Document M4Nkay9VdbXezQYKD09MeDbpz

AR226-2802 TRADE SECRET Study Title H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice Laboratory Project ID: DuPont-5206 AUTHOR: Susan A. MacKenzie, V.M.D., Ph.D., D.A.B.T. STUDY COMPLETED ON: June 13,2001 PERFORMING LABORATORY: E.I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Company Sanit8'?'"* nnnn . r>n"fain T<?^A f*m Page 1 of 71 .Company SanKized. Does not contain TSCA c6l H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Approved by: D.A.B.T.Date Qu^MfL^. -JU-oAhj^l //Judith C. Stadler, Ph.D., ^/ Director, Genera) Toxicology /.g-JW-gOO/ Issued by Study Director: DAB.T.Date SM*^I Q. '^SJ^KfA^^fJL,______ Susan A. MacKenzie, V.MS., PKD., Senior Research Scientist I 3-\J'UA>. S.OQ | Company Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 TABLE OF CONTENTS Page CERTinCATION........................................................................................................................2 STUDY INFORMATION.............................................................................................................5 STUDY PERSONNEL.................................................................................................................. 7 SUMMARY....................................................................................................................................8 10 INTRODUCTION....................................................................................................................... MATERIALS AND METHODS ............................................................................................... 10 A. Test Guidelines..................................................................................................................10 B. Test Substance................................................................................................................... 10 C. Test Species....................................................................................................................... 10 D. Animal Husbandry............................................................................................................ 11 E. Quarantine and Pretest Period........................................................................................... 12 F. Study Design..................................................................................................................... 12 G. Assignment to Groups and Study Start............................................................................. 12 H. Diet Preparation and Administration................................................................................. 13 I. Body Weights.................................................................................................................... 13 J. Food Consumption, Food Efficiency, and Intake of H-24648 and H-24020.................... 13 K. Clinical Observations and Mortality................................................................................. 13 L. Liver Weights.................................................................................................................... 13 M. Statistical Analyses............................................................................................................ 14 RECORDS AND SAMPLE STORAGE................................................................................... 14 RESULTS AND DISCUSSION ................................................................................................. 15 A. Mean Body Weights and Body Weight Gain.................................................................... 15 B. Mean Food Consumption, Food Efficiency, and Intake of H-24648 and H-24020.......... 15 C. Clinical Observations and Mortality................................................................................. 16 D. Liver Weights.................................................................................................................... 16 CONCLUSIONS......................................................................................................................... 18 19 REFERENCES............................................................................................................................ ^CompanySanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice____________________________________DuPont-5206 TABLE OF CONTENTS (Continued) Page 20 TABLES....................................................................................................................................... TABLE 1 MEAN BODY WEIGHTS OF MALE MICE ............................................................................................21 TABLE 2 MEAN BODY WEIGHTS OF FEMALE MICE........................................................................................22 TABLE 3 MEAN BODY WEIGHT GAINS OF MALE MICE..................................................................................23 TABLE 4 MEAN BODY WEIGHT GAINS OF FEMALE MICE.............................................................................24 TABLE 5 MEAN DAILY FOOD CONSUMPTION BY MALE MICE ....................................................................25 TABLE 6 MEAN DAILY FOOD CONSUMPTION BY FEMALE MICE................................................................26 TABLE 7 MEAN DAILY FOOD EFFICIENCY OF MALE MICE...........................................................................27 TABLE 8 MEAN DAILY FOOD EFFICIENCY OF FEMALE MICE ......................................................................28 TABLE 9 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY MALE MICE.............................................29 TABLE 10 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY FEMALE MICE......................................30 TABLE 11 SUMMARY OF CLINICAL OBSERVATIONS OF MALE MICE ........................................................31 TABLE 12 SUMMARY OF CLINICAL OBSERVATIONS OF FEMALE MICE....................................................32 TABLE 13 MEAN FINAL BODY AND LIVER WEIGHTS OF MALE MICE........................................................33 TABLE 14 MEAN FINAL BODY AND LIVER WEIGHTS OF FEMALE MICE ...................................................34 APPENDICES.............................................................................................................................35 APPENDDC A INDIVIDUAL BODY WEIGHTS ......................................................................................................36 APPENDIX B INDIVIDUAL FOOD CONSUMPTION............................................................................................42 APPENDIX C INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY.................................................48 APPENDDC D INDIVIDUAL FINAL BODY AND LIVER WEIGHTS ...................................................................62 Company Sanitized. Does not contain TSCA CBI M-/4t)4!< and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study m Mice ___ STUDY INFORMATION Test Substance No. 1 9th Collective Nomenclature: Synonyms/Codes: H-24648 DuPont-5206 Haskell Number: 24648 CAS Registry Number: Composition: Known Impurities: Physical Characteristics: Colorless liquid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. CompanySanKtzed. Does not contain TSCA CBI n-24048 and H-2W2U: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice STUDY INFORMATION (CONTINUED) Test Substance No. 2 9th Collective Nomenclature: Synonyms/Codes: DuPont-5206 Haskell Number: 24020 CAS Registry Number: Compositions Physical Characteristics: White solid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: Daikin Industries, Ltd. 1-1, Nishi-Hitotsuya, Settsu-shi Osaka 566-8585 Japan Study Initiated/Completed: 03-Nov-2000 / (see report cover page) In-Life Initiated/Completed: 06-Nov-2000 / 20-Nov-2000 Company Sani-hzed. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice _________ STUDY PERSONNEL Study Director: Susan A. MacKenzie, V.M.D., Ph.D. Management: Judith C. Stadler, Ph.D. Primary Technician: Robert E. Walker, Jr. Report Preparation: Cecilia R. Kee, B.S. Laboratory Veterinarian: William Singleton, D.V.M., A.C.L.A.M. Wanda L. West, D.V.M., A.C.L.A.M. DuPont Pharmaceuticals Company DuPont-5206 CompanySanded. Does not confa.n rsCACm H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 SUMMARY This study evaluated the relative potency of the two test substances, H-24020 and H-24648, to produce liver enlargement in mice. Groups of 5 male and 5 female mice were exposed for 14 days to control diet (0 ppm) or diet containing H-24020 or H-24648. Dietary concentrations for the two test substances were 1, 3,10, 30,100, or 300 ppm. Body weights, food consumption, and clinical observations were evaluated weekly. After the 14-day exposure period, all nonfasted mice were sacrificed and livers were removed and weighed. Mean overall (test day 0-14) daily intake of H-24020 in male mice exposed to 1, 3,10, 30,100, or 300 ppm was 0.20, 0.57,1.84, 5.76, 24.1, or 62.4 mg/kg/day, respectively; mean daily intake in female mice was 0.28, 0.68,2.52, 7.28,26.0, or 102 mg/kg/day, respectively. Mean daily intake of H-24648 in male mice exposed to 1, 3,10, 30,100, or 300 ppm was 0.19, 0.57, 1.83, 6.41, 23.8, or 83.0 mg/kg/day, respectively; mean daily intake in female mice was 0.21, 0.66, 2.37, 7.38, 25.6, or 98.8 mg/kg/day, respectively. No compound-related deaths occurred and no clinical observations were considered to be a direct response to exposure to either test substance, Overall (test day 0-14) body weight loss was observed in male mice fed 100 or 300 ppm of each test substance. Body weight losses were also observed in female mice fed 100 or 300 ppm of H-24648 or 300 ppm of H-24020. This