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8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats TRADE SECRET DuPont-10157 AR226-1939 Study Title 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Laboratory Project ID: DuPont-10157 RECEIVED OPPT NCIC 2005 MAR -4 PM 12:01 Test Gu 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 Prenatal Developmental Toxicity Study. (August 1998). Organisation for Economic Cooperation and Development (OECD/OCDE). Guidelines for Testing of Chemicals, 414. (22nd January 2001). Au th o r : Susan M. Munley, M.A. Study Co m pleted o n : January 30, 2004 Perfo r m in g La bo r a t o r y : EI. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Wo r k Re q u est Nu m b e r : 13690 Ser v ic e Code Nu m b e r : 841 Page 1 of 156 8-2 Telomer B Alcohol: Developmental 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 ISO9002 regulations. All of the analyses are considered valid and sufficient for the purposes of this study. Research Scientist 2 8-2 Telomer B Alcohol: Developmental 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 3 8-2 Telomer B Alcohol: 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. 4 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT.................................. 2 QUALITY ASSURANCE STATEMENT.................................................................................. 3 CERTIFICATION.........................................................................................................................4 LIST OF TABLES.........................................................................................................................7 LIST OF APPENDICES...............................................................................................................7 STUDY INFORMATION............................................................................................................ 8 STUDY INFORMATION............................................................................................................ 8 STUDY PERSONNEL...................................................................................................................9 SUMMARY..................................................................................................................................10 OBJECTIVE................................................................................................................................11 SPONSOR AND TEST FACILITY...........................................................................................11 Regulatory Compliance...............................................................................................................11 Study Design.................................................................................................................................12 A. Experimental Design.........................................................................................................12 Group............................................................................................................................................12 MATERIALS AND METHODS................................................................................................12 A. Test Substance...................................................................................................................12 B. Vehicle...............................................................................................................................12 C. Preparation, Administration, and Analyses of Dosing Formulations................................13 D. Test Species.......................................................................................................................15 E. Animal Husbandry.............................................................................................................15 F. Quarantine and Pretest Period............................................................................................16 G. Randomization...................................................................................................................16 H. Parameters Studied.............................................................................................................16 I. Animal Euthanasia.............................................................................................................17 J. Control of Bias...................................................................................................................18 K. Statistical Analyses............................................................................................................18 RESULTS AND DISCUSSION..................................................................................................19 5 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ANALYTICAL EVALUATIONS..............................................................................................19 A. Chromatography.................................................................................................................19 B. Recovery Samples..............................................................................................................19 C. Homogeneity and Stability Samples..................................................................................19 D. Concentration Verification Samples................................................................................. 20 E. Analytical Conclusions..................................................................................................... 21 DEVELOPMENTAL TOXICOLOGY......................................................................................22 A. Mortality, Post Mortem Findings, and Clinical Observations.......................................... 22 B. Body Weights and Body Weight Changes........................................................................ 22 C. Food Consumption............................................................................................................ 22 D. Postmortem Findings........................................................................................................ 23 E. Reproductive Outcome and Litter D ata............................................................................ 23 F. Fetal Alterations................................................................................................................ 23 G. Malformations................................................................................................................... 23 H. Variations.......................................................................................................................... 23 CONCLUSIONS......................................................................................................................... 25 RECORDS AND SAMPLE STORAGE................................................................................... 25 REFERENCES............................................................................................................................ 26 TABLES........................................................................................................................................27 APPENDICES..............................................................................................................................42 6 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 LIST OF TABLES TABLE 1 SUMMARY OF DOSING ANALYSES..........................................................................................................29 TABLE 2 CLINICAL OBSERVATIONS........................................................................................................................... 30 TABLE 3 MEAN MATERNAL BODY WEIGHTS.........................................................................................................31 TABLE 4 MEAN MATERNAL BODY WEIGHT CHANGES......................................................................................34 TABLE 5 MEAN MATERNAL FOOD CONSUMPTION............................................................................................. 36 TABLE 6 REPRODUCTIVE OUTCOME.........................................................................................................................38 TABLE 7 INCIDENCE OF FETAL MALFORMATIONS............................................................................................. 39 TABLE 8 INCIDENCE OF FETAL VARIATIONS........................................................................................................40 LIST OF APPENDICES APPENDIX A ANALYTICAL CHEMISTRY REPORT................................................................................................ 43 APPENDIX B INDIVIDUAL CLINICAL OBSERVATIONS........................................................................................51 APPENDIX C INDIVIDUAL BODY WEIGHTS............................................................................................................. 65 APPENDIX D INDIVIDUAL BODY WEIGHT CHANGES.........................................................................................79 APPENDIX E INDIVIDUAL FOOD CONSUMPTION................................................................................................. 89 APPENDIX F INDIVIDUAL REPRODUCTIVE DATA................................................................................................ 99 APPENDIX G GROSS POSTMORTEM FINDINGS.....................................................................................................105 APPENDIX H INDIVIDUAL FETAL WEIGHTS AND ALTERATIONS................................................................ 111 7 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 STUDY INFORMATION 9th Collective Nomenclature: 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluoro-1decanol Synonyms/Codes: (Perfluorooctyl)ethanol P.-(Heptadecafluorooctyl)ethanol 1.1.2.2- Tetrahydroheptadecafluorodecanol 1.1.2.2- Tetrahydroperfluorodecan-1 -ol 1.1.2.2- Tetrahydroperfluorodecanol 1.1.2.2- Tetrahydroperfluorodecyl alcohol 1H, 1H,2H,2H-Perfluorodecan-1-ol 1H, 1H,2H,2H-Perfluorodecanol 2-(Heptadecafluorooctyl)ethanol 2-(Perfluorooctyl)ethanol 2-(Perfluorooctyl)ethyl alcohol C-8 Telomer B Alcohol 2-Perfluorooctyl ethanol 8-2 Telomer B Alcohol P.00/001 (Lot No.) Haskell Number: 24691 CAS Registry Number: 678-39-7 Composition: C-8 Telomer B Alcohol Purity: 99.2 Wt. % Known Impurities: C7F 15CF=CHCH2OH (0.8 Wt. %) 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: Telomer Research Program 1200 South Hayes Street Arlington, Virginia 22202-5050 U.S.A. Study Initiated/Completed: January 30, 2003 / (see report cover page) In-Life Initiated/Completed: February 3, 2003 / February 24, 2003 8 8-2 Telomer B Alcohol: Developmental 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 9 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 SUMMARY The objective of this study was to evaluate the potential maternal and developmental toxicity of 8-2 Telomer B Alcohol when administered by oral gavage to pregnant rats daily from around the time of implantation to the 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 non adverse, 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. a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U.S. EPA(13) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(14) 10 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 OBJECTIVE The objective of this study was to evaluate the potential maternal and developmental toxicity of 8-2 Telomer B Alcohol when administered by oral gavage to pregnant rats daily from around the time of implantation to the end of gestation, days 6-20 of gestation (days 6-20G). The test substance, 8-2 Telomer B Alcohol, is an organofluorine compound. The 50, 200, and 500 mg/kg/day dose levels were selected for the current study based on findings from two previously conducted studies. The first study was an 84-day range-finding study(1) with 8-2 Telomer B Alcohol 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 second study dataset that was considered was from a rat developmental toxicity study with a similar fluorotelomer-based alcohol in which dose levels of 50, 200, and 500 mg/kg/day were evaluated.