 28.4 26.1 26.0 25.6 29.5 30.3 30.5 29.8 28.4 3.28 0.70 22 DuPont-10157 16-18 33.1 31.X 30.3 31.2 38.6 33.8 33.3 38.1 30.7 37.3 33.2 31.0 31.1 29.1 28.5 28.3 30.7 27.7 30.6 32.1 31.9 30.0 31.9 2.96 0.63 22 0|*lPai 95 arn rSQA CBf Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP III: 200 MG/KG/DAY ANIMAL NUMBER 18-21 DAYS OF GESTATION 6-21 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 30.3 26.5 31.2 27.7 26.9 23.3 28.9 26.1 31.8 32.0 30.3 26.9 24.9 24.8 34.1 29.9 30.4 27.2 37.7 30.6 21.9 22.1 28.7 25.3 27.6 26.2 26.5 25.4 21.7 22.5 23.2 23.4 26.9 25.2 29.3 26.1 29.3 26.4 30.9 28.2 29.6 26.9 23.7 25.3 GROUP MEAN S.D. S.E. N 28.4 3.88 0.83 22 26.3 2.46 0.52 22 DuPont-10157 Company Sanitized. Does no! contain TSCA C B l 96 Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 4-6 6-8 8-10 10-12 12-14 670971 17.0 15.8 28.1 10.9 28.4 670973 (SE) 670977 670982 570991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 20.2 24.4 24.5 24.1 23.2 27.9 21.6 27.3 25.9 25.3 22.9 26.8 14.9 12.8 20.1 20.6 17.3 20.8 14.3 24.8 24.5 23.1 9.7 31.4 1.1 14.4 17.2 25.1 20.8 22.4 2.0 21.6 24.5 20.9 22.6 20.1 7.1 28.3 28.3 27.6 21.8 26.1 0.5 28.3 22.8 25.5 17.7 11.9 -- 30.7 25.2 29.6 25.0 29.3 -- 22.8 23.9 22.7 17.0 27.6 671021 (SE) 671022 671023 26.2 25.0 19.8 33.4 29.6 17.7 4.5 22.6 21.1 10.3 13.7 26.2 17.3 671041 (SE) 671046 671047 671051 (R) 671053 (FD) 671057 22.0 20.0 20.5 29.4 28.3 25.1 16.0 17.8 12.6 15.8 22.7 19.1 0.0 18.3 23.5 17.8 22.8 19.7 23.6 13.2 0.9 5.2 19.4 27.4 29.5 8.3 0.2 30.8 GROUP MEAN S.D. S.E. tf 24.0 3.20 0.68 22 19.8 6.18 1.32 22 17.8 8.21 1.75 22 17.2 9.34 2.09 20 23.4 8.18 1.93 18 14-16 30.8 30.7 28.8 31.6 24.3 29.0 30.3 26.1 24.1 23.9 34.4 33.0 18.2 23.8 24.8 22.1 0.1 32.7 26.0 7.82 1-84 18 DuPont-10157 16-18 38.8 37.1 37.4 31.1 29.4 35.1 38.5 32.6 31.7 28.4 34.9 31.4 28.3 18.4 25.9 17.1 -- 29.7 30.9 6.26 1.52 17 Company Sanitized. Does not contain TSCAC 97 Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER 18-21 DAYS OF GESTATION 6-21 670971 670973 (SE) 670977 670982 670991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 671021 (SE) 671022 671023 671041 (SE) 671046 571047 671051 (R) 671053 (FD) 671057 33.0 -- 30.8 33.3 33.4 23.1 18.6 -- 29.2 26.1 28.6 19.2 23.8 -- 18.8 16.6 -- 22.6 25.7 10.8 -- 23.9 27.0 -- 26.7 27.6 28.7 23.1 25.4 -- 28.0 25.8 25.4 19.8 26.1 -- 24.2 18.8 -- 21.8 22.4 13.1 -- 25.0 GROUP MEAN S.D. .E. 24.6 6.44 1.56 17 24.1 3.97 0.96 17 DuPont-10157 23 CQ Com oaw Sanitized. Does not cnntzin tsca C8f eveiopmental Toxicity Study in Rats DuPont-10157 APPENDIX F Individual Reproductive Data Comnnv SanWrerl. Ti,C4 CB* developmental Toxicity Study in Rats Individual Reproductive Data Explanatory Notes Note Nidations = Implantations Abbreviations = No Data S.E. = Standard Error N = Number in Group NP = Not Pregnant FD = Found Dead SE = Sacrificed in extremis R = Litter totally resorbed DuPont-10157 GotflPan* S' ed- poe* no' staintSCA C& 100 ) Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL CORPORA NIDA- NUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL i EARLY LATE DEAD FETUSES 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 MEAN S.E. V(30) N N(a0 Ooa3Ot IP oo3 . 5' otf) > 03 18 16 13 17 13 15 16 19 15 16 16 16 16 14 15 17 15 16 13 15 18 17 15.7 0-34 22 17 15 13 16 13 15 15 17 15 15 16 16 14 13 12 14 14 13 12 14 17 17 14.7 0.34 22 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.,0 0..05 22 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0..0 0..05 22 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.,0 0..00 22 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0,.0 0..00 22 101 Company LIVE FETUSES MEAN FETAL TOTAL FEMALE MALE WEIGHT (G) 17 15 13 16 13 15 15 16 15 15 16 16 14 13 12 14 14 13 12 14 17 17 14..6 0..33 22 98 96 67 5 11 58 78 87 10 6 87 96 79 97 10 4 67 66 86 10 4 76 48 77 89 6 11 7..5 7.2 0..37 0.38 22 22 5.21 6.02 5.31 5.86 5.69 5.66 5.71 5.78 5.30 5.94 5.28 4.94 6.05 5.64 5.65 5.22 5.57 5.14 5.73 5.72 5.61 5.14 5.55 0.07 22 DuPont-10157 C om ply GROUP II: 50 MG/KG/DAY ANIMAL CORPORA NIDANUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL EARLY LATE DEAD FETUSES LIVE FETUSES MEAN FETAL TOTAL FEMALE MALE WEIGHT (G) 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008(NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 15 14 16 16 16 13 21 20 17 12 16 11 16 15 13 20 14 23 14 18 15 MEAN S.E. tW9fi N rt* S' & Q 16..0 0. 66 21 15 0/ 14 0 16 0 15 2 15 2 12 0 14 0 17 1 15 . 3 12 0 14 0 11 3 13 0 13 0 13 0 12 0 12 0 14 1 14 2 16 0 14 0 13.9 0.34 21 0..7 0..23 21 0 0 0 2 2 0 0 1 3 0 0 3 0 0 0 0 0 1 2 0 0 0.7 0.23 21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0 0.00 21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0 0.00 21 15 14 16 13 13 12 14 16 12 12 14 8 13 13 13 12 12 13 12 16 14 13.2 0.39 21 87 86 10 6 85 67 66 77 79 75 75 95 53 58 67 10 3 57 48 76 84 97 95 7.2 6 . 0 0.37 0.35 21 21 5.63 5.33 5.33 5.71 5.83 6.28 5.59 5.17 5.60 5.90 5.99 5.63 5.47 5.68 5.67 5.90 5.68 5.19 6.07 5.79 5.38 5.66 0.06 21 9o a o % o13-a-4t > 102 D u P on t-10157 evdopmental Toxicity Study in Rats Oo 3o 1 tfl I oo GROUP III: 200 MG/KG/DAY ANIMAL CORPORA NIDANUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS DEAD TOTAL EARLY LATE FETUSES 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 MEAN S.E. N 16 16 13 18 17 28 18 14 16 19 10 17 16 18 14 14 17 14 15 13 14 16 16.0 0.73 22 16 1 15 0 13 0 14 1 13 0 14 3 16 0 14 0 13 2 17 0 10 0 15 0 13 0 15 0 12 0 11 0 15 0 14 0 15 1 13 0 13 0 14 0 13.9 0.4 0.35 0.17 22 . 22 1 0 0 1 0 3 0 0 2 0 0 0 0 0 0 0 0 0 1 0 0 0 0.4 0.17 22 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0 0.00 27 o o o o o o o o o o o o o o o o o o o o o 0 0.0 DO0.00 l8*U 3 (OIt > CL 103 LIVE FETUSES MEAN FETAL TOTAL FEMALE MALE WEIGHT (G) 15 15 13 13 13 11 16 14 11 17 10 15 13 15 12 11 15 14 14 13 13 14 13.5 0.38 22 87 10 5 94 94 76 74 6 10 4 10 47 89 55 4 11 76 96 93 47 96 59 86 58 67 68 6. 