severe toxicity prevents meaningful interpretation of liver weight effects in these groups. Compound-related reductions (compared to control) in body weight and body weight gain were also observed in male mice fed 30 ppm H-24648. No reductions in food consumption were observed in any group, therefore, effects on body weight gain reflected effects on food efficiency in male and female mice exposed to both test substances. Both test substances produced compound-related increases in liver weights compared to controls. No consistent differences in absolute or relative liver weight were observed between the two test substances. In male mice, statistically significant increases in both absolute and relative liver weights were observed in all groups fed diets containing either test substance. With both test substances, a monotonic dose-response was observed in mice exposed up to 100 ppm. No further increases in liver weight were observed in either male 300 ppm group. This lack of further increase was attributed to the body weight loss in these mice. In female mice, statistically significant increases in both absolute and relative liver weights were observed in mice fed diets that contained 3 ppm and above, with both test substances. With both test substances, a monotonic dose-response was observed up to 300 ppm, except for the absolute liver weight in female mice exposed to H-24020, where a plateau was observed in mice exposed to the two highest doses. Company Sanitized. Does not contain TSCA CB1 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice______________________________________DuPont-5206 Dietary exposure to H-24020 and H-24648 produced similar effects on liver weight in mice. Exposure to H-24648 produced a small, but consistently greater, effect on in-life parameters compared to H-24020. Under the conditions of this study, the no-observed-effect level (NOEL) for increased liver weight was less than 1 ppm in male mice (0.20 and 0.19 mg/kg/day for H-24020 and H-24648, respectively) and 1 ppm in female mice (0.28 and 0.21 mg/kg/day for H-24020 and H-24648, respectively). No notable differences in the magnitude of liver weight effect were observed between the two test substances. Males were more sensitive than females to the in-life and liver weight effects of both test substances; however, the magnitude of effect at the highest exposure level was similar for males and females exposed to both test substances. Company SanHfaed. Does not contain TSCA CB H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice______________________________________DuPont-5206 INTRODUCTION The test substances, H-24648 and H-24020, are isomeric mixtures ofRM^^I^------ ^^UUUJ----bontaining different amounts of straight and branched chain forms of me test substance. H-24648 contains only the straight chain form, while H-24020 contains both straight chain and branched chain forms. The sample of H-24020 tested in this study contained approximately 75% straight chain and 25% branched chain forms. In a previous study/0 the isomeric mixture contained in H-24020 produced elevated liver weights in male and female mice following dietary exposures of 3 ppm or greater for either 14 or 21 days. No increase was observed with dietary exposures of 1 ppm or less/0 No data are available to assess the potential for the isomeric mixture contained in H-24648. The objective of this study was to compare the 2 isomers for their relative potential to produce liver enlargement in male and female mice. The oral route of administration was selected because it was the route of exposure previously used to demonstrate liver enlargement with H-24020/0 MATERIALS AND METHODS A. Test Guidelines None were applicable. B. Test Substance The following substances were tested: H-24648 (10% solution in water of active ingredient) H-24020 (white solid) H-24648 was supplied by Daikin Industries, Ltd. H-24020 was supplied by DuPont Chemical Solutions Enterprise. The test substance appeared to be stable under the conditions of the study. No evidence of instability, such as a change in color or physical state, was observed. C. Test Species On 26-0ct-2000, 71 male and 71 female Crl:CD-l(ICR)BR mice, with an assigned birth date of 18-Sep-2000, were received from Charles River Laboratories, me., Raleigh, North Carolina. The Crl:CD-l(ICR)BR strain was chosen because the Crl:CD-l mouse was the strain and species used previously to evaluate liver responses to H-24020.0) Furthermore, extensive background information is available from the literature, the supplier and previous studies at 10 Company Sanlfaed. Does not contain T8CA CBI ^Qb ^y- H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice______________________________________DuPont-5206 Haskell Laboratory. This species/strain also is considered suitable relative to longevity, hardiness, sensitivity to the test substance, and low incidence of spontaneous diseases. D. Animal Husbandry 1. Housing and Environmental Conditions All mice were housed in stainless steel, wire-mesh cages suspended above cage boards. Mice were housed 3 per cage, sexes separate, prior to assignment to groups and individually after assignment to groups. Cage racks were relocated within the animal room each week. Animal rooms were maintained on a 12-hour light/dark cycle (fluorescent light) and at a temperature of 22 3C and a relative humidity of 50 20%. 2. Feed and Water Tap water was provided ad libitum. All mice were fed PMI Nutrition International, me. Certified Rodent LabDiet 5002 ad libitum. During the test (exposure) period, test substance was incorporated into the food at concentrations specified by study design. 3. Identification Prior to assignment to groups, each mouse was temporarily identified by either the presence or absence of a colored tail mark and cage identification. The information on the cage labels included the unique 6-digit Haskell animal number and the individual identification number assigned to each mouse. After assignment to groups, the last 3-4 digits of the individual identification number were marked on the tail of each mouse. 4. Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence ofcoliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fimgal 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. 11 Company Sanded. Does not contain TSCA C H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Data are maintained separately from study records and are not included in the final report. Evaluation of these data did not indicate any conditions that affected the validity of the study. E. Quarantine and Pretest Period Upon arrival at Haskell Laboratory, the mice were quarantined for 6 days of the 11 day pretest period. The mice were observed daily for any clinically apparent signs of disease or injury and were weighed 3 times. On the bases of acceptable body weight gains and clinical observations, all mice were released from quarantine on test day -5 by the laboratory animal veterinarian designee. F. Study Design Gr oup Male Female I n m V vn IX XI Xffl XV xvn XIX XXI XXffl XXV IV VI vm x xn xrv XVI XVffl XX xxn XXIV XXVI No./Group 5 5 5 5 5 5 5 5 5 5 5 5 5 Dietary Cone. (ppm)' 0 ppm 1 ppm 3 ppm 10 ppm 30 ppm 100 ppm 300 ppm 1 ppm 3 ppm 10 ppm 30 ppm 100 ppm 300 Ppm Test Substance Control H-24020 H-24020 H-24020 H-24020 H-24020 H-24020 H-24648 H-24648 H-24648 H-24648 H-24648 H-24648 a Weight/weight concentration of test substance (adjusted for purity). G. Assignment to Groups and Study Start Mice were selected for study use on the bases of adequate body weight gain, freedom from any clinical signs of disease or injury, and a body weight within 20% of the mean within a sex. The selected mice were distributed by computerized, stratified randomization so that there were no statistically significant differences among group body weight means within a sex. 12 Company Sanitized. Does not contain TSCA cm H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice____________________________________DuPont-5206 Dietary administration of H-24648 and H-24020 began on test day 0 when the mice were approximately 42 days of age. H. Diet Preparation and Administration H-24648 was received from the sponsor as a 10% solution in water. H-24020 was dissolved in deionized water, to the same concentration of active ingredient as H-24648, prior to mixing with diet. The same vehicle, deionized water, was added to control diets at the same volume as that used in the high concentration diets. H-24020 and H-24648 were added to PMI Nutrition International, me. Certified Rodent LabDiet 5002 and thoroughly mixed for 3 minutes. Control diets were mixed for the same period of time. Diets were prepared once, prior to the first day of dietary exposure, and refrigerated until used, I. Body Weights All mice were weighed once per week. J. Food Consumption, Food Efficiency, and Intake of H-24648 and H-24020 The amount of food consumed by each mouse over each weighing interval was determined throughout the study. From these determinations and body weight data, mean daily food consumption, mean food efficiency, and mean daily intake of H-24648 and H-24020 were calculated. K. Clinical Observations and Mortality Cage-site examinations to detect moribund or dead mice and abnormal behavior and appearance among mice were conducted at least once daily throughout the study. At every weighing, each mouse was individually handled and examined for abnormal behavior and appearance. Animal 124579 in Group IV was found dead on test day 1 and discarded without pathological evaluation. L. Liver Weights Surviving, non-fasted mice were sacrificed following the 14-day exposure period (test day 14). Mice were euthanatized by carbon dioxide anesthesia and exsanguination. The order of sacrifice was random among all treatment groups within a sex. The liver from one mouse in group XXin (male; 100 ppm H-24648) was inadvertently not weighed. The livers from all other mice sacrificed by design were removed and weighed. Relative liver weights (percent of final body weight) were calculated, using final body weights determined just prior to necropsy. 