(2) Maternal and developmental 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 the Telomer Research Program, 1200 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). 11 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats STUDY DESIGN DuPont-10157 A. Experimental Design The study design is as follows: Group I Dosea (mg/kg/day) 0c Concentration (mg/mL)b 0.0 Time-Mated Females 22 II 50 10.0 22 III 200 40.0 22 IV 500 100.0 22 a Formulations of test substance in 0.5% aqueous methylcellulose were administered once daily by oral gavage on days 6-20G at a dosing volume of 5 mL/kg. b To achieve these concentrations of 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 of 5 mL/kg. MATERIALS AND METHODS A. Test Substance The test substance, a waxy solid with known purity (99.2%) and composition, was supplied by the Sponsor. The test substance was assigned the Haskell 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) was 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 file for the study. A reserve sample of the test substance was collected and retained by the Testing Facility. B. Vehicle The vehicle was 0.5% aqueous methylcellulose. Lot number(s) and expiration date(s) were recorded in the study records. 12 8-2 Telomer B Alcohol: 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 of 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 manner 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 approximately 0.09 mg/mL. Each sample (final dilution) was adjusted to have an equivalent amount 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 testing 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 FID;250C Helium (2.1 mL/min) 13 8-2 Telomer B Alcohol: Developmental 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 the target concentration of the diluted dosing samples. A stock solution of internal standard (1H, 1H, 2H, 2H-perfluoro-9-methyldecan-1-ol, 98% pure) was prepared in methanol and added to each calibration standard and test sample to give a final concentration of approximately 0.09 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 of 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 the baseline for comparing the corresponding stability results. Spiked recoveries samples at each level were prepared and monitored to show the effect on the quantitation of the study due to sampling into 100 mL volumetric flasks. Based on the spiked recovery for each level on the day of the analysis, a correction was applied to all results in the study. 14 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 D. 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. 15 8-2 Telomer B Alcohol: Developmental 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 requirements 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 LA003-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 0G body weights and assigned to control and experimental groups by random sampling from the ranked list. The distribution resulted in mean body weights for all groups that were not statistically different (p > 0.05). H. Parameters Studied 1. In-life Observations of Females a. Clinical Observations Clinical observations were recorded on the day after arrival and daily until the end of the study; clinical observations were recorded twice daily on days 6-20G. b. Body Weight Body 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. 16 8-2 Telomer B Alcohol: Developmental 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 of Woo and Hoar.(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. After 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 were injected with sodium pentobarbital. All other fetuses also were injected with sodium pentobarbital before fixation. 17 8-2 Telomer B Alcohol: 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 two tailed 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.*8 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.*9 Param eter M aternal w eight M aternal w eight changes M aternal food consum ption Live fetuses D ead fetuses R esorptions (total, early, late) Im plantations Incidence o f fetal alterations Incidence o f pregnancy C linical observations M aternal m ortality Fem ales w ith total resorptions E arly deliveries Fetal w eight (C ovariates: litter size, sex ratio) Sex ratio (C ovariate: litter size) Trend Test L in e a r c o n tr a s t o f m e a n s (10) J o n c k h e e re 's te s t(11) C o c h ra n -A rm ita g e te s t(10) L in e a r c o n tra s t o f le a s t s q u a re m e a n s (12) 18 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats 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 I. 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 Table 1 and Appendix A, Table II. 19 8-2 Telomer B Alcohol: 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 Sam ple Type Test Day 1 H om ogeneity N om inal m g/m L M e a s u re d T ,M ,B ab m g/m L M ean (T,M ,B ) % N om inal 0 NDd 10 8 .9 2 e, 8 .7 3 e, 10.0 40 40.5, 40.0, 39.8 100 9 6 .5 , 9 8 .3 e, 9 4 .8 92.2 100.3 96.5 C .V . (% ) S ta b ility 0 % N om inal 7 95.6 1 102.8 2 104.0 a Mean results for the analysis of the top (T), middle (M), and bottom (B) samples. b All results corrected for spiked recovery based on the level and day of analysis (Refer to Table I). c Samples held 5 hours at room temperature. d Denotes none detected. e Mean result of the original analysis and duplicate reanalysis of 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 III. The following table summarizes the results for concentration verification analyses of the the test substance samples for test days 11 and 20. P re p a ra tio n Day N om inal m g/m L M e a s u r e d 3'b m g/m L A verage % N om inal CV % T e s t D a y 11 Test Day 20 10 40 100 10 40 100 7 .2 8 c, 7 .2 3 c, 8 .7 1 d 3 9 .9c, 3 9 .7 c, 4 1 .1 d 1 0 0 c, 101c, 9 8 .2 d 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 of analysis (Refer to Table I). c Mean result of the original analysis and duplicate reanalysis of the original sample. d Results of the analysis of 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 the targeted concentration ( 0.5% of nominal) for all samples except for the 10 mg/mL level 20 8-2 Telomer B Alcohol: Developmental 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. 21 8-2 Telomer B Alcohol: 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 and 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 group. There were no test substance-related effects or maternal body weight or weight gain at either 50 or 200 mg/kg/day; data from these two groups were generally comparable to control group data. C. Food Consumption (Table 5, Appendix E) There were slight and occasionally statistically significant test substance-related reductions in mean 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 was no appreciable impact on food consumption at these levels when data were averaged over the course of the dosing period. Therefore, these slight test substance-related, transient reductions were not considered indicative of adverse toxicity. 22 8-2 Telomer B Alcohol: Developmental 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 lutea 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 at 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 incidences of delayed skull bone ossification. These findings were all considered to be test substance-related and are consistent with skeletal variations produced by a similar fluorotelomerbased alcohol.(2) However, the effects on skull bone ossification, in particular, the increase observed at 200 mg/kg, were not considered adverse for several reasons. Retarded skull bone ossification is a relatively common observation in general and is therefore, not typically considered a tremendously reliable indicator of developmental toxicity, especially in the absence of 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 range of historical control data. 23 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Historical Control Incidence for Retarded Skull Bone Ossification Year Study Conducted Reference No. Affected Fetuses No. Affected Litters 1997 1998-01367 19 10 1998 1998-01382 24 11 1998 DuPont-1165 11 8 1998 DuPont-1559 37 13 1999 1998-01500 18 8 1999 DuPont-2287 19 12 1999 DuPont-1454 21 10 1999 DuPont-3378 36 14 2000 DuPont-4177 47 14 2000 DuPont-4341 6 6 2000 DuPont-4902 35 7 2001 DuPont-5676 58 19 2001 DuPont-5991 7 7 2001 DuPont-6515 25 10 2002 DuPont-10309 54 16 2002 DuPont-11347 16 7 2002 DuPont-11358 15 11 24 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 CONCLUSIONS 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 non adverse, 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 Haskell 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 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.(14) 25 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 REFERENCES 1. DuPont Haskell Laboratory. (2001). Repeated-Dose Oral Toxicity, Gavage Range-Finding Study in Rats. Unpublished Report. DuPont Haskell Laboratory Report No. DuPont-6357. 2. DuPont Haskell Laboratory. (2001). Developmental Toxicity Study in Rats. Unpublished Report. DuPont Haskell Laboratory Report No. DuPont-5991. 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 Aspect 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 Malformations 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. Applied Statistics 31:32-43. 10. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th ed. The Iowa State University Press, Iowa, pp. 246-248, 349-352. 11. Jonckheere, A.R. (1954). 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 and 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. Paynter, O.E. et al. United States Environmental Protection Agency, Office of Pesticide Programs, Washington, D.C., 20460. EPA-540/9-85-020, June 1985. 14. Risk Assessment of Notified New Substances Technical Guidance Document (XI/283/94-EN), Chapter I, Sections 2.24 and 2.25. 26 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 TABLES 27 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Tables 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. Abbreviations --= S.D. = S.E. = N= No Data Standard Deviation Standard Error Number in Group 28 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 TABLE 1 SUMMARY OF DOSING ANALYSES Nominal: Homogeneity Samples Test Day 1 Top Middle Bottom Dosing Concentration of 8-2 Telomer B Alcohol ___________________ (mg/mL)_________________ 10 40 100 8.92 a (89.2) b 8.73 a (87.3) 10.0 (100.0) 40.5 (101.3) 40.0 (100.0) 39.8 (99.5) 96.5 (96.5) 98.3a (98.3) 94.8 (94.8) Average Measured Conc.c Average Percent Nominal Standard Deviationc Coefficient of Variationc 9.22 (92.2) 0.69 7% 40.1 (100.3) 0.37 1% 96.5 (96.5) 1.8 2% Stability Samples 5 Hour Room Temperature Concentration Verification Test Day 11 #1 #2 #3 9.56 (95.6) 7.28 a (72.8) 7.23 a (72.3) 8.71 d (87.1) 41.1 (102.8) 39.9 a (99.8) 39.7 a (99.3) 41.1 d (102.6) 104 (104.0) 100a (100.0) 101 a (101.0) 98.2d (98.2) Average Measured Conc. e Average Percent Nominal e Standard Deviation e Coefficient of Variation e Test Day 20 #1 7.74 (77.4) 0.84 11% 9.45 (94.5) 40.2 (100.5) 0.76 2% 35.0 (87.5) 99.7 (99.7) 1.4 1% 94.6 (94.6) #2 9.57 37.8 91.9 (95.7) (94.5) (91.9) Average Measured Conc.f Average Percent Nominalf Standard Deviation f Coefficient of Variationf 9.51 (95.1) 0.09 1% 36.4 (91.0) 2.0 5% 93.2 (93.2) 1.9 2% a Mean result of the original analysis and duplicate reanalysis of original sample. b Numbers in parentheses are the respective percent of nominal values. c Statistics based on the average measured concentration of the top, middle and bottom of each dosing level. d Result of the analysis for the third sample collected from the dosing preparations. e Statistics based on the average measured concentration of triplicate samples for the dosing level. f Statistics based on the average measured concentration of duplicate samples for the dosing level. 