8 6.7 0.42 0.46 22 22 5.91 6.17 5.77 5.86 6.21 4.98 6.05 6.40 5.83 6.07 6.29 5.45 5.25 5.29 5.58 5.48 5.18 6.16 5.82 6.08 5.54 5.64 5.77 0.08 22 ) DuPont-10157 developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL CORPORA NIDANUMBER LUTEA TIONS 670971 670973(SE) 670977 670982 670991 671001 671004 671005(SE) 671006 671011 671013 671014 671018 671021(SE) 671022 671023 671041(SE) 671046 671047 671051(R) 671053(FD) 671057 MEAN S .E. N 15 15 17 15 19 15 22 19 12 14 19 17 14 *.. 14 14 16 16 16.1 0.65 16 15 14 14 14 16 14 17 17 10 12 18 15 14 13 10 1 14 14.2 0.56 16 INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL EARLY LATE DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 0 0 0 1 0 1 3 1 0 0 1 0 0 0 0 1 0 0.4 0.20 16 0 0 0 1 0 1 3 1 0 0 0 0 0 0 0 1 0 0.4 0.20 16 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0.1 0.06 16 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0 0.00 16 15 14 14 13 16 13 14 16 10 12 17 15 14 13 10 0 14 13.8 0.49 16 96 77 86 94 6 10 76 4 10 88 55 66 7 10 10 5 77 58 37 00 68 6.7 7.1 0.47 0.46 16 16 5.40 5.68 5.70 5.49 5.54 4.95 5.92 5.25 5.87 5.16 5.00 4.98 4.29 5.49 5.94 5.71 5.40 0.11 16 DuPont-10157 9 (/> o > Developmental Toxicity Study in Rats DuPont-10157 APPENDIX G Gross Postmortem Findings Company Sanitized. Does not contain TSCA CBJ 105 Developmental Toxicity Study in Rats Gross Postmortem Findings Explanatory Notes Abbreviations = No Data NAD = No Abnormalities Detected NP = Not Pregnant FD = Found Dead SE = Sacrificed in extremis R = Litter totally resorbed DuPont-10157 Company Sanitized. Does not contain TSCA GBI Developmental Toxicity Study in Rats Group I: Omg/kg/day Animal Number 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 GROSS POSTMORTEM FINDINGS StructureCs) 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-10157 Company Sanitize* Dobs m* contain TSCACgl 107 'evelopmental Toxicity Study in Rats Group II: 50mg/kg/day Animal Number 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 (NP) 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 GROSS POSTMORTEM FINDINGS Structurefs) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- Findingfs) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD - NAD NAD NAD NAD NAD DuPont-10157 Company Sanitized. Does not coidain TSGACS1 108 >evelopmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS Group HI: 200mg/kg/day Animal Number 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 671036 671037 671038 671040 671049 Structured) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- 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-10157 Companys'18" 4 109 fSCA CBl evelopmental Toxicity Study in Rats DuPont-10157 GROSS POSTMORTEM FINDINGS Group IV: 500mg/kg/day Animal Number 670971 670973 (SE) 670977 670982 670991 671001 671004 671005 (SE) 671006 671011 671013 671014 671018 6 7 1 0 2 1 (SE) 671022 671023 671041 (SE) 671046 671047 671051 (R) 671053 (ED) 671057 Structure(s) -- Lungs -- -- -- -- Kidney Liver Lungs Kidney -- -- -- -- -- -- -- Kidney -- -- -- -- -- F in d in g fs ) NAD Discoloration - several areas Black, raised, 1-5 mm diameter NAD NAD NAD NAD Pale, bilateral Discoloration dark Discoloration dark, diffuse Pale, bilateral NAD NAD NAD NAD NAD NAD NAD NAD Pale, bilateral NAD NAD NAD NAD NAD Company SsnH iz^ Does "o* contain TSCACSI evelopmental Toxicity Study in Rats DuPont-10157 APPENDIX H Individual Fetal Weights and Alterations 0 omP -yS aniifeK tQ o e s not contain tsca cbi ill developmental Toxicity Study in Rats Individual Fetal Weights and Alterations DuPont-10157 Explanatory Notes For ease of recording, many of the findings have been abbreviated or coded, as listed below: ar bil cen It lu NAD rt th -- = arch(es) = bilateral = centrum or centra = left = lumbar = No Abnormalities Detected = right = thoracic = No Data * Subcutaneous hemorrhage that was not present in utero. Renal papillary sizes refer to papillary development using the scheme of Woo and Hoar.fl 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. Supraoccipital 13. Hyoid a W oo, 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. Company SanHizetf. Doeg not 112 cei >evelopmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIFICATION 670974 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 670981 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.11 5.43 5.18 5.73 4.97 5.72 5.11 4.74 4.29 5.40 5.03 5.32 5.42 5.44 4.97 5.39 5.38 Rib Rib Rib Rib 5.91 6.02 5.83 5.73 6.20 6.52 6.59 6.53 5.74 6.54 6.27 5.45 5.90 5.22 5.80 Vertebra Vertebra Vertebra Supernumerary ( s it e 14 b il) Supernumerary ( s it e 14 b il) NAD NAD NAD NAD NAD NAD Supernumerary ( s it e 14 rt) Supernumerary ( s it e 14 b il) NAD NAD NAD NAD NAD NAD NAD Retarded O ssifica tio n (cen th ll) , NAD Retarded O ssification (cen thl2) NAD NAD NAD NAD NAD NAD NAD Retarded O ssification (cen th ll) NAD NAD NAD NAD DV DV DV DV VR VR VR Corner*,, ^^odLDoes *>**> TSCA c 113 I evelopmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) 670985 1 2 3 4 5 6 7 8 9 10 11 12 13 670986 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.29 5.42 5.76 5.17 5.25 5.29 5.33 5.05 5.46 5.22 5.11 5.21 5.48 Skull Skull 5.37 5.82 5.83 5.88 5.79 6.11 6.07 5.75 5.48 6.25 5.87 5.64 6.14 6.04 Vertebra Vertebra Vertebra Vertebra Pelvis Skull NAD NAD NAD NAD NAD Retarded O ssification (6,7,8 bil) NAD NAD NAD Retarded O ssification (6,7 b il) NAD NAD NAD NAD Retarded O ssification (cen thlO) Retarded O ssification (cen th 9,12) Retarded O ssification (cen th ll) Retarded O ssification . (cen thl2) NAD NAD NAD NAD NAD NAD Retarded O ssification (pubis It) Retarded O ssification (6,7,8 b il) NAD NAD DuPont-10157 CLASSIFICATION