13 Company Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice M. Statistical Analyses __ ^^ DuPont-5206 Significance was judged at p < 0.05. The following statistical methods were used to compare data from the test groups to data from the control group. Parameter Body Weight Body Weight Gain Food Consumption Food Efficiency Liver Weight Preliminary Test Test for lack of trend^ Levene's test for homogeneity^ and Shapiro-Wilktest^ for normality1' Method of Statistical Analysis If preliminary test is If preliminary test is not significant significant Sequential application^ of the Preliminary tests for Jonckheere-Terpstra pairwise comparison trend testw OR3 One-way analysis of variance^ followed with Dunnett's test^ Kruskal-Wallis test^ followed with Dunn's test^ Incidence of Clinical Observations None Cochran-Armitage test for trend^0 a Pairwise comparisons and associated preliminary tests were only conducted if the test for lack of trend was significant. b If the Shapiro-Wilk test was not significant but Levene's test was significant, a robust version of Dunnett's test was used. c If the incidence was not significant, but a significant lack of fit occurred, then Fisher's exact test0^ with a Bonferroni correction was used. Absolute and relative (to body weight) liver weights were also compared between mice exposed to the two test substances using 2-way analysis of variance, followed by linear contrasts.^ RECORDS AND SAMPLE STORAGE All data and records for analytical characterizations conducted by the sponsor will be archived by the sponsor. Raw data and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware -CompanySanitized. Does not contain TSCA CM 14 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice_______________ RESULTS AND DISCUSSION DuPont-5206 A. Mean Body Weights and Body Weight Gain (Tables 1-4, Appendix B) In mice exposed to H-24020, exposure to 100 ppm (males only) or 300 ppm (males and females) produced reductions (compared to control) in mean final body weight and overall body weight gain (variable statistical significance). In males, mean final body weight in the 100 and 300 ppm groups was 84% and 72% of control, respectively. Both groups lost weight over the 14-day exposure period. Males exposed to 100 and 300 ppm H-24020 lost 8% and 23%, respectively, of initial body weight. Mean body weight and body weight gain in male groups exposed to 30 ppm or below were comparable to control. In females, mean final body weight in the 300 ppm group was 78% of control and this group lost 13% of initial body weight over the 14-day exposure period. The female groups exposed to 30 and 100 ppm had mean body weight loss over the first week of exposure (3% and 1% of initial body weight, respectively), but body weight gain over the second week exceeded that of control, resulting in overall (test day 0-14) body weight gain that was comparable to control. Some of this increased weight gain over the second week of exposure represents increased liver weight (observed at necropsy). In mice exposed to H-24648, exposure to 30 ppm and above (males) and to 100 or 300 ppm (females) produced reductions (compared to control) in mean final body weight and overall body weight gain (variable statistical significance). Exposure to 100 or 300 ppm produced mean overall (test day 0-14) body weight loss in both sexes. Mean final body weight in males exposed to 100 and 300 ppm were 81% and 70% of control, respectively. Males exposed to 100 and 300 ppm of H-24648 lost 12% and 22%, respectively, of initial body weight. Mean final body weight in females exposed to 100 and 300 ppm were 89% and 76% of control, respectively. Females exposed to 100 and 300 ppm of H-24648 lost 2% and 18%, respectively, of initial body weight. In males exposed to 30 ppm, mean overall body weight gain was 53% of control (not statistically significant), due to body weight loss over the second week of exposure. Mean final body weight in this group was 93% of control. These differences were all considered biologically significant due to the magnitude of effect, although not all were statistically significant. Males were more sensitive than females to the body weight effects of exposure to both compounds. Exposure to H-24648 produced effects on body weight and body weight gain that were generally of greater magnitude than those produced by exposure to H-24020. B. Mean Food Consumption, Food Efficiency, and Intake of H-24648 and H-24020 (Tables 5-10, Appendix C) No compound-related effects on food consumption were produced by exposure to H-24020 in male or female mice or by exposure to H-24648 in male mice. Statistically significant increases in mean food consumption over test days 0-7 and 0-14 were observed in female mice exposed to 15 CompanySanitized. Does no* contam TSCA CB H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice______________________________________DuPont-5206 300 ppm H-24648. Food consumption in female mice exposed to 100 ppm and below of H-24648 was comparable to control. In mice exposed to H-24020, exposure to 100 ppm (males only) or 300 ppm (males and females) produced reductions in overall food efficiency, compared to controls. In mice exposed to H-24648, exposure to 30 ppm and above in males and 100 ppm and 300 ppm in females produced reductions in overall food efficiency, compared to controls. Food efficiency reflected body weight gain effects in all groups. The gender- and compound-related patterns observed with body weight gain were also observed with food efficiency Mean overall (test day 0-14) daily intake of H-24020 in male mice exposed to 1, 3,10,30,100, or 300 ppm was 0.20, 0.57,1.84, 5.76, 24.1, or 62.4 mg/kg/day, respectively. Mean daily intake of H-24020 in female mice exposed to 1, 3, 10, 30,100, or 300 ppm was 0.28, 0.68,2.52, 7.28, 26.0, or 102 mg/kg/day, respectively. Mean daily intake of H-24648 in male mice exposed to 1, 3,10, 30, 100, or 300 ppm was 0.19, 0.57,1.83, 6.41, 23.8, and 83.0 mg/kg/day, respectively. Mean daily intake of H-24648 in female mice exposed to 1, 3,10, 30,100, or 300 ppm was 0.21, 0.66, 2.37, 7.38,25.6, or 98.8 mg/kg/day, respectively. Overall (test day 0-14) intake of H-24648 by male mice in the 300 ppm group was 33% higher than intake by the 300 ppm males exposed to H-24020. However, in general, mean daily intake of the 2 test substances was similar between groups of the same gender exposed to the same dietary concentration. Therefore, responses were compared in mice exposed to the same approximate administered dose, as well as the same dietary concentration. C. Clinical Observations and Mortality (Tables 11-12, Appendix D) One female mouse exposed to 1 ppm of H-24020 was found dead on test day 1. The cause of death was not determined but it was not considered to be compound related as there were no deaths in mice exposed to higher concentrations of H-24020. No other early deaths and no compound-related clinical observations occurred in mice exposed to H-24020. No early deaths occurred in mice exposed to H-24648. Enophthalmus was observed in 2 male and 1 female mouse exposed to 300 ppm H-24648 (not statistically significant). This effect is not considered to be a direct compound-related effect, but may have been secondary to the severe body weight effect observed in this group. No other clinical signs were observed that were attributed to exposure to H-24648. D. Liver Weights (Tables 11-12, Appendix E) Exposure to H-24020 and H-24648 produced statistically significant increases in absolute and relative (liver weight/final body weight) liver weights in all treated male groups. Exposure to H-24020 and H-24648 produced statistically significant increases in absolute and relative liver weights in female groups exposed to 3 ppm and above. 16 CompanySanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice______________________________________DuPont-5206 In male mice exposed to H-24020, the increase in absolute and relative liver weights demonstrated a dose-response up to the 100 ppm concentration. Absolute and relative liver weights were also increased in the 300 ppm group (compared to control) but the magnitude of the effect was less than that of the 100 ppm group. Mean absolute liver weights in the 1-100 ppm groups ranged from 117%-275% of control; mean absolute liver weight in the 300 ppm group was 229% of control. Mean relative liver weights in the 1-100 ppm groups ranged from 116%329% of control; mean relative liver weight in the 300 ppm group was 319% of control. In male mice exposed to H-24648, the increase in absolute and relative liver weights demonstrated a dose-response up to the 100 ppm concentration. Absolute and relative liver weights were also increased in the 300 ppm group (compared to control) but the magnitude of the effect was less than that of the 100 ppm group. Mean absolute liver weights in the 1-100 ppm groups ranged from 131%-279% of control; mean absolute liver weight in the 300 ppm group was 213% of control. Mean relative liver weights in the 1-100 ppm groups ranged from 124%- 344% of control; mean relative liver weight in the 300 ppm group was 305% of control. Therefore, exposure to H-24020 and H-24648 produced the same effect on liver weight, relative to control, in male mice. In female mice exposed to H-24020, the increase in absolute and relative liver weights demonstrated a dose-response in mice