29 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats TABLE 2 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 Statistically significant trend (Cochran-Armitage test) p < 0.05. II 50 22 0 0 2 0 0 0 0 0 0 0 0 0 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 30 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 TABLE 3 MEAN MATERNAL BODY WEIGHTS (grams)a 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. N 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 31 8-2 Telomer B Alcohol: 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 32 8-2 Telomer B Alcohol: 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, sacrificed i n e x t r e m i s , or had litters consisting entirely of resorptions. Statistically significant trend (linear contrast of means); p < 0.05. 33 8-2 Telomer B Alcohol: 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 12-14 14-16 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 11.8 4.38 0.93 22 18.2 4.48 0.96 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. N 26.7 6.12 1.33 21 11.7 3.67 0.80 21 11.5 5.27 1.15 21 9.2 4.23 0.92 21 14.8 6.61 1.44 21 12.3 5.72 1.25 21 16.0 7.95 1.74 21 GROUP III: 200 MG/KG/DAY GROUP MEAN S.D. S.E. N 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 12.6 6.31 1.35 22 20.8 5.71 1.22 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. N 28.1 7.99 2.00 16 14.2 5.09 1.27 16 0.5* 9.68 2.42 16 9.5 9.26 2.31 16 8.2* 14.95 3.74 16 17.2* 10.08 2.52 16 18.0 8.65 2.16 16 34 8-2 Telomer B Alcohol: Developmental 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 9.91 2.11 22 156.4 21.46 4.58 22 52.9 16.15 3.44 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 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 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. N 29.3 7.50 1.88 16 34.6* 24.96 6.24 16 117.4* 34.43 8.61 16 22.6* 30.68 7.67 16 a Data were excluded from females that were not pregnant, found dead, sacrificed i n e x t r e m i s , or had litters consisting entirely of resorptions. * Statistically significant trend (linear contrast of means); p < 0.05. 35 8-2 Telomer B Alcohol: 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 3.47 0.74 22 24.1 2.35 0.50 22 25.5 2.94 0.63 22 26.1 2.68 0.57 22 27.2 2.65 0.56 22 16-18 29.3 3.83 0.82 22 GROUP II: 50 MG/KG/DAY GROUP MEAN S.D. S.E. N 23.8 2.56 0.56 21 21.9 2.42 0.53 21 23.4 2.49 0.54 21 25.7 2.71 0.59 21 26.4 2.29 0.50 21 26.8 3.68 0.80 21 30.2 3.42 0.75 21 GROUP III: 200 MG/KG/DAY GROUP MEAN S.D. S.E. 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 28.4 3.28 0.70 22 31.9* 2.96 0.63 22 GROUP IV: 500 MG/KG/DAY GROUP MEAN S.D. S.E. N 23.7 3.03 0.76 16 19.9* 5.91 1.48 16 21.4* 3.25 0.81 16 20.6* 6.76 1.69 16 25.8 4.28 1.07 16 27.9 4.44 1.11 16 31.8* 5.31 1.33 16 36 8-2 Telomer B Alcohol: Developmental 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. N 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. N 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. N 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, sacrificed i n e x t r e m i s , or had litters consisting entirely of resorptions. * Statistically significant trend (linear contrast of means); p < 0.05. 37 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 TABLE 6 REPRODUCTIVE OUTCOME Group: Dose (mg/kg/day): I 0 II 50 No. Mated No. Pregnant No Delivered Early No. Deaths No. With Total Resorptions 22 22 0 0 0 22 21 0 0 0 No. Litters Mean Corpora Luteaa 22 15.7 (1.61)b 21 16.0 (3.04) III 200 22 22 0 0 0 22 16.0 (3.40) IV 500 22 22 0 5* 1 16 16.1 (2.51) Implantations (Nidations) Resorptions: Total Early Late Dead Fetuses Live Fetusesc : Total Males Females Mean Fetal Weight: Total Males Females 14.7 (1.62) 0.0 (0.21) 0.0 (0.21) 0.0 0.0 14.6 (1.56) 7.2 (1.79) 7.5 (1.74) 5.55 (0.31) 5.68 (0.33) 5.43 (0.32) 13.9 (1.56) 0.7 (1.06) 0.7 (1.06) 0.0 0.0 13.2 (1.81) 6.0 (1.58) 7.2 (1.69) 5.66 (0.29) 5.83 (0.34) 5.51 (0.26) 13.9 (1.64) 0.4 (0.79) 0.4 (0.79) 0.0 0.0 13.5 (1.77) 6.7 (2.16) 6.8 (1.97) 5.77 (0.39) 5.94 (0.40) 5.59 (0.42) 13.4 (3.87) 0.4 (0.81) 0.4 (0.81) 0.1 (0.25) 0.0 13.8 (1.95) 7.1 (1.84) 6.7 (1.89) 5.40 (0.44) 5.57 (0.47) 5.20 (0.39) Sex Ratiod 0.49 (0.11) 0.45 (0.11) 0.50 (0.14) 0.51 (0.12) a Statistical analyses are not conducted on mean corpora lutea data; these data ari presented for information only. b Standard deviation is reported in parentheses. c Statistical analyses are only conducted on the mean total number of live fetuses per litter and total mean fetal weight. The means for males and females are presented for information only. d Number male fetuses/total number fetuses per litter. Note: The pregnancy rate data, adult mortality data, and the total resorption data were statistically analyzed using the Cochran-Armitage test. All litter mean data (except for fetal weight and sex ratio) were analyzed using Jonckheere's test. Fetal weight and sex ratio were analyzed using a linear contrast of least square means. * Statistically significant trend; p < 0.05. 38 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 EXTERNAL No. Examineda No. Affected TABLE 7 INCIDENCE OF FETAL MALFORMATIONS Group : Dose (mg/kg/day): I 0 II III 50 200 IV 500 322 [22] 0[ 0] 277[21] 0[ 0] 297 [22] 0[ 0] 220 [16] 0[ 0] VISCERAL No. Examined No. Affected 167 [22] 0[ 0] 142 [21] 0[ 0] 156 [22] 0[ 0] 113[16] 0[ 0] HEAD No. Examined No. Affected 167 [22] 0[ 0] 142 [21] 0[ 0] 156 [22] 0[ 0] 113[16] 0[ 0] SKELETAL No. Examined No. Affected 322 [22] 0[ 0] 277 [21] 0[ 0] 297[22] 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 listed malformations are expressed as Fetuses[Litters] or Fetuses (Litters). b For ease of reading, zeros have been replaced with dashes for the listed malformations. No significant trends were detected (Jonckheere-Terpstra Trend test); p < 0.05. Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam type are presented for information only. 39 8-2 Telomer B Alcohol: 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] 0[ 0] 277 [21] 0[ 0] 297 [22] 0[ 0] VISCERAL No. Examined No. Affected 167 [22] 0[ 0] 142 [21] 0[ 0] 156 [22] 0[ 0] HEAD No. Examined No. Affected 167 [22] 0[ 0] 142 [21] 0[ 0] 156 [22] 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) VARIATIONS DUE TO RETARDED DEVELOPMENT EXTERNAL No. Examined3 No. Affected VISCERAL No. Examined Kidneyb Small Papilla - Size 1 Small Papilla - Size 2 Papilla - Size 3 No. Affected 322 [22] 0[ 0] 277 [21] 0[ 0] 297 [22] 0[ 0] 167 [22] 142 [21] 156 [22] 2( 2) 4( 3) 6( 6) 12[ 9] 2( 2) 5( 5) 7[ 7] 1( 1) 1( 1) 3( 3) 5[ 5] IV 500 220 [16] 0[ 0] 113[16] 0[ 0] 113[16] 0[ 0] 220 [16] 1( 1) 34(10) 1( 1) 35(11) 35(11) 220 [16] 0[ 0] 113[16] 2( 2) 1( 1) 2( 1) 5[ 3] 40 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats TABLE 8 (Continued) INCIDENCE OF FETAL VARIATIONS DuPont-10157 VARIATIONS DUE 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 Ossification Rib - Wavy Skull - Retarded Ossification Sternebra - Retarded Ossification Vertebra - Retarded Ossification No. Affected 322 [22] 1( 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 affected, including the number affected with the listed variations, are expressed as Fetuses[Litters] or Fetuses (Litters). b Statistical analyses are conducted on the combined incidences of small renal papillae; the details for each size are presented for information only. * Significant trend (Jonckheere's test); p < 0.05. Note: Statistical analyses are only conducted on the individual endpoints. overall total and totals by exam are presented for information only. The 41 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDICES 42 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX A Analytical Chemistry Report 43 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Table I. Recovery of 8-2 Telomer B Alcohol Added to Dosing Vehicle Sample mg/ml 8-2 Telomer B Alcohol Percent Type Recovery(a) RECOVERY(B) Recovery(c) Recovery(d) Recovery(e) Recovery Nominal 10.5 10.5 14.8 14.8 14.8 11.8 Measured 9.37 9.55 13.7 12.5 12.6 10.7 Nominal 89.2 91.0 92.6 84.5 85.1 90.7 M ean: 88.9 3.3, C.V. 4% Recovery(a) Recovery(c) Recovery(d) Recovery Recovery 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 M ean: 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 of the original samples collected test day 11 (February 12, 2003). (E) Processed with concentration verification analysis for re-sampling of the original formulations prepared test day 11 (February 12, 2003). (F) Processed with concentration verification samples collected on test day 20 (February 21, 2003). 44 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Table II. Homogeneity and Stability of 8-2 Telomer B Alcohol in Dosing Formulations Sample mg/mL 8-2 Telomer B Alcohol(A) Percent Type Nominal Measured Nominal Test Day 1 (3-Feb-2003) Homogeneity Co n t r o l To p Middle Bo t t o m 0.00 10-O 10-1 10-2 M ean(C): 10-O 10-1 10-2 M ean(C): 10 M ean(D\- n d (B) 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 Bo t t o m 40 40 40 M ean(D\- 40.5 40.0 39.8 40.1 0.37 C.V. 1% 101.3 100.0 99.5 (100.3% ) ToP Middle Bo t t o m Stability 5 HOUR(E) 100 100-O 100-1 100-2 M ean(C): 100 Mean(D): 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 of analysis (Refer to Table I). (B) Denotes not detected. (C) Mean result of the original analysis (-O) and duplicate reanalysis of original sample (-1, -2). (D) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of top, middle, and bottom. (E) Stability samples held 5 hours a room temperature. 45 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Table III. Concentration Verification of 8-2 Telomer B Alcohol in Dosing Solutions Preparation Day mg/mL 8-2 Telomer B Alcohol(A) Percent Sample Type Nominal Measured Nominal Test Day 11 (12-Feb-2003) Concentration Verification(B) Control 0.0 10-1 10-1A 10-1B M ean(D): 10-2 10-2A 10-2B M ean(D): 10-3 M ean(E): N D (C) 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 72.3 87.1 (77.4) 40-1 40-1A 40-1B M ean(D): 40-2 40-2A 40-2B M ean(D): 40-3 M ean(E): 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(D): 100-2 100-2A 100-2B M ean(D): 100-3 M ean(E): 102 98.7 99.2 100 97.1 102 105 101 98.2 99.7 1.4 C.V. 1% 102.0 98.7 99.2 100.0 97.1 102.0 105.0 101.0 98.2 (99.7) (A) All results corrected for spiked recovery based on the level and day of analysis (Refer to Table I). (B) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (C) Denotes not detected. (D) The average measured concentration, average percent of nominal for duplicate samples (-1, and -2), and duplicate reanalysis analysis of the original sample (-1A, -1B and -2A, -2B). (E) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation for duplicate samples based on footnote (D) and the analysis of the 3rd sample from the original dosing preparation (-3). 46 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Table III. Concentration Verification of 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day mg/mL 8-2 Telomer B Alcohol(A) Percent Sample Type Nominal Measured Nominal Test Day 20 (21-Feb-2003) Concentration Verification(B) Control 0.0 n d (C) --- 10-1 10-2 M ean(F): 9.45 9.57 9.51 0.09 C.V. 1% 94.5 95.7 (95.1) 40-1 40-2 M ean(F): 35.0 37.8 36.4 2.0 C.V. 5% 87.5 94.5 (91.0) 100-1 100-2 M ean(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 of analysis (Refer to Table I). (B) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (C) Denotes not detected. (F) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation for duplicate samples 47 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Figure 1 Representative Analytical Calibration Curve DuPont-10157 Figure 1: Calibration curve showing linear fit (line) to replicate peak height ratio measurements (squares) for calibration solutions of 8-2 Telomer B Alcohol 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. 