VR VR VR VR VR VR VR VR Company Sanitised. Does not contain TSCA CBI 114 evelopmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY DAM #/, FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIFICATION 670986 (Cont.) 15 6.07 16 5.69 Skull 670987 1 2 3 4 5 6 7 8 9 10 11 12 13 670989 1 2 3 4 5 6 7 8 9-.....10 5.70 5.67 5.88 5.60 5.70 6.53 5.57 5.67 5.53 5.52 5.22 5.78 5.60 Skull Skull Rib Vertebra Skull 5.97 6.08 5.46 5.97 6.09 5.68 5.43 5.69 5.97 5.22 Vertebra Sternebra Vertebra Sternebra Vertebra Rib NAD Retarded O ssification (6,7,8 b il) VR NAD Retarded O ssification (12,-2 b il) NAD NAD NAD Retarded O ssifica tio n (6 b il) Supernumerary (s ite 14 It) NAD NAD NAD Retarded O ssification (cen thl0,12) Retarded O ssification (6 rt) NAD VR VR DV VR VR NAD NAD Retarded O ssification (cen thl2) NAD NAD Retarded O ssification (6) Retarded O ssification (cen thl3) Retarded O ssification (6) Retarded O ssification (cen thl2) NAD Supernumerary (s ite 14 It) NAD VR VR VR ST VR DV Company Sanitized. Doe , woes not contain T5CA CSI 115 'evelopmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIF ICATION 670989 (Cont.) 11 5.53 12 5.87 13 4.85 14 5.86 15 5.26 Kidney Sternebra 670994 1 2 6.09 Kidney 6.09 Skull Vertebra 3 5.74 Vertebra 4 5.57 Skull 5 5.81 Vertebra 6 6.13 Vertebra 7 5.43 Kidney Vertebra 8 5.52 Skull 9 5.49 Vertebra 10 5.77 Skull 11 5.63 12 5.65 Skull 13 5.83 Kidney 14 5.44 Skull Vertebra 15 5.52 670998 1 2 5.80 5.51 Papilla - Size 3 (bil) NAD Retarded O ssification (6) NAD NAD VR VR Small Papilla - Size 2 (b il) Retarded O ssification (2 b il) Retarded O ssification (cen th ll) Retarded O ssification (cen th ll-1 2 ) Retarded O ssification (1,12;2 b il) Retarded O ssification (cen th.10-12) Retarded O ssification (cen th ll) Papilla - Size 3 (It) Retarded O ssification (cen th ll-1 2 ) Retarded O ssification (2 b il) Retarded O ssification (cen thl0-12) Retarded O ssification (2 b il) NAD Retarded O ssification (12;2 b il) Small Papilla - Size 2 (b il) Retarded O ssification (2 b il) Retarded O ssification (cen th ll-1 2 ) NAD VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR NAD NAD C o if in g Smtff Does 116 evelopmentalToxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY dam #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIFICATION 570998 (Cont.) 3 6.22 4 6.26 5 6.18 5 5.54 7 5.67 8 5.85 9 5.55 10 5.83 11 5.91 12 5.63 13 5.53 14 5.46 15 5.72 16 5.88 Skull Rib Kidney Rib 570999 1 4.88 Vertebra 2 5.61 3 5.43 4 4.89 5 5.26 6 5.72 Skull 7 5.51 Kidney 8 5.15 9 5.40 Vertebra 10 5.40 11 5.13 12 5.14 13 4.9-8 14 5.61 15 5.34 671002 1 6.15 NAD NAD NAD NAD NAD Retarded O ssification (2 It) NAD NAD NAD Supernumerary (s ite 14 It) Small Papilla - Size 1 (It) NAD Supernumerary ( s it e 14 It) NAD VR DV VR DV Retarded O ssification (cen thl2) NAD NAD NAD NAD Retarded O ssification (6 b il,8 rt) Papilla - Size 3 (rt) NAD Retarded O ssification (cen thl2) NAD NAD NAD NAD NAD NAD VR VR VR VR NAD contain TSCAcSf 117 developmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIFICATION 671002 (Cont.) 2 6.67 Skull 3 6.29 Vertebra 4 5.81 Skull Vertebra 5 5.52 6 6.18 Skull 7 5.98 Kidney 8 5.90 Skull 9 5.76 10 6.40 Skull Vertebra 11 5.24 Kidney Rib Vertebra 12 5.95 13 5.37 14 6.18 Skull Vertebra 15 5.65 Vertebra 571007 1 2 3 4 5 6 7 5.74 5.53 5.56 5.70 5.52 5.68 5.53 Kidney Vertebra Retarded O ssification (2 b il) Retarded O ssification (cen th 11,13) Retarded O ssification (2 b il) Retarded O ssification (cen th ll) NAD Retarded O ssification (1,12,-2,6 b il) Small Papilla - Size 2 (rt) Retarded O ssification (1;2 b il) NAD Retarded O ssification (1;2 b il) Retarded O ssification (cen th ll) Small P apilla - Size 1 (b il) Supernumerary (short 14 rt) Retarded O ssification (cen th9~13) NAD NAD Retarded O ssification (2 b il) Retarded O ssifica tio n (cen th ll) Retarded O ssification (cen th ll-1 3 ) VR VR VR VR VR VR VR VR VR VR DV VR VR VR VR NAD NAD Papilla - Size 3 (rt) NAD Retarded O ssification (cen thl2) NAD NAD VR VR r>ofCompany Sanitized. D oes contain TSCA Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) 671007 (Cont.) 8 4.10 Sternebra Vertebra 9 3.50 Sternebra 10 5.29 11 5.45 12 4.80 13 5.21 14 5.61 15 5.65 16 5.62 671015 1 2 3 4.79 4.84 4.78 Vertebra 4 5.38 5 4.98 6 5.09 7 4.84 8 4.66 9 5.30 10 4.14 11 5.32 12 4.46 13 5.01 14 5.61 15 4.97 16 4.89 671017 1 2 3 4 5 6 5.35 Kidney 5.87 5.79 6.45 6.15 5.89 Retarded O ssification (6) Retarded O ssification (cen thl2) Retarded O ssification (6) NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded O ssification (cen thl2) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Papilla - Size 3 (rt) NAD NAD NAD NAD NAD DuPont-10157 CLASSIF ICATION VR VR VR VR VR Company SanHfced. Does not contain TSCA CBI 119 6 evelopmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) 671017 (Cont.: 7 6.17 8 5.97 9 6.11 10 6.57 11 6.18 12 5.89 13 5.92 14 6.33 671031 1 2 3 4 5 6 7 8 9 10 11 12 13 5.64 5.19 5.79 6.08 5.86 5.78 4.94 5.53 5.85 5.18 5.79 5.98 5.66 671033 1 2 3 4 5 6 7 8 9 10 11 12 5.62 5.15 5.37 5.45 5.78 6.16 5.78 5.84 5.80 5.71 5.62 5.48 Rib Kidney Rib NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Supe: NAD NAD NAD NAD NAD NAD NAD NAD Papi] Supei DuPont-10157 CLASSIF ICATION DV VR DV Company Sanitized. D oes not contain TSCA CBi 120  evelopmental Toxicity Study in Rats ALTERATIONS IN INDIVIDUAL FETUSES GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) DuPont-10157 CLASSIFICATION 671035 1 2 3 4 5 6 7 8 9 10 11 12 13 14 671039 1 2 3 4 5 6 7 8 9 10 11 12 13 14 671042 1 2 3 4 4.95 5.64 5.31 5.21 4.94 5.13 5.44 4.72 5.44 5.26 5.36 5.53 5.15 5.01 Rib Stemebra Rib 5.33 5.93 5.67 5.57 5.42 5.51 5.54 5.72 5.60 5.59 5.66 5.27 5.74 5.37 Rib 5.14 Vertebra 5.49 5.13 Vertebra 5.31 Supernumerary (s ite 14 rt) NAD