exposed to 3-300 ppm. Mean absolute liver weights in the 3-300 ppm groups ranged from 108%-254% of control. Mean relative liver weights in the 3-300 ppm groups ranged from 114%-314% of control. Mean absolute and relative liver weights in the 1 ppm group were comparable to control (101% and 104% of control, respectively). In female mice exposed to H-24648, the increase in absolute and relative liver weights demonstrated a dose-response in mice exposed to 3-300 ppm. Mean absolute liver weights in the 3-300 ppm groups ranged from 123%-275% of control. Mean relative liver weights in the 3300 ppm groups ranged from 125%-358% of control. Mean absolute and relative liver weights in the 1 ppm group were higher than in control (106% and 111% of control, respectively). These differences were not statistically significant from control nor from each other and there was overlap between the ranges of the 2 groups. Therefore, the small increase in liver weight in the 1 ppm groups was not considered biologically significant, but was probably close to the threshold for liver weight effects. Thus, exposure to H-24020 and H-24648 produced the same effect on liver weight, relative to control, in female mice. Similar general trends in liver weight responses were observed with both test substances, although males demonstrated greater sensitivity than females to the liver effects of both test substances. Males demonstrated enlarged livers in all exposed groups. Liver enlargement was not observed in females exposed to 1 ppm of H-24020. Small increases in liver weight were observed in females exposed to 1 ppm of H-24648 but the differences were not considered biologically significant. The magnitude of the liver weight effect reached a plateau and/or decreased at the highest concentration in males, while the effect increased or demonstrated a plateau up to the highest concentration tested in females. This was attributed to the body weight loss observed in these mice. The magnitude of the peak effect was similar in males and females. .CompanySanitized. Does not contain TSCA CB ^ H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice______________________________________DuPont-5206 In a previous study,0)increased liver weights were not observed in male mice fed 1 ppm of the isomeric mixture contained in H-24020. The mean daily intake of the test substance was not reported for that study; therefore, the reason for the difference in the no-observed-effect level cannot be determined. There was no biologically significant difference observed in the liver response to the two test substances. Both demonstrated the same approximate NOEL, the same sex difference in sensitivity, and the same plateau and/or decrease in response at the highest concentration in males. At a given dietary concentration and for a given gender, the magnitude of response to H-24648 was almost always higher than that of the response to H-24020, when compared to control. When the absolute and relative liver weights were compared statistically between mice exposed to the 2 test substances, a few statistically significant differences were observed. However, they occurred sporadically (only at one or two doses per sex). There was no consistent pattern to the differences, and the magnitude of differences was small. Therefore, they were not considered to be biologically significant. CONCLUSIONS Under the conditions of this study, there was no biologically significant difference in the liver response of mice fed the two test substances. There was no NOEL for liver weight gain in male mice exposed to H-24020 or H-24648, as increases in absolute and relative (liver weight/final body weight) liver weights were observed in all treated male groups. The NOEL for liver weight effects in female mice exposed to H-24020 and H-24648 was 1 ppm, as statistically significant increases in absolute and relative liver weights were observed in female groups exposed to 3 ppm and above. Exposure to H-24648 produced a small but consistently greater effect on in-life parameters than H-24020. Company Sanitized. Does not contain TSCA CBI 18 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice _______ REFERENCES 1. Kennedy G.L. (1987). Increase in mouse liver weight following feeding of| DuPont-5206 2. Draper, N.R. and Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. Wiley, New York. 3. 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. 4. Jonckheere, A.R. (1954). A distribution-free K-sample test against ordered alternatives. Biometrika 41, 133-145. 5. Levene, H. (1960). Robust test for equality of variances. Contributions to Probability and Statistics (J. Olldn, ed.), pp 278-292. Stanford University Press, Palo Alto. 6. Shapiro, S.S. and Wilk., M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611. 7. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th edition, pp 246-248 and 349-352. The Iowa State University Press, Iowa. 8. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50, 1096-1121. 9. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Amer. Statist. Assoc. 47, 583-621. 10. Fisher, R.A. (1985). Statistical Methods for Research Workers, 13th edition. Hafmer, New York. CompanySanltteea. Does not contain TSCA CBi 19 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ______ DuPont-5206 TABLES 9 CompanySanKfeed. Does not contain TSCA CBI 20 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE 1 MEAN BODY WEIGHTS OF MALE MICE Day 0 Day 7 Day 14 Mean Body Weights (g) of Mice Fed Diet Containing H-24020 Gr oup I 0 :ppm III Gr oup 1 ppm Group V 3 ppm Group VII 10 ppm Gro up IX 30 ppm Group XI 10 0 ppm 29 .3 1 .8(5) 30 .6 2 .1(5) 32 .3 2 .4(5) 29 .2 1 .9(5) 31 .3 1 .7(5) 32 .8 2 .0(5) 29.4 2.6(5) 31.0 2.9(5) 32.5 3.3(5) 29.5 2.2(5) 31.2 2.2(5) 32.8 2.4(5) 29. 5 1. 7<5) 31. 8 1. 6(5) 33. 0 1. 2(5) 29. 3 1. 2(5) 29. 3 1. 2(5) 27. 0 1. 3(5) Mean Body Weights (g) of Mice Fed Diet Containing H-24648 Gr oup I 0 ppm Gr oup XV 1 ppm Group XVII Group XIX 3 ppm 10 ppm Gro up XXI 30 ppm Group XXI 100 ppm Day 0 Day 7 29 .3 1 .8(5) 30 .6 2 .1(5) 30 .0 1 .4(5) 32 .7 1 .6(5) 29.7 1.5(5) 31.6 2.0(5) 28.0 1.8(5) 30.0 1.4(5) 28. 4 1. 7.(5) 30. 3 2. 0(5) 29. 7 3. 0(5) 27. 5# 2. 3(5) Day 14 32 .3 2 .4(5) 34 .1 1 .8(5) 33.8 1.8(5) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0 .05. 32.2 2.0(5) 30. 0 2. 7(5) 26. 2# 1. 2(5) 21 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE 2 MEAN BODY WEIGHTS OF FEMALE MICE Day 0 Day 7 Day 14 Mean Body Weights (g) of Mice Fed Diet Containing H-24020 I I G n 3Up 0 ]ppm Gro up IV 1 P pm GrOU]p VI 3 :ppim Group VII I Grioup X 10 ppm 30 ppm Group X 100 ppm 24 .2 1 .0(5) 25 .0 1 .7(5) 26 .8 0 .8(5) 23. 7 0. 6(5) 24. 6 0. 4(4) 25. 7 0. 2(4) 23 .5 0 .7 (5) 24 .8 0 .7 (5) 25 .3 1 .0 (5) 23.5 1.4(5) 25.4 2.0(5) 26.5 2.0(5) 24 .0 1 .3(5) 23 .4 0 .9(5) 26 .5 0 .9(5) 23. 9 1. 2(5) 23. 6 1. 4(5) 26. 1 2. 6(5) Mean Body Weights (g) of Mice Fed Diet Containing H-24648 I I Group 0 ppm Group XVI Group XVIII Group XX 1 ppm 3 ppm 10 ppm Gr oup XXII Group X 30 ppm 100 ppm Day 0 24 .2 1 .0(5) 23. 7 1. 4(5) 24 .0 1 .2 (5) Day 7 25 .0 1 .7(5) 24. 6 1. 5(5) 25 .3 1 .4 (5) Day 14 26 .8 0 .8(5) 25. 6 1. 7(5) 26 .4 1 .3 (5) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0.05. 23.6 1.7(5) 24.2 1.9(5) 26.0 2.6(5) 23 .1 1 .3(5) 24 .5 0 .9(5) 26 .5 1 .1(5) 24. 4 1. 8(5) 24. 4 1. 4(5) 23. 8 1. 9(5) 22 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLES MEAN BODY ^WEIGHT GAINS (3FMALEMICE Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Body Weight Gains (g) of Mice Fed Diet Contclining H-240;i0 Group I 0 ppm I I I Gr oup 1 ppm Group V 3 ppm G roup VII 10 ppm Group IX 30 ppm Group X 100 ppm 1.4 0.5(5) 2 .1 0 .6(5) 1.6 0.4(5) 1.6 0.5(5) 2.3 0.5(5) -0 .0 1 .0(5) 1.7 0.4(5) 1 .4 0 .4(5) 1.5 0.5(5) 1.6 0.5(5) 1.2 0.5(5) -2 .3# 1 .1(5) 3.0 0.8(5) 3 .5 0 .8(5) 3.1 0.9(5) 3.3 0.6(5) 3.5 0.9(5) -2 .4 1 .3(5 Mean Body Weight Gains (g) of Mice Fed Diet Containing H-24648 1 Group I Group XV Group XVII Group XIX Group XXI Group 0 0 ppm 1 ppm 3 ppm ,10 ppm 30 ppm 100 pp Day 0 - Day 7 1.4 0.5(5) 2 .7 0 .3(5) 1.8 0.9(5) 2.1 0.6(5) 1.9 1.0(5) -2 .2 2 .9(5) H w 0) Day 7 - Day 14 1.7 1 .5 3 0.4(5) 0 .3(5) 9 Q. Day O - Day 14 3.0 4 .1 0 0.8(5) 0 .6(5) 0 to Data summarized as: Mean (0 3 Standard Deviation (n) 2.3 0.4(5) 4.1 0.6(5) 0 Statistical Methods: Trend test (Jonckheere-Terpstra). 0 0 # Statistically significant difference at p < 0.05. S ^ 0 l 23 0 CO 2.1 0.8(5) 4.2 1.0(5) -0.3 2.0(5) 1.6 1.7(5) -1 3# 1 .4(5) -3 .5# 3 .0(5) H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice______________ TABLE 4 MEAN BODY WEIGHT GAINS OF FEMALE MICE Day 0 - Day 7 Day 7 - Day 14 Day O - Day 14 Mean Body Weight Gains (g) of Mice Fed Diet Containing H-24020 I I G r o u p 0 ppm Group IV 1 ppm G roup VI 3 ppm Group VIII 10 ppm Group X 30 ppm Group 100 p 0.8 1.1(5) 0.7 0.6(4) 1.3 0.8(5) 1.9 1.3(5) -0.6 1.1(5) -0.3# 0.5( 1.8 1.1 0.5 1.1 3.1 2.5 1.1(5) 0.5(4) 0.5(5) 0.6(5) 0.7(5) 1.8( 2.6 1.9 1.8 3.0 2.5 2.2 0.7(5) 0.4(4) 1.2(5) 1.2(5) 0.7(5) 1.7( Mean Body Weights Gains (g) of Mice Fed Diet Containing H-24648 I I G r o u p 0 ppm Group XVI 1 ppm Gr oup XVIII Group XX 3 ppm 10 ppm Group XXII Group 30 ppm 100 pp Day 0 - Day 7 Day 7 - Day 14 0.8 1.1(5) 1.8 1.1(5) 0.8 0.5(5) 1.0 0.3(5) 1.2 0.5(5) I.I 0.6(5) 0.6 0.4(5) 1.8 1.3(5) 1.4 0.7(5) 1.9 0.3(5) 0.1 1.9( -0.6 1.1( Day 0 - Day 14 2.6 0.7(5) 1.8 0.7(5) 2.3 0.9(5) 2.4 1.2(5) 3.3 0.4(5) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra) and/or non-parametric test # Statistically significant difference at p < 0.05 using Jonckheere-Terpstra. @ Statistically significant difference at p < 0.05 using Dunn's test. -0.6 2.6( (Dunn's). 