48 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Figure 2 Representative High Performance Liquid Chromatography Chromatograms Figure 2a: Representative HPLC chromatogram of 0 mg/mL (control) sample with internal standard (1H,1H,2H,2H-perfluoro-9-methyldecan-1-ol) added. Retention time for 8-2 Telomer B Alcohol is approximately 3.7 minutes. Retention time for internal standard is approximately 4.1 minutes. Figure 2b: Representative HPLC chromatogram of 40.0 mg/mL 8-2 Telomer B Alcohol dosing solution diluted to a nominal concentration of 0.06 mg/mL. The measured concentration of the representative solution is 41.1 mg/mL 49 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 Figure 2 (continued) Representative High Performance Liquid Chromatography Chromatograms Figure 2c: Representative HPLC chromatogram of 0.0618 mg/mL 8-2 Telomer B Alcohol analytical reference solution. Figure 2d: Representative HPLC chromatogram of 40.3 mg/mL 8-2 Telomer B Alcohol 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. 50 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX B Individual Clinical Observations 51 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Individual 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. 52 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 a: , , , , , , , , , , , , , , , , ,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: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,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 a: , , , , , , , , , , , , , , , , ,21 53 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 671015 SACRIFICED BY DESIGN 02/20/03 671017 SACRIFICED BY DESIGN 02/20/03 671031 ALOPECIA RIGHT FRONT LEG SACRIFICED BY DESIGN 02/20/03 671033 ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 02/20/03 671035 SACRIFICED BY DESIGN 02/20/03 671039 SACRIFICED BY DESIGN 02/24/03 671042 SACRIFICED BY DESIGN 02/24/03 671044 SACRIFICED BY DESIGN 02/24/03 671045 SACRIFICED BY DESIGN 02/24/03 671054 SACRIFICED BY DESIGN 02/24/03 671055 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: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , ,16,17,18,19,20, b: , , , , , , , , , , , ,16,17,18,19, , a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , ,19,20,21 b: , , , , , , , , , , , , , , ,19,20, a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 54 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 671000 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 OBSERVEDi: 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 21 a 21 a 21 a 21 a 21 a 21 a 21 a 21 a 21 a 21 a 21 a 21 a 21 55 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 02/24/03 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: / / III / b: I I I I I I a: I I I I I I b: I I I I I I a: I I I I I I ,133, ,1133, ,14,15,16,17,18,19,20,21 ,14,15,16,17,18,19,20, ! ! ! ! ! ! ! ! ^21-L 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ -L 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ -L 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ -L a: ! I l I I ! ! ! ! ,14,15,16,17,18,19,20,21 b: , , , , , , , , , ,14,15,16,17,18,19,20, a: , , , , , , , , , I 14^ 15 I I I II b: , , , , , , , , , I 14^ 15 I I I II a: , , , , , , , , , , , ,16,17,18,19,20,21 b: , , , , , , , , , , , ,16,17,18,19,20, a: , , , , , , , , , ! ! ! ! ! ! ! ! ^21- 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ - 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ - 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ - 21! I l II ! ! ! ! ! ! ! ! ! ! ! ! ^ - 21! I l II ! ! ! ! ! ! ! ! ! ! ! !^ 56 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 670970 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 2/18/03 670972 SACRIFICED BY DESIGN 2/18/03 670979 SACRIFICED BY DESIGN 2/18/03 670983 SACRIFICED BY DESIGN 2/18/03 670988 SACRIFICED BY DESIGN 2/18/03 670992 SACRIFICED BY DESIGN 02/19/03 670995 SACRIFICED BY DESIGN 02/19/03 670996 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 02/19/03 670997 SACRIFICED BY DESIGN 02/19/03 671009 SACRIFICED BY DESIGN 02/19/03 671010 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 a: , , , , , , , , ,13,14,15,16,17,18,19,20,21 b: , , , , , , , , ,13,14,15,16,17,18,19,20, a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , ,14,15,16,17,18,19,20,21 b: , , , , , , , , ,13,14,15,16,17,18,19,20, a: , , , , , , , , , , ,15,16,17,18,19,20,21 b: , , , , , , , , , , ,15,16,17,18,19,20, a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 a: , , , , , , , , , , , , , , , , ,21 57 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 671024 ALOPECIA BOTH REAR LEG ALOPECIA LEFT HIND QUARTERS ALOPECIA RIGHT REAR LEG SACRIFICED BY DESIGN 02/20/03 671027 SACRIFICED BY DESIGN 02/20/03 671028 SACRIFICED BY DESIGN 02/20/03 671029 SACRIFICED BY DESIGN 02/20/03 671030 ALOPECIA BOTH FRONT LEG ALOPECIA CHEST SACRIFICED BY DESIGN 02/20/03 671032 SACRIFICED BY DESIGN 02/20/03 671036 SACRIFICED BY DESIGN 02/24/03 671037 STAIN CAGEBOARD RED ALOPECIA RIGHT FRONT LEG 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: , , , , , , ,11,12,13,14,15,16,17, , , , b: , , , , , , ,11,12,13,14,15,16,17, , , , a: , , , , , , , , , , , , ,17,18,19,20,21 b: , , , , , , , , , , , , ,17,18,19,20, a: , , , b: , , , ,21 ,21 ,21 ,21 a: , ,11,12,13,14,15,16,17,18,19,20,21 b: ,10,11,12,13,14,15,16,17,18,19,20, a: , , , ,13,14,15,16,17,18,19,20,21 b: , , , ,13,14,15,16,17,18,19,20, a: 21! ! ! ! ! ! ! ! ! ! ! ! ^ -1- ,21 ,21 a: ,133, b: ,133, a: ,19,20,21 b: ,19,20, a: , , ,21 CO CO MM N) N) OO N) DuPont-10157 a Clinical observations for this rat were inadvertently not recorded on gestation day 10. Rat had "No Abnormalities Detected" for the morning of gestation day 10 and the morning of gestation day 11. 58 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP III: 200 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 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 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: 12 t ^ t t t t b: 12 t ^ t t t t a: , , , ,13,14,15,16,17,18,19,20,21 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: , , ,, , , , , , , ,20,21 b: ,20, a: ,21 a ,21 DuPont-10157 59 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 670971 SACRIFICED BY DESIGN 2/18/03 a ,21 670973 HUNCHED OVER DIARRHEA STAIN PERINEUM BROWN WEAK SACRIFICED IN EXTREMIS 02/10/03 670977 SACRIFICED BY DESIGN 2/18/03 a: , , , t ! ! ! ! 1-1-2^ ! 1-L3-' b: , , , t t t r 11 r 12^ r a: , , , ! ! ! ! ! /*1--3> a: , , , ! ! ! ! ! /*1--3> a: , , , ! ! ! ! ! /*1--3> a: , , , ! ! ! ! ! /*1--3> a ,, ,, ,21 670982 ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 2/18/03 670991 SACRIFICED BY DESIGN 2/18/03 a: b: a: a ,15,16,17,18,19,20,21 ,15,16,17,18,19,20, 21! ! ! ! ! ! t ^ ,21 671001 ALOPECIA BOTH FRONT LEG ALOPECIA BOTH FRONT PAW SACRIFICED BY DESIGN 02/19/03 671004 ALOPECIA LEFT FRONT LEG ALOPECIA BOTH FRONT LEG ALOPECIA ABDOMINAL PALLOR SACRIFICED BY DESIGN 02/19/03 a: b: a: b: a: a: b: a: b: a: b: a: a: 19, 20, 21 19, 20, 19, 20, 21 19, 20, , ,21 , , , ,15,16,17, , , , , ,15,16,17, , , , CO CO 19, 20, 21 19, 20, ,, , 20, 21 , 20, , ,21 , ,21 CO CO CO CO 60 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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: , , , , , ,1X00,1X1X, a: , , ! ! ! ! ! 12 b: , , ! ! ! ! r 11 r a: , , ! ! ! ! ! 12 a: , , ! ! ! ! ! 12 ,, ,, a: ,14, , , , , , , b: ,14, , , , , , , a: , ,15,16,17,18, 19, 20, 21 b: , ,15,16,17,18, 19, 20, a: ,21 a: 19, 20, 21 b: 19, 20, a: 19, 20, 21 b: 19, 20, a: ,21 a ,21 a: ,10,11,12, b: ,10,11,12, a: ,13,14,15,16,17,18,19,20,21 b: ,13,14,15,16,17,18,19,20, a: 13 14! A- ' - > ! -1- ^ / ! ! ! ! ! ! b: 13 14! A- ' - > ! -1- ^ / ! ! ! ! ! ! a: , , ,15,16,17,18,19,20,21 b: , , ,15,16,17,18,19,20, a: , , ,15,16,17,18,19,20,21 b: , , ,15,16,17,18,19,20, a: 21! ! ! ! ! ! ! ! ! ^ -1- 61 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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: 6,7,8,9,10,11,12,13,14,15,16, 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: , , , , ,11,12,13,14,15,16, 17.18, 19.20, 21 b: , , , ,10,11,12,13,14,15,16, 17.18, 19.20, a: , , , , , ,12,13,14,15,16, 177, , b: , , , , , ,12,13,14,15,16, 177, , a: , , , , , ,12,13,14,15,16, b: , , , , , ,12,13,14,15,16, a: , , , , , , ,13,14,15,16, 177, ,19.20, 21 b: , , , , , , ,13,14,15,16, 177, ,19.20, a: 17.18, 19.20, 21 b: , , 17.18, 19.20, a: ,21 a 11 a 11 a 11 a 11 a 11 a 11 a 11 ,, ,, a ,21 a ,21 62 DuPont-10157 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 ,9,10, b ,9,10, a ,9,10, b ,9,10, a , ,10, b ,9,10, a , ,10, b , ,10, a b ,10, a: , , , ,8,9,10, b: , , , ,8,9,10, a: , , , , ,9,10,11 12-L ^'/ ! ! ! ! ! ! !! b: , , , , ,9 ,1X00,1X1X 12-L ^'/ ! ! ! ! ! ! !! a: , , , , ,99 ,1X00,1X1X 12.13.14.15.16.17.18, , , b: , , , , ,9 ,1X00,1X1X 12.13.14.15.16.17.18, , , a: , ! ! ! ! ! !>1-1>- 12.13.14.15.16.17.18.19.20, 21 b: , ! ! ! ! ! !>1-1>- 12.13.14.15.16.17.18.19.20, a: , , , , , , , ,13,14,15,16,17,18,19,20, 21 b: , , , , , , , ,13,14,15,16,17,18,19,20, a: , , , , , , , , , , , , ,18, , , b: , , , , , , , ,18, a: , , , , , , , ,19,20, 21 b: , , , , , , , ,19,20, a: , , , , , , , 21 a ,21 DuPont-10157 63 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 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 NO FECES/FEED ON CB 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: 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 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: , , , , , ,12,13,14,15,16,17,18,19,20,21 b: , , , , , ,12,13,14,15,16,17,18,19,20, a: , , , , , , ,13,14,15,16,17,18,19,20,21 b: , , , , , , ,13,14,15,16,17,18,19,20, a: ! ! ! ! ! ! /-L1-3W-L1^4/ ! ! ! ! ! ! b: ,133, a: b: ,18, a: , , b: ,18, a: ,19,20,21 b: ,19,20, a: , , ,21 a: f 13-11 t ,, b: ,13, , , a: , ,14,15, b: ,13,14,15, a: , ,14, , a: , ,14, , a: 15r ! ! A-'->! b: 15t t r L 'J r a: ,16, ,, a ,21 DuPont-10157 64 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX C Individual Body Weights 65 8-2 Telomer B Alcohol: 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 --= 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 66 8-2 Telomer B Alcohol: 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 S.D. S.E. N 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 7 293.3 281.3 277.3 283.9 268.7 272.7 277.4 292.5 270.9 297.8 283.4 298.4 299.9 296.9 292.2 289.9 275.0 273.3 280.8 258.5 297.4 297.0 284.5 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 9 308.8 291.2 285.0 298.6 286.1 292.8 283.0 300.2 282.5 311.1 297.4 305.0 313.1 303.3 293.6 298.6 278.2 282.7 283.0 268.3 299.2 303.2 293.9 11.65 2.48 22 67 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 10 INDIVIDUAL ADULT BODY WEIGHTS DAYS OF GESTATION DAY 11 DAY 12 DAY 13 DAY 14 DAY 15 DAY 16 670974 670981 670985 670986 670987 670989 670994 670998 670999 671002 671007 671015 671017 671031 671033 671035 671039 671042 671044 671045 671054 671055 312.3 298.9 292.4 307.3 294.2 300.1 290.6 301.1 287.2 314.5 294.3 307.9 324.0 313.2 299.0 303.1 286.2 287.5 283.4 271.6 313.1 308.3 320.3 299.0 291.1 312.8 297.3 296.4 295.3 309.0 296.4 323.5 300.1 315.7 341.8 330.8 310.6 312.1 296.4 296.8 289.4 281.3 316.9 316.0 324.5 300.4 301.7 324.2 308.4 304.3 306.9 316.0 306.1 339.2 311.0 323.9 348.3 333.1 318.8 312.6 305.5 297.2 299.7 288.1 322.7 321.6 337.9 315.0 310.7 334.5 316.0 319.5 315.3 328.2 311.0 342.8 321.3 325.0 352.6 335.8 321.5 320.6 312.5 308.9 306.4 294.7 332.4 330.1 341.0 317.1 310.2 337.9 318.8 324.9 316.3 333.5 315.4 347.9 320.4 327.8 366.2 343.7 328.3 317.5 321.3 310.7 306.8 299.3 336.4 331.4 346.7 323.9 315.4 351.2 328.7 326.4 328.6 337.0 322.3 359.7 325.7 335.3 364.4 345.9 336.5 327.9 330.6 317.0 305.1 307.7 345.9 339.4 362.9 339.0 328.7 359.8 336.2 345.2 341.0 357.7 336.1 373.0 335.1 340.5 380.5 357.2 343.4 329.5 340.8 326.0 315.5 316.5 356.9 352.6 GROUP MEAN S.D. S.E. N 299.6 12.50 2.67 22 306.8 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 22 332.8 15.39 3.28 22 344.3 16.87 3.60 22 68 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 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 380.6 355.5 341.0 374.7 353.9 360.2 345.2 370.5 350.8 385.8 347.7 354.6 393.0 371.4 355.3 352.8 352.6 341.6 323.6 329.0 373.1 367.5 391.4 365.3 352.9 387.0 363.9 368.4 367.2 390.4 370.4 402.8 372.5 369.1 414.6 387.1 374.8 365.6 372.3 358.6 339.3 346.8 393.9 385.7 412.3 389.0 370.0 407.4 381.2 385.2 381.5 411.6 385.1 428.8 391.2 384.5 428.9 402.2 383.8 382.2 385.7 367.1 349.3 364.6 412.4 400.0 429.0 404.9 389.2 437.9 392.9 407.3 402.6 430.9 398.4 442.8 412.6 399.0 454.4 417.2 393.3 396.0 406.4 387.6 364.0 384.1 432.3 416.1 465.1 435.1 406.2 457.0 410.2 428.2 427.4 440.6 431.0 482.4 433.9 422.6 489.5 448.0 419.4 419.3 432.2 409.2 382.5 402.3 459.5 442.4 355.8 321.2 314.5 338.5 315.1 321.6 319.4 322.1 325.3 366.9 322.8 316.5 381.2 353.5 334.1 326.2 336.1 324.6 296.1 301.9 339.8 334.1 GROUP MEAN S.D. S.E. N 358.2 17.52 3.74 22 374.5 18.14 3.87 22 391.1 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 DuPont-10157 69 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAY 0 INDIVIDUAL ADULT BODY WEIGHTS DAYS OF GESTATION DAY 4 DAY 5 DAY 6 DAY 7 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 239.0 261.0 246.0 256.0 248.0 242.0 250.0 232.0 237.0 254.0 253.0 270.0 268.0 234.0 257.0 258.0 249.0 242.0 237.0 251.0 242.0 270.0 250.6 267.9 260.3 264.6 260.2 260.8 268.1 247.5 256.4 280.6 261.5 289.0 283.7 257.5 279.3 269.1 267.2 251.8 253.7 265.9 256.4 285.8 259.4 278.1 267.5 273.6 269.2 266.0 280.4 251.6 254.6 287.6 270.6 294.8 285.1 266.4 283.8 273.6 280.3 252.8 254.0 266.0 267.1 296.2 263.6 282.4 276.1 273.8 268.0 265.8 283.9 255.3 270.5 291.6 276.1 299.5 301.5 272.5 291.5 281.7 280.6 258.1 264.7 270.8 269.1 297.4 269.4 288.5 276.7 279.1 274.8 269.1 293.0 261.0 271.3 302.2 280.4 301.1 305.7 279.1 295.5 284.6 275.1 270.4 271.2 285.2 277.4 303.9 GROUP MEAN S.D. S.E. 