NAD NAD NAD NAD NAD Retarded O ssification (6) NAD NAD NAD Supernumerary (s ite 14 rt) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary (s ite 14 b il) Retarded O ssification (cen thl2) NAD Retarded O ssification (cen t h l0 ,ll) NAD DV VR DV DV VR VR TSC C8I 121 'evelopmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIF ICATION 671042 (Cont.) 5 5.60 Lung 6 5.20 7 5.25 8 4.79 9 5.03 10 5.23 Vertebra 11 4.96 12 4.26 13 5.38 671044 1 2 3 4 .5 6 7 8 9 10 11 12 5.72 5.94 5.58 5.94 5.75 5.83 5.40 5.61 6.24 5.50 5.41 5.88 Rib Rib Rib Rib 671045 1 2 3 4 5 6 7 8 9 10 11 5.26 5.67 5.95 5.84 5.86 6.10 5.32 5.84 6.10 5.59 5.86 Rib Rib Rib Colored {rt lobe, tan, 1mm dia) NAD NAD NAD NAD Retarded O ssification (cen th ll) NAD NAD NAD N VR NAD NAD NAD Supernumerary (short 14 b il) Supernumerary (s ite 14 b il) Supernumerary (s ite 14 b il) NAD NAD NAD Supernumerary (s ite 14 b il) NAD NAD DV DV DV DV NAD Supernumerary (s ite 14 It) NAD Supernumerary (s ite 14 b il) Supernumerary (s ite 14 It) NAD NAD NAD NAD NAD NAD DV DV DV Company S a n i t y - DoesnOTC tscacbi 122 evelopmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) CLASSIF ICATION 671045 (Cont.) 12 5.49 13 5.26 14 5.94 671054 1 2 5.69 5.66 Vertebra 3 5.48 4 5.73 Vertebra 5 5.54 6 5.94 7 5.75 8 5.75 9 5.34 Rib 10 5.31 11 5.28 Rib 12 5.79 13 5.31 14 5.46 Vertebra 15 5.68 Rib Vertebra 16 5.94 Rib 17 5.71 Kidney 671055 1 2 3 4 5 6 4.98 5.23 5.03 4.90 5.24 4.94 Skull Vertebra 7 5.21 NAD NAD NAD NAD Retarded O ssification (cen thlO) NAD Retarded O ssification (cen thl3) NAD NAD NAD NAD Supernumerary ( s it e 14 It) NAD Supernumerary ( s it e 14 rt) NAD NAD Retarded O ssification (cen th 9 ,ll) Supernumerary ( s it e 14 It) Retarded O ssification (cen thl3) Supernumerary ( s it e 14 It) Small Papilla - Size 2 (rt) NAD NAD NAD NAD NAD Retarded O ssification (2 It) Retarded O ssification (cen th ll) NAD VR VR DV DV VR DV VR DV VR VR VR OoMnm n"' TSCACBI Com pany Sa""1" 4 123 Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) 671055 (Cont.) 8 5.28 9 5.20 10 5.42 11 5.03 12 5.14 13 5.61 14 5.54 15 5.11 16 5.20 17 4.40 NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-10157 CLASSIFICATION Company Sanitized. D ees not contain TSCA CBI 124 developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670975 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 670976 1 2 3 4 5 6 7 8 9 10 11 12 1314 5.30 5.64 5.79 5.46 5.95 5.32 5.64 5.70 5.15 5.35 5.47 5.86 6.10 5.45 6.29 Stemebra Vertebra Vertebra Skull Vertebra Vertebra 6.05 5.07 5.77 5.47 5.32 5.80 6.09 4.04 5.14 4.61 5.29 5.53 4.98 5.41 Vertebra Vertebra Skull Skull Kidney NAD Retarded O ssification NAD Retarded O ssifica tio n <cen t h l l , 12} Retarded O ssification (cen thl2) NAD NAD Retarded O ssifica tio n NAD NAD Retarded O ssification (cen th ll) NAD NAD NAD Retarded O ssification (cen thlO) (6) (5b il) VR VR VR VR VR VR NAD NAD NAD Retarded O ssification (cen thl2) NAD Retarded O ssification (cen th ll) NAD Retarded O ssification NAD Retarded O ssification NAD NAD Papilla - Size 3 (rt) NAD VR VR (2b il) VR (2 b il) VR VR Company Sanitized. Does not contain TSCACBI 125 evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670978 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 670980 1 2 3 4 5 6 7 8 9 10 11 12 13 670984 1 2 3 4 5 5.67 5.72 5.21 5.82 5.41 5.64 5.39 5.28 4.87 5.27 5.14 4.37 5.27 5.07 5.86 5.29 5.83 5.87 5.59 6.10 6.12 5.27 5.50 5.36 5.89 5.89 5.68 5.43 5.65 Rib Rib Skull 5.38 5.87 5.88 5.36 5.66 NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary (s ite 14 b il) NAD Supernumerary ( s it e 14 b il) Retarded O ssification (6 rt) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DV DV VR not contain TSCA CB1 Company Sanitteed - Does 126 'evelopmental Toxicity Study in Rats DuPont-10157 f ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 670984 (Cont.) 6 6.11 7 5.92 8 5.83 9 6.05 Rib Vertebra 10 5.72 11 5.76 12 6.20 13 6.11 670990 1 2 3 4 5 6 5.99 6.49 6.67 Kidney 5.96 6.12 5.77 Skull 7 6.43 8 6.57 9 6.53 10 5.99 Skull 11 6.50 12 6.38 Rib 670993 1 2 3 5.47 5.41 6.11 Vertebra 4 5.52 5 5.57 6 5.60 7 5.74 Kidney 8 4.48 Skull 9 5.79 NAD NAD Supernumerary (s ite 14 rt) Retarded O ssification (cen th ll) NAD NAD NAD NAD NAD NAD Papilla - Size 3 (bil) NAD NAD Retarded O ssification (1; 2,6 b il) NAD NAD NAD Retarded O ssification (2,6 b il) NAD Supernumerary (short 14 b il) NAD NAD Retarded O ssification (cen thl2) NAD NAD NAD Papilla - Size 3 (rt) Retarded O ssification (2 b i l ; 1) NAD DV VR VR VR VR DV VR VR VR Sanitized. Does not conte'1TSCACBI Company 127 'evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 570993 (Cont.) 10 5.94 11 5.96 12 6.16 13 5.21 14 5.27 Skull Rib Skull 671000 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 67,1003 1 2 3 4 5 6 7 8 9 10 11 5.65 5.25 5.24 4.90 4.97 4.64 5.02 4.90 5.05 5.19 5.32 5.08 5.53 5.14 5.65 5.21 Stemebra Skull 5.97 5.64 5.57 5.24 5.63 5.68 4.91 6.27 5.57 5.91 5.47 NAD NAD Retarded O ssification (2 b i l ;1) Supernumerary (s ite 14 b il) Retarded O ssification (2 ,6 ,7 ,8 b i l ; 1) NAD NAD NAD NAD . NAD Retarded O ssification NAD NAD NAD NAD NAD Retarded O ssification NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD VR DV VR ,d 00* no' a* *SC* 128 /""V Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671003 (Cont.) 12 5.34 671012 1 2 3 4 5 6 7 8 9 10 11 12 6.16 6.62 5.64 6.28 5.53 5.66 5.58 5.87 5.98 6.01 5.64 5.87 Rib Kidney 671016 1 2 3 4 5 6 7 8 9 10 11 12 5.92 6.64 6.07 5.96 6.13 5.75 5.56 Rib 5.61 5.80 6.08 6.08 6.17 Skull 13 6.13 14 5.96 671019 1 2 5.65 5.74 Skull NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary ( s it e 14 b il) NAD Papilla - Size 3 (bil) NAD DV VR NAD NAD NAD NAD NAD NAD Supernumerary (s ite 14 It) NAD NAD NAD NAD Retarded O ssifica tio n (2 b il; l ) NAD NAD DV VR NAD Retarded O ssifica tio n (2 b il) VR 129  evelopmental Toxicity Study in Rats ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) DuPont-10157 CLASSIF ICATION 571019 (Cont.) 3 5.50 4 6.31 5 5.10 6 5.61 7 5.52 8 5.60 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra 671020 1 2 3 4 5 6 7 8 9 10 11 12 13 671025 1 2 3 4 5 - 6..... 