24 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________ TAB LE5 MBAN DAILY FOOECO]SrSUMPTI ON BY M.ALEMK:E Mean Da:Lly Fc>od Corisumption (g) by Mice Fed Diet Contairling H-24020 Gr oup I 0 ppm I I I Gr oup 1 ppm Gro up V 3 ppm (3roup VII 10 ppm Group IX 30 ppm Groupi XI 100 ppm Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 5. 9 0. 7(5) 6. 1 0. 9(5) 6. 0 0. 7(5) 6 .2 0 .8(5) 6 .3 0 .5(5) 6 .3 0 .6(5) 5. 6 0. 3(5) 6. 3 0. 6(5) 6. 0 0. 3(5) 5.9 0.3(5) 5.9 0.3(5) 5.9 0.2(5) 5. 7 0. 5(5) 6. 7 1. 4(5) 6. 2 0. 9(5) 5. 6 0. 7(5 7. 8 1. 1(5 6. 7 0. 8(5 Mean Daily Food Consumption (g) by Mice Fed Diet Containing H-24648 Group I 0 ppm Group XV 1 ppm Group XVII 3 ppm Group XIX 10 ppm Group XXI 30 ppm Group 100 p 0' 0 1 Day 0 - Day 7 5. 9 6 .2 6. 3 5.9 5. 9 6. 6 so 0. 7(5) 0 .3(5) 0. 4(5) 0.2(5) 0. 8(5) 1. 6(5 ^ W Day 7 - Day 14 6. 1 6 .5 6. 1 5.5 6. 8 6. 0 B) 0. 9(5) 0 .5(5) 0. 5(5) 0.5(5) 0. 8(5) 1. 1(5 S W t0 Day 0 - Day 14 6. 0 6 .4 a. 0. 7(5) 0 .4(5) a Data summarized as: Mean (0 Standard Devi ation (n) 6. 2 0. 4(5) 5.7 0.3(5) 6. 4 0. 6(5) 6. 3 1. 2(5 0 Statistical Methods: Trend test (Jonckheere-Terpstra). ? # Statistically significant difference at p < 0. 05. 5sr. 5' ^ 0 25 s o C3 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TAB LE6 MEi\NDAD.Y FOOD (:ON;SUMPTICN BY FE^IALE MICE Mean Da.ily E'ood Corisumption (g) by Mice Fed Diet Containing H-241020 I I G]roup 0 ppm Gr.oup IV 1 Ppm Gro up VI 3 ppm Gro 10 u p p p V m I I I Group X 30 ppm Group 100 p Day 0 - Day 7 5 .9 1 .1(5) 7 .2 2 .6(4) 5. 1 0. 5(5) 6.0 0.8(5) 5.8 0.5(5) 6.0 1.0(5 Day 7 - Day 14 6 .2 1 .3(5) 7 .0 0 .9(4) 6. 3 0. 9(5) 6.9 1.4(5) 6.3 0.9(5) 7.0 1.6(5 Day 0 - Day 14 6 .1 1 .2(5) 7 .1 1 .6(4) 5. 7 0. 6(5) 6.5 1.0(5) 6.1 0.5(5) 6.5 1.0(5 Mean Daily Food Consumption (g) by Mice Fed Diet Containing H-24648 II Group Group XVI Group XVIII Group XX Group XXII Group 0 Ppm 1 ppm 3 ppm 10 ppm 30 ppm 100 p 3 1 Day 0 - Day 7 5 .9 5 .5 5. 5 6.1 5.7 6.4 1 1 .1(5) 0 .5(5) 0. 5(5) 1.5(5) 0.8(5) 0.4(5 1< w Day 7 - Day 14 6 .2 5 .1 5. 8 5.8 6.8 5.9 1 .3(5) 0 .2(5) 1. 0(5) 0.8(5) 1.9(5) 0.7(5 N" Day 0 - Day 14 6 .1 5 .3 . 1 .2(5) 0 .4(5) S' Data summarized as: Mean n> w Standard Deviation (n) 5. 7 0. 6(5) 5.9 1.1(5) 6.3 1.3(5) 6.1 0.4(5 0 Statistical Methods: Trend test (Jonckheere-Terpstra). ? # Statistically significant difference at p < 0. 05. 3 a? 5" ^ ? 26 g 5 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE? M EA]N DAILY F OOD EFFICIENCY OF MALE MICE 0 o u ^ S? 3 ?? (D P. a a CD m a 0 ? = ST 5" M -> &> 0 x Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Da:ily Foiod Efficiesncy of Mic<3 Fed Diet Ccintaining H-2 4020 (Sr body wei ght gain/g food consump tion) Gr oup I 0 :ppm I I I (Sroup 1. Ppm Group V 3 ppm Group VI][ . 10 ppm Group IX 30 ppm Group 100 p 0. 032 0. 009 (5) 0.049 0.017(5) 0.040 0.010(5 ) 0.040 0.011(5) 0.059 0.011(5 ) -0.00 0.02 0. 039 0. 009 (5) 0. 036 0. 007 (5) 0.033 0.009(5) 0.041 0.009(5) 0.034 0.009(5 ) 0.037 0.008(5 ) 0.040 0.012(5)i 0.040 0.007(5)i 0.024 0.008(5 ) 0.040 . 0.006(5 ) -0.04 0.02 -0.02 0.01 Mean Da:ily Foiod Efficitmcy of Micia Fed Diet Ccmtaining H-2 4648 (SF body wei ght gain/g food consump tion) Gr oup I 0 :ppm G:roup XV 1 ppm Group XVII 3 ppm Group XIX 10 ppm Group XXI 30 ppm Group XX 100 ppm Day 0 - Day 7 0. 032 0. 009 (5) 0 .061 0 .007(5) 0.042 0.019(5) 0.051 0.017(5) 0.046 0.022(5) -0.058 0.076(5 Day 7 - Day 14 0. 039 0. 009 (5) 0 .032 0 .006(5) 0.054 0.012(5) 0.056 0.020(5) -0.005 0.044(5) -0.036# 0.036(5 Day 0 - Day 14 0. 036 0. 007 (5) 0 .046 0 .005(5) 0.048 0.008(5) Data summarized as: Mean Standard Devi ati on (n) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0.05. 0.053 0.013(5) 0.019 0.022(5) -0.046 0.046(5) 27 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice 77 \BLES ME^WD^ULY FOOD I EFFICIENCY OF FEMAL]EMIC:E Mean Daily Pood Efficiency of Mice Fed Diet Cont<aining H-24020 (g b<sdy weight cjain/g food consumptic>n) I I G:r o u p 0 ppm Group XVI 1 ppm G roup XVIII 3 ppm Group XX 10 ppm Group XXII 30 ppm Grou p 100 p Day 0 - Day 7 0 .017 0 .026(5) 0. 018 0. 020(4) 0 .038 0 .024(5) 0.049 0.038(5) -0 .014 0 .026(5) -0 .0 0 .0 Day 7 - Day 14 0 .044 0. 023 0 .010 0.024 0 .070 0 .0 0 .029(5) 0. 010(4) 0 .008(5) 0.013(5) 0 .009(5) 0 .0 Day 0 - Day 14 0 .031 0. 020 0 .022 0.036 0 .030 0 .0 0 .010(5) 0. 008(4) 0 .013(5) 0.018(5) 0 .011(5) 0 .0 0 1 Mean Daily Food Efficiency of Mice Fed Diet Containing H-24648 (g body weight gain/g food consumption) II 1y Group Group XVI Group XVIII Group XX Group XXII Group 0 ppm 1 ppm 3 ppm 10 ppm 30 ppm 100 p ? Day 0 - Day 7 0 .017 0. 022 0 .032 0.015 0. 036 0. 00 n. 0 .026(5) 0. 011(5) 0 .014(5) 0.011(5) 0. 020(5) 0. 04 0 0 S (n Day 7 - Day 14 0 .044 0. 028 0 .029 0.044 0. 042 -0. 01 3 0 .029(5) 0. 010(5) 0 .021(5) 0.028(5) 0. 009(5) 0. 02 0 Day 0 - Day 14 0 .031 0. 025 0 .031 0.029 0. 039 -0. 00 3 sr 0 .010(5) 0. 009(5) 0 .016(5) 0.011(5) 0. 010(5) 0. 03 5' Data summarized as: Mean 5 Standard Deviation (n) 0 Statistical Methods : Trend test (Jonckheere-Terpstra). > 0 # Statistically significant difference at p < 0.05. 0 28 <b H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE 9 Ml3ANDAJ[LY INTAKE OF THE TEST SUBSTANCE BY I^1ALEMKSE Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 G roup I 0 Ppm 0 .00 0 .00(5) 0 .00 0 .00(5) 0 .00 0 .00(5) Mean Daily Intake of H-;24020 (mg/kg/day) Group II]: 1 ppm Group V 3 ppm Group VII 10 ppm G roup IX 30 ppm 0.20 0.02(5) 0.55 0.06(5) 1.89 0.11(5) 5.38 0.67(5) 0.19 0.02(5) 0.58 0.03(5) 1.80 0.08(5) 6.14 1.35(5) 0.20 0.01(5) 0.57 0.03(5) 1.84 0.08(5) 5.76 0.97(5) Grou p 100 p 19. 09 1. 87 29. 07 4. 72 24. 08 2. 83 Mean Daily Intake of H-24648 (mg/kg/day) 0 0 3 Group I Group XV Group XVII Group XIX Group XXI Group X ^ 0 ppm 1 ppm 3 ppm 10 ppm 30 ppm 100 ppm .5 01 Day 0 - Day 7 0 .00 0.19 0.60 1.97 5. 88 24.44 as 0 .00(5) 0.01(5) 0.07(5) 0.11(5) 0. 68(5) 6.76 (5 S 5 Day 7 - Day 14 0 .00 0.19 0.54 1.70 6. 94 23.08 p0 . 0 .00(5) 0.01(5) 0.07(5) 0.10(5) 1. 38(5) 4.88 (5 0 0 m Day 0 - Day 14 0 .00 0.19 0.57 1.83 6. 41 23.76 03 0 .00(5) 0.01(5) 0.07(5) 0.07(5) 0. 94(5) 5.52 (5 8 Data summarized as: Mean 3 3" Standard Deviation (n) 5" 3 0 > 0 co 29 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________ TABLE 10 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY FEMALE MICE Day 0 - Day 7 Day 7 - Day 14 Day O - Day 14 Mean Daily Intake of H-24020 (mg/kg/day) I I Group 0 ppm Group XVI 1 ppm Group XVIII 3 ppm Group XX 10 ppm Group XXII 30 ppm Group 100 p 0.00 0.00(5) 0.29 0.11(4) 0.62 0.06(5) 2.38 0.44(5) 7.41 0.64(5) 25.33 4.13 0.00 0.00(5) 0.27 0.03(4) ' 0.75 0.08(5) 2.66 0.76(5) 7.16 0.86(5) 26.70 5.43 0.00 - 0.00(5) 0.28 0.07(4) 0.68 0.05(5) 2.52 0.58(5) 7.28 0.53(5) 26.01 3.82 Mean Daily Intake of H-24648 (nig/kg/day) I I Group 0 ppm Group XVI 1 ppm Group XVIII Group XX 3 ppm 10 ppm Group XXII 30 ppm Group 100 p Day 0 - Day 7 0.00 0.00(5) 0.29 0.11(4) 0.62 0.06(5) 2.38 0.44(5) 7.41 0.64(5) 25.33 4.13 Day 7 - Day 14 0.00 0.00(5) 0.27 0.03(4) 0.75 0.08(5) 2.66 0.76(5) 7.16 0.86(5) 26.70 5.43 Day O - Day 14 0.00 0.00(5) 0.21 0.02(5) Data summarized as: Mean Standard Deviation (n) 0.66 __0.08(5) 2.37 7.38 25.55 0.35(5)____1.49(5)____2.48 30 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE 11 SUMMARY OF CLINICAL OBSERVATIONS OF MALE MICE Group Concentration (ppm) Animals in Group Clinical Observations of Mice Fed Diet Containing H-24020 III I V 0 1 3 5 5 5 VII IX XI 10 30 100 5 5 5 There were no abnormalities detect ed. Clinical Obs<srvations of Mice Fed Diet Cont.aining H-24648 Group Concentration (ppm) Animals in Group I XV XVII XIX XXI XXIII 0 1 3 10 30 100 5 5 5 5 5 5 Eye Observations Enophthalmus Incidence Mean onset (Days) 0 (0% ) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the first test day an observation was recorded for that grou Statistical Methods: Trend test (Cochran-Armitage). There were no statistically significant differences at p < 0.05. 31 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice (,v$ I 'Ie> ,' ^3 '-^ < CO W f g 1 P" a 0 d> (0 a a | 22.' 5 3 39 3" 3" 3' 3 n > l & > 5 ^ I j TABLE 12 SUMMARY' OF CLINIQ\L OBSERVATIONS5 OF FEMALE MK:E Group Concentration (ppm) Animals in Group Wound Superficial Incidence Mean onset (Days) Misshapen Tail Incidence Mean onset (Days) Clinical 01aservations of Mice Fed Diet Containing H-24(320 II IV VI 0 1 3 5 5 5 VI:II X XII 10 30 100 5 5 5 0 (0%) 0 (0%) 1 (20%) 7 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Clinical Observations of Mice Fed Diet Containing H-24648 Group Concentration (ppm) Animals in Group II XVI XVIII XX 0 1 3 10 5 5 5 5 XXII 30 5 XXIV 100 5 Eye Observations Enophthalmus Incidence Mean onset (Days) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Incidence - The number of animals (percent of group) for which an Mean onset (Days) - The mean of the first test day an observation Statistical Methods: Trend test (Cochran-Armitage). There were no'statistically significant differences at p < 0.05. observation was recorded. was recorded for that gro 32 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE 13 I^EAN FINAL,BODY^\NDLW.ER WEIGHTS OFW\LEMIC:E Mean Final Body Weights , Absolul:e Liver Weights, and Relatere Liver Weights (g) 0 f Mice F<sd Diet C'ontaining H-2 4020 WEIGHT LIVER FINAL BODY LIVER/ FINAL BODY * 100 Group I 0 ppm 1.72 0.20(5) 32.30 2.39(5) 5.32 0.44(5) Group I][I 1 ppm 2.02ft 0.11(5) 32.78 2.02(5) 6.17ft 0.32(5) Gr oup V 3 ppm 2. 22ft 0. 16(5) 32. 50 3. 34(5) 6. 85ft 0. 21(5) Group VII 10 ppm 2.79ft 0.27(5) 32.80 2.40(5) 8.50ft 0.38(5) Gr oup IX 30 ppm 4. 01# 0. 22(5) 32. 98 1. 20(5) 12. 18# 0. 88(5) Group XI 100 ppm 4.72ft 0.46(5) 26.98 1.29(5) 17.48ft* 0.91(5) g0 i sso '< CO 1 WEIGHT i5" LIVER <B P- Mean Final Body Weights , Absolulte Liver Weights, and Relative Liver Weights (g) of Mice Fed Diet Containing H-24648 Group I 0 ppm Group XV 1 ppm Group XVII 3 ppm Group XIX 10 ppm Group XXI 30 ppm Group XX 100 ppm 1.72 0.20(5) 2.26ft 0.11(5) 2. 