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 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 70 8-2 Telomer B Alcohol: 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 DAY 15 DAY 16 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 287.5 308.0 306.4 300.1 297.1 296.1 306.0 275.0 293.5 313.1 296.4 315.7 317.5 291.3 302.4 288.9 293.5 280.7 279.6 300.1 287.4 315.3 291.4 313.5 307.3 305.2 303.6 297.2 308.8 285.9 297.8 316.5 299.6 322.3 330.4 303.9 311.2 300.5 301.0 294.9 288.1 304.8 302.5 320.4 299.4 320.1 313.9 308.5 306.7 297.7 319.2 300.9 312.6 322.2 304.7 326.1 342.7 312.5 318.4 303.0 304.3 302.1 292.9 319.1 313.4 330.3 309.6 336.2 325.2 321.0 320.0 315.9 325.3 307.5 315.3 316.6 314.8 328.5 341.9 314.3 319.2 306.2 304.4 307.1 300.7 322.4 319.6 333.9 313.1 343.5 332.4 331.3 326.9 319.2 330.1 312.1 319.9 305.7 313.6 335.3 351.9 323.3 324.9 310.3 306.9 310.7 304.2 331.3 323.9 341.1 319.4 326.4 338.0 333.1 333.6 321.6 342.9 326.4 322.7 309.9 328.4 336.2 353.7 328.4 329.4 316.1 316.8 315.8 312.8 333.9 338.7 345.9 331.9 334.5 357.0 343.4 343.0 335.4 354.3 338.5 334.7 315.6 335.7 347.3 357.6 339.4 338.2 323.6 324.6 325.8 322.6 343.7 352.8 358.8 GROUP MEAN S.D. S.E. N 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 22 328.6 11.32 2.41 22 339.0 12.27 2.62 22 71 8-2 Telomer B Alcohol: 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 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 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 72 8-2 Telomer B Alcohol: 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 .2 276.7 281.6 299.0 273.6 298.4 280.7 301.3 304.1 305.3 266.6 261.5 271.9 272.3 304.1 283.5 264.3 280.7 284.8 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 73 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP III: 200 MG/KG/DAY ANIMAL NUMBER DAY 10 DAYS OF GESTATION DAY 11 DAY 12 DAY 13 DAY 14 DAY 15 DAY 16 670970 670972 670979 670983 670988 670992 670995 670996 670997 671009 671010 671024 671027 671028 671029 671030 671032 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 .6 303.9 313.6 299.2 317.9 309.3 308.4 305.3 331.1 301.1 339.8 298.7 321.9 321.1 327.1 283.6 284.1 301.5 301.4 316.3 299.7 292.5 299.6 316.7 329.8 318.8 328.3 336.4 314.6 314.1 337.0 305.5 344.9 303.9 327.4 327.1 327.7 286.4 287.2 308.6 302.8 328.3 312.5 303.4 305.5 325.2 331.4 313.5 336.2 336.2 317.7 316.6 345.3 305.0 352.1 298.7 326.5 332.2 336.7 289.0 294.1 312.3 313.1 329.0 321.9 308.5 313.7 331.0 334.3 316.7 344.0 344.2 328.2 326.8 364.2 328.0 370.0 306.2 338.3 342.0 344.4 298.6 298.6 310.4 318.6 349.6 329.8 317.7 323.6 346.3 346.9 335.3 356.9 352.6 329.6 339.6 372.2 328.9 383.0 322.2 353.2 351.2 356.7 310.3 305.2 321.3 334.9 360.3 345.0 326.9 333.5 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 74 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHTS GROUP III: 200 MG/KG/DAY ANIMAL NUMBER DAY 17 DAYS OF GESTATION 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 364.9 357.5 346.1 367.6 370.5 349.1 364.3 401.7 344.5 405.6 336.5 365.8 368.6 367.4 326.1 317.7 338.0 344.2 374.6 355.9 337.8 345.6 382.3 381.9 359.2 383.8 391.0 363.9 382.1 419.6 360.5 427.3 346.3 380.5 383.2 380.8 336.4 327.0 350.2 359.6 393.2 373.2 362.1 366.7 403.4 400.3 376.3 397.3 403.7 379.8 391.2 434.7 374.4 453.5 355.3 400.9 401.3 397.9 345.1 339.4 367.7 378.8 408.4 386.8 383.7 383.6 416.0 420.2 388.8 411.8 421.3 396.1 414.0 455.8 391.2 479.3 370.1 415.9 416.0 413.9 355.6 351.0 384.4 399.3 432.4 406.6 381.5 394.8 444.9 451.1 405.6 439.8 441.3 413.6 434.2 473.0 414.5 507.4 376.9 440.3 437.1 432.0 367.3 363.3 402.3 427.6 449.9 429.3 413.4 418.3 332.9 332.0 311.4 343.3 336.0 340.4 310.0 359.5 330.7 373.2 285.2 337.9 345.4 330.8 284.1 286.7 299.2 317.6 343.1 330.6 321.5 314.2 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 DuPont-10157 75 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 INDIVIDUAL ADULT BODY WEIGHTS GROUP :IV: 500 MG/KG/DAY ANIMAL NUMBER DAY 0 DAYS OF GESTATION DAY 4 DAY 5 DAY 6 DAY 7 670971 670973 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 244.0 250.0 238.0 263.0 249.0 242.0 254.0 230.0 256.0 251.0 236.0 243.0 269.0 250.0 253.0 262.0 264.0 232.0 234.0 247.0 251.0 269.0 235.0 273.1 246.0 282.6 260.1 260.5 272.7 238.3 269.7 272.4 258.9 246.7 284.0 266.8 277.2 281.9 275.8 240.3 246.7 256.4 264.7 282.0 246.2 274.5 257.4 287.8 272.3 265.1 285.8 251.4 278.9 273.2 265.9 254.9 285.8 279.8 287.5 284.6 271.2 238.0 247.0 267.3 266.8 286.2 258.8 277.2 263.1 299.8 275.7 274.4 293.7 254.9 285.8 278.9 275.4 265.7 292.9 280.0 292.0 292.6 286.1 246.7 255.3 279.5 273.5 293.7 261.7 255.8 241.0 289.9 264.7 269.6 294.3 255.2 289.6 285.9 271.1 247.9 289.8 268.2 290.2 278.0 279.2 249.5 235.4 266.8 263.3 291.5 GROUP MEAN S.D. S.E. N 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 9 271.2 246.0 226.2 308.0 290.5 279.2 301.4 224.3 304.6 297.8 290.8 265.8 292.3 242.8 300.6 295.4 243.1 257.6 261.2 286.8 277.2 303.9 275.8 26.25 5.60 22 76 8-2 Telomer B Alcohol: Developmental 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 DAY 15 DAY 16 670971 670973 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 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 -- 286.6 281.4 231.5 220.7 332.1 304.7 -- 311.5 345.1 328.0 320.0 354.6 -- 338.8 337.2 331.1 276.7 332.4 -- 324.5 297.5 -- 289.2 286.3 247.9 207.7 338.6 325.5 -- 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 GROUP MEAN S.D. S.E. N 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 18 309.5 37.41 8.82 18 326.2 30.54 7.41 17 77 8-2 Telomer B Alcohol: 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 DAY 21 DAY C21 670971 670973 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 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 -- 407.5 411.7 -- 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 GROUP MEAN S.D. S.E. N 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 78 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX D Individual Body Weight Changes 79 8-2 Telomer B Alcohol: 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 --= 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 80 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 0-6 4-6 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 81 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP I: 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 69.8 53.3 70.0 46.3 59.8 60.2 50.2 60.6 79.6 61.4 53.5 74.9 60.9 44.6 53.7 59.9 50.6 43.2 55.5 65.6 56.7 180.0 160.4 129.1 176.4 146.6 161.3 162.5 158.8 164.6 190.8 160.2 126.8 199.4 155.3 134.4 127.1 168.5 146.1 112.4 150.8 171.9 156.5 70.7 46.5 37.4 57.9 51.5 54.7 54.5 40.3 58.9 75.3 49.1 20.7 91.1 60.8 49.1 34.0 72.4 61.5 26.0 50.4 52.2 48.2 GROUP MEAN S.D. S.E. N 30.3 4.18 0.89 22 59.3 9.91 2.11 22 156.4 21.46 4.58 22 52.9 16.15 3.44 22 DuPont-10157 82 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 0-6 4-6 6-8 8-10 10-12 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 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 83 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 6-18 DAYS OF GESTATION 18-21 6-21 6-C21 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 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 62.1 70.3 45.4 58.1 55.9 58.5 59.9 49.2 11.9 54.6 62.6 38.7 56.1 66.3 53.6 49.3 55.5 55.7 61.9 73.4 60.3 158.3 160.0 178.2 150.0 160.9 141.4 159.1 178.2 141.5 33.0 145.6 143.1 119.7 144.6 140.6 126.6 116.9 152.4 135.5 169.6 197.0 146.7 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. N 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 84 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP III: 200 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 0-6 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 GROUP MEAN S.D. S.E. N 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 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 11.1 9.6 5.4 10.0 10.8 11.7 12.7 22.2 16.0 14.1 12.6 6.31 1.35 22 DuPont-10157 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 85 8-2 Telomer B Alcohol: 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 35.0 23.9 26.9 38.4 34.3 42.5 47.4 31.6 44.3 24.1 27.3 32.0 24.1 26.1 21.8 28.9 24.7 32.9 28.2 35.2 33.2 62.6 69.2 46.4 56.0 50.3 49.7 52.1 53.4 54.0 80.1 30.6 59.8 53.9 51.2 30.9 36.3 52.1 68.0 56.7 56.1 51.3 51.6 183.0 175.0 136.9 161.8 173.7 145.9 163.6 188.6 153.7 221.3 110.8 140.6 142.6 135.1 102.6 101.2 126.4 164.9 153.8 151.4 155.5 154.2 71.0 55.9 42.6 65.3 68.4 72.7 39.4 75.1 69.9 87.1 19.1 38.2 50.9 33.9 19.4 24.6 23.3 54.9 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 86 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL ADULT BODY WEIGHT CHANGES GROUP IV: 500 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 0-6 4-6 6-8 8-10 10-12 670971 670973 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 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 4.1 17.1 17.2 15.6 13.9 21.0 16.6 16.1 6.5 16.5 19.0 8.9 13.2 14.8 10.7 10.3 6.4 8.6 23.1 8.8 11.7 -11.6 -14.8 -9.0 4.4 5.4 -2.4 -0.7 -17.5 11.5 11.4 12.9 -20.6 -9.2 -16.5 1.8 -2.0 -30.1 8.6 -2.6 6.2 3.0 10.7 34.6 -30.9 6.2 -5.7 16.0 6.8 15.5 -27.5 8.0 12.0 6.3 9.7 8.7 -40.8 9.1 7.1 -29.6 3.1 18.6 -18.7 5.5 -3.9 -20.5 -21.7 17.0 28.8 7.2 16.6 25.6 -26.9 22.0 12.7 18.7 6.9 -1.8 -- -14.7 1.3 --- 14.4 -16.3 -37.2 -35.2 12.6 GROUP MEAN S.D. S.E. N 27.7 7.08 1.51 22 13.8 5.42 1.16 22 -2.8 11.94 2.54 22 0.5 18.72 3.99 22 0.5 20.81 4.65 20 12-14 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 13.9 14.24 3.36 18 DuPont-10157 14-16 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 17.9 8.39 2.03 17 87 8-2 Telomer B Alcohol: Developmental 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 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 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 88 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX E Individual Food Consumption 89 8-2 Telomer B Alcohol: Developmental 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 90 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 4-6 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 24.4 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 S.D. 