7 8 5.03 5.98 5.57 5.71 5.60 5.74 5.48 5.05 5.24 5.38 4.84 5.50 6.03 Rib 5.62 5.83 Skull 6.07 5.72 5.55 Kidney 5.85 5.56 4.66 Retarded O ssification (cen thlO-12) Retarded O ssification (cen thlO-12) Retarded O ssification (cen th ll) Retarded O ssification (cen thl0-13) NAD Retarded O ssification (cen thlO-13) Retarded O ssification (cen thl0,12) VR VR VR VR VR VR NAD NAD NAD NAD NAD Supernumerary ( s it e 14 rt) NAD NAD NAD NAD NAD NAD NAD DV NAD Retarded O ssification (6 b il) NAD NAD Small Papilla - Size 2 (b il) NAD NAD NAD VR VR COtOPanY 130 tsc& cS' noteon*aVn  evelopmental Toxicity Study in Rats ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 571025 (Cont.) 9 5.76 10 5.59 11 5.30 12 6.55 13 5.75 671026 1 5.66 Vertebra 2 5.49 Skull Vertebra 3 6.03 4 6.38 Skull 5 5,5.1 6 5.14 Skull Vertebra 7 5.84 Vertebra 8 5.42 Skull 9 5.39 Vertebra 10 5.71 Rib Skull 11 5.87 Vertebra 12 5.49 Skull Vertebra NAD NAD NAD NAD NAD Retarded O ssification (cen th ll-12) Retarded O ssification (1,-2 b il) Retarded O ssification (cen th 8 ,11-12) NAD Retarded O ssification (1,12 ;2 b il) NAD Retarded O ssification (1,12;2 bil) Retarded O ssification (cen thlO-13) Retarded O ssification (cen thlD) Retarded O ssification (1,12,-2 b il ) Retarded O ssification (cen thl3) Supernumerary (s ite 14 lt ) Retarded O ssification (2 b i l , 8 l t , 12) Retarded O ssification (cen th ll-12) Retarded O ssification (1;2 b il) Retarded O ssification (cen thlO-13) DuPont-10157 CLASSIF ICATION VR VR VR VR VR VR VR VR VR DV VR VR VR VR Compaq 131 tscacbi not corrtain /"N 'evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671026 (Cont.) 13 5.75 Vertebra 671034 1 2 3 4 5 6 7' 8 9 10 11 12 671043 1 2 3 4 5 6 7 8 9 10 11 12 6.16 6.21 5.66 6.24 5.62 5.73 Subcutis 5.74 6.20 6.08 Rib 5.45 Rib 5.97 5.75 Rib 5.78 5.28 6.07 5.47 5.98 5.47 5.80 5.83 5.67 5.75 5.31 5.81 Vertebra Skull Skull Vertebra Vertebra Skull Kidney Skull Skull Retarded O ssification (cen th ll-12) VR NAD NAD NAD NAD NAD Hemorrhage (back*) NAD NAD Supernum erary ( s it e 14 b il) .Supernumerary ( s it e 14 It) NAD Supernumerary ( s it e 14 b il) N DV DV DV Retarded O ssification (cen thl2) Retarded O ssification (2 b il) NAD Retarded O ssification (1,12;2 b il) Retarded O ssification (cen thl2) Retarded O ssification (cen thlO) NAD Retarded O ssification (1;2 b il) Small Papilla - Size 2 (rt) Retarded O ssification (1,12) NAD Retarded O ssification (1,-2 b il) VR VR VR VR VR VR VR VR VR CompanysanffiiBdL Doe* not confa/n TSCA CB| 132 Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671048 1 2 3 4 5 6 7 8 9 10 11 12 13 5.46 4.93 5.13 5.51 4.90 4.77 5.16 4.98 5.49 5.47 5.24 5.51 4.93 Rib 671050 1 2 3 4 5 6 7 8 9 10 11 12 6.35 6.23 6.01 5.97 6.19 5.39 5.91 6.09 5.74 6.51 6.40 6.00 Rib Kidney 671052 1 5.75 Rib 2 6.21 3 5.49 1 4 5.66 5 6.01 Rib 6 5.80 7 5.82 8 5.86 Rib 9 6.14 Supernumerary ( s it e 14 It) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary ( s it e 14 It) NAD NAD Papilla - Size 3 (bil) NAD Supernumerary ( s it e 14 It) NAD NAD NAD Supernumerary ( s it e 14 It) NAD NAD Supernumerary ( s it e 14 It) NAD DV DV VR DV DV ' DV ,, ,,w tscac note Ssntti**. o oe s comp0* 133 'evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671052 (Cont.) 10 6.15 11 5.79 12 5.45 13 5.71 14 5.34 15 5.40 > 16 6.11 Rib Subcutis 671056 1 2 5.04 5.70 Skull Vertebra 3 5.63 Vertebra 4 5.63 Skull Vertebra 5 5.20 6 4.82 Rib Skull Vertebra 7 5.60 8 5.44 Skull 9 5.24 10 5.49 Skull 11 5.36 Vertebra 12 4.78 Skull 13 5.61 Supernumerary ( s it e 14 It) NAD NAD NAD NAD Hemorrhage (chin*) NAD NAD Retarded O ssification (1,12;2,3 b i l , 6 It) Retarded O ssification (cen th ll) Retarded O ssification (cen thl2) Retarded O ssification (1,12;2,3,6,7,8 b il) Retarded O ssification (cen thl2) NAD Supernumerary ( s it e 14 It) Retarded O ssification (1,12;2,3,6,7,8 bil) Retarded O ssification (cen thl2) NAD Retarded O ssification (1,12,2 bil) NAD Retarded O ssification (1,12;2 b il) Retarded O ssification (cen thl2) Retarded O ssification (1,12;2,3 bil) NAD DV N VR VR VR VR VR DV. VR VR VR VR VR VR g* c 134 developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671056 (Cont.) 14 5.73 Rib Skull Supermunerary (s ite l4 It) DV Retarded O ssification (2 b il) VR #* 135 0 evelopmental Toxicity Study in Rats ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) DuPont-10157 CLASSIFICATION 670970 I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 570972 1 2 3 4 5 6 7 8 9 10 11 5.99 4.97 6.14 5.43 5.97 5.62 6.00 5.99 5.98 5.68 5.12 6.45 6.10 6.06 6.10 Vertebra Skull Sternebra Vertebra Skull Rib Skull Vertebra Skull Skull Skull Vertebra 6.35 6.01 6.32 6.42 5.69 6.39 6.86 6.40 6.29 6.12 5.63 Retarded O ssification (cen th ll) Retarded O ssification (2,6,7,8 b ilfl) Retarded O ssification (6) Retarded O ssification (cen thl2) NAD NAD NAD Retarded O ssification (6 b il) NAD Supernumerary (short 13 rt) Retarded O ssification (2 ,b i l ;7 r t ;12) Retarded O ssification (cen th ll) Retarded O ssification (6 b i l , 1) NAD Retarded O ssification (6 b il) NAD Retarded O ssification (6 It) Retarded O ssification (cen thlO) VR VR VR VR VR DV VR VR VR VR VR VR NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD 136 evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670972 (Cont.) 12 6.14 13 6.11 14 5.58 15 6.31 670979 1 2 3 4 5 6 7 8 9 10 11 5.70 5.95 5.99 6.18 5.77 5.56 5.58 5.52 5.60 5.47 5.58 12 5.69 13 6.39 670983 1 