56ft 0. 31(5) 2.96ft 0.30(5) 4. 10# 0. 44(5) 4.79ft 0.41(4) S? FINAL BODY 0 32.30 (0 M 2.39(5) 3' LIVER/ 3. FINAL BODY * 100 5.32 r 0.44(5) 0 34.12 1.81(5) 6.62ft 0.18(5) 33. 84 1. 84(5) 7. 56ft 0. 67(5) 32.18 2.03(5) 9.20ft 0.53(5) 29. 98 2. 69(5) 13. 69ft 0. 88(5) 26.20ft 1.16(5) 18.30ft* 1.79(4) 3 of 3" Data summarized as: Mean 5 Standard Deviation (n) 2 # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra tren j& 0 * Statistically significant difference between test substances at p < 0. 05 by linear contra (D 33 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________ TABLE 14 M BAN FINAL ]30DYAJMDLIVE R WEIGHTS 0:FFE^IALEM][CE WEIGHT LIVER FINAL BODY LIVER/ FINAL BODY * 100 Mean Final Body Weights , Absolul:e Liver Weights, and R elati\re Liver Weights (g) 0 f Mice F<3d Diet C'ontaining H-24 020 I I Group 0 ppm Group I\/ 1 ppm Gr oup VI 3 ppm Group VIII 10 ppm Gr oup X 30 ppm Group XII 100 ppm 1.44 0.15(5) 26.78 0.81(5) 5.40 0.61(5) 1.45 0.04(4) 25.73 0.22(4) 5.64 0.19(4) 1. 56# 0. 07(5) 25. 32 1. 01(5) 6. 16ft 0. 26(5) 2.12ft 0.18(5) 26.54 2.02(5) 8.01ft* 0.80(5) 2. 95# 0. 16(5) 26. 50 0. 91(5) 11. 14# 0. 35(5) 3.67ft 0.48(5) 26.12 2.65(5) 14.08ft 1.56(5) Mean Final Body Weights , Absolulce Liver Weights, and Relative Liver Weights (g) of Mice Fed Diet Containing H-24648 't? 5 WEIGHT 01 Group I 0 ppm Group XV 1 ppm Group XVII 3 ppm Group XIX 10 ppm Group XXI 30 ppm Group XX 100 ppm ^ LIVER w Stt 1.44 0.15(5) 1.53 0.07(5) 1. 78# 0. 19(5) 2.38# 0.34(5) 3. 15# 0. 19(5) 3.71ft 0.52(5) a ss FINAL BODY 8 p. 26.78 0.81(5) 25.56 1.73(5) 26. 36 1. 25(5) 25.98 2.59(5) 26. 48 1. 07(5) 23.78 1.85(5) 0 LIVER/ 5.40 0 (0 FINAL BODY * 100 0.61(5) m 5.99 0.27(5) 6. 75# 0. 53(5) 9.14#* 0.38(5) 11. 89# 0. 42(5) 15.59ft 1.42(5) 0 ? Data summarized as: Mean Standard Deviation (n) 3 3" # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra tren 5' * Statistically significant difference between test substances at p < 0. 05 by linear contra -1 w 0 > a(X) 34 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____ _______ DuPont-5206 APPENDICES CompanySanitized. Does not confafn r^s ^ 35 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 APPENDIX A INDIVIDUAL BODY WEIGHTS CompanySanded. Does not conta.n TSCA CB 36 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Body Weights (g) of Control Mice Day 0 Male, I Control 124503 124504 124505 124506 124507 31.9 28.0 27.8 30.3 28.4 Day 7 33.2 29.0 28.8 32.6 29.6 Day 14 35.3 30.7 30.4 34.5 30.6 Female, 124574 124575 124576 124577 124578 II Control 24.1 24.1 24.8 22.7 25.2 24.7 23.3 26.7 23.3 26.8 26.1 26.1 27.8 26.4 27.5 DuPont-5206 CompanySanllhed. Does not contain TSCA CM 37 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24020 Day 0 Male, III 1 ppm H-24020 124508 124509 124510 124511 124512 30. 4 27. 1 27. 6 31. 8 29. 3 Day 7 32 .7 30 .2 29 .2 33 .4 31 .2 Day 14 34 .7 31 .4 30 .2 34 .8 32 .8 Male, V 3 ppm H-24020 124513 124514 124515 124516 124517 29. 9 29. 5 25. 7 29. 0 32. 9 31 .4 30 .6 26 .9 30 .9 35 .0 32 .7 32 .0 28 .0 32 .4 37 .4 Male, VII 10 ppm H-24020 124518 124519 124520 124521 124522 29. 4 26. 8 28. 2 30. 9 32. 3 31 .8 28 .1 30 .0 32 .2 33 .7 33 .1 29 .5 31 .9 33 .4 36 .1 Male, IX 30 ppm H-24020 124523 124524 124525 124526 124527 32. 1 30. 3 28. 5 27. 8 28. 7 34 .0 32 .6 31 .1 29 .7 31 .7 34 .4 33 .5 32 .3 31 .3 33 .4 Male, XI 100 ppm H-24020 124528 124529 124530 124531 124532 30. 5 27. 7 30. 2 28. 6 29. 7 30 .9 28 .6 30 .2 28 .9 28 .0 27 .2 26 .9 29 .0 25 .6 26 .2 Male, XIII 300 ppm H-24020 124533 124534 124535 124536 124537 30. 3 29. 2 32. 4 27. 7 30. 7 24 .4 24 .4 25 .4 25 .0 26 .6 23 .8 21 .5 23 .1 24 .2 23 .8 CompanySanitized. Does not contain TSCA CBI 38 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24020 Day 0 Female. IV 1 ppm H-24020 124579 124580 124582 124583 124640 23.0 24.2 23.1 24.3 23.8 Day 7 24 .4 24 .7 25 .1 24 .1 Day 14 25.8 25.4 25.8 25.9 Female, VI 3 ppm H-24020 124584 124585 124586 124587 124588 22.9 23.3 23.3 23.3 24.7 25 .6 24 .1 24 .2 24 .9 25 .4 26.8 24.7 24.2 25.1 25.8 Female, 124589 124590 124591 124592 124593 VIII 10 ppm H-24020 22.4 23.8 21.9 23.9 25.5 23 .1 26 .2 23 .6 27 .7 26 .4 23.7 27.0 25.3 28.4 28.3 Female, X 30 ppm H-24020 124594 124596 124597 124598 124641 23.8 22.1 23.7 24.8 25.7 23 .3 22 .0 24 .5 23 .4 23 .7 26.0 25.4 26.9 26.4 27.8 Female, XII 100 ppm H-24020 124599 124600 124601 124602 124603 23.2 24.9 22.2 24.1 25.2 23 .0 25 .1 21 .5 24 .2 24 .4 22.4 28.2 24.4 27.0 28.6 Female, XIV 300 ppm H-24020 124604 124605 124606 124607 124608 23.5 23.9 22.8 23.5 26.1 21 .3 21 .9 21 .8 21 .1 20 .5 20.2 21.2 22.2 20.4 21.1 Company Sanitized. Does not contain TSCA CBf 39 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24648 Day 0 Male, XV 1 ppm H-24648 124538 124539 124540 124541 124542 30. 6 30. 9 28. 0 31. 3 29. 2 Day 7 33 .4 33 .6 30 .5 34 .3 31 .5 Day 14' 34 .9 35 .2 32 .0 36 .1 32 .4 Male, XVII 3 ppm H-24648 124543 124544 124545 124546 124547 28. 5 28. 1 31. 8 30. 7 29. 6 30 .0 29 .2 33 .0 33 .9 31 .8 32 .8 31 .4 35 .6 35 .7 33 .7 Male, XIX 10 ppm H-24648 124548 124549 124550 124552 124569 30. 5 26. 5 26. 8 29. 2 26. 8 31 .8 29 .1 29 .6 31 .1 28 .6 34 .7 31 .5 31 .8 33 .5 29 .4 Male, XXI 30 ppm H-24648 124553 124554 124555 124556 124557 29. 9 27. 7 25. 9 28. 3 30. 1 30 .4 30 .4 27 .2 30 .9 32 .6 32 .5 29 .2 25 .9 32 .3 30 .0 Male, XXIII 100 ppm H-2468 124558 124559 124560 124561 124562 29. 4 27. 6 26. 8 34. 6 30. 2 27 .7 23 .4 28 .8 29 .0 28 .6 26 .6 24 .3 27 .3 26 .8 26 .0 Male, XXV 300 ppm H-24648 124563 124564 124566 124567 124570 30. 6 28. 2 28. 7 30. 2 27. 6 22 .7 27 .0 23 .9 25 .1 21 .2 22 .9 23 .9 23 .3 22 .7 20 .6 CompanySanitized. Does not contain TSCA CBj 40 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24648 Day 0 Day 7 Female, XVI 1 ppm H-24648 124609 124610 124611 124612 124613 23. 4 24. 6 22. 4 22. 5 25. 7 23 .6 25 .9 23 .1 23 .8 26 .4 Day 14 24 .3 27 .4 24 .1 24 .5 27 .5 Female, XVIII 3 ppm H-24648 124614 124615 124616 124617 124618 25. 5 23. 8 22. 5 23. 6 24. 8 27 .1 24 .2 24 .0 24 .8 26 .3 27 .7 24 .9 26 .1 25 .5 27 .6 Female, XX 124619 124620 124621 124622 124623 10 ppm H-24648 22. 5 24. 4 21. 7 23. 1 26. 1 22 .6 25 .5 22 .2 23 .9 26 .6 24 .1 26 .2 24 .6 24 .6 30 .4 Female, XXII 30 ppm H-24648 124624 124625 124626 124627 124628 21. 6 23. 3 22. 3 23. 5 25. 0 23 .1 24 .8 24 .7 24 .7 25 .4 24 .9 26 .6 26 .3 26 .7 27 .9 Female, XXIV 100 ppm H-24648 124629 124630 124632 124633 124639 23. 0 24. 7 24. 4 27. 2 22. 5 22 .1 24 .7 24 .4 25 .2 25 .7 21 .8 24 .4 22 .1 24 .3 26 .3 Female, XXVI 300 ppm H-24648 124634 124635 124636 124637 124638 25. 0 23. 8 24. 1 24. 8 27. 2 23 .1 19 .5 20 .6 20 .3 22 .8 21 .2 20 .2 19 .2 19 .6 22 .2 Company Sanitized. Does not contatn TCSFA CBt 41 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice _________ DuPont-5206 APPENDIX B INDIVIDUAL FOOD CONSUMPTION CompanySanitized. Does nntcnn^ T<^ ^ 42 ^'ir'\ml pany Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_______________________________________DuPont-5206 Individual Food Consumption (g/day) by Control Mice Day 7 Male, I Control 124503 6.3 124504 5.1 124505 5.7 124506 6.9 124507 5.6 Day 14 7.3 5.0 5.9 6.4 5.9 Female, II Control 124574 6.3 6.6 124575 4.9 5.2 124576 7.7 8.3 124577 5.3 5.9 124578 5.2 5.3 CompanySanltfzed. Does not contain TSCA CBI 43 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice _____ Individual Food Consumption (g/day) DuPont-5206 by Mice Fed Diet Containing H-24020 Day 7 Male, III 1 ppm H-24020 124508 7. 4 124509 5. 8 124510 5. 7 124511 6. 6 124512 5. 5 Day 14 6 .8 6 .3 6 .3 6 .7 5 .5 Male, V 3 ppm H-24020 124513 5. 1 6 .6 124514 5. 8 5 .8 124515 5. 7 5 .6 124516 5. 7 6 .8 124517 5. 9 6 .9 Male, VII 10 ppm H-24020 124518 5. 9 6 .0 124519 5. 4 5 .5 124520 6. 2 5 .8 124521 5. 8 6 .2 124522 6. 1 6 .0 Male, IX 30 ppm H-24020 124523 5. 3 5 .4 124524 5. 2 5 .8 124525 5. 6 6 .3 124526 6. 2 7 .2 124527 6. 2 9 .0 Male, XI 100 ppm H-24020 124528 5. 7 6 .9 124529 5. 3 6 .5 124530 6. 4 8 .4 124531 6. 0 9 .2 124532 4. 7 8 .1 Male, XIII 300 ppm H-24020 124533 5. 3 4 .2 124534 4. 8 5 .0 124535 3. 9 3 .7 124536 6. 4 7 .8 124537 4. 7 4 .6 CompanySanded. Does not contafn TSCA C8I 44 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Food Consumption (g/day) by Mice Fed Diet Containing H-24020 Day 7 Day 14 Female, IV 1 ppm H-24020 124580 5 .3 7 .3 124582 4 .8 5 .7 124583 8 .0 7 .6 124640 10 .5 7 .5 Female, VI 124584 124585 124586 124587 124588 ppm H-24020 5 .1 7 .8 5 .7 6 .1 4 .7 5 .5 4 .6 5 .9 5 .4 6 .2 Female, 124589 124590 124591 124592 124593 VIII 10 ppm H-24020 6 .9 9 .1 6 .3 6 .4 5 .4 7 .4 4 .9 5 .3 6 .4 6 .6 Female, X 30 ppm H-24020 124594 5 .7 6 .0 124596 5 .2 6 .0 124597 5 .4 6 .0 124598 6 .5 5 .6 124641 6 .0 8 .0 Female, XII 100 ppm H-24020 124599 6 .4 6 .4 124600 7 .4 6 .7 124601 5 .9 7 .1 124602 4 .8 5 .1 124603 5 .4 9 .4 Female, XIV 300 ppm H-24020 124604 8 .9 8 .4 124605 4 .9 6 .5 124606 7 .4 8 .9 124607 5 .8 5 .1 124608 8 .0 8 .2 Company Sanitized. Does not contain TSCA CB1 45 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice _____ Individual Food Consumption (g/day) by Mice DuPont-5206 Fed Diet Containing H-24648 Day 7 Male, XV 1 ppm H-24648 124538 6.1 124539 6.8 124540 6.3 124541 6.1 124542 6.0 Day 14 6.5 7.1 6.3 6.8 5.8 Male, XVII 3 ppm H-24648 124543 6.6 6.0 124544 6.7 6.8 124545 5.7 5.6 124546 6.5 5.7 124547 6.0 6.2 Male, XIX 10 ppm H-24648 124548 5.9 5.7 124549 5.8 4.9 124550 5.6 5.6 124552 6.0 6.0 124569 6.2 5.0 Male, XXI 30 ppm H-24648 124553 5.6 6.7 124554 7.2 7.7 124555 5.3 7.6 124556 5.5 6.0 124557 6.1 6.2 Male, XXIII 100 ppm H-2468 124558 5.2 6.2 124559 7.6 7.4 124560 8.0 6.4 124561 4.7 4.5 124562 7.8 5.6 Male, XXV 300 ppm H-24648 124563 5.5 5.8 124564 6.6 5.0 124566 7.6 7.3 124567 6.5 6.6 124570 7.8 5.6 Company SanH.zed. Does not contain TSCA CBI 46 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Pood Consumption (g/day) by Mice Fed Diet Containing H-24648 Day 7 Day 14 Female, XVI 1 ppm H-24648 124609 5 .6 5 .3 124610 5 .8 5 .1 124611 5 .4 4 .9 124612 6 .0 5 .4 124613 4 .6 4 .8 Female, XVIII 3 ppm H-24648 124614 5. 