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 2.68 0.57 22 14-16 31.4 25.4 23.9 31.4 24.8 26.8 26.0 29.9 24.5 29.8 26.5 24.1 33.4 29.1 27.3 25.7 28.4 25.8 25.0 26.2 27.6 24.9 27.2 2.65 0.56 22 DuPont-10157 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 28.3 26.5 24.6 28.2 29.1 26.1 29.3 3.83 0.82 22 91 8-2 Telomer B Alcohol: Developmental 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 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 4-6 6-8 8-10 10-12 12-14 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 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 93 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 18-21 DAYS OF GESTATION 6-21 670975 670976 670978 670980 670984 670990 670993 671000 671003 671008 671012 671016 671019 671020 671025 671026 671034 671043 671048 671050 671052 671056 (NP) 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. S.E. N 27.8 3.09 0.66 22 26.0 2.19 0.47 22 DuPont-10157 94 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats INDIVIDUAL MEAN DAILY FEED CONSUMPTION GROUP III: 200 MG/KG/DAY ANIMAL NUMBER DAYS OF GESTATION 4-6 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 S.D. S.E. 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 28.3 29.8 28.4 3.28 0.70 22 DuPont-10157 16-18 33.1 31.1 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 95 8-2 Telomer B Alcohol: 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 31.2 26.9 28.9 31.8 30.3 24.9 34.1 30.4 37.7 21.9 28.7 27.6 26.5 21.7 23.2 26.9 29.3 29.3 30.9 29.6 23.7 26.5 27.7 23.3 26.1 32.0 26.9 24.8 29.9 27.2 30.6 22.1 25.3 26.2 25.4 22.5 23.4 25.2 26.1 26.4 28.2 26.9 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 96 8-2 Telomer B Alcohol: 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 670973 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 17.0 20.2 24.4 24.5 24.1 23.2 27.9 21.6 27.3 25.9 25.3 22.9 26.8 26.2 25.0 19.8 22.0 20.0 20.5 29.4 28.3 25.1 15.8 14.9 12.8 20.1 20.6 17.3 20.8 14.3 24.8 24.5 23.1 9.7 31.4 33.4 29.6 17.7 16.0 17.8 12.6 15.8 22.7 19.1 28.1 1.1 14.4 17.2 25.1 20.8 22.4 2.0 21.6 24.5 20.9 22.6 20.1 4.5 22.6 21.1 0.0 18.3 23.5 17.8 22.8 19.7 10.9 7.1 28.3 28.3 27.6 21.8 26.1 0.5 28.3 22.8 25.5 17.7 11.9 --10.3 13.7 --23.6 13.2 0.9 5.2 19.4 28.4 -- 30.7 25.2 29.6 25.0 29.3 --22.8 23.9 22.7 17.0 27.6 --26.2 17.3 --27.4 29.5 8.3 0.2 30.8 GROUP MEAN S.D. S.E. N 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 97 8-2 Telomer B Alcohol: 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 670977 670982 670991 671001 671004 671005 671006 671011 671013 671014 671018 671021 671022 671023 671041 671046 671047 671051 671053 671057 (SE) (SE) (SE) (SE) (R) (FD) 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. S.E. N 24.6 6.44 1.56 17 24.1 3.97 0.96 17 DuPont-10157 98 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX F Individual Reproductive Data 99 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Individual Reproductive Data Explanatory Notes Note Nidations = Implantations Abbreviations _= S.E. = N= NP = FD = SE = R= No Data Standard Error Number in Group Not Pregnant Found Dead Sacrificed in extremis Litter totally resorbed DuPont-10157 100 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL CORPORA NIDANUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL EARLY LATE DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 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. N 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 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 101 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP II: 50 MG/KG/DAY ANIMAL CORPORA NIDA NUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL EARLY LATE DEAD LIVE FETUSES MEAN FETAL FETUSES 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. N 16.0 0.66 21 15 14 16 15 15 12 14 17 15 12 14 11 13 13 13 12 12 14 14 16 14 13.9 0.34 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 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 DuPont-10157 102 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP III : 200 MG/KG/DAY ANIMAL CORPORA NIDANUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL EARLY LATE DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 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 15 13 14 13 14 16 14 13 17 10 15 13 15 12 11 15 14 15 13 13 14 13.9 0.35 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 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 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 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 103 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP IV: 500 MG/KG/DAY ANIMAL CORPORA NIDA NUMBER LUTEA TIONS INDIVIDUAL REPRODUCTIVE DATA RESORPTIONS TOTAL EARLY LATE DEAD LIVE FETUSES MEAN FETAL FETUSES TOTAL FEMALE MALE WEIGHT (G) 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 15 15 17 15 19 15 22 19 12 14 19 17 14 14 14 16 16 MEAN S.E. N 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 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 104 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX G Gross Postmortem Findings 105 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Gross Postmortem Findings Explanatory Notes Abbreviations __ = NAD = NP = FD = SE = R= No Data No Abnormalities Detected Not Pregnant Found Dead Sacrificed in extremis Litter totally resorbed DuPont-10157 106 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Group I: 0 mg/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 Structure(s) --------------------------------------------- Finding(s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-10157 107 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats Group II: 50 mg/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 Structure(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- Finding(s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-10157 108 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS Group III: 200 mg/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 Structure(s) --------------------------------------------- Finding(s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-10157 109 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 GROSS POSTMORTEM FINDINGS Group IV: 500 mg/kg/day Animal Number 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 Structure(s) -- Lungs -- -- ___ Kidney Liver Lungs Kidney -- -- -- -- -- -- ___ Kidney -- -- -- -- -- Finding(s) 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 110 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 APPENDIX H Individual Fetal Weights and Alterations 111 8-2 Telomer B Alcohol: 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 lt lu NAD rt th -- = arch(es) = bilateral = centrum or centra = left = lumbar = No Abnormalities Detected = right = thoracic = No Data * Subcutaneous hemorrhage that was not present in utero. Renal papillary sizes refer to papillary development using the scheme of Woo and Hoar. Alterations are classed as: N = Notes DV = Developmental Variations VR = Variation due to Retarded Development M = Malformations Numbers are used to: Indicate renal papillary size Identify specific sternebra 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 Woo, D.C. and Hoar, R.M. (1972). Apparent Hydronephrosis as a Normal Aspect of Renal Development in Late Gestation of Rats: The Effect of Methyl Salicylate. Teratology, 6:191-196. 112 8-2 Telomer B Alcohol: 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 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 Supernumerary NAD NAD NAD NAD NAD NAD Supernumerary Supernumerary NAD NAD NAD NAD NAD NAD NAD (site 14 bil) (site 14 bil) (site 14 rt) (site 14 bil) Retarded Ossification (cen th11) NAD Retarded Ossification (cen th12) NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (cen th11) NAD NAD NAD NAD DV DV DV DV VR VR VR 113 8-2 Telomer B Alcohol: Developmental 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 Ossification (6,7,8 bil) NAD NAD NAD Retarded Ossification (6,7 bil) NAD NAD NAD NAD Retarded Ossification (cen th10) Retarded Ossification (cen th 9,12) Retarded Ossification (cen th11) Retarded Ossification (cen th12) NAD NAD NAD NAD NAD NAD Retarded Ossification (pubis lt) Retarded Ossification (6,7,8 bil) NAD NAD DuPont-10157 CLASSIF ICATION VR VR VR VR VR VR VR VR 114 8-2 Telomer B Alcohol: 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 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 Ossification (6,7,8 bil) VR NAD Retarded Ossification (12;2 bil) NAD NAD NAD Retarded Ossification (6bil) Supernumerary (site 14 lt) NAD NAD NAD Retarded Ossification (cen th10,12) Retarded Ossification (6rt) NAD VR VR DV VR VR NAD NAD Retarded Ossification (cen th12) NAD NAD Retarded Ossification (6) Retarded Ossification (cen th13) Retarded Ossification (6) Retarded Ossification (cen th12) NAD Supernumerary (site 14 lt) NAD VR VR VR ST VR DV 115 8-2 Telomer B Alcohol: 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 670989 11 12 13 14 15 (Cont.) 5.53 5.87 4.85 5.86 5.26 670994 1 2 6.09 6.09 3 5.74 4 5.57 5 5.81 6 6.13 7 5.43 8 5.52 9 5.49 10 5.77 11 5.63 12 5.65 13 5.83 14 5.44 15 670998 1 2 5.52 5.80 5.51 Kidney Sternebra Kidney Skull Vertebra Vertebra Skull Vertebra Vertebra Kidney Vertebra Skull Vertebra Skull Skull Kidney Skull Vertebra Papilla - Size 3 (bil) NAD Retarded Ossification (6) NAD NAD VR VR Small Papilla - Size 2 (bil) Retarded Ossification (2 bil) Retarded Ossification (cen th11) Retarded Ossification (cen th11-12) Retarded Ossification (1,12,-2 bil) Retarded Ossification (cen th10-12) Retarded Ossification (cen th11) Papilla - Size 3 (lt) Retarded Ossification (cen th11-12) Retarded Ossification (2 bil) Retarded Ossification (cen th10-12) Retarded Ossification (2 bil) NAD Retarded Ossification (12;2 bil) Small Papilla - Size 2 (bil) Retarded Ossification (2 bil) Retarded Ossification (cen th11-12) NAD VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR VR NAD NAD 116 8-2 Telomer B Alcohol: 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 670998 3 4 5 6 7 8 9 10 11 12 13 14 15 16 (Cont.) 6.22 6.26 6.18 5.54 5.67 5.85 5.55 5.83 5.91 5.63 5.53 5.46 5.72 5.88 670999 1 4.88 2 5.61 3 5.43 4 4.89 5 5.26 6 5.72 7 5.51 8 5.15 9 5.40 10 5.40 11 5.13 12 5.14 13 4.98 14 5.61 15 5.34 671002 1 6.15 Skull Rib Kidney Rib Vertebra Skull Kidney Vertebra NAD NAD NAD NAD NAD Retarded Ossification (2 lt) NAD NAD NAD Supernumerary (site 14 lt) Small Papilla - Size 1 (lt) NAD Supernumerary (site 14 lt) NAD VR DV VR DV Retarded Ossification (cen th12) NAD NAD NAD NAD Retarded Ossification (6 bil,8 rt) Papilla - Size 3 (rt) NAD Retarded Ossification (cen th12) NAD NAD NAD NAD NAD NAD VR VR VR VR NAD 117 8-2 Telomer B Alcohol: 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 3 6.29 4 5.81 5 5.52 6 6.18 7 5.98 8 5.90 9 5.76 10 6.40 11 5.24 12 5.95 13 5.37 14 6.18 15 5.65 Skull Vertebra Skull Vertebra Skull Kidney Skull Skull Vertebra Kidney Rib Vertebra Skull Vertebra Vertebra 671007 1 2 3 4 5 6 7 5.74 5.53 5.56 5.70 5.52 5.68 5.53 Kidney Vertebra Retarded Ossification (2 bil) Retarded Ossification (cen th 11,13) Retarded Ossification (2 bil) Retarded Ossification (cen th11) NAD Retarded Ossification (1,12,-2,6 bil) Small Papilla - Size 2 (rt) Retarded Ossification (1;2 bil) NAD Retarded Ossification (1;2 bil) Retarded Ossification (cen th11) Small Papilla - Size 1 (bil) Supernumerary (short 14 rt) Retarded Ossification (cen th9-13) NAD NAD Retarded Ossification (2 bil) Retarded Ossification (cen th11) Retarded Ossification (cen th11-13) VR VR VR VR VR VR VR VR VR VR DV VR VR VR VR NAD NAD Papilla - Size 3 (rt) NAD Retarded Ossification (cen th12) NAD NAD VR VR 118 8-2 Telomer B Alcohol: 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 671007 (Cont.) 8 4.10 9 10 11 12 13 14 15 16 671015 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 671017 1 2 3 4 5 6 3.50 5.29 5.45 4.80 5.21 5.61 5.65 5.62 4.79 4.84 4.78 5.38 4.98 5.09 4.84 4.66 5.30 4.14 5.32 4.46 5.01 5.61 4.97 4.89 5.35 5.87 5.79 6.45 6.15 5.89 Sternebra Vertebra Sternebra Vertebra Kidney Retarded Ossification Retarded Ossification (cen th12) Retarded Ossification NAD NAD NAD NAD NAD NAD NAD (6) (6) NAD NAD Retarded Ossification (cen th12) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Papilla - Size 3 (rt) NAD NAD NAD NAD NAD VR VR VR VR VR 119 8-2 Telomer B Alcohol: Developmental 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 671017 7 8 9 10 11 12 13 14 (Cont.) 6.17 5.97 6.11 6.57 6.18 5.89 5.92 