2 3 4 5 6 7 8 9 10 11 12 13 5.47 5.73 5.74 5.54 5.72 5.20 6.25 5.67 6.11 6.26 6.04 6.29 6.22 670988 1 6.05 Rib Skull Rib Skull Vertebra Skull Rib Supernumerary ( s it e 14 It) NAD Retarded O ssification (2 b il) NAD DV VR NAD NAD NAD NAD NAD NAD Supernumerary (s ite 14 b il) NAD NAD Retarded O ssification (8 rt) Retarded O ssification (cen th ll) NAD NAD DV VR VR NAD NAD NAD NAD NAD Retarded O ssifica tio n i(2 b il) NAD Supernumerary ( s it e 14 It) - NAD NAD NAD NAD NAD VR DV NAD 10* 137 >evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670988 (Cont.) 2 6.13 3 6.66 4 6.33 5 5.71 6 6.23 7 6.41 8 6.06 9 6.30 10 6.58 11 6.40 12 5.65 13 6.24 Skull Skull Vertebra Skull Skull Vertebra Vertebra Vertebra Skull Vertebra 670992 1 2 3 4 5 6 7 8 9 5.37 5.13 4.52 5.20 5.15 5.01 5.08 4.39 5.25 Rib Skull Skull Rib Vertebra Retarded O ssifica tio n (6 b il) NAD Retarded O ssification (2,6,7,8 b il; 1,12) Retarded O ssification (cen thlO) NAD Retarded O ssification (2,6,7,8 bil) NAD Retarded O ssification (2,6 b il) Retarded O ssification (cen th ll) Retarded O ssification (cen thl0,12) Retarded O ssification (cen thlO,13) NAD Retarded O ssification (2,6,7,8 b il) Retarded O ssification (cen th ll) VR VR VR VR VR VR VR VR VR VR NAD NAD Rudimentary Cervical (7 rt) Retarded O ssifica tio n (6,7 It) NAD Retarded O ssification (6,7 b il) NAD NAD Rudimentary Cervical (7 rt) Retarded O ssifica tio n (cen th ll) DV VR VR DV VR XSCACSI t ,o t c o ^ a'n San' Oo5 138 >evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 670992 (Cont.) 10 4.71 Subcutis 11 4.96 670995 1 5.69 Vertebra 2 5.99 Skull 3 5.90 Vertebra 4 5.98 Skull 5 5.90 6 6.23 Skull 7 6.51 Kidney Vertebra 8 6.51 Skull 9 6.05 Vertebra 10 6.11 11 5.44 12 6.77 Skull Vertebra 13 5.19 Vertebra 14 5.90 Skull 15 6.06 16 6.63 Skull 670996 1 2 3 5.90 6.76 6.64 Hemorrhage (chin*) NAD Retarded O ssification (cen thl0,12) Retarded O ssification (1,12;2 b il;7 It) Retarded O ssification {cen thl2) Retarded O ssification (1;2 b il) NAD Retarded O ssification (2,6 bil) Papilla - Size 3 (rt) Retarded O ssification (cen th ll) Retarded O ssification (1) Retarded O ssification (cen th 9 -ll) NAD NAD Retarded O ssification {1 ?2 b il) Retarded O ssification (cen thlO,12) Retarded O ssification (cen th ll) Retarded O ssification (1,-2 b il) NAD Retarded O ssification (6 rt) NAD NAD NAD N VR VR VR VR VR VR VR VR VR VR VR VR VR VR ComrspaW 139 TSCA CB1 evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670996 (Cont.) 4 6.33 5 6.37 6 6.84 7 6.04 8 6.27 9 6.73 10 6.40 11 6.68 12 6.24 13 6.20 14 6.17 Rib Skull 670997 1 2 3 4 5 6 7 8 9 10 11 5.93 6.68 Rib 5.82 5.58 5.32 5.23 5.85 5.81 Skull 6.54 5.92 5.47 671009 1 2 3 4 5 6 7 8 9 1011 6.21 5.87 5.73 6.31 5.63 5.77 6.17 6.20 6.15 6.27 6.50 Skull Skull Rib | NAD NAD Supernumerary ( s it e 14 rt) NAD NAD NAD NAD NAD Retarded O ssification (6 b il) NAD NAD DV VR NAD Supernumerary ( s it e 14 b il) NAD NAD NAD NAD NAD Retarded O ssification (2 b il) NAD NAD NAD DV VR NAD Retarded O ssification (6 b il) NAD Retarded O ssification (1) NAD NAD NAD NAD NAD Supernumerary (s ite 14 rt) NAD VR VR DV Comoany SanW*ed. Does not contam t s c a c b i 140 evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671009 (Cont.) 12 6.29 13 6.28 14 5.77 Rib Skull Skull 15 5.46 16 6.30 Rib 17 6.24 671010 1 2 3 4 5 6 6.05 5.89 6.40 6.25 6.21 6.71 Vertebra 7 6.43 8 6.27 9 6.44 10 6.28 671024 1 2 5.31 4.85 Subcutis Skull 3 5.21 4 5.47 5 5.89 6 5.66 7 5.28 Rib 8 5.68 9 5.27 10 5.31 11 5.04 Supernumerary ( s it e 14 b il) Retarded O ssification (1) NAD Retarded O ssification (2,7 b i l ;1) NAD Supernumerary ( s it e 14 It) NAD NAD NAD NAD NAD NAD Retarded O ssification (cen th ll) NAD NAD NAD NAD NAD Hemorrhage (back*) Retarded O ssification (6,7 I t ; 1,12) NAD NAD NAD NAD Supernumerary (short 13 b il) NAD NAD NAD NAD DV VR VR DV VR N VR DV Comparjy Sanitized. Does not contain TSCA CBf 141 [Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY LAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671024 (Cont.) 12 5.74 13 5.33 14 5.48 15 6.17 671027 1 2 3 4 5 6 7 8 9 10 11 12 13 5.48 5.43 5.59 4.99 5.37 4.75 5.21 5.31 5.08 5.39 5.25 5.32 5.11 671028 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 5.47 5.42 5.16 5.38 5.66 5.08 5.81 5.75 5.29 5.05 5.27 4.67 4.63 5.29 5.39 Skull Kidney Skull Rib Rib Rib Subcutis Retarded O ssification (2,6 b i l ;1,12) Small Papilla - Size 2 (rt) Retarded O ssification (6 b il) NAD VR VR VR NAD NAD NAD NAD Supernumerary (s ite 14 b il) NAD NAD NAD NAD Supernumerary (s ite 14 b il) NAD Supernumerary (s ite 14 b il) NAD DV DV DV Hemorrhage (right shoulder*) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD N CewP80* fSCfcCBi Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 67X029 1 2 3 4 5 6 7 8 9 10 11 12 671030 1 2 3 4 5 6 7 8 9 10 11 671032 1 2 3 4 5 5.81 5.78 6.15 5.51 5.61 5.45 5.65 5.67 5.95 5.87 4.31 5.22 Rib Kidney Rib Rib Vertebra 5.57 5.49 5.71 5.97 5.14 5.23 6.06 5.28 5.17 5.06 5.59 Skull Rib Skull Vertebra 5.04 Vertebra 5.37 4.71 5.00 5.58 NAD NAD NAD Supernumerary (short 14 b il) Small Papilla - Size 1 (rt) Supernumerary (short 14 b il) NAD NAD Supernumerary (short 14 b il) NAD NAD NAD Retarded O ssification (cen thl2) DV VR DV DV VR NAD NAD NAD NAD NAD NAD NAD Retarded O ssification (6 b il) NAD Supernumerary (s ite 14 rt) Retarded O ssification (6 b il) Retarded O ssification (cen thl2) NAD VR DV VR VR Retarded O ssification (cen th9) NAD NAD NAD NAD VR 143 velopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671032 (Cont.) 6 5.07 7 5.72 8 5.28 9 4.81 10 5.37 11 4.99 12 5.06 13 4.88 14 5.32 15 5.44 Kidney Skull 671036 1 2 5.94 Kidney 6.49 Rib Vertebra 3 6.35 4 6.30 5 6.06 6 6.07 Rib 7 6.53 Rib 8 5.80 9 6.39 10 5.94 Rib Skull 11 6.00 12 6.14 Rib Skull 13 5.72 14 6.57 671037 1 2 3 