8 5. 4 124615 5. 6 7. 4 124616 4. 7 4. 7 124617 5. 6 5. 7 124618 5. 9 5. 8 Female, XX 10 ppm H-24648 124619 6. 5 6. 1 124620 5. 2 4. 8 124621 4. 8 5. 2 124622 5. 5 5. 9 124623 8. 6 6. 8 Female, XXII 30 ppm H-24648 124624 5. 5 6. 7 124625 5. 0 4. 8 124626 5. 5 5. 6 124627 7. 1 9. 6 124628 5. 6 7. 4 Female, XXIV 100 ppm H-24648 124629 6. 4 5. 2 124630 5. 8 5. 7 124632 6. 4 6. 9 124633 6. 9 6. 1 124639 6. 4 5. 4 Female, XXVI 300 ppm H-24648 124634 5. 9 5. 1 124635 10. 1 6. 4 124636 8. 5 5. 4 124637 7. 8 5. 4 124638 7. 5 6. 2 Company Sanitized. Does not contain TSCA CB1 47 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 APPENDIX C INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY Company Sanilizea. Does not contain TSCA CB? 48 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Control Mice Male, I Control Animal Observation Days 124503 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124504 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124505 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124506 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124507 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female, II Control . Animal Observation 124574 General observation. No Abnormality Detected Sacrificed by design 124575 General observation. No Abnormality Detected Sacrificed by design 124576 General observation. No Abnormality Detected Sacrificed by design 124577 General observation. No Abnormality Detected Sacrificed by design 124578 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 49 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ______ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-2 Male, III 1 ppm H-24020 Animal Observation 124508 General observation. No Abnormality Detected Sacrificed by design 124509 General observation. No Abnormality Detected Sacrificed by design 124510 General observation. No Abnormality Detected Sacrificed by design 124511 General observation. No Abnormality Detected Sacrificed by design 124512 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Male, V 3 ppm H-24020 Animal Observation 124513 General observation. No Abnormality Detected Sacrificed by design 124514 General observation. No Abnormality Detected Sacrificed by design 124515 General observation. No Abnormality Detected Sacrificed by design 124516 General observation. No Abnormality Detected Sacrificed by design 124517 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 50 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-240 Male, VII 10 ppm H-24020 Animal Observation Days 124518 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124519 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124520 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124521 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124522 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Male, IX 30 ppm H-24020 Animal Observation 124523 General observation. No Abnormality Detected Sacrificed by design 124524 General observation. No Abnormality Detected Sacrificed by design 124525 General observation. No Abnormality Detected Sacrificed by design 124526 General observation. No Abnormality Detected Sacrificed by design 124527 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 51 Ill H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice " Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-240 Male, XI 100 ppm H-24020 Animal Observation Days 124528 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124529 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124530 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124531 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124532 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Male, XIII 300 ppm H-24020 Animal Observation 124533 General observation. No Abnormality Detected Sacrificed by design 124534 General observation. No Abnormality Detected Sacrificed by design 124535 General observation. No Abnormality Detected Sacrificed by design 124536 General observation. No Abnormality Detected Sacrificed by design 124537 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 52 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice___ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24 Female, IV 1 ppm H-24020 Animal Observation . Days 124579 General observation. No Abnormality Detected 0-1 Found dead in cage. 1 124580 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124582 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124583 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124640 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female, VI 3 ppm H-24020 Animal Observation 124584 General observation. No Abnormality Detected Sacrificed by design 124585 General observation. No Abnormality Detected Wound, Superficial, Neck Sacrificed by design 124586 General observation. No Abnormality Detected Sacrificed by design 124587 General observation. No Abnormality Detected Sacrificed by design 124588 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0,14 7 14 0-14 14 0-14 14 0-14 14 53 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24 Female, VIII 10 ppm H-24020 Animal Observation . Days 124589 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124590 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124591 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124592 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124593 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female, X 30 ppm H-24020 Animal Observation 124594 General observation. No Abnormality Detected Sacrificed by design 124596 General observation. No Abnormality Detected Sacrificed by design 124597 General observation. No Abnormality Detected Sacrificed by design 124598 General observation. No Abnormality Detected Sacrificed by design 124641 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 54 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice individual Clinical Observations and Mortality of Mice Fed Diet Containing H-2 Female, XII 100 ppm H-24020 Animal Observation Days 124599 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124600 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124601 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124602 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124603 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female, XIV 300 ppm H-24020 Animal Observation 124604 General observation. No Abnormality Detected Misshapen Observations, Tail Sacrificed by design 124605 124606 General observation. No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design 124607 General observation. No Abnormality Detected Sacrificed by design 124608 General observation. No Abnormality Detected Sacrificed by design 0-7 14 14 0-14 14 0-14 14 0-14 14 0-14 14 55 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-2 Male, XV 1 ppm H-24648 Animal Observation . Days 124538 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124539 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124540 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124541 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124542 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Male, XVII 3 ppm H-24648 Animal Observation 124543 General observation. No Abnormality Detected Sacrificed by design 124544 General observation. No Abnormality Detected Sacrificed by design 124545 General observation. No Abnormality Detected Sacrificed by design 124546 General observation. No Abnormality Detected Sacrificed by design 124547 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 56 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-2 Male, XIX 10 ppm H-24648 Animal Observation Days 124548 General observation. No Abnormality Detected . Sacrificed by design 0-14 14 124549 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124550 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124552 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124569 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Male, XXI 30 ppm H-24648 Animal Observation 124553 General observation, No Abnormality Detected Sacrificed by design 124554 General observation, No Abnormality Detected Sacrificed by design 124555 General observation. No Abnormality Detected Sacrificed by design 124556 General observation, No Abnormality Detected Sacrificed by design 124557 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 57 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ______ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-2 Male, XXIII 100 ppm H-2468 Animal Observation, Days 124558 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124559 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124560 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124561 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124562 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Male, XXV 300 ppm H-24648 Animal Observation Days 124563 General observation. No Abnormality Detected 0 Eye Observations, Enophthalmus, Left Sacrificed by design o CD 124564 General observation. No Abnormality Detected -3 Sacrificed by design w 124566 General observation. No Abnormality Detected ^' Sacrificed by design S & 0 124567 General observation. No Abnormality Detected Sacrificed by design u> i 124570 General observation. No Abnormality Detected 0 Eye Observations, Enophthalmus, Right 1 Sacrificed by design fi) 3" -< m 0 > 0 5 58 0 7-14 14 0-14 14 0-14 14 0-14 14 0 