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 Sup<ernumerary (site 14 bil) NAD NAD NAD NAD NAD NAD NAD NAD Pap.illa - Size 3 (bil) Sup ernumerary (site 14 lt) DV VR DV 120 8-2 Telomer B Alcohol: Developmental 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 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 Sternebr 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 5.49 5.13 5.31 Vertebra Vertebra Supernumerary (site 14 rt) NAD NAD NAD NAD NAD NAD Retarded Ossification (6) NAD NAD NAD Supernumerary (site 14 rt) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary (site 14 bil) Retarded Ossification (cen th12) NAD Retarded Ossification (cen th10,11) NAD DV VR DV DV VR VR 121 8-2 Telomer B Alcohol: Developmental 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 6 5.20 7 5.25 8 4.79 9 5.03 10 5.23 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 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 Lung Vertebra Rib Rib Rib Rib Rib Rib Rib Colored (rt lobe, tan, 1mm dia) NAD NAD NAD NAD Retarded Ossification (cen th11) NAD NAD NAD N VR NAD NAD NAD Supernumerary Supernumerary Supernumerary NAD NAD NAD Supernumerary NAD NAD (short 14: bil) (site 14 bil) (site 14 bil) (site 14 bil) DV DV DV DV NAD Supernumerary NAD Supernumerary Supernumerary NAD NAD NAD NAD NAD NAD (site 14 lt) (site 14 bil) (site 14 lt) DV DV DV 122 8-2 Telomer B Alcohol: 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 671045 12 13 14 (Cont.) 5.49 5.26 5.94 671054 1 2 5.69 5.66 3 5.48 4 5.73 5 5.54 6 5.94 7 5.75 8 5.75 9 5.34 10 5.31 11 5.28 12 5.79 13 5.31 14 5.46 15 5.68 16 17 671055 1 2 3 4 5 6 5.94 5.71 4.98 5.23 5.03 4.90 5.24 4.94 7 5.21 Vertebra Vertebra Rib Rib Vertebra Rib Vertebra Rib Kidney Skull Vertebra NAD NAD NAD NAD Retarded Ossification (cen th10) NAD Retarded Ossification (cen th13) NAD NAD NAD NAD Supernumerary (site 14 lt) NAD Supernumerary (site 14 rt) NAD NAD Retarded Ossification (cen th9,11) Supernumerary (site 14 lt) Retarded Ossification (cen th13) Supernumerary (site 14 lt) Small Papilla - Size 2 (rt) VR VR DV DV VR DV VR DV VR NAD NAD NAD NAD NAD Retarded Ossification Retarded Ossification (cen th11) NAD (2 lt) VR VR 123 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY DAM #/ FETUS # FETUS WT. ALTERATIONS IN INDIVIDUAL FETUSES STRUCTURE FINDING(S) 671055 8 9 10 11 12 13 14 15 16 17 (Cont.) 5.28 5.20 5.42 5.03 5.14 5.61 5.54 5.11 5.20 4.40 NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD DuPont-10157 CLASSIFICATION 124 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 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 13 14 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 Sternebra 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 Ossification NAD Retarded Ossification (cen th11,12) Retarded Ossification (cen th12) NAD NAD Retarded Ossification NAD NAD Retarded Ossification (cen th11) NAD NAD NAD Retarded Ossification (cen th10) (6) (6 bil) VR VR VR VR VR VR NAD NAD NAD Retarded Ossification (cen th12) NAD Retarded Ossification (cen th11) NAD Retarded Ossification NAD Retarded Ossification NAD NAD Papilla - Size 3 (rt) NAD (2 bil) (2 bil) VR VR VR VR VR 125 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 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 (site 14 bil) NAD Supernumerary (site 14 bil) Retarded Ossificati on (6 rt) NAD NAD NAD NAD NAD NAD NAD DV DV VR NAD NAD NAD NAD NAD 126 8-2 Telomer B Alcohol: 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 670984 6 7 8 9 (Cont.) 6.11 5.92 5.83 6.05 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 5.96 6.12 5.77 7 6.43 8 6.57 9 6.53 10 5.99 11 6.50 12 6.38 670993 1 2 3 5.47 5.41 6.11 4 5.52 5 5.57 6 5.60 7 5.74 8 4.48 9 5.79 Rib Vertebra Kidney Skull Skull Rib Vertebra Kidney Skull NAD NAD Supernumerary (site 14 rt) Retarded Ossification (cen th11) NAD NAD NAD NAD DV VR NAD NAD Papilla - Size 3 (bil) NAD NAD Retarded Ossification (1;2,6 bil) NAD NAD NAD Retarded Ossification (2,6 bil) NAD Supernumerary (short 14 bil) VR VR VR DV NAD NAD Retarded Ossification (cen th12) NAD NAD NAD Papilla - Size 3 (rt) Retarded Ossification (2 bil;1) NAD VR VR VR 127 8-2 Telomer B Alcohol: 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 670993 10 11 12 (Cont.) 5.94 5.96 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 671003 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 Sternebra 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 Ossification (2 bil;1) Supernumerary (site 14 bil) Retarded Ossification (2,6,7,8 bil;1) VR DV VR NAD NAD NAD NAD NAD Retarded Ossification NAD NAD NAD NAD NAD Retarded Ossification NAD NAD NAD NAD (6) (6 lt) VR VR NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD 128 8-2 Telomer B Alcohol: 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 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 5.61 5.80 6.08 6.08 6.17 13 6.13 14 5.96 671019 1 2 5.65 5.74 Rib Kidney Rib Skull Skull NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary (site 14 bil) NAD Papilla - Size 3 (bil) NAD DV VR NAD NAD NAD NAD NAD NAD Supernumerary (site 14 lt) NAD NAD NAD NAD Retarded Ossification (2 bil;1) NAD NAD DV VR NAD Retarded Ossification (2 bil) VR 129 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671019 (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 6.07 5.72 5.55 5.85 5.56 4.66 Skull Kidney Retarded Ossification (cen th10-12) Retarded Ossification (cen th10-12) Retarded Ossification (cen th11) Retarded Ossification (cen th10-13) NAD Retarded Ossification (cen th10-13) Retarded Ossification (cen th10,12) VR VR VR VR VR VR NAD NAD NAD NAD NAD Supernumerary NAD NAD NAD NAD NAD NAD NAD (site 14 rt) DV NAD Retarded Ossification (6 bil) NAD NAD Small Papilla - Size 2 (bil) NAD NAD NAD VR VR 130 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671025 9 10 11 12 13 (Cont.) 5.76 5.59 5.30 6.55 5.75 671026 1 5.66 2 5.49 3 6.03 4 6.38 5 5.51 6 5.14 7 5.84 8 5.42 9 5.39 10 5.71 11 5.87 12 5.49 Vertebra Skull Vertebra Skull Skull Vertebra Vertebra Skull Vertebra Rib Skull Vertebra Skull Vertebra NAD NAD NAD NAD NAD Retarded Ossification (cen th11-12) Retarded Ossification (1;2 bil) Retarded Ossification (cen th8,11-12) NAD Retarded Ossification (1,12;2 bil) NAD Retarded Ossification (1,12;2 bil) Retarded Ossification (cen th10-13) Retarded Ossification (cen th10) Retarded Ossification (1,12;2 bil) Retarded Ossification (cen th13) Supernumerary (site 14 lt) Retarded Ossification (2 bil,8 lt,12) Retarded Ossification (cen th11-12) Retarded Ossification (1;2 bil) Retarded Ossification (cen th10-13) VR VR VR VR VR VR VR VR VR DV VR VR VR VR 131 8-2 Telomer B Alcohol: 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 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 5.74 6.20 6.08 5.45 5.97 5.75 Subcutis Rib Rib 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 Ossification (cen th11-12) VR NAD NAD NAD NAD NAD Hemorrhage (back*) NAD NAD Supernumerary (site 14 bil) Supernumerary (site 14 lt) NAD Supernumerary (site 14 bil) N DV DV DV Retarded Ossification (cen th12) Retarded Ossification (2 bil) NAD Retarded Ossification (1,12,-2 bil) Retarded Ossification (cen th12) Retarded Ossification (cen th10) NAD Retarded Ossification (1;2 bil) Small Papilla - Size 2 (rt) Retarded Ossification (1,12) NAD Retarded Ossification (1;2 bil) VR VR VR VR VR VR VR VR VR 132 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671048 1 2 3 4 5 6 7 8 9 10 11 12 13 671050 1 2 3 4 5 6 7 8 9 10 11 12 671052 1 2 3 4 5 6 7 8 9 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 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 5.75 6.21 5.49 5.66 6.01 5.80 5.82 5.86 6.14 Rib Rib Rib Supernumerary NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD (site 14 lt) NAD NAD NAD NAD NAD NAD NAD Supernumerary (site 14 lt) NAD NAD Papilla - Size 3 (bil) NAD Supernumerary NAD NAD NAD Supernumerary NAD NAD Supernumerary NAD (site 14 lt) (site 14 lt) (site 14 lt) DV DV VR DV DV DV 133 8-2 Telomer B Alcohol: 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 671052 10 11 12 13 14 15 16 (Cont.) 6.15 5.79 5.45 5.71 5.34 5.40 6.11 671056 1 2 5.04 5.70 3 5.63 4 5.63 5 5.20 6 4.82 7 5.60 8 5.44 9 5.24 10 5.49 11 5.36 12 4.78 13 5.61 Rib Subcutis Skull Vertebra Vertebra Skull Vertebra Rib Skull Vertebra Skull Skull Vertebra Skull Supernumerary (site 14 lt) NAD NAD NAD NAD Hemorrhage (chin*) NAD NAD Retarded Ossification (1,12,-2,3 bil,6 lt) Retarded Ossification (cen th11) Retarded Ossification (cen th12) Retarded Ossification (1,12-2,3,6,7,8 bil) Retarded Ossification (cen th12) NAD Supernumerary (site 14 lt) Retarded Ossification (1,12-2,3,6,7,8 bil) Retarded Ossification (cen th12) NAD Retarded Ossification (1,12,2 bil) NAD Retarded Ossification (1,12-2 bil) Retarded Ossification (cen th12) Retarded Ossification (1,12-2,3 bil) NAD DV N VR VR VR VR VR DV VR VR VR VR VR VR 134 8-2 Telomer B Alcohol: Developmental Toxicity Study in Rats DuPont-10157 ALTERATIONS IN INDIVIDUAL FETUSES GROUP II: 50 MG/KG/DAY DAM #/ FETUS # FETUS WT. STRUCTURE FINDING(S) CLASSIF ICATION 671056 (Cont.) 14 5.73 Rib Skull Supernumerary (site14 lt) Retarded Ossification (2 bil) DV VR 135 8-2 Telomer B Alcohol: 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 670970 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 670972 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 6.12 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 Ossification (cen th11) Retarded Ossification (2,6,7,8 bil;1) Retarded Ossification (6) Retarded Ossification (cen th12) NAD NAD NAD Retarded Ossification (6 bil) NAD Supernumerary (short :13 rt) Retarded Ossification (2,bil;7 rt;12) Retarded Ossification (cen th11) Retarded Ossification (6 bil,1) NAD Retarded Ossification (6 bil) NAD Retarded Ossification (6 lt) Retarded Ossification (cen th10) VR VR VR VR VR DV VR VR VR VR VR VR NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD 136 8-2 Telomer B Alcohol: Developmental 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 670972 12 13 14 15 (Cont.) 6.14 6.11 5.58 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 (site 14 lt) NAD Retarded Ossification (2 bil) NAD DV VR NAD NAD NAD NAD NAD NAD Supernumerary (site 14 bil) NAD NAD Retarded Ossification (8 rt) Retarded Ossification (cen th11) NAD NAD DV VR VR NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD Supernumerary (site 14 lt) NAD NAD NAD NAD NAD VR DV NAD 137 8-2 Telomer B Alcohol: 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 670988 2 3 4 (Cont.) 6.13 6.66 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 Ossification NAD Retarded Ossification (2,6,7,8 bil;1,12) Retarded Ossification (cen th10) NAD Retarded Ossification (2,6,7,8 bil) NAD Retarded Ossification (2,6 bil) Retarded Ossification (cen th11) Retarded Ossification (cen th10,12) Retarded Ossification (cen th10,13) NAD Retarded Ossification (2,6,7,8 bil) Retarded Ossification (cen th11) (6 bil) VR VR VR VR VR VR VR VR VR VR NAD NAD Rudimentary Cervical Retarded Ossification NAD Retarded Ossification (6,7 bil) NAD NAD Rudimentary Cervical Retarded Ossification (cen th11) (7 rt) (6,7 lt) (7 rt) DV VR VR DV VR 138 8-2 Telomer B Alcohol: 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 670992 (Cont.) 10 4.71 11 4.96 670995 1 5.69 2 5.99 3 5.90 4 5.98 5 5.90 6 6.23 7 6.51 8 6.51 9 6.05 10 6.11 11 5.44 12 6.77 13 14 15 16 670996 1 2 3 5.19 5.90 6.06 6.63 5.90 6.76 6.64 Subcutis Vertebra Skull Vertebra Skull Skull Kidney Vertebra Skull Vertebra Skull Vertebra Vertebra Skull Skull Hemorrhage (chin*) NAD N Retarded Ossification (cen th10,12) Retarded Ossification (1,12;2 bil;7 lt) Retarded Ossification (cen th12) Retarded Ossification (1;2 bil) NAD Retarded Ossification (2,6 bil) Papilla - Size 3 (rt) Retarded Ossification (cen th11) Retarded Ossification Retarded Ossification (cen th9-11) NAD NAD Retarded Ossification (1;2 bil) Retarded Ossification (cen th10,12) Retarded Ossification (cen th11) Retarded Ossification (1;2 bil) NAD Retarded Ossification (1) (6 rt) VR VR VR VR VR VR VR VR VR VR VR VR VR VR NAD NAD NAD 139 8-2 Telomer B Alcohol: 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 