4 5 6.12 6.14 5.97 5.93 5.96 NAD Papilla - Size 3 (bil) NAD NAD Retarded O ssification (6 b il) NAD NAD NAD NAD NAD VR VR Papilla - Size 3 (bil) Supernumerary (s ite 14 It) Retarded O ssification (cen thl2) NAD NAD NAD Supernumerary ( s it e 14 rt) Supernumerary ( s it e 14 b il) NAD NAD Supernumerary (s ite 14 b il) Retarded O ssification (6 It) NAD Supernumerary (s ite 14 It) Retarded O ssification (6,7 b i l ; 1) NAD NAD VR DV VR DV DV DV VR DV VR NAD NAD NAD NAD NAD "^onfam TSCACBf 144 evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 671037 (Cont.) 6 5.98 7 6.13 8 5.32 9 6.01 10 5.74 11 5.64 12 5.44 13 5.40 14 5.69 671038 1 5.86 Stemebra Vertebra 2 6.07 3 6.28 4 6.51 Vertebra 5 5.64 Rib Vertebra 6 6.38 Vertebra 7 6.08 Rib 8 6.19 Vertebra 9 5.67 Vertebra 10 6.34 Rib 11 5.66 12 5.92 Stemebra Vertebra 13 6.49 671040 1 2 6.06 6.05 NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded O ssification (6) Retarded O ssification (cen th 9 -ll) NAD NAD Retarded O ssification (cen th ll) Supernumerary ( s it e 14 lt ) Retarded O ssification (cen th ll) Retarded O ssification (cen thl3) Supernumerary ( s it e 14 lt ) Retarded O ssification (cen thlO) Retarded O ssification (cen th 8 ,10,11,13 lu i) Supernumerary ( s it e 14 lt ) NAD Retarded O ssification (6) Retarded O ssification (cen thl3) NAD NAD NAD CLASSIFICATION VR VR VR DV VR VR DV VR VR DV VR VR Company SaoiKjg^ D e S "0,M n,intS C A cB , 145 Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671040 (Cont.) 3 6.04 4 4.15 5 5.87 6 5.18 7 5.41 8 5.16 9 6.04 Rib Skull Rib Vertebra 10 5.03 Rib 11 5.82 Rib 12 5.92 13 5.33 671049 1 2 6.01 Rib 5.04 Skull 3 5.70 4 6.13 Skull 5 5.72 6 5.43 Skull Vertebra 7 5.50 8 5.84 Skull 9 6.00 Vertebra 10 5.51 Skull 11 5.59 Vertebra 12 5.98 Skull 13 4.97 Rib Supernumerary ( s it e 14 lt ) NAD NAD Retarded O ssifica tio n (6 b il) NAD NAD Supernumerary ( s it e 14 b il) Retarded O ssifica tio n (cen thl3) Supernumerary (s ite 14 lt ) Supernumerary ( s it e 14 b il) NAD NAD DV VR DV VR DV DV Supernumerary (s ite l4 b il) Retarded O ssification (1,12/2,3,6,7,8 bil) NAD Retarded O ssification (2 b il) NAD Retarded O ssifica tio n (1,12/2,3 b il; 6 rt) Retarded O ssification (cen th ll) NAD Retarded O ssification (1,12/2,3,6,7,8 b il) Retarded O ssification (cen thlO) Retarded O ssification (1,12 ;2 ,3 ,b i l ;6 rt) Retarded O ssification (cen thl2) Retarded O ssification (1,12;2,3,6 bil) Supernumerary (s ite l4 lt ) DV VR VR VR VR VR VR VR VR VR DV Company SanifeetL D oes a d e w M tlS C H 091 146 f*'**'' [Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP III: 200 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) 'CLASSIFICATION 671049 (Cont.) 14 5.55 Rib Skull Vertebra Supernumerary (s ite l4 rt) Retarded O ssification (1,12;2,3,6,7,8 bil) Retarded O ssification (cen thlO) DV VR VR Company Sanitized. Does not contain TSCA CBi 147 >evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 670971 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 670977 1 2 3 4 5 6 7 8 9 10 11 12 13 14 670982 1 2 3 5.48 5.40 5.65 5.32 5.43 5.49 5.36 5.27 5.68 5.28 5.17 5.26 5.43 5.16 5.56 Skull Skull Skull Skull Skull Skull 5.84 5.92 5.55 5.63 5.88 5.73 5.69 5.73 5.44 5.34 5.52 5.54 5.70 6.04 Skull Skull Skull 5.65 5.44 Skull 5.42 Rib NAD Retarded O ssifica tio n (6 lt ) NAD NAD NAD Retarded O ssification (6 b il) NAD Retarded O ssification (6 b il) NAD Retarded O ssification (6 rt) NAD Retarded O ssification (6 rt) NAD Retarded O ssification (6 lt ) NAD VR VR VR VR VR VR NAD Fused (1 to 12) ND Retarded O ssification (6, b i l ; 7,8 lt) NAD Retarded O ssification {2 b il) NAD NAD NAD NAD NAD NAD NAD NAD DV VR VR NAD Retarded O ssification (2 b il) Rudimentary Cervical (7 lt ) VR DV -omp 148 Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670982 (Cont.) 4 5.10 5 6.26 6 5.30 7 6.33 8 5.23 9 5.83 10 6.13 11 5.90 12 5.66 13 5.71 14 5.79 Rib Skull Rib Skull Rib Skull Skull Rib 670991 1 2 5.32 5.32 Skull Vertebra 3 5.80 4 4.99 Skull Vertebra 5 5.49 6 5.75 Skull 7 6.07 Rib Vertebra 8 6.01 Rib Skull 9 5.47 Pelvis 10 5.74 Skull 11 5.04 12 4.81 Supernumerary ( s it e 14 b il) Retarded O ssification (2 b il) Supernumerary (s ite 14 lt ) Retarded O ssification (2 b il) Supernumerary (short 14 b il) Retarded O ssification (2 b il) NAD Retarded O ssification (2 b il) NAD NAD Supernumerary ( s it e 14 lt ) NAD DV VR DV VR DV VR VR DV NAD Retarded O ssification (2,6,7 b il,-1,12) Retarded O ssification (cen th ll) NAD Retarded O ssification (2 ,6 ,7 ,8 b i l ; 12) Retarded O ssification (cen thlO ,11,12) NAD Retarded O ssification (6,7,8 b il) Supernumerary (s ite 14 b il) Retarded O ssification (cen t h l l , 12) Supernumerary ( s it e 14 rt) Retarded O ssification (6 b il) Retarded O ssification (pubis b il) Retarded O ssification (2 ,6 ,7 ,8 b i l ; 12) NAD NAD VR VR VR VR VR DV VR DV VR VR VR 0 mTM y s ^ . D ' M notconlslnT SQ ^ Bi 149 )evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 670991 (Cont.) 13 5.51 Vertebra 671001 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5.94 6.01 5.74 5.40 5.31 5.14 4.96 5.73 5.74 5.69 5.35 5.66 5.90 5.71 5.18 5.14 Skull Skull Skull Vertebra Vertebra 4 Skull Subcutis Vertebra Skull Rib Skull Rib Skull Skull 671004 1 2 4.90 5.01 Skull Retarded O ssification (cen th ll,1 2 ) VR NAD Retarded O ssification (2 b i l , 7 rt) NAD Retarded O ssification (2 b il) NAD Retarded O ssification (2 b il) Retarded O ssification (cen th ll-12) Retarded O ssification (cen th 9 -ll) Retarded O ssification (2,6,7 bil) NAD Hemorrhage (neck*) Retarded O ssification (cen th ll) NAD Retarded O ssification (2 b il) Supernumerary ( s it e 14 b il) Retarded O ssification (1;'2 b il) Supernumerary ( s it e 14 b il) Retarded O ssification (1,12;2 b il) Retarded O ssification (6,7,8 bil) VR VR VR