7-14 14 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24 Female, XVI 1 ppm H-24648 Animal Observation . Days 124609 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124610 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124611 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124612 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124613 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female. XVIII 3 ppm H-24648 Animal Observation 124614 General observation. No Abnormality Detected Sacrificed by design 124615 General observation. No Abnormality Detected Sacrificed by design 124616 General observation. No Abnormality Detected Sacrificed by design 124617 General observation. No Abnormality Detected Sacrificed by design 124618 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 59 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ____ ^^ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24 Female, XX 10 ppm H-24648 Animal Observation Days 124619 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124620 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124621 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124622 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124623 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female, XXII 30 ppm H-24648 Animal Observation 124624 General observation. No Abnormality Detected Sacrificed by design 124625 General observation. No Abnormality Detected Sacrificed by design 124626 General observation. No Abnormality Detected Sacrificed by design 124627 General observation. No Abnormality Detected Sacrificed by design 124628 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 60  H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24 Female, XXIV 100 ppm H-24648 Animal Observation . Days 124609 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124610 General observation, Mo Abnormality Detected Sacrificed by design 0-14 14 124611 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124612 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124613 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Female, XXVI 300 ppm H-24648 124634 General observation. No Abnormality Detected Sacrificed by design 124635 General observation. No Abnormality Detected Sacrificed by design 124636 General observation. No Abnormality Detected Eye Observations, Enophthalmus, Right Sacrificed by design 124637 General observation. No Abnormality Detected Sacrificed by design 124638 General observation. No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0 7-14 14 0-14 14 0-14 14 61 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 APPENDIX D INDIVIDUAL FINAL BODY AND LIVER WEIGHTS CompanySanded. Does not contain TSCA CBI 62 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 INDIVIDUAL FINAL BODY (FEW) AND LIVER WEIGHTS OF CONTROL MICE Sroup : I 0 ppm Control Sex : MALES ANIMAL FBW (Gms) LIVER (Gms) %PBW 124503 124504 124505 124506 124507 35.30 30.70 30.40 34.50 30.60 2.044 1.501 1.753 1.695 1.608 5.7904 4.8893 5.7664 4.9130 5.2549 3roup : I][ 0 ppm C:ontrol Sex : FEMALES ANIMAL FBW (Gms) LIVER (Gms) %PBW 124574 124575 124576 124577 124578 26.10 26.10 27.80 26.40 27.50 1.294 1.487 1.375 1.674 1.385 4.9579 5.6973 4.9460 6.3409 5.0364 Company Sanitized. Does not contain TSCA CBI 63 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24020 DuPont-5206 Group : III 1 ppm H-24020 Sex : MALES ANIMAL FBW (Gms) | LIVER |(Gms) %FBW 124508 124509 124510 124511 124512 34.70 [ 31.40 30.20 34.80 32.80 2.097 2.076 1.827 2.018 2.088 6.0432 6.6115 6.0497 5.7989 6.3659 Group : V 3 ppm H-24020 Sex : MALES | ANIMAL | FBW | | (Gms) | LIVER |(Gms) %FBW 124513 124514 124515 124516 124517 32.70 32.00 28.00 32.40 37.40 2.244 2.206 1.975 2.248 2.432 6.8624 6.8938 7.0536 6.9383 6.5027 Group : VII 10 ppm H-24020 Sex : MALES ANIMAL FBW (Gms) LIVER (Gms) %FBW 124518 124519 124520 124521 124522 33.10 29.50 31.90 33.40 36.10 2.947 2.344 2.722 2.934 3.009 8.9033 7.9458 8.5329 8.7844 8.3352 Group : IX 30 ppm H-24020 Sex : MALES ANIMAL FBW (Gms) | LIVER |(Gms) %FBW 124523 124524 124525 124526 124527 34.40 33.50 32.30 31.30 33.40 4.175 3.676 4.195 4.095 3.922 12.137 10.973 12.988 13.083 11.743 CompanySanitized. Does no! conlain TSCA CBI 64 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ^^ ___ Individual Final Body (FBW) and Liver Weights of Mice Fed.Diet Containing H-24020 DuPont-5206 3roup : X3I 100 ppnn H-24020 Sex : MALES ANIMAL FBW (Gms) LIVER (Gms) %FBW 124528 124529 124530 124531 124532 27.20 26.90 29.00 25.60 26.20 4.866 4.672 5.392 4.121 4.572 17.890 17.368 18.593 16.098 17.450 3roup : XIII 300 ppm H-24020 Sex : MALE ANIMAL FBW (Gms) LIVER (Gms) %FBW 124533 124534 124535 124536 124537 23.80 21.50 23.10 24.20 23.80 3.887 3.839 4.239 4.028 3.741 16.332 17.856 18.351 16.645 15.718 Company Sanitized. Does not conan TSCA C 65 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ^^ Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24020 DuPont-5206 Group : IV 1 ppm H-24020 Sex : FEMALES | ANIMAL | FBW | | (Gms) | LIVER |(Gms) %FBW 124579 124580 124582 124583 124640 -- 25.80 25.40 25.80 25.90 _ 1.449 1.487 1.391 1.473 - 5.6163 5.8543 5.3915 5.6873 Group : VI 3 ppm H-24020 Sex : FEMALES | ANIMAL | FBW | LIVER | | | (Gms) |(Gms) %FBW | 124584 124585 124586 124587 124588 26.80 | 24.70 24.20 25.10 25.80 | 1.654 1.611 1.519 1.496 1.512 6.1716 6.5223 6.2769 5.9602 5.8605 Group : VIII 10 ppm H-24020 Sex : FEMALES | ANIMAL | FBW | | (Gms) | LIVER |(Gms) %FBW 124589 124590 124591 124592 124593 23.70 27.00 25.30 28.40 28.30 2.013 2.314 2.102 1.881 2.285 8.4937 8.5704 8.3083 6.6232 8.0742 Group : X 30 ppm H-24020 Sex : FEMALES | ANIMAL FBW LIVER | (Gms) (Gms) %FBW | 124594 124596 124597 124598 124641 26.00 25.40 26.90 26.40 27.80 2.906 2.789 3.141 2.834 3.094 11.177 10.980 11.677 10.735 11.129 ' Mouse was found dead on test day 1. Company Sanitized. Does not contain TSCA CS^ 66 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice____________ Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24020 DuPont-5206 Group : X]n 100 pi3m H-24020 Sex : FEMAL ANIMAL FBW LIVER | (Gms) (Gms) %FBW | 124599 124600 124601 124602 124603 22.40 28.20 24.40 27.00 28.60 3.610 3.872 3.123 3.374 4.358 16.116 13.730 12.799 12.496 15.238 3roup : XI[V 300 PE3m H-24020 Sex : FEMAL ANIMAL FBW (Gms) LIVER (Gms) %FBW 124604 124605 124606 124607 124608 20.20 21.20 22.20 20.40 21.10 3.753 3.604 3.998 3.443 3.025 18.579 17.000 18.009 16.877 14.336 Company Sanitized. Does not contain TSCA CS1 67 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Final Body (FEW) and Liver Weights of Mice Fed Diet Containing H-24648 DuPont-5206 Group : XV 1 ppm H-24648 Sex : MALES ANIMAL | FBW | (Gms) | LIVER [(Gms) %FBW 124538 124539 124540 124541 124542 34.90 35.20 32.00 36.10 | 32.40 2.312 2.396 2.123 2.285 2.165 6.6246 6.8068 6.6344 6.3296 6.6821 Group : XVII 3 ppm H-24648 Sex : MALES ANIMAL FBW | (Gms) | LIVER [(Gms) %PBW 124543 124544 124545 124546 124547 32.80 31.40 35.60 35.70 33.70 2.299 2.453 2.669 3.055 2.329 7.0091 7.8121 7.4972 8.5574 6.9110 Group : XIX 10 ppm H-24648 Sex : MALES ANIMAL | FBW | (Gms) | LIVER |(Gms) %FBW 124548 124549 124550 124552 124569 34.70 31.50 31.80 33.50 29.40 3.387 2.629 3.014 3.077 2.714 9.7608 8.3460 9.4780 9.1851 9.2313 Group : XXI 30 ppm H-24648 Sex : MALES | ANIMAL | FBW | | (Gms) | LIVER |(Gms) %PBW 124553 124554 124555 124556 124557 32.50 29.20 25.90 32.30 30.00 3.988 4.117 3.481 4.696 4.222 12.271 14.099 13.440 14.539 14.073 Company Sanitized. Does not contain TSCA CBI 68 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24648 DuPont-5206 Group : XXIII 100 ppm H-24648 ANIMAL | FBW | (Gms) j LIVER |(Gms) %FBW Sex : MALES 124558 124559 124560 124561 124562 26.60 24.30 27.30 26.80 26.00 5.084 4.806 5.075 4.214 a 19.113 19.778 18.590 15.724 Sroup : X?W 300 pr3m H-24648 Sex : MALES ANIMAL FBW (Gms) LIVER (Gms) %FBW 124563 124564 124566 124567 124570 22.90 23.90 23.30 22.70 20.60 3.736 3.313 3.538 4.225 3.530 16.314 13.862 15.185 18.612 17.136 ' Due to error, the liver was not weighed. Company Sanitized- Does not contain TSCA CBS 69 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Final Body (FEW) and Liver Weights of Mice Fed.Diet Containing H-24648 DuPont-5206 Group : XVI 1 ppm H-24648 Sex ; FEMALES | ANIMAL FEW | LIVER | (Gms) |(Gms) %FBW | 124609 124610 124611 124612 124613 24.30 27.40 24.10 24.50 27.50 1.480 1.611 1.547 1.429 1.580 6.0905 5.8796 6.4191 5.8327 5.7455 Group : XVIII 3 ppm H-24648 Sex : FEMALES | ANIMAL FBW (Gins) LIVER (Gms) %FBW 124614 124615 124616 124617 124618 27.70 24.90 26.10 25.50 27.60 | 1.742 1.605 1.828 1.644 2.091 6.2888 6.4458 7.0038 6.4471 7.5761 Group : XX 10 ppm H-24648 Sex : FEMALES ANIMAL | FBW | LIVER | | (Gms) |(Gms) %FBW | 124619 124620 124621 124622 124623 24.10 | 26.20 24.60 24.60 30.40 2.095 2.449 2.196 2.232 2.942 8.6929 9.3473 8.9268 9.0732 9.6776 Mean S.D. 25.98 2.59 2.383 9.1436 0.338 0.3814 Group : XXII 30 ppro H-24648 Sex : FEMALES ANIMAL FBW (Gms) LIVER (Gms) %FBW 124624 124625 124626 124627 124628 24.90 26.60 26.30 26.70 27.90 2.857 3.248 3.050 3.325 3.264 11.474 12.211 11.597 12.453 11.699 Company Sanitized. Does not co"ta'i T8CA cat 70 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice _______ Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24648 DuPont-5206 3roup ; XXIV 100 ppm H-24648 Sex : FEW ANIMAL FBW (Gms) LIVER (Gms) %FBW 124629 124630 124632 124633 124639 21.80 24.40 22.10 24.30 26.30 3.307 3.299 3.421 4.185 4.360 15.170 13.520 15.480 17.222 16.578 Group : XXVI 300 ppm H-24648 Sex : FEMALES ANIMAL FBW LI\^ER | (Gms) (Gms) %FBW | 124634 124635 124636 124637 124638 21.20 20.20 19.20 19.60 22.20 4.741 4.019 3.246 3.588 4.258 22.363 19.896 16.906 18.306 19.180 Company Sanitized. Does not contain TSCA CBI 71