670996 4 5 6 7 8 9 10 11 12 13 14 (Cont.) 6.33 6.37 6.84 6.04 6.27 6.73 6.40 6.68 6.24 6.20 6.17 670997 1 2 3 4 5 6 7 8 9 10 11 5.93 6.68 5.82 5.58 5.32 5.23 5.85 5.81 6.54 5.92 5.47 671009 1 2 3 4 5 6 7 8 9 10 11 6.21 5.87 5.73 6.31 5.63 5.77 6.17 6.20 6.15 6.27 6.50 Rib Skull Rib Skull Skull Skull Rib NAD NAD Supernumerary (site 14 rt) NAD NAD NAD NAD NAD Retarded Ossification (6 bil) NAD NAD DV VR NAD Supernumerary (site 14 bil) NAD NAD NAD NAD NAD Retarded Ossification (2 bil) NAD NAD NAD DV VR NAD Retarded Ossification (6 bil) NAD Retarded Ossification (1) NAD NAD NAD NAD NAD Supernumerary (site 14 rt) NAD VR VR DV 140 8-2 Telomer B Alcohol: 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 671009 (Cont.) 12 6.29 13 6.28 14 5.77 15 5.46 16 6.30 17 6.24 671010 1 2 3 4 5 6 6.05 5.89 6.40 6.25 6.21 6.71 7 6.43 8 6.27 9 6.44 10 6.28 671024 1 2 5.31 4.85 3 5.21 4 5.47 5 5.89 6 5.66 7 5.28 8 5.68 9 5.27 10 5.31 11 5.04 Rib Skull Skull Rib Vertebra Subcutis Skull Rib Supernumerary (site 14 bil) Retarded Ossification (1) NAD Retarded Ossification (2,7 bil;1) NAD Supernumerary (site 14 lt) NAD DV VR VR DV NAD NAD NAD NAD NAD Retarded Ossification (cen th11) NAD NAD NAD NAD VR NAD Hemorrhage (back*) Retarded Ossification (6,7 lt;1,12) NAD NAD NAD NAD Supernumerary (short 13 bil) NAD NAD NAD NAD N VR DV 141 8-2 Telomer B Alcohol: 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 671024 (Cont.) 12 5.74 13 5.33 14 5.48 15 6.17 1027 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 1028 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 Ossification (2,6 bil;1,12) Small Papilla - Size 2 (rt) Retarded Ossification (6 bil) NAD VR VR VR NAD NAD NAD NAD Supernumerary NAD NAD NAD NAD Supernumerary NAD Supernumerary NAD (site 14 bil) (site 14 bil) (site 14 bil) DV DV DV Hemorrhage NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD (right shoulder*) N 142 8-2 Telomer B Alcohol: Developmental 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 671029 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 5.37 4.71 5.00 5.58 Vertebra NAD NAD NAD Supernumerary (short 14 bil) Small Papilla - Size 1 (rt) Supernumerary (short 14 bil) NAD NAD Supernumerary (short 14 bil) NAD NAD NAD Retarded Ossification (cen th12) DV VR DV DV VR NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (6 bil) NAD Supernumerary (site 14 rt) Retarded Ossification (6 bil) Retarded Ossification (cen th12) NAD VR DV VR VR Retarded Ossification (cen th9) NAD NAD NAD NAD VR 143 8-2 Telomer B Alcohol: 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 671032 6 7 8 9 10 11 12 13 14 15 (Cont.) 5.07 5.72 5.28 4.81 5.37 4.99 5.06 4.88 5.32 5.44 671036 1 2 5.94 6.49 3 6.35 4 6.30 5 6.06 6 6.07 7 6.53 8 5.80 9 6.39 10 5.94 11 6.00 12 6.14 13 14 671037 1 2 3 4 5 5.72 6.57 6.12 6.14 5.97 5.93 5.96 Kidney Skull Kidney Rib Vertebra Rib Rib Rib Skull Rib Skull NAD Papilla - Size 3 (bil) NAD NAD Retarded Ossification (6 bil) NAD NAD NAD NAD NAD VR VR Papilla - Size 3 (bil) Supernumerary (site 14 lt) Retarded Ossification (cen th12) NAD NAD NAD Supernumerary (site 14 rt) Supernumerary (site 14 bil) NAD NAD Supernumerary (site 14 bil) Retarded Ossification (6 lt) NAD Supernumerary (site 14 lt) Retarded Ossification (6,7 bil;1) NAD NAD VR DV VR DV DV DV VR DV VR NAD NAD NAD NAD NAD 144 8-2 Telomer B Alcohol: 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 671037 6 7 8 9 10 11 12 13 14 (Cont.) 5.98 6.13 5.32 6.01 5.74 5.64 5.44 5.40 5.69 671038 1 5.86 2 6.07 3 6.28 4 6.51 5 5.64 6 6.38 7 6.08 8 6.19 9 5.67 10 6.34 11 5.66 12 5.92 13 671040 1 2 6.49 6.06 6.05 Sternebra Vertebra Vertebra Rib Vertebra Vertebra Rib Vertebra Vertebra Rib Sternebra Vertebra NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (6) Retarded Ossification (cen th9-11) NAD NAD Retarded Ossification (cen th11) Supernumerary (site 14 lt) Retarded Ossification (cen th11) Retarded Ossification (cen th13) Supernumerary (site 14 lt) Retarded Ossification (cen th10) Retarded Ossification (cen th8,10,11,13 lu1 ) Supernumerary (site 14 lt) NAD Retarded Ossification (6) Retarded Ossification (cen th13) NAD NAD NAD VR VR VR DV VR VR DV VR VR DV VR VR 145 8-2 Telomer B Alcohol: 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 3 4 5 6 7 8 9 (Cont.) 6.04 4.15 5.87 5.18 5.41 5.16 6.04 10 11 12 13 671049 1 2 3 4 5 6 5.03 5.82 5.92 5.33 6.01 5.04 5.70 6.13 5.72 5.43 7 5.50 8 5.84 9 6.00 10 5.51 11 5.59 12 5.98 13 4.97 Rib Skull Rib Vertebra Rib Rib Rib Skull Skull Skull Vertebra Skull Vertebra Skull Vertebra Skull Rib Supernumerary (site 14 lt) NAD NAD Retarded Ossification (6 bil) NAD NAD Supernumerary (site 14 bil) Retarded Ossification (cen th13) Supernumerary (site 14 lt) Supernumerary (site 14 bil) NAD NAD DV VR DV VR DV DV Supernumerary (site14 bil) Retarded Ossification (1,12;2,3,6,7,8 bil) NAD Retarded Ossification(2 bil) NAD Retarded Ossification (1,12;2,3 bil;6 rt) Retarded Ossification (cen th11) NAD Retarded Ossification (1,12;2,3,6,7,8 bil) Retarded Ossification (cen th10) Retarded Ossification (1,12;2,3,bil;6 rt) Retarded Ossification (cen th12) Retarded Ossification (1,12;2,3,6 bil) Supernumerary (site14 lt) DV VR VR VR VR VR VR VR VR VR DV 146 8-2 Telomer B Alcohol: 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 (site14 rt) Retarded Ossification (1,12;2,3,6,7,8 bil) Retarded Ossification (cen th10) DV VR VR 147 8-2 Telomer B Alcohol: 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 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 5.42 Skull Rib NAD Retarded Ossification NAD NAD NAD Retarded Ossification NAD Retarded Ossification NAD Retarded Ossification NAD Retarded Ossification NAD Retarded Ossification NAD (6 lt) (6 bil) (6 bil) (6 rt) (6 rt) (6 lt) VR VR VR VR VR VR NAD Fused (1 to 12) NAD Retarded Ossification (6, bil;7,8 lt) NAD Retarded Ossification NAD NAD NAD NAD NAD NAD NAD NAD (2 bil) DV VR VR NAD Retarded Ossification (2 bil) Rudimentary Cervical (7 lt) VR DV 148 8-2 Telomer B Alcohol: 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 670991 1 2 5.32 5.32 3 5.80 4 4.99 5 5.49 6 5.75 7 6.07 8 6.01 9 5.47 10 5.74 11 5.04 12 4.81 Rib Skull Rib Skull Rib Skull Skull Rib Skull Vertebra Skull Vertebra Skull Rib Vertebra Rib Skull Pelvis Skull Supernumerary (site 14 bil) Retarded Ossification (2 bil) Supernumerary (site 14 lt) Retarded Ossification (2 bil) Supernumerary (short 14 bil) Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) NAD NAD Supernumerary (site 14 lt) NAD DV VR DV VR DV VR VR DV NAD Retarded Ossification (2,6,7 bil;1,12) Retarded Ossification (cen th11) NAD Retarded Ossification (2,6,7,8 bil;12) Retarded Ossification (cen th10,11,12) NAD Retarded Ossification (6,7,8 bil) Supernumerary (site 14 bil) Retarded Ossification (cen th11,12) Supernumerary (site 14 rt) Retarded Ossification (6bil) Retarded Ossification (pubis bil) Retarded Ossification (2,6,7,8 bil;12) NAD NAD VR VR VR VR VR DV VR DV VR VR VR 149 8-2 Telomer B Alcohol: 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 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 Skull Subcutis Vertebra Skull Rib Skull Rib Skull Skull 671004 1 2 4.90 5.01 Skull Retarded Ossification (cen th11,12) VR NAD Retarded Ossification (2 bil,7 rt) NAD Retarded Ossification (2 bil) NAD Retarded Ossification (2 bil) Retarded Ossification (cen th11-12) Retarded Ossification (cen th9-11) Retarded Ossification (2,6,7 bil) NAD Hemorrhage (neck*) Retarded Ossification (cen th11) NAD Retarded Ossification (2 bil) Supernumerary (site 14 bil) Retarded Ossification (1;2 bil) Supernumerary (site 14 bil) Retarded Ossification (1,12;2 bil) Retarded Ossification (6,7,8 bil) VR VR VR VR VR VR N VR VR DV VR DV VR VR NAD Retarded Ossification (2,6,7,8 bil;1,12) VR 150 8-2 Telomer B Alcohol: 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 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 Ossification (pubis,ischium bil) Retarded Ossification (6) Retarded Ossification (2,6,7,8 bil;1,12) NAD Wavy (7-10 rt,11 bil) Retarded Ossification (2,3,6,7,8 bil;1) NAD Retarded Ossification (pubis,ischium bil) Retarded Ossification (2,3,6,7,8 bil;1,12) NAD Retarded Ossification (pubis,ischium bil) Retarded Ossification (2,3,7,8 bil;1) Retarded Ossification (ischium bil) Retarded Ossification (2,3,6,7,8 bil;1,12) Retarded Ossification (pubis,ischium bil) VR VR VR VR VR VR VR VR VR VR VR VR NAD NAD Small Papilla - Size 2 (bil) NAD NAD Supernumerary (site 14 rt) NAD NAD NAD NAD NAD VR DV 151 8-2 Telomer B Alcohol: 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 12 13 14 (Cont.) 5.75 6.29 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 13 5.13 14 5.23 15 5.21 16 5.05 671013 1 2 3 6.45 5.84 6.53 4 5.63 5 5.35 6 5.61 7 5.79 8 6.39 9 5.80 10 5.35 Skull Rib Skull Kidney Kidney Skull Skull Kidney Vertebra NAD NAD NAD NAD Retarded Ossification (6 bil) Supernumerary (site 14 rt) NAD NAD Retarded Ossification (6 bil) NAD NAD Papilla - Size 3 (bil) NAD Papilla - Size 3 (bil) Retarded Ossification (6,7,8 bil) NAD Retarded Ossification (2,6,7,8 bil) Small Papilla - Size 1 (lt) NAD VR DV VR VR VR VR VR VR NAD NAD Retarded Ossification (cen th10) NAD NAD NAD NAD NAD NAD NAD VR 152 8-2 Telomer B Alcohol: 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 8 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 Sternebra 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 (site 14 lt) Retarded Ossification (6 bil) NAD Supernumerary (site 14 bil) Supernumerary (site 14 rt) Retarded Ossification (6 bil) Retarded Ossification (6) Small Papilla - Size 1 (rt, size3 lt) Hemorrhage (back*) NAD Supernumerary (site 14 rt) Supernumerary (site 14 lt) Supernumerary (short 14 bil) DV VR DV DV VR VR VR N DV DV DV NAD Retarded Ossification (cen th11) NAD NAD NAD NAD Supernumerary (short 14 lt) Retarded Ossification (pubis lt) Supernumerary (site 14 lt) Supernumerary (short 14 lt) Retarded Ossification (6 lt) NAD NAD Retarded Ossification (cen th12) NAD Supernumerary (site 14 bil) Retarded Ossification (6 rt) NAD VR DV VR DV DV VR VR DV VR 153 8-2 Telomer B Alcohol: 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 7 8 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 Ossification (6) Retarded Ossification (2,6 bil) NAD Retarded Ossification (2,6,7,8 bil;12,) Retarded Ossification (6) NAD Retarded Ossification (pubis bil) Retarded Ossification (2 bil;1,12) Retarded Ossification (6) NAD Retarded Ossification (6 bil) NAD Retarded Ossification (2,6 bil) NAD Supernumerary (site 14 rt) Retarded Ossification (6 bil) NAD Retarded Ossification (2,6,7,8 bil;1,12) Hemorrhage (back*) VR VR VR VR VR VR VR VR VR DV VR VR N Retarded Ossification (pubis lt) Supernumerary (site 14 bil) Supernumerary (site 14 rt) Retarded Ossification (6) Retarded Ossification (6 lt) Retarded Ossification (6) NAD NAD Retarded Ossification (6 bil) NAD VR DV DV VR VR VR VR 154 8-2 Telomer B Alcohol: 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 671023 10 11 12 13 14 (Cont.) 4.17 4.74 4.34 4.36 4.14 Skull Rib Skull 671046 1 2 3 4 5 6 7 8 9 10 11 12 13 671047 1 2 3 4 5 6 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 Ossification (6 bil) Supernumerary (site 14 lt) Retarded Ossification (6,8 bil) VR DV VR NAD Wavy (6-10 rt) Retarded Ossification (2,6,7,8 bil;1,12) NAD Retarded Ossification (cen th10) Wavy (6-11 rt,10,11 lt) Wavy (4-13 bil) Retarded Ossification (2,6,7,8 bil;1,12) Retarded Ossification (6) NAD Wavy (5-13 bil) Retarded Ossification (6 rt;1) NAD NAD NAD Retarded Ossification (2,6,7,8 bil) NAD VR VR VR VR VR VR VR VR VR VR NAD NAD NAD NAD NAD NAD NAD 155 8-2 Telomer B Alcohol: 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 671047 8 9 10 (Cont.) 6.00 5.92 5.94 671057 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 (site 14 bil) Supernumerary (site 14 bil) Supernumerary (site 14 bil) Supernumerary (site 14 lt) Supernumerary (site 14 lt) NAD NAD Supernumerary (site 14 rt) Supernumerary (site 14 lt) Supernumerary (site 14 bil) NAD Supernumerary (short. 14: bil) Supernumerary (site 14 rt) Retarded Ossification (cen th11,13) NAD DV DV DV DV DV DV DV DV DV DV VR 156