VR VR VR N VR VR DV VR DV VR VR NAD Retarded O ssification (2,6,7,8 b i l ; 1,12) VR 9 0i'S*o1 ed 150 >evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671004 (Cont.) 3 4.74 4 4.94 5 4.60 6 5.15 7 5.21 8 4.88 9 5.16 10 5.16 11 4.82 12 4.63 13 5.21 Pelvis Sternebra Skull Rib Skull Pelvis Skull Pelvis Skull Pelvis Skull Pelvis 671006 1 2 3 4 5 6 7 8 9 10 11 6.24 5.84 6.01 5.44 6.38 6.20 5.24 6.49 5.71 5.53 5.38 Kidney Rib Retarded O ssification (pubis,ischium b il) Retarded O ssifica tio n (6) Retarded O ssification (2,6,7,8 b i l ; 1,12) NAD Wavy (7-10 r t , l l b il) Retarded O ssification (2,3,6,7,8 bil,-l) NAD Retarded O ssification (pubis,ischium b il) Retarded O ssification (2 ,3 ,6 ,7 ,8 b i l ; 1,12) NAD Retarded O ssification (pubis,ischium b il) Retarded O ssification (2 ,3 ,7 ,8 b i l ;1) Retarded O ssifica tio n (ischium b il) Retarded O ssification (2,3,6,7,8 b il; 1,12) Retarded O ssification (pubis,ischium b il) NAD NAD Small Papilla - Size 2 (b il) NAD NAD Supernumerary ( s it e 14 rt) NAD NAD NAD NAD NAD VR VR VR VR VR VR VR VR VR VR VR VR VR DV po>' s >VC<,o ^scfv 151 Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 671006 (Cont.) 12 5.75 13 6.29 14 6.34 671011 1 2 3 4 5 6 7 8" 9 10 11 12 5.01 5.28 5.65 5.46 5.61 5.17 5.58 4.59 5.38 5.28 5.29 5.10 Skull Rib Skull Kidney Kidney Skull 13 5.13 14 5.23 Skull 15 5.21 Kidney 16 5.05 671013 1 2 3 6.45 5.84 6.53 Vertebra 4 5.63 5 5.35 6 5.61 7 5.79 8 6.39 9 5.80 10 5.35 NAD NAD NAD NAD Retarded O ssification (6 b il) Supernumerary (s ite 14 rt) NAD NAD Retarded O ssification (6 b il) NAD NAD .Papilla - Size 3 (bil) NAD Papilla - Size 3 (bil) Retarded O ssification (6,7,8 bil) NAD Retarded O ssification (2,6,7,8 bil) Small Papilla - Size 1 (It) NAD VR DV VR VR VR VR VR VR NAD NAD Retarded O ssification (cen thlO) NAD NAD NAD NAD NAD NAD NAD VR 152 Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671014 1 2 3 4 5 6 7 S 9 10 11 12 671018 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 5.62 5.65 5.11 5.53 4.92 5.23 4.37 4.78 5.51 5.11 4.85 5.24 Rib Skull Rib Rib Skull Stemebra Kidney Subcutis Rib Rib Rib 5.17 4.83 4.99 5.66 5.22 4.80 4.13 4.66 5.12 5.12 5.30 5.08 5.07 5.06 4.83 5.12 4.85 Vertebra Rib Pelvis Rib Rib Skull Vertebra Rib Skull NAD Supernumerary ( s it e 14 It) Retarded O ssification (6 b il) NAD Supernumerary ( s it e 14 b il) Supernumerary ( s it e 14 rt)' Retarded O ssification (6 b il) Retarded O ssifica tio n (6) Small Papilla - Size 1 (rt, size3 It) Hemorrhage (back*) NAD Supernumerary (s ite 14 rt) Supernumerary ( s it e 14 It) Supernumerary (short 14 b il) DV VR DV DV VR VR VR N DV DV DV NAD Retarded O ssification (cen th ll) NAD NAD NAD NAD Supernumerary (short 14 It) .Retarded O ssification (pubis It) Supernumerary ( s it e 14 It) Supernumerary (short 14 It) Retarded O ssifica tio n (6 It) NAD NAD Retarded O ssification (cen thl2) NAD Supernumerary ( s it e 14 b il) Retarded O ssification (6 rt) NAD VR DV VR DV DV VR VR DV VR 00^ ' t>o .ed 3^ ,VC!o'**1 c$>' 153 i Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671022 1 2 3 4 5 6. 7 8 9 10 11 12 13 14 15 671023 1 2 3 4 5 6 78 9 5.16 5.19 5.06 4.82 5.00 4.99 4.87 4.93 5.06 5.03 4.52 5.34 4.74 4.69 5.35 Sternebra Skull Skull Sternebra Pelvis Skull Sternebra Skull Skull Rib Skull Skull Subcutis 4.62 4.35 4.86 4.13 3.94 4.09 4:16 4.01 4.11 Pelvis Rib Rib Sternebra Skull Sternebra Skull Retarded O ssification (6) Retarded O ssification (2,6 b il) NAD Retarded O ssification (2,6,7,8 b i l ;12,) Retarded O ssification (6) NAD Retarded O ssification (pubis b il) Retarded O ssification (2 b i l ; 1,12) Retarded O ssifica tio n (6) NAD Retarded O ssifica tio n (6 b il) NAD Retarded O ssification (2,6 b il) NAD Supernumerary ( s it e 14 rt) Retarded O ssification (6 b il) NAD Retarded O ssification (2,6,7,8 b i l ; 1,12) Hemorrhage (back*) VR VR VR VR VR VR VR VR VR DV VR VR N Retarded O ssification (pubis lt) Supernumerary ( s it e 14 b il) Supernumerary ( s it e 14 rt) Retarded O ssifica tio n (6) Retarded O ssifica tio n (6 lt ) Retarded O ssifica tio n (6) NAD NAD Retarded O ssifica tio n (6 b il) NAD VR DV DV VR VR VR VR g8*^ 154 C' y Developmental Toxicity Study in Rats ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) DuPont-10157 CLASSIF ICATION 671023 (Cont.) 10 4.17 11 4.74 12 4.34 13 4.36 14 4.14 Skull Rib Skull 671046 1 2 3 4 5 6 7 8 9 10 11 12 13 671047 1 2 3 4 56 7 6.23 5.00 5.60 5.82 5.23 4.72 5.98 4.93 5.72 5.39 5.46 5.80 5.50 Rib Skull Vertebra Rib Rib Skull Sternebra Rib Skull Skull 5.64 6.46 6.01 5.89 5.30 5.85 6.38 NAD NAD Retarded O ssifica tio n (6 b il) Supernumerary ( s it e 14 lt ) Retarded O ssifica tio n (6,8 b il) VR DV VR NAD Wavy (6-10 rt) Retarded O ssification (2,6,7,8 b il,-1,12) NAD Retarded O ssification (cen thlO) Wavy (6-11 r t , 1 0 , l l lt) Wavy (4-13 b il) Retarded O ssification (2,6,7,8 b il;1 ,2) Retarded O ssification (6) NAD Wavy (5-13 b il) Retarded O ssifica tio n (6 rt,-l) NAD NAD NAD Retarded O ssification (2,6,7,8 bil) NAD VR VR VR VR VR VR VR VR VR VR NAD NAD NAD NAD NAD NAD NAD G& <*>v 155 evelopmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP IV: 500 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 571047 (Cont.) 8 6.00 9 5.92 10 5.94 571057 1 2 3 4 5 6 7 8 9 10 11 12 13 5.26 5.64 5.88 6.15 5.70 5.60 6.15 5.51 5.70 5.66 6.13 5.57 5.17 14 5.85 Rib Rib Rib Rib Rib Rib Rib Rib Rib Rib Vertebra NAD NAD NAD Supernumerary (s ite 14 b il) Supernumerary (s ite 14 b il) Supernumerary (s ite 14 b il) Supernumerary (s ite 14 It) Supernumerary (s ite 14 It) NAD NAD Supernumerary (s ite 14 rt) Supernumerary (s ite 14 It) Supernumerary (s ite 14 b il) NAD Supernumerary (short; 14 b il) Supernumerary (s ite 14 rt) Retarded O ssification (cen th ll,1 3 ) NAD DV DV